NCBI Conserved Domain Search

First immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409547 Cd Length: 99 Bit Score: 217.28 E-value: 1.06e-65

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203   38 GPVFLKEPTNRIDFSNSTGAEIECKASGNPMPEIIWIRSDGTAVGDVPGLRQISSDGKLVFPPFRAEDYRQEVHAQVYAC 117
Cdd:cd20955    1 GPVFLKEPTNRIDFSNSTGAEIECKASGNPMPEIIWIRSDGTAVGDVPGLRQISSDGKLVFPPFRAEDYRQEVHAQVYAC 80

                         90
                 ....*....|....*....
gi 24586203  118 LARNQFGSIISRDVHVRAV 136
Cdd:cd20955   81 LARNQFGSIISRDVHVRAV 99

Down syndrome cell adhesion molecule C terminal; This domain family is found in eukaryotes, and is approximately 120 amino acids in length. The family is found in association with pfam00047, pfam07679, pfam00041. The Down syndrome cell adhesion molecule (Dscam) belongs to a family of cell membrane molecules involved in the differentiation of the nervous system. This is the C terminal cytoplasmic tail region of Dscam.

Pssm-ID: 463546 Cd Length: 118 Bit Score: 205.64 E-value: 2.09e-61

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203   1871 PGPEYDDPANCApEEDQYGSQYGGPYGQPYDHYGSRGSMGRRSIGSARN-PGNGSPEPPPPPPRNHDMSNSSFNDSKESN 1949
Cdd:pfam12355    3 PGPEYDDPANCA-EDDQYGSQYSGPYGAPYDHYGSRGSLGRRSVGSARNlPGNGSPEPPPPPPRNHDVSNSSFNDSKESN 81

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 24586203   1950 EISEAECDRDHGPRGNYGAVKRSPQPKDQRTTEEMRK 1986
Cdd:pfam12355   82 EISEAECDRDHLVNRNYGVGIRTMNSKDGMSTEEMRK 118

Second immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. DSCAM is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409545 Cd Length: 95 Bit Score: 201.23 E-value: 4.08e-60

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  246 PPKINALT-YKPNIVESMASTAILCPAQGYPAPSFRWYKFIEGTTRKQAVVLNDRVKQVSGTLIIKDAVVEDSGKYLCVV 324
Cdd:cd20953    1 APKIPGLSkSQPLTVSSASSIALLCPAQGYPAPSFRWYKFIEGTTRKQAVVLNDRVKQVSGTLIIKDAVVEDSGKYLCVV 80

                         90
                 ....*....|....*
gi 24586203  325 NNSVGGESVETVLTV 339
Cdd:cd20953   81 NNSVGGESVETVLTV 95

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 179.82 E-value: 1.17e-52

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  714 PPRWILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKAVGDTPGEYKDLKKSDNIRVEE-GTLHVDNIQKTNEGYYLCEA 792
Cdd:cd20954    1 PPRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKATGSTPGEYKDLLYDPNVRILPnGTLVFGHVQKENEGHYLCEA 80

                         90
                 ....*....|....*.
gi 24586203  793 INGIGSGLSAVIMISV 808
Cdd:cd20954   81 KNGIGSGLSKVIFLKV 96

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 171.97 E-value: 5.79e-50

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  428 PPVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVGQYVTVNGDVVSYLNITSVHANDGGLYKCI 507
Cdd:cd20956    1 APVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDGFPIPESPRFRVGDYVTSDGDVVSYVNISSVRVEDGGEYTCT 80

                         90
                 ....*....|....*.
gi 24586203  508 AKSKVGVAEHSAKLNV 523
Cdd:cd20956   81 ATNDVGSVSHSARINV 96

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 164.66 E-value: 1.69e-47

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  527 PYIRQMEKKAIVAGETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVFPNGTLIIENVERNSDQATYTCVAKNQEGYSA 606
Cdd:cd20958    2 PFIRPMGNLTAVAGQTLRLHCPVAGYPISSITWEKDGRRLPLNHRQRVFPNGTLVIENVQRSSDEGEYTCTARNQQGQSA 81


                 ....*...
gi 24586203  607 RGSLEVQV 614
Cdd:cd20958   82 SRSVFVKV 89

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 148.45 E-value: 9.70e-42

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  342 PLSAKIDPPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIGHS-------EPVLRIESVKKEDKGMYQCFVRNDQESA 414
Cdd:cd20957    1 PLSATIDPPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSsrvqilsEDVLVIPSVKREDKGMYQCFVRNDGDSA 80


                 ....*...
gi 24586203  415 EASAELKL 422
Cdd:cd20957   81 QATAELKL 88

Sixth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the sixth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409551 Cd Length: 94 Bit Score: 127.99 E-value: 1.40e-34

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  617 PPQVLPFSFGESAADVGDIASANCVVPKGDLPLEIRWSLNSAPIVNgENGFTLVRLNKRTSLLNIDSLNAFHRGVYKCIA 696
Cdd:cd20959    1 PPRIIPFAFGEGAAQVGMRAQLHCGVPGGDLPLNIRWTLDGQPISD-DLGITVSRLGRRSSILSIDSLEASHAGNYTCHA 79

                         90
                 ....*....|....*
gi 24586203  697 TNPAGTSEYVAELQV 711
Cdd:cd20959   80 RNSAGSASYTAPLTV 94

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 91.99 E-value: 1.40e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  892 ATNAFGSDDASINMIV---QEVPEMPYALKVLDKSGRSVQLSWAQPydGNSPLDRYIIEfkRSRAS---WSEIDRVIvpg 965
Cdd:COG3401  211 ATDTGGESAPSNEVSVttpTTPPSAPTGLTATADTPGSVTLSWDPV--TESDATGYRVY--RSNSGdgpFTKVATVT--- 283

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  966 hTTEAQVQKLSPATTYNIRIVAENAIG-TSQSSEAVTIITAEEAPSgKPQNIKVEPVNQTTMRVTWKPPPrtewNGEILG 1044
Cdd:COG3401  284 -TTSYTDTGLTNGTTYYYRVTAVDAAGnESAPSNVVSVTTDLTPPA-APSGLTATAVGSSSITLSWTASS----DADVTG 357

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1045 YYVgYKLSNTNSSYVfetinFITEEGKEHNLELQNLRVYTQYSVVIQAFNKIGAGPLSEEEKQFTAEGTPSQPPSDTACT 1124
Cdd:COG3401  358 YNV-YRSTSGGGTYT-----KIAETVTTTSYTDTGLTPGTTYYYKVTAVDAAGNESAPSEEVSATTASAASGESLTASVD 431

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1125 TLTSQTIrVGWVSPPLESANGVIKTYKVVYAPSDEWYDETkrhykkTASSDTVLHGLKKYTNYTMQVLATTAGGDGVRSV 1204
Cdd:COG3401  432 AVPLTDV-AGATAAASAASNPGVSAAVLADGGDTGNAVPF------TTTSSTVTATTTDTTTANLSVTTGSLVGGSGASS 504


                 .
gi 24586203 1205 P 1205
Cdd:COG3401  505 V 505

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 77.15 E-value: 8.67e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  911 PEMPYALKVLDKSGRSVQLSWAQPYDGNSPLDRYIIEFKRSRAS-WSEIDRVivPGHTTEAQVQKLSPATTYNIRIVAEN 989
Cdd:cd00063    1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGdWKEVEVT--PGSETSYTLTGLKPGTEYEFRVRAVN 78

                         90
                 ....*....|....*
gi 24586203  990 AIGTSQSSEAVTIIT 1004
Cdd:cd00063   79 GGGESPPSESVTVTT 93

Immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409398 Cd Length: 101 Bit Score: 75.22 E-value: 6.77e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  823 ARRGEPAVLQCEAKGEKPIGILWNMNNMRLDPKNDNRYTIREEILSTGVMSSLSIKRTERSDSALFTCVATNAFGSDDAS 902
Cdd:cd05735   15 ATKGQKKEMSCTAHGEKPIIVRWEKEDTIINPSEMSRYLVTTKEVGDEVISTLQILPTVREDSGFFSCHAINSYGEDRGI 94


                 ....*..
gi 24586203  903 INMIVQE 909
Cdd:cd05735   95 IQLTVQE 101

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 73.06 E-value: 2.78e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203    429 PVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQvgqyVTVNGDVVSyLNITSVHANDGGLYKCIA 508
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFK----VTYEGGTYT-LTISNVQPDDSGKYTCVA 75

                           90
                   ....*....|....*
gi 24586203    509 KSKVGVAEHSAKLNV 523
Cdd:pfam07679   76 TNSAGEAEASAELTV 90

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 81.59 E-value: 2.89e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1084 TQYSVVIQAFNKIGAGPLSEEeKQFTAEGTPSQPPSDTACTTLTSQTIRVGWVSPPLESANGviktYKVVYAPSDewyDE 1163
Cdd:COG3401  203 TTYYYRVAATDTGGESAPSNE-VSVTTPTTPPSAPTGLTATADTPGSVTLSWDPVTESDATG----YRVYRSNSG---DG 274

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1164 TKRHYKKTASSDTVLHGLKKYTNYTMQVLA-TTAGGDGVRSVPIHCQTEPDVPEAPTDVKALVMGNAAILVSWRPPAQPN 1242
Cdd:COG3401  275 PFTKVATVTTTSYTDTGLTNGTTYYYRVTAvDAAGNESAPSNVVSVTTDLTPPAAPSGLTATAVGSSSITLSWTASSDAD 354

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1243 giITQYTVYSKAEG-------AETETKTqkvphyqmSFEATELEKNKPYEFWVTASTTIG-EGQQSKSIVAMPSDQVPAK 1314
Cdd:COG3401  355 --VTGYNVYRSTSGggtytkiAETVTTT--------SYTDTGLTPGTTYYYKVTAVDAAGnESAPSEEVSATTASAASGE 424


                 ...
gi 24586203 1315 IAS 1317
Cdd:COG3401  425 SLT 427

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 71.68 E-value: 5.84e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203    914 PYALKVLDKSGRSVQLSWAQPYDGNSPLDRYIIEFKRSRASWSEIdRVIVPGHTTEAQVQKLSPATTYNIRIVAENAIGT 993
Cdd:pfam00041    3 PSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPWN-EITVPGTTTSVTLTGLKPGTEYEVRVQAVNGGGE 81


                   ....
gi 24586203    994 SQSS 997
Cdd:pfam00041   82 GPPS 85

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 71.76 E-value: 7.95e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1011 GKPQNIKVEPVNQTTMRVTWKPPPrtEWNGEILGYYVGYKLSNTNSSYVFEtinfiTEEGKEHNLELQNLRVYTQYSVVI 1090
Cdd:cd00063    2 SPPTNLRVTDVTSTSVTLSWTPPE--DDGGPITGYVVEYREKGSGDWKEVE-----VTPGSETSYTLTGLKPGTEYEFRV 74

                         90
                 ....*....|....*....
gi 24586203 1091 QAFNKIGAGPLSEEEKQFT 1109
Cdd:cd00063   75 RAVNGGGESPPSESVTVTT 93

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 71.29 E-value: 9.88e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203   1011 GKPQNIKVEPVNQTTMRVTWKPPPrtEWNGEILGYYVGYKLSNTNssyvfETINFITEEGKEHNLELQNLRVYTQYSVVI 1090
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPPP--DGNGPITGYEVEYRPKNSG-----EPWNEITVPGTTTSVTLTGLKPGTEYEVRV 73

                           90
                   ....*....|..
gi 24586203   1091 QAFNKIGAGPLS 1102
Cdd:pfam00041   74 QAVNGGGEGPPS 85

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 70.36 E-value: 2.30e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203    812 PEFTEKLRNQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLdpKNDNRYTIREEilstGVMSSLSIKRTERSDSALFTCV 891
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPL--RSSDRFKVTYE----GGTYTLTISNVQPDDSGKYTCV 74

                           90
                   ....*....|....*.
gi 24586203    892 ATNAFGSDDASINMIV 907
Cdd:pfam07679   75 ATNSAGEAEASAELTV 90

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 69.90 E-value: 2.62e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203    428 PPVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDryqvgQYVTVNGDVVSYLNITSVHANDGGLYKCI 507
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGS-----TRSRSLSGSNSTLTISNVTRSDAGTYTCV 75


                   ..
gi 24586203    508 AK 509
Cdd:pfam13927   76 AS 77

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 68.29 E-value: 1.28e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1215 PEAPTDVKALVMGNAAILVSWRPPAQPNGIITQYTVYSKAEGAETETKTQKVPHYQMSFEATELEKNKPYEFWVTASTTI 1294
Cdd:cd00063    1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRAVNGG 80

                         90
                 ....*....|.
gi 24586203 1295 GEGQQSKSIVA 1305
Cdd:cd00063   81 GESPPSESVTV 91

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 76.19 E-value: 1.33e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  975 LSPATTYNIRIVAENAIGTSQSSEAVTIITAEEAPSgKPQNIKVEPVNQTTMRVTWKPPPrtewNGEILGYYVgYKLSNT 1054
Cdd:COG3401  199 IEPGTTYYYRVAATDTGGESAPSNEVSVTTPTTPPS-APTGLTATADTPGSVTLSWDPVT----ESDATGYRV-YRSNSG 272

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1055 NSSYV---FETINFITEEGKEHNlelqnlrvyTQYSVVIQAFNKIG-AGPLSEEEKqFTAEGTPSQPPSDTACTTLTSQT 1130
Cdd:COG3401  273 DGPFTkvaTVTTTSYTDTGLTNG---------TTYYYRVTAVDAAGnESAPSNVVS-VTTDLTPPAAPSGLTATAVGSSS 342

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1131 IRVGWVSppleSANGVIKTYKVVYAPSDEW-YDETKRHYKKTASSDTvlhGLKKYTNYTMQVLATTAGGD-GVRSVPIHC 1208
Cdd:COG3401  343 ITLSWTA----SSDADVTGYNVYRSTSGGGtYTKIAETVTTTSYTDT---GLTPGTTYYYKVTAVDAAGNeSAPSEEVSA 415

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1209 QTEPDVP-EAPTDVKALVMGNAAILVSWRPPAQPNGIITQYTVYSKAEGAEtetktqKVPHYQMSFEATELEKNKPYEFW 1287
Cdd:COG3401  416 TTASAASgESLTASVDAVPLTDVAGATAAASAASNPGVSAAVLADGGDTGN------AVPFTTTSSTVTATTTDTTTANL 489

                        330       340       350
                 ....*....|....*....|....*....|....*...
gi 24586203 1288 VTASTTIGEGQQSKSIVAMPSDQVPAKIASFDDTFTAT 1325
Cdd:COG3401  490 SVTTGSLVGGSGASSVTNSVSVIGASAAAAVGGAPDGT 527

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 66.37 E-value: 5.25e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  429 PVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVgqYVTVNGdVVSyLNITSVHANDGGLYKCIA 508
Cdd:cd05744    1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKM--LVRENG-RHS-LIIEPVTKRDAGIYTCIA 76

                         90
                 ....*....|....*
gi 24586203  509 KSKVGVAEHSAKLNV 523
Cdd:cd05744   77 RNRAGENSFNAELVV 91

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 65.94 E-value: 6.82e-13

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24586203 1332 MPCLAVGAPQPEITWKiKGVE-FSANDRMRVLPDGSLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1399
Cdd:cd04969   22 IECKPKASPKPTISWS-KGTElLTNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 65.71 E-value: 7.14e-13

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203    1011 GKPQNIKVEPVNQTTMRVTWKPPPRTEWNGEILGYYVGYKLSNTNSSYVfetinfiTEEGKEHNLELQNLRVYTQYSVVI 1090
Cdd:smart00060    2 SPPSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYREEGSEWKEV-------NVTPSSTSYTLTGLKPGTEYEFRV 74


                    ....*....
gi 24586203    1091 QAFNKIGAG 1099
Cdd:smart00060   75 RAVNGAGEG 83

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 65.04 E-value: 9.17e-13

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24586203  269 CPAQGYPAPSFRWYKfiEGTTRKQAVVLNDRVKQVSGTLIIKDAVVEDSGKYLCVVNNSVGGESVETV 336
Cdd:cd00096    5 CSASGNPPPTITWYK--NGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 65.36 E-value: 1.34e-12

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24586203   1328 EDAKMPCLAVGAPQPEITWKIKGVEFSANDRMRVLPDG---SLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1399
Cdd:pfam07679   16 ESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGgtyTLTISNVQPDDSGKYTCVATNSAGEAEASAELTV 90

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 64.83 E-value: 1.66e-12

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203     436 QEETMEPGPSVFLKCVAGGNPTPEISWELDG-KKIANNDRYQVgqyvtVNGDVVSYLNITSVHANDGGLYKCIAKSKVGV 514
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGgKLLAESGRFSV-----SRSGSTSTLTISNVTPEDSGTYTCAATNSSGS 76


                    ....*....
gi 24586203     515 AEHSAKLNV 523
Cdd:smart00410   77 ASSGTTLTV 85

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 64.83 E-value: 2.47e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1497 PKLPEKPRFIEVSSNSVSLHFKAWKDGGCPMSHFVVESKKRDQIEWNQISNNVKPDNNYVVLDLEPATWYNLRITAHNSA 1576
Cdd:cd00063    1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRAVNGG 80


                 .
gi 24586203 1577 G 1577
Cdd:cd00063   81 G 81

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 64.06 E-value: 3.48e-12

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203     349 PPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDG-KAIGHSE----------PVLRIESVKKEDKGMYQCFVRNDQESAEAS 417
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGgKLLAESGrfsvsrsgstSTLTISNVTPEDSGTYTCAATNSSGSASSG 80


                    ....
gi 24586203     418 AELK 421
Cdd:smart00410   81 TTLT 84

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 63.97 E-value: 3.71e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203   1217 APTDVKALVMGNAAILVSWRPPAQPNGIITQYTVYSKAEGAETETKTQKVPHYQMSFEATELEKNKPYEFWVTASTTIGE 1296
Cdd:pfam00041    2 APSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPWNEITVPGTTTSVTLTGLKPGTEYEVRVQAVNGGGE 81


                   ....
gi 24586203   1297 GQQS 1300
Cdd:pfam00041   82 GPPS 85

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 63.29 E-value: 5.05e-12

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203     819 RNQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLdPKNDNRYTIREEilstGVMSSLSIKRTERSDSALFTCVATNAFGS 898
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKL-LAESGRFSVSRS----GSTSTLTISNVTPEDSGTYTCAATNSSGS 76


                    ....*....
gi 24586203     899 DDASINMIV 907
Cdd:smart00410   77 ASSGTTLTV 85

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 63.05 E-value: 8.54e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203    349 PPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIGHSEPV----------LRIESVKKEDKGMYQCFVRNDQESAEASA 418
Cdd:pfam07679    7 PKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFkvtyeggtytLTISNVQPDDSGKYTCVATNSAGEAEASA 86


                   ...
gi 24586203    419 ELK 421
Cdd:pfam07679   87 ELT 89

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 61.96 E-value: 1.04e-11

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24586203 1330 AKMPCLAVGAPQPEITWKIKGVEFSANDRMR---VLPDGSLLIKSVNRQDAGDYSCHAENSI 1388
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSrrsELGNGTLTISNVTLEDSGTYTCVASNSA 62

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 62.25 E-value: 1.26e-11

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203     911 PEMPYALKVLDKSGRSVQLSWAQPYDGN--SPLDRYIIEFKRSRASWSeidRVIVPGHTTEAQVQKLSPATTYNIRIVAE 988
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGitGYIVGYRVEYREEGSEWK---EVNVTPSSTSYTLTGLKPGTEYEFRVRAV 77


                    ....*.
gi 24586203     989 NAIGTS 994
Cdd:smart00060   78 NGAGEG 83

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 61.25 E-value: 3.11e-11

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24586203 1328 EDAKMPCLAVGAPQPEITWKIKGVEFSANDRMRVLPDGSLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1399
Cdd:cd20978   17 QDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVEDGTLTIINVQPEDTGYYGCVATNEIGDIYTETLLHV 88

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 61.44 E-value: 3.30e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  428 PPVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVGQyvtvNGDVVSYLnITSVHANDGGLYKCI 507
Cdd:cd20972    1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQ----EGDLHSLI-IAEAFEEDTGRYSCL 75

                         90
                 ....*....|....*.
gi 24586203  508 AKSKVGVAEHSAKLNV 523
Cdd:cd20972   76 ATNSVGSDTTSAEIFV 91

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 68.11 E-value: 3.77e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1109 TAEGTPSQPPSDTACTTLTSQTIRVGWVSPPLESANGVIKTYKVVYAPSDEWYDETKRHYKKTASSDTVLHGL--KKYTN 1186
Cdd:COG3401  125 ATTATAVAGGAATAGTYALGAGLYGVDGANASGTTASSVAGAGVVVSPDTSATAAVATTSLTVTSTTLVDGGGdiEPGTT 204

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1187 YTMQVLATTAGGDGVRSVPIHCQTEPDVPEAPTDVKALVMGNAAILVSWRPPAQPNgiITQYTVYSKAEGAETETKTQKV 1266
Cdd:COG3401  205 YYYRVAATDTGGESAPSNEVSVTTPTTPPSAPTGLTATADTPGSVTLSWDPVTESD--ATGYRVYRSNSGDGPFTKVATV 282

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 24586203 1267 PhyQMSFEATELEKNKPYEFWVTASTTIG-EGQQSKSIVAMPSDQVPA 1313
Cdd:COG3401  283 T--TTSYTDTGLTNGTTYYYRVTAVDAAGnESAPSNVVSVTTDLTPPA 328

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 61.10 E-value: 3.99e-11

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1330 AKMPCLAVGAPQPEITWkIKGVE-FSANDRMRVLPDGSLLIKSVNRQDAGDYSCHAENSI 1388
Cdd:cd20968   17 AVLPCTTMGNPKPSVSW-IKGDDlIKENNRIAVLESGSLRIHNVQKEDAGQYRCVAKNSL 75

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 60.60 E-value: 5.73e-11

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24586203    1328 EDAKMPCLAVGAPQPEITW-KIKGVEFSANDRMRVLPDG---SLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1399
Cdd:smart00410   10 ESVTLSCEASGSPPPEVTWyKQGGKLLAESGRFSVSRSGstsTLTISNVTPEDSGTYTCAATNSSGSASSGTTLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 59.89 E-value: 8.45e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24586203    347 IDPPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIGH----------SEPVLRIESVKKEDKGMYQCFVRN 409
Cdd:pfam13927    6 VSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSgstrsrslsgSNSTLTISNVTRSDAGTYTCVASN 78

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 60.20 E-value: 8.48e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  348 DPPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIGHSEP--------VLRIESVKKEDKGMYQCFVRNDQESAEASAE 419
Cdd:cd20952    5 GPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDErittlengSLQIKGAEKSDTGEYTCVALNLSGEATWSAV 84


                 .
gi 24586203  420 L 420
Cdd:cd20952   85 L 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 59.50 E-value: 9.88e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24586203    527 PYIRQMEKKAIVA-GETLIVTCPVAGYPIDSIVWERDNRALPINRKQK---VFPNGTLIIENVERnSDQATYTCVAKN 600
Cdd:pfam13927    2 PVITVSPSSVTVReGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSrslSGSNSTLTISNVTR-SDAGTYTCVASN 78

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 59.27 E-value: 1.13e-10

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24586203  446 VFLKCVAGGNPTPEISWELDGKKIANNDRYQVgqyvtVNGDVVSYLNITSVHANDGGLYKCIAKSKVGVAEHS 518
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSR-----RSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASA 68

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 59.36 E-value: 1.60e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  812 PEFTEKLRNQTARRGEPAVLQCEAKGE-KPIgILWNMNNMRLDP-KNDNRYTIREEilstGVMSSLSIKRTERSDSALFT 889
Cdd:cd20951    1 PEFIIRLQSHTVWEKSDAKLRVEVQGKpDPE-VKWYKNGVPIDPsSIPGKYKIESE----YGVHVLHIRRVTVEDSAVYS 75

                         90
                 ....*....|....*....
gi 24586203  890 CVATNAFGSDDASINMIVQ 908
Cdd:cd20951   76 AVAKNIHGEASSSASVVVE 94

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 59.19 E-value: 1.86e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203    529 IRQMEKKAIVAGETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVFPNG---TLIIENVERnSDQATYTCVAKNQEGyS 605
Cdd:pfam07679    4 TQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGgtyTLTISNVQP-DDSGKYTCVATNSAG-E 81


                   ....*....
gi 24586203    606 ARGSLEVQV 614
Cdd:pfam07679   82 AEASAELTV 90

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 58.11 E-value: 2.35e-10

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 24586203  543 LIVTCPVAGYPIDSIVWERDNRALPINRKQKVF---PNGTLIIENVERnSDQATYTCVAKNQEGYSARGSL 610
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRselGNGTLTISNVTL-EDSGTYTCVASNSAGGSASASV 70

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 59.18 E-value: 2.49e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  428 PPVI--RQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDryqvgQYVTVNGDvVSYLNITSVHANDGGLYK 505
Cdd:cd05730    1 PPTIraRQSEVNATANLGQSVTLACDADGFPEPTMTWTKDGEPIESGE-----EKYSFNED-GSEMTILDVDKLDEAEYT 74

                         90
                 ....*....|....*....
gi 24586203  506 CIAKSKVGVAEHSAKLNVY 524
Cdd:cd05730   75 CIAENKAGEQEAEIHLKVF 93

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 58.81 E-value: 2.67e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24586203    264 STAIL-CPAQGYPAPSFRWYKfiEGTTRKQAVVLNDRVKQVSGTLIIKDAVVEDSGKYLCVVNNSVGGESVETVLTV 339
Cdd:pfam07679   16 ESARFtCTVTGTPDPEVSWFK--DGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAGEAEASAELTV 90

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409435 Cd Length: 96 Bit Score: 58.80 E-value: 2.69e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203   38 GPVFLKEPTNRIDFSNSTGAEI--ECKASGNPMPEIIWIRsDGTAVGDVPGLRQISSDGKLVFP-PFRAEDYRQevhaqv 114
Cdd:cd05848    1 GPVFVQEPDDAIFPTDSDEKKVilNCEARGNPVPTYRWLR-NGTEIDTESDYRYSLIDGNLIISnPSEVKDSGR------ 73

                         90
                 ....*....|....*.
gi 24586203  115 YACLARNQFGSIISRD 130
Cdd:cd05848   74 YQCLATNSIGSILSRE 89

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 58.35 E-value: 2.78e-10

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24586203   1328 EDAKMPCLAVGAPQPEITWKIKGVEFSAND---RMRVLPDGSLLIKSVNRQDAGDYSCHAEN 1386
Cdd:pfam13927   17 ETVTLTCEATGSPPPTITWYKNGEPISSGStrsRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 58.35 E-value: 2.86e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203    811 PPEFTEKLRNQTARRGEPAVLQCEAKGEKPIGILWNMNNMrldPKNDNRYTIREEILSTgvmSSLSIKRTERSDSALFTC 890
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGE---PISSGSTRSRSLSGSN---STLTISNVTRSDAGTYTC 74


                   ....
gi 24586203    891 VATN 894
Cdd:pfam13927   75 VASN 78

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 58.42 E-value: 2.97e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203    715 PRWILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKavGDTPgeykdLKKSDNIRV----EEGTLHVDNIQKTNEGYYLC 790
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFK--DGQP-----LRSSDRFKVtyegGTYTLTISNVQPDDSGKYTC 73


                   ....*...
gi 24586203    791 EAINGIGS 798
Cdd:pfam07679   74 VATNSAGE 81

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 58.11 E-value: 3.06e-10

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24586203  360 AVFTCQYTGNPIKTVSWMKDGKAIGHSEP----------VLRIESVKKEDKGMYQCFVRNDQESAEAS 417
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPSSRdsrrselgngTLTISNVTLEDSGTYTCVASNSAGGSASA 68

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 58.35 E-value: 3.07e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203    246 PPKInalTYKPNIVESMA-STAIL-CPAQGYPAPSFRWYKfiEGTTRKQAVVLNDRVKQVSGTLIIKDAVVEDSGKYLCV 323
Cdd:pfam13927    1 KPVI---TVSPSSVTVREgETVTLtCEATGSPPPTITWYK--NGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75


                   ...
gi 24586203    324 VNN 326
Cdd:pfam13927   76 ASN 78

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 58.81 E-value: 3.20e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  429 PVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNdryQVGQY-VTVNGdvvSYLNITSVHANDGGLYKCI 507
Cdd:cd05736    1 PVIRVYPEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMDINPK---LSKQLtLIANG---SELHISNVRYEDTGAYTCI 74

                         90
                 ....*....|....*.
gi 24586203  508 AKSKVGVAEHSAKLNV 523
Cdd:cd05736   75 AKNEGGVDEDISSLFV 90

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 58.66 E-value: 3.90e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  714 PPRWILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKAVG-DTPGEYKDLKKSDNIRV-EEGTLHVDNIQKTNEGYYLCE 791
Cdd:cd05734    1 PPRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWKHSKGsGVPQFQHIVPLNGRIQLlSNGSLLIKHVLEEDSGYYLCK 80

                         90
                 ....*....|....*..
gi 24586203  792 AINGIGSGLSAVIMISV 808
Cdd:cd05734   81 VSNDVGADISKSMYLTV 97

Sixth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the sixth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409551 Cd Length: 94 Bit Score: 58.27 E-value: 4.20e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  428 PPVIRQAFQEETMEPGPSVFLKC-VAGGNPTPEISWELDGKKIANNdryqVGQYVTVNGDVVSYLNITSVHANDGGLYKC 506
Cdd:cd20959    2 PRIIPFAFGEGAAQVGMRAQLHCgVPGGDLPLNIRWTLDGQPISDD----LGITVSRLGRRSSILSIDSLEASHAGNYTC 77

                         90
                 ....*....|....*..
gi 24586203  507 IAKSKVGVAEHSAKLNV 523
Cdd:cd20959   78 HARNSAGSASYTAPLTV 94

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 57.58 E-value: 4.43e-10

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24586203 1331 KMPCLAVGAPQPEITWKIKGVEFSANDRMRVLPDGSLLIKSVNRQDAGDYSCHAENSIAKDSITHKL 1397
Cdd:cd05746    2 QIPCSAQGDPEPTITWNKDGVQVTESGKFHISPEGYLAIRDVGVADQGRYECVARNTIGYASVSMVL 68

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 57.80 E-value: 4.58e-10

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24586203 1328 EDAKMPCLA-VGAPQPEITWKIKGVEF-SANDRMRVLPDGSLLIKSVNRQDAGDYSCHAENSI-AKDSITHKLIV 1399
Cdd:cd05724   13 EMAVLECSPpRGHPEPTVSWRKDGQPLnLDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVgERESRAARLSV 87

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 57.86 E-value: 4.73e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  727 AQGSDAKVECKADGFPKPQVTWKKavGDtpgeyKDLKKSDNIRV-EEGTLHVDNIQKTNEGYYLCEAINGIGSGLSAVIM 805
Cdd:cd04969   15 AKGGDVIIECKPKASPKPTISWSK--GT-----ELLTNSSRICIlPDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSL 87


                 .
gi 24586203  806 I 806
Cdd:cd04969   88 S 88

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 57.90 E-value: 4.95e-10

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24586203     269 CPAQGYPAPSFRWYKfiegtTRKQAVVLNDRVKQV----SGTLIIKDAVVEDSGKYLCVVNNSVGGESVETVLTV 339
Cdd:smart00410   16 CEASGSPPPEVTWYK-----QGGKLLAESGRFSVSrsgsTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTLTV 85

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 57.89 E-value: 5.63e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  430 VIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIA-NNDRYQVGQyvtvNGDvvsyLNITSVHANDGGLYKCIA 508
Cdd:cd20952    1 IILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLgKDERITTLE----NGS----LQIKGAEKSDTGEYTCVA 72

                         90
                 ....*....|....*
gi 24586203  509 KSKVGVAEHSAKLNV 523
Cdd:cd20952   73 LNLSGEATWSAVLDV 87

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 57.51 E-value: 7.12e-10

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24586203  537 IVAGETLIVTCPVAGYPIDSIVWERDNRALPI-NRKQKVFPNGTLIIENVERNsDQATYTCVAKNQEG-YSARGSLEV 612
Cdd:cd20952   11 VAVGGTVVLNCQATGEPVPTISWLKDGVPLLGkDERITTLENGSLQIKGAEKS-DTGEYTCVALNLSGeATWSAVLDV 87

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 57.19 E-value: 7.18e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203    714 PPRWILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKaVGDTPGEYKDLKKSDNIrvEEGTLHVDNIQKTNEGYYLCEAI 793
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYK-NGEPISSGSTRSRSLSG--SNSTLTISNVTRSDAGTYTCVAS 77


                   .
gi 24586203    794 N 794
Cdd:pfam13927   78 N 78

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 57.41 E-value: 7.19e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  820 NQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLdPKndNRYTIREEilstgvmSSLSIKRTERSDSALFTCVATNAFGSD 899
Cdd:cd05725    6 NQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGEL-PK--GRYEILDD-------HSLKIRKVTAGDMGSYTCVAENMVGKI 75


                 ....*...
gi 24586203  900 DASINMIV 907
Cdd:cd05725   76 EASATLTV 83

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 57.24 E-value: 8.36e-10

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24586203 1330 AKMPCLAVGAPQPEITW-KIKGVEFSA--NDRMRVLP-DGSLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIVL 1400
Cdd:cd05763   17 ARLECAATGHPTPQIAWqKDGGTDFPAarERRMHVMPeDDVFFIVDVKIEDTGVYSCTAQNSAGSISANATLTVL 91

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 57.13 E-value: 9.80e-10

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203     538 VAGETLIVTCPVAGYPIDSIVWERDNRALPINRK----QKVFPNGTLIIENVERnSDQATYTCVAKNQEGySARGSLEVQ 613
Cdd:smart00410    7 KEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGrfsvSRSGSTSTLTISNVTP-EDSGTYTCAATNSSG-SASSGTTLT 84


                    .
gi 24586203     614 V 614
Cdd:smart00410   85 V 85

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 57.16 E-value: 9.85e-10

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24586203  539 AGETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVFPNGTLIIENVERNsDQATYTCVAKNqEGYSARGSLEVQV 614
Cdd:cd20957   15 FGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSEDVLVIPSVKRE-DKGMYQCFVRN-DGDSAQATAELKL 88

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 57.12 E-value: 1.04e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1117 PPSDTACTTLTSQTIRVGWVSPPleSANGVIKTYKVVYAPSDEwydETKRHYKKTASSDT--VLHGLKKYTNYTMQVLAT 1194
Cdd:cd00063    3 PPTNLRVTDVTSTSVTLSWTPPE--DDGGPITGYVVEYREKGS---GDWKEVEVTPGSETsyTLTGLKPGTEYEFRVRAV 77

                         90
                 ....*....|....*.
gi 24586203 1195 TAGGDGVRSVPIHCQT 1210
Cdd:cd00063   78 NGGGESPPSESVTVTT 93

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 57.13 E-value: 1.18e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  429 PVIRQAFQEETM--EPGPSVFLKCVAGGNPTPEISWELDGKKI-ANNDRYQVGQyvtvNGDVvsyLNITSVHANDGGLYK 505
Cdd:cd20970    1 PVISTPQPSFTVtaREGENATFMCRAEGSPEPEISWTRNGNLIiEFNTRYIVRE----NGTT---LTIRNIRRSDMGIYL 73

                         90
                 ....*....|....*....
gi 24586203  506 CIAKSKV-GVAEHSAKLNV 523
Cdd:cd20970   74 CIASNGVpGSVEKRITLQV 92

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 56.87 E-value: 1.19e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  428 PPVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIA-NNDRYQVGQyvtvngdVVSYLNITSVHANDGGLYKC 506
Cdd:cd20976    1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQyAADRSTCEA-------GVGELHIQDVLPEDHGTYTC 73

                         90
                 ....*....|....*..
gi 24586203  507 IAKSKVGVAEHSAKLNV 523
Cdd:cd20976   74 LAKNAAGQVSCSAWVTV 90

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 56.74 E-value: 1.38e-09

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24586203 1329 DAKMPCLAVGAPQPEITWKIKGVEFSAND-RMRVLPDGSLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1399
Cdd:cd20952   16 TVVLNCQATGEPVPTISWLKDGVPLLGKDeRITTLENGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 87

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 56.40 E-value: 1.51e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1312 PAKIASFDDTFTATFKEDAKMPCLAVGAPQPEITW-KIKGVEFSANDRMRvlPDGSLLIKSVNRQDAGDYSCHAENSIAK 1390
Cdd:cd04968    1 PSIKVRFPADTYALKGQTVTLECFALGNPVPQIKWrKVDGSPSSQWEITT--SEPVLEIPNVQFEDEGTYECEAENSRGK 78


                 ....*....
gi 24586203 1391 DSITHKLIV 1399
Cdd:cd04968   79 DTVQGRIIV 87

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 56.74 E-value: 1.56e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1402 PPQSPHVTLSATTTDALTVKLKPHEGDTAPLHGYTLHYKPEF-GEWET-SEVSVDSQKHNIEGLLCGSRYQVYATGFNNI 1479
Cdd:cd00063    1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGsGDWKEvEVTPGSETSYTLTGLKPGTEYEFRVRAVNGG 80

                         90
                 ....*....|...
gi 24586203 1480 GAGEASDILNTRT 1492
Cdd:cd00063   81 GESPPSESVTVTT 93

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 56.07 E-value: 2.09e-09

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24586203  540 GETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVFPNGTLIIENVERnSDQATYTCVAKNQEGySARGSLEVQV 614
Cdd:cd05876   10 GQSLVLECIAEGLPTPTVKWLRPSGPLPPDRVKYQNHNKTLQLLNVGE-SDDGEYVCLAENSLG-SARHAYYVTV 82

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 55.68 E-value: 2.53e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  443 GPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVgqyvtVNGDvvsyLNITSVHANDGGLYKCIAKSKVGVAEHSAKLN 522
Cdd:cd05728   14 GSSLRWECKASGNPRPAYRWLKNGQPLASENRIEV-----EAGD----LRITKLSLSDSGMYQCVAENKHGTIYASAELA 84


                 .
gi 24586203  523 V 523
Cdd:cd05728   85 V 85

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 55.48 E-value: 2.79e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  529 IRQMEKKAIVAGETLIVTCPVAGYPIDSIVWERDNRALPINRKQkVFPNGTLIIENVErNSDQATYTCVAKNQEG-YSAR 607
Cdd:cd05725    1 VKRPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKGRYE-ILDDHSLKIRKVT-AGDMGSYTCVAENMVGkIEAS 78


                 ....*
gi 24586203  608 GSLEV 612
Cdd:cd05725   79 ATLTV 83

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 55.71 E-value: 2.92e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  721 PTDKAFAQGSDAKVECKADGFPKPQVTWKKavGDTPgeykdLKKSDNIRV-EEGTLHVDNIQKTNEGYYLCEAINGIGSG 799
Cdd:cd20968    6 PTNVTIIEGLKAVLPCTTMGNPKPSVSWIK--GDDL-----IKENNRIAVlESGSLRIHNVQKEDAGQYRCVAKNSLGIA 78

                         90
                 ....*....|
gi 24586203  800 LSAVIMISVQ 809
Cdd:cd20968   79 YSKPVTIEVE 88

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 55.48 E-value: 3.05e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1307 PSDQVpakiASFDDTftATFKedakmpCLAVGAPQPEITWKIKGVEFSANdRMRVLPDGSLLIKSVNRQDAGDYSCHAEN 1386
Cdd:cd05725    4 PQNQV----VLVDDS--AEFQ------CEVGGDPVPTVRWRKEDGELPKG-RYEILDDHSLKIRKVTAGDMGSYTCVAEN 70

                         90
                 ....*....|...
gi 24586203 1387 SIAKDSITHKLIV 1399
Cdd:cd05725   71 MVGKIEASATLTV 83

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 55.58 E-value: 3.64e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1312 PAKIASFDDtFTATFKEDAKMPCLAVGAPQPEITWKIKG--VEFSANDRMRVLPDG--SLLIKSVNRQDAGDYSCHAENS 1387
Cdd:cd05744    1 PHFLQAPGD-LEVQEGRLCRFDCKVSGLPTPDLFWQLNGkpVRPDSAHKMLVRENGrhSLIIEPVTKRDAGIYTCIARNR 79

                         90
                 ....*....|..
gi 24586203 1388 IAKDSITHKLIV 1399
Cdd:cd05744   80 AGENSFNAELVV 91

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 55.16 E-value: 4.29e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  531 QMEKKAIVA-GETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVFPNGTLIIENVERnSDQATYTCVAKNQEGY-SARG 608
Cdd:cd04969    7 PVKKKILAAkGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILPDGSLKIKNVTK-SDEGKYTCFAVNFFGKaNSTG 85


                 ....
gi 24586203  609 SLEV 612
Cdd:cd04969   86 SLSV 89

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 55.25 E-value: 4.38e-09

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24586203  721 PTDKAFAQGSDAKVECKADGFPKPQVTWKKAVGDTPGEYKdlkksdnIRVEEGTLHVDNIQKTNEGYYLCEAINGIG 797
Cdd:cd04968    8 PADTYALKGQTVTLECFALGNPVPQIKWRKVDGSPSSQWE-------ITTSEPVLEIPNVQFEDEGTYECEAENSRG 77

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 55.09 E-value: 4.56e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  715 PRWILEP-TDKAFAQGSDAKVECKADGFPKPQVTW---KKAVGDTPGEYKdlkksdnirVEEGTLHVDNIQKTNEGYYLC 790
Cdd:cd20978    1 PKFIQKPeKNVVVKGGQDVTLPCQVTGVPQPKITWlhnGKPLQGPMERAT---------VEDGTLTIINVQPEDTGYYGC 71


                 ....*..
gi 24586203  791 EAINGIG 797
Cdd:cd20978   72 VATNEIG 78

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 54.89 E-value: 4.76e-09

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24586203  361 VFTCQYTGNPIKTVSWMKDGKAIGHS-------EPVLRIESVKKEDKGMYQCFVRNDQESAEASAEL 420
Cdd:cd05723   16 VFECEVTGKPTPTVKWVKNGDVVIPSdyfkivkEHNLQVLGLVKSDEGFYQCIAENDVGNAQASAQL 82

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 55.09 E-value: 5.02e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  527 PYIRQMEKKAIVA--GETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVFPNGTLIIENVeRNSDQATYTCVAKNQEGY 604
Cdd:cd20978    1 PKFIQKPEKNVVVkgGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVEDGTLTIINV-QPEDTGYYGCVATNEIGD 79

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 55.30 E-value: 5.44e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  443 GPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVGQyvtvNGDVVSYLNITSVHANDGGLYKCIAKSKVGVAEHSAKLN 522
Cdd:cd05729   19 ANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTK----VEEKGWSLIIERAIPRDKGKYTCIVENEYGSINHTYDVD 94


                 .
gi 24586203  523 V 523
Cdd:cd05729   95 V 95

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 54.26 E-value: 5.99e-09

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24586203  732 AKVECKADGFPKPQVTWKKAVGDTPGEYKDLKKSDNirvEEGTLHVDNIQKTNEGYYLCEAINGIGSGLSAVI 804
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSEL---GNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 54.91 E-value: 6.10e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  347 IDPPTQT-VDFGRPAVFTCQYTGNPIKTVSWMKDGKAIGHSEPV------LRIESVKKEDKGMYQCFVRNDQESAEASAE 419
Cdd:cd05728    3 LKVISDTeADIGSSLRWECKASGNPRPAYRWLKNGQPLASENRIeveagdLRITKLSLSDSGMYQCVAENKHGTIYASAE 82


                 ...
gi 24586203  420 LKL 422
Cdd:cd05728   83 LAV 85

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 54.92 E-value: 6.29e-09

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24586203  269 CPAQGYPAPSFRWYKfiEGTTRKQAVVLN-DRVKQVSGTLIIKDAVVEDSGKYLCVVNNSVG 329
Cdd:cd05729   26 CGAGGNPMPNITWLK--DGKEFKKEHRIGgTKVEEKGWSLIIERAIPRDKGKYTCIVENEYG 85

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 54.54 E-value: 6.62e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203    1215 PEAPTDVKALVMGNAAILVSWRPPAQPNGI--ITQYTVYSKAEGaeTETKTQKVPHYQMSFEATELEKNKPYEFWVTAST 1292
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGITgyIVGYRVEYREEG--SEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVN 78


                    ....*
gi 24586203    1293 TIGEG 1297
Cdd:smart00060   79 GAGEG 83

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 54.32 E-value: 6.79e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  720 EPTDKAFAQGSDAKVECKADGFPKPQVTWKKAVGDTP-GEYKDLkksdnirvEEGTLHVDNIQKTNEGYYLCEAINGIGS 798
Cdd:cd05725    3 RPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPkGRYEIL--------DDHSLKIRKVTAGDMGSYTCVAENMVGK 74

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 54.76 E-value: 6.98e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  716 RWILEPTDKAFAQGSDAKVECKADGFPKPQVTW---KKAVGDTPGEYKDlkksdniRVEEGTLHVDNIQKTNEGYYLCEA 792
Cdd:cd04978    1 YWIIEPPSLVLSPGETGELICEAEGNPQPTITWrlnGVPIEPAPEDMRR-------TVDGRTLIFSNLQPNDTAVYQCNA 73


                 ....*
gi 24586203  793 INGIG 797
Cdd:cd04978   74 SNVHG 78

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 54.34 E-value: 7.72e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203   1500 PEKPRFIEVSSNSVSLHFKAWKDGGCPMSHFVVE-SKKRDQIEWNQIsNNVKPDNNYVVLDLEPATWYNLRITAHNSAGF 1578
Cdd:pfam00041    3 PSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEyRPKNSGEPWNEI-TVPGTTTSVTLTGLKPGTEYEVRVQAVNGGGE 81

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 53.95 E-value: 1.00e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 24586203  728 QGSDAKVECKADGFPKPQVTWKKAVGDTPgeyKDLKKSDNIRveeGTLHVDNIQKTNEGYYLCEAINGIGS 798
Cdd:cd05731    9 RGGVLLLECIAEGLPTPDIRWIKLGGELP---KGRTKFENFN---KTLKIENVSEADSGEYQCTASNTMGS 73

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 54.10 E-value: 1.16e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1321 TFTATFKEDAKMP-------CLAVGAPQPEITWKIKGVEFSANDRMR----VLPDGSLL----IKSVNRQDAGDYSCHAE 1385
Cdd:cd20956    3 VLLETFSEQTLQPgpsvslkCVASGNPLPQITWTLDGFPIPESPRFRvgdyVTSDGDVVsyvnISSVRVEDGGEYTCTAT 82

                         90
                 ....*....|
gi 24586203 1386 NSIAkdSITH 1395
Cdd:cd20956   83 NDVG--SVSH 90

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 53.74 E-value: 1.42e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  811 PPEFTEKLRNQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLDPKNDNrytireEILSTGVMSSLSIKRTERSDSALFTC 890
Cdd:cd20972    1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDI------QIHQEGDLHSLIIAEAFEEDTGRYSC 74

                         90
                 ....*....|....*..
gi 24586203  891 VATNAFGSDDASINMIV 907
Cdd:cd20972   75 LATNSVGSDTTSAEIFV 91

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 53.34 E-value: 1.76e-08

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24586203 1323 TATFKEDAKMPCLAVGAPQPEITWKIKGVEFSANDRMRVLPDGSLLIKSVNR-QDAGDYSCHAENS 1387
Cdd:cd20958   11 TAVAGQTLRLHCPVAGYPISSITWEKDGRRLPLNHRQRVFPNGTLVIENVQRsSDEGEYTCTARNQ 76

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 53.28 E-value: 1.76e-08

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203     721 PTDKAFAQGSDAKVECKADGFPKPQVTWKKavgdtpGEYKDLKKSDNIRVEE----GTLHVDNIQKTNEGYYLCEAINGI 796
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYK------QGGKLLAESGRFSVSRsgstSTLTISNVTPEDSGTYTCAATNSS 74


                    ..
gi 24586203     797 GS 798
Cdd:smart00410   75 GS 76

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 53.39 E-value: 1.90e-08

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203    1117 PPSDTACTTLTSQTIRVGWVSPPLESANGVIKTYKVVYAPSDewyDETKRHYKKTASSDTVLHGLKKYTNYTMQVLATTA 1196
Cdd:smart00060    3 PPSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYREEG---SEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNG 79


                    ....
gi 24586203    1197 GGDG 1200
Cdd:smart00060   80 AGEG 83

Fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 (also known as Neph2). This protein has five Ig-like domains, one transmembrane domain, and a cytoplasmic tail. Included in this group is mammalian Kirrel (also known as Neph1), Kirrel2 (also known as Neph3), and Drosophila RST (also known as irregular chiasm C-roughest) protein. These proteins contain multiple Ig domains, have properties of cell adhesion molecules, and are important in organ development.

Pssm-ID: 319310 Cd Length: 98 Bit Score: 53.69 E-value: 1.96e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  810 APPEFTeKLRNQTARRGEPAVLQCEAKGE-KPIGILWNMNNMRLDPKNDNRYTIREEILSTGVMSSLSIKRTERSD-SAL 887
Cdd:cd05758    1 GPPIIT-AEATQPAILGEKARLECLVFSSpPPDRIVWSWDEGFLESGSSGRFSVETFPTEPGVISVLHISGTQRSDfQTS 79

                         90
                 ....*....|....*...
gi 24586203  888 FTCVATNAFGSDDASINM 905
Cdd:cd05758   80 FNCSAWNRFGEGTAIVSL 97

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 53.48 E-value: 2.05e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24586203  258 IVESMASTAILCPAQGYPAPSFRWYK-FIEGTTRKQavvlNDRVKQV-SGTLIIKDAVVEDSGKYLCVVNNSVG 329
Cdd:cd05738   10 VVEKARTATMLCAASGNPDPEISWFKdFLPVDTATS----NGRIKQLrSGALQIENSEESDQGKYECVATNSAG 79

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 53.02 E-value: 2.08e-08

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24586203 1333 PCLAVGAPQPEITWKIKGVEFSANDRMRVLPDGSLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1399
Cdd:cd05745    8 LCEAQGYPQPVIAWTKGGSQLSVDRRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 53.18 E-value: 2.24e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24586203  443 GPSVFLKCVAGGNPTPEISWELDGKKIANnDRYQVGQYVTVngdvvsyLNITSVHANDGGLYKCIAKSKVGVAEH 517
Cdd:cd05731   10 GGVLLLECIAEGLPTPDIRWIKLGGELPK-GRTKFENFNKT-------LKIENVSEADSGEYQCTASNTMGSARH 76

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

Pssm-ID: 409408 [Multi-domain] Cd Length: 92 Bit Score: 53.28 E-value: 2.25e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24586203  269 CPAQG-YPAPSFRWYKFIEGTTRKQAVVLNDRVKQVSGTLIIKDAVVEDSGKYLCVVNNSVGGESVETVLTV 339
Cdd:cd05750   21 CEATSeNPSPRYRWFKDGKELNRKRPKNIKIRNKKKNSELQINKAKLEDSGEYTCVVENILGKDTVTGNVTV 92

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 53.18 E-value: 2.76e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  429 PVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVgqYVTVNGdvVSYLNITSVHANDGGLYKCIA 508
Cdd:cd20990    1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKM--LVRENG--VHSLIIEPVTSRDAGIYTCIA 76

                         90
                 ....*....|....*
gi 24586203  509 KSKVGVAEHSAKLNV 523
Cdd:cd20990   77 TNRAGQNSFNLELVV 91

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 52.88 E-value: 2.96e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24586203  264 STAIL-CPAQGYPAPSFRWYKfiEGttrKQAVVLNDRVKQV-SGTLIIKDAVVEDSGKYLCVVNNSVGGESVETVLTV 339
Cdd:cd20952   15 GTVVLnCQATGEPVPTISWLK--DG---VPLLGKDERITTLeNGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 87

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 52.79 E-value: 3.08e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  719 LEPTDKAFAQGSDAKVECKAD-GFPKPQVTWKKavgdtPGEYKDLkksDNIR---VEEGTLHVDNIQKTNEGYYLCEAIN 794
Cdd:cd05724    2 VEPSDTQVAVGEMAVLECSPPrGHPEPTVSWRK-----DGQPLNL---DNERvriVDDGNLLIAEARKSDEGTYKCVATN 73

                         90
                 ....*....|....
gi 24586203  795 GIGSGLSAVIMISV 808
Cdd:cd05724   74 MVGERESRAARLSV 87

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 52.88 E-value: 3.84e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24586203  269 CPAQGYPAPSFRWyKFIEGTTRKQ---AVVLNDRVKQVS-GTLIIKDAVVEDSGKYLCVVNNSVGGE-SVETVLTV 339
Cdd:cd05734   23 CSADGYPPPTIVW-KHSKGSGVPQfqhIVPLNGRIQLLSnGSLLIKHVLEEDSGYYLCKVSNDVGADiSKSMYLTV 97

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 52.87 E-value: 4.11e-08

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24586203 1332 MPCLAVGAPQPEITWKIKGV--EFSANDRMRVLPDGSLLIKSV-----NRQDAGDYSCHAEN 1386
Cdd:cd05722   21 LNCSAESDPPPKIEWKKDGVllNLVSDERRQQLPNGSLLITSVvhskhNKPDEGFYQCVAQN 82

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 52.45 E-value: 4.59e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  436 QEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVgqyVTVNGDVVSYLNITSvhaNDGGLYKCIAKSKVGVA 515
Cdd:cd04978    7 PSLVLSPGETGELICEAEGNPQPTITWRLNGVPIEPAPEDMR---RTVDGRTLIFSNLQP---NDTAVYQCNASNVHGYL 80


                 ....*...
gi 24586203  516 EHSAKLNV 523
Cdd:cd04978   81 LANAFLHV 88

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 52.03 E-value: 4.80e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203   1117 PPSDTACTTLTSQTIRVGWVSPPleSANGVIKTYKVVYAPSDEwyDETKRHYKKTASSDTV-LHGLKKYTNYTMQVLATT 1195
Cdd:pfam00041    2 APSNLTVTDVTSTSLTVSWTPPP--DGNGPITGYEVEYRPKNS--GEPWNEITVPGTTTSVtLTGLKPGTEYEVRVQAVN 77


                   ....*...
gi 24586203   1196 AGGDGVRS 1203
Cdd:pfam00041   78 GGGEGPPS 85

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 52.53 E-value: 4.80e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  429 PVIRQAFQEETMEpGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVGQyVTVNGDV-VSYLNITSVHANDGGLYKCI 507
Cdd:cd05732    3 PKITYLENQTAVE-LEQITLTCEAEGDPIPEITWRRATRGISFEEGDLDGR-IVVRGHArVSSLTLKDVQLTDAGRYDCE 80

                         90
                 ....*....|....*.
gi 24586203  508 AKSKVGVAEHSAKLNV 523
Cdd:cd05732   81 ASNRIGGDQQSMYLEV 96

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 52.31 E-value: 5.05e-08

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24586203 1329 DAKMPCLAVGAPQPEITWKiKGV--------EFSANDRMRVLPDGSLLIKSVNRQDAGDYSCHAENSI 1388
Cdd:cd20954   18 DVMLHCQADGFPTPTVTWK-KATgstpgeykDLLYDPNVRILPNGTLVFGHVQKENEGHYLCEAKNGI 84

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 52.18 E-value: 5.74e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24586203  357 GRPAVFTCQYTGNPIKTVSWMKDGKA--IGHSEPV-----LRIESV-KKEDKGMYQCFVRNDQ-ESAEASAELK 421
Cdd:cd20958   15 GQTLRLHCPVAGYPISSITWEKDGRRlpLNHRQRVfpngtLVIENVqRSSDEGEYTCTARNQQgQSASRSVFVK 88

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 143259 Cd Length: 88 Bit Score: 51.95 E-value: 6.06e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  428 PPVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWeldgKKIanNDRYQVGQYVTVNGDVVSYLNItsvHANDGGLYKCI 507
Cdd:cd05851    1 PADINVKFKDTYALKGQNVTLECFALGNPVPVIRW----RKI--LEPMPATAEISMSGAVLKIFNI---QPEDEGTYECE 71

                         90
                 ....*....|....*.
gi 24586203  508 AKSKVGVAEHSAKLNV 523
Cdd:cd05851   72 AENIKGKDKHQARVYV 87

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 51.24 E-value: 1.17e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24586203 1334 CLAVGAPQPEITWKIKG---VEFSANDRMRVLPDGSLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1399
Cdd:cd20969   24 CRADGDPPPAILWLSPRkhlVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLHV 92

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 50.86 E-value: 1.20e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24586203  349 PPTQTVDFGRPAVFTCQYTGNPIKTVSW------MKDGKAIGHSEPVLRIESVKKEDKGMYQCFVRNDQESAEASAEL 420
Cdd:cd05725    4 PQNQVVLVDDSAEFQCEVGGDPVPTVRWrkedgeLPKGRYEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIEASATL 81

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 51.52 E-value: 1.21e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  429 PVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVGQYVTVNGDVVSYLNITSVHANDGGLYKCIA 508
Cdd:cd05869    3 PKITYVENQTAMELEEQITLTCEASGDPIPSITWRTSTRNISSEEKTLDGHIVVRSHARVSSLTLKYIQYTDAGEYLCTA 82

                         90
                 ....*....|....*
gi 24586203  509 KSKVGVAEHSAKLNV 523
Cdd:cd05869   83 SNTIGQDSQSMYLEV 97

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 51.40 E-value: 1.23e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  440 MEP-GPSVFLKCVAGGNPTPEISWELDGKKIannDRYQVGQyvtvNGDVVSYLNITSVHANDGGLYKCIAKSKVGVAEHS 518
Cdd:cd05856   15 ARPvGSSVRLKCVASGNPRPDITWLKDNKPL---TPPEIGE----NKKKKWTLSLKNLKPEDSGKYTCHVSNRAGEINAT 87


                 ....*
gi 24586203  519 AKLNV 523
Cdd:cd05856   88 YKVDV 92

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 51.50 E-value: 1.29e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  716 RWILEPTDKAFAQGSDAKVECKADGFPKPQVTWKK-AVGDTPGEYKDLKKSDNIRVEE-GTLHVDNIQKTNEGYYLCEAI 793
Cdd:cd05726    1 QFVVKPRDQVVALGRTVTFQCETKGNPQPAIFWQKeGSQNLLFPYQPPQPSSRFSVSPtGDLTITNVQRSDVGYYICQAL 80


                 ....*...
gi 24586203  794 NGIGSGLS 801
Cdd:cd05726   81 NVAGSILA 88

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 51.37 E-value: 1.36e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1323 TATFKEDAKMPCLAVGAPQPEITWK--IKGVEFSANDrmrvlPDG-----------SLLIKSVNRQDAGDYSCHAENSIA 1389
Cdd:cd05732   12 TAVELEQITLTCEAEGDPIPEITWRraTRGISFEEGD-----LDGrivvrgharvsSLTLKDVQLTDAGRYDCEASNRIG 86


                 ...
gi 24586203 1390 KDS 1392
Cdd:cd05732   87 GDQ 89

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 50.79 E-value: 1.60e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1328 EDAKMPCLAVGAPQPEITWKIKGVEFSAN----DRMRVLPDGsLLIKSVNRQDAGDYSCHAE--NSIAKD 1391
Cdd:cd20949   15 QSATILCEVKGEPQPNVTWHFNGQPISASvadmSKYRILADG-LLINKVTQDDTGEYTCRAYqvNSIASD 83

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 50.47 E-value: 1.81e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  436 QEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNdRYQVGQYVTvngdvvsyLNITSVHANDGGLYKCIAKSKVGVA 515
Cdd:cd05725    5 QNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKG-RYEILDDHS--------LKIRKVTAGDMGSYTCVAENMVGKI 75


                 ....*...
gi 24586203  516 EHSAKLNV 523
Cdd:cd05725   76 EASATLTV 83

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 50.70 E-value: 1.86e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203   38 GPVFLKEPTNRI--DFSNSTGAEIECKASGNPMPEIIWIRsDGTAVGDVPGLRQISSDGKLVFP-PFRAEDyrqevhAQV 114
Cdd:cd04967    1 GPVFEEQPDDTIfpEDSDEKKVALNCRARANPVPSYRWLM-NGTEIDLESDYRYSLVDGTLVISnPSKAKD------AGH 73

                         90       100
                 ....*....|....*....|
gi 24586203  115 YACLARNQFGSIISRDVHVR 134
Cdd:cd04967   74 YQCLATNTVGSVLSREATLQ 93

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 50.60 E-value: 2.03e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  810 APPEFTeKLRNQTARRGEPAVLQCEAKGEKPIGILW-----NMNNMRLDPknDNRYTIREEILstgvMSSLSIKRTERSD 884
Cdd:cd05732    1 VQPKIT-YLENQTAVELEQITLTCEAEGDPIPEITWrratrGISFEEGDL--DGRIVVRGHAR----VSSLTLKDVQLTD 73

                         90
                 ....*....|....*....
gi 24586203  885 SALFTCVATNAFGSDDASI 903
Cdd:cd05732   74 AGRYDCEASNRIGGDQQSM 92

Immunoglobulin (Ig)-like domain of human neurofascin (NF); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of human neurofascin (NF). NF belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and a cytoplasmic domain. NF has many alternatively spliced isoforms having different temporal expression patterns during development. NF participates in axon subcellular targeting and synapse formation, however little is known of the functions of the different isoforms. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409459 Cd Length: 95 Bit Score: 50.36 E-value: 2.50e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203   59 IECKASGNPMPEIIWIR-SDGTAVGDVPGLRQISSDGKLVFPPF---RAEDYRQEvhaqvYACLARNQFGSIISRDVHVR 134
Cdd:cd05875   21 IECEAKGNPVPTFHWTRnGKFFNVAKDPRVSMRRRSGTLVIDFRgggRPEDYEGE-----YQCFARNKFGTALSNKIRLQ 95

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 50.20 E-value: 2.82e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24586203 1321 TFTATFKEDAKMPCLAVGAPQPEITWKIKGVEFSA-NDRMRVLPDGSLL-IKSVNRQDAGDYSCHAEN 1386
Cdd:cd20970   11 TVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEfNTRYIVRENGTTLtIRNIRRSDMGIYLCIASN 78

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 50.55 E-value: 2.83e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  814 FTEKLRNQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLDPKNDNRYtireEILSTG--VMSSLSIKRTERSDSALFTCV 891
Cdd:cd05722    4 FLSEPSDIVAMRGGPVVLNCSAESDPPPKIEWKKDGVLLNLVSDERR----QQLPNGslLITSVVHSKHNKPDEGFYQCV 79


                 ....*...
gi 24586203  892 ATN-AFGS 898
Cdd:cd05722   80 AQNeSLGS 87

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 50.19 E-value: 3.05e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  349 PPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAI----GHSEPV-------LRIESVKKEDKGMYQCFVRNDQESAEAS 417
Cdd:cd05744    7 PGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVrpdsAHKMLVrengrhsLIIEPVTKRDAGIYTCIARNRAGENSFN 86


                 ...
gi 24586203  418 AEL 420
Cdd:cd05744   87 AEL 89

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 50.22 E-value: 3.28e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24586203  728 QGSDAKVECKADGFPKPQVTWKKAVGDTPGEYKDLKKSDNIRVEEG--TLHVDNIQKTNEGYYLCEAINGIG 797
Cdd:cd05732   15 ELEQITLTCEAEGDPIPEITWRRATRGISFEEGDLDGRIVVRGHARvsSLTLKDVQLTDAGRYDCEASNRIG 86

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 49.25 E-value: 3.38e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24586203   57 AEIECKASGNPMPEIIWIRSDGT-AVGDVPGLRQISSDGKLVFPPFRAEDyrqevhAQVYACLARNQFGSIISRDV 131
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPlPPSSRDSRRSELGNGTLTISNVTLED------SGTYTCVASNSAGGSASASV 70

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 49.54 E-value: 3.97e-07

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203    1497 PKLPEKPRFIEVSSNSVSLHFKAWKDGGCpmSHFVVE---SKKRDQIEWNQISNNVkPDNNYVVLDLEPATWYNLRITAH 1573
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGI--TGYIVGyrvEYREEGSEWKEVNVTP-SSTSYTLTGLKPGTEYEFRVRAV 77


                    ....
gi 24586203    1574 NSAG 1577
Cdd:smart00060   78 NGAG 81

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 49.52 E-value: 4.36e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  717 WILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKAvgdtpGEykDLKKSDNIRVEEGTLHVDNIQKTNEGYYLCEAINGI 796
Cdd:cd05728    2 WLKVISDTEADIGSSLRWECKASGNPRPAYRWLKN-----GQ--PLASENRIEVEAGDLRITKLSLSDSGMYQCVAENKH 74


                 ..
gi 24586203  797 GS 798
Cdd:cd05728   75 GT 76

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 49.63 E-value: 4.52e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 24586203 1330 AKMPCLAVGAPQPEITWKIKGV---EFSANDRMRVLPDGSLLIKSVNRQDAGDYSCHAENS 1387
Cdd:cd05738   17 ATMLCAASGNPDPEISWFKDFLpvdTATSNGRIKQLRSGALQIENSEESDQGKYECVATNS 77

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 49.31 E-value: 4.62e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24586203  349 PPTQTV-DFGRPAVFTCQYTGNPIKTVSWMKDGKAIGHSEP-------VLRIESVKKEDKGMYQC 405
Cdd:cd20978    7 PEKNVVvKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMEratvedgTLTIINVQPEDTGYYGC 71

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 49.54 E-value: 4.79e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24586203  721 PTDKAFAQGSDAKVECKADGFPKPQVTWKKAVG-DTPGEYkdlKKSDNIRVEEGTLHVDNIQKTNEGYYLCEAINGIGS 798
Cdd:cd05763    6 PHDITIRAGSTARLECAATGHPTPQIAWQKDGGtDFPAAR---ERRMHVMPEDDVFFIVDVKIEDTGVYSCTAQNSAGS 81

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 49.33 E-value: 4.81e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24586203  540 GETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVFPNGTLIIENVErNSDQATYTCVAKNQEGySARGSLEVQV 614
Cdd:cd05731   10 GGVLLLECIAEGLPTPDIRWIKLGGELPKGRTKFENFNKTLKIENVS-EADSGEYQCTASNTMG-SARHTISVTV 82

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409438 Cd Length: 89 Bit Score: 49.23 E-value: 5.16e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24586203 1334 CLAVGAPQPEITWKiKGVEFSAND-RMRVLPDGSLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1399
Cdd:cd05852   24 CKPKAAPKPKFSWS-KGTELLVNNsRISIWDDGSLEILNITKLDEGSYTCFAENNRGKANSTGVLSV 89

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 49.37 E-value: 5.22e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24586203 1328 EDAKMPCLAVGAPQPEITWKIKGV---EFSANDRMRVLPDgSLLIKSVNRQDAGDYSCHAEN 1386
Cdd:cd04978   15 ETGELICEAEGNPQPTITWRLNGVpiePAPEDMRRTVDGR-TLIFSNLQPNDTAVYQCNASN 75

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 2 (NCAM-2); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is organized similarly to NCAM, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143278 [Multi-domain] Cd Length: 98 Bit Score: 49.59 E-value: 5.28e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24586203  728 QGSDAKVECKADGFPKPQVTWKKAV-GDTpgeYKDLKKSDNIRVE------EGTLHVDNIQKTNEGYYLCEAINGIG 797
Cdd:cd05870   15 ENGAATLSCKAEGEPIPEITWKRASdGHT---FSEGDKSPDGRIEvkgqhgESSLHIKDVKLSDSGRYDCEAASRIG 88

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 49.13 E-value: 5.78e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24586203 1337 VGAPQPEITWKIKGVEFSANDRMRV---LPDGSLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1399
Cdd:cd05748   17 KGRPTPTVTWSKDGQPLKETGRVQIettASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSATINVKV 82

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 49.04 E-value: 6.34e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  719 LEPTDKAFAQGSDAKVECKADGFPKPQVTWKKavgdtpgeykdlkksDNIRVEEG-----------TLHVDNIQKTNEGY 787
Cdd:cd20970    7 QPSFTVTAREGENATFMCRAEGSPEPEISWTR---------------NGNLIIEFntryivrengtTLTIRNIRRSDMGI 71

                         90       100
                 ....*....|....*....|.
gi 24586203  788 YLCEAINGIGSGLSAVIMISV 808
Cdd:cd20970   72 YLCIASNGVPGSVEKRITLQV 92

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 48.33 E-value: 7.37e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24586203  266 AILCPAQGYPAPSFRWykfiegttRKQAVVLNDRVK-QVS--GTLIIKDAVVEDSGKYLCVVNNSVGGESVETVLT 338
Cdd:cd05746    2 QIPCSAQGDPEPTITW--------NKDGVQVTESGKfHISpeGYLAIRDVGVADQGRYECVARNTIGYASVSMVLS 69

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 48.89 E-value: 7.59e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  340 TAPLSAKIDPPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIGHS----------EPVLRIESVKKEDKGMYQCFVRN 409
Cdd:cd05747    1 TLPATILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSqrhqitsteyKSTFEISKVQMSDEGNYTVVVEN 80

                         90
                 ....*....|.
gi 24586203  410 DQESAEASAEL 420
Cdd:cd05747   81 SEGKQEAQFTL 91

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 48.79 E-value: 8.06e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1312 PAKIASFDDTFTATFKEDAKMPCLAVGAPQPEITWKIKGVEFS-ANDRMRVLPD-GSLLIKSVNRQDAGDYSCHAENSIA 1389
Cdd:cd20976    1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQyAADRSTCEAGvGELHIQDVLPEDHGTYTCLAKNAAG 80

                         90
                 ....*....|
gi 24586203 1390 KDSITHKLIV 1399
Cdd:cd20976   81 QVSCSAWVTV 90

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 48.78 E-value: 8.40e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24586203  349 PPTQ-TVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIGHSEPV-------LRIESVKKEDKGMYQCFVRNDQESA 414
Cdd:cd20968    5 PPTNvTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRIavlesgsLRIHNVQKEDAGQYRCVAKNSLGIA 78

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 48.76 E-value: 8.52e-07

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203    1402 PPQSPHVTLSATTTDALTVKLKP--HEGDTAPLHGYTLHYKPEFGEWETSEVSVDSQKHNIEGLLCGSRYQVYATGFNNI 1479
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPppDDGITGYIVGYRVEYREEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNGA 80


                    ...
gi 24586203    1480 GAG 1482
Cdd:smart00060   81 GEG 83

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 49.21 E-value: 8.70e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1314 KIASFDDTFTATFKEDAKMPCLAVGAPQPEITWKIKGVEFSAND-----RMRVLPD---GSLLIKSVNRQDAGDYSCHAE 1385
Cdd:cd05869    4 KITYVENQTAMELEEQITLTCEASGDPIPSITWRTSTRNISSEEktldgHIVVRSHarvSSLTLKYIQYTDAGEYLCTAS 83


                 ....*..
gi 24586203 1386 NSIAKDS 1392
Cdd:cd05869   84 NTIGQDS 90

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 48.72 E-value: 8.80e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  432 RQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVGQyvtvNGDVVSYLNITSVHANDGGLYKCIAKSK 511
Cdd:cd20973    1 IQTLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQ----DEDGLCSLIISDVCGDDSGKYTCKAVNS 76

                         90
                 ....*....|..
gi 24586203  512 VGVAEHSAKLNV 523
Cdd:cd20973   77 LGEATCSAELTV 88

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 48.78 E-value: 8.82e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24586203  537 IVAGETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVFPNGTLIIENVERnSDQATYTCVAKNQEG--YSARGSLEVQ 613
Cdd:cd20968   11 IIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRIAVLESGSLRIHNVQK-EDAGQYRCVAKNSLGiaYSKPVTIEVE 88

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 48.74 E-value: 8.86e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24586203  717 WILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKAVGDTPGEYKDLKKsdniRVEEGTLHVDNIQKTNEGYYLCEAIN 794
Cdd:cd05867    2 WTRRPQSHLYGPGETARLDCQVEGIPTPNITWSINGAPIEGTDPDPRR----HVSSGALILTDVQPSDTAVYQCEARN 75

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 48.65 E-value: 1.03e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  715 PRWILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKAvgdtpGEYKDLKKSDNIRVEEG---TLHVDNIQKTNEGYYLCE 791
Cdd:cd05744    1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLN-----GKPVRPDSAHKMLVRENgrhSLIIEPVTKRDAGIYTCI 75


                 ....*.
gi 24586203  792 AINGIG 797
Cdd:cd05744   76 ARNRAG 81

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 48.70 E-value: 1.11e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  812 PEFTEKLRNQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLDPKNDNRYTiREEILSTGVMSSLSI--KRTERSDSALFT 889
Cdd:cd07693    1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDKDDPRS-HRIVLPSGSLFFLRVvhGRKGRSDEGVYV 79

                         90
                 ....*....|....*..
gi 24586203  890 CVATNAFG---SDDASI 903
Cdd:cd07693   80 CVAHNSLGeavSRNASL 96

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 48.30 E-value: 1.11e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24586203 1323 TATFKEDAKMPCLAVGAPQPEITWKIKGVEFSANDRMRVLPDGSLLIKSVNRQDAGDYSCHAEN 1386
Cdd:cd20957   12 TVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSEDVLVIPSVKREDKGMYQCFVRN 75

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 47.71 E-value: 1.26e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24586203  829 AVLQCEAKGEKPIGILWNMNNMRLDPKNDNRYTIREEIlstgvmSSLSIKRTERSDSALFTCVATNAFGSDDASI 903
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGN------GTLTISNVTLEDSGTYTCVASNSAGGSASAS 69

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

Pssm-ID: 409443 [Multi-domain] Cd Length: 95 Bit Score: 48.31 E-value: 1.26e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  443 GPSVFLKCVAGGNPTPEISWELDGKKIANNDRyqVGQYVTVNGDvvSYLNITSVHANDGGLYKCIAKSKVGVAEHSAKLN 522
Cdd:cd05857   19 ANTVKFRCPAAGNPTPTMRWLKNGKEFKQEHR--IGGYKVRNQH--WSLIMESVVPSDKGNYTCVVENEYGSINHTYHLD 94


                 .
gi 24586203  523 V 523
Cdd:cd05857   95 V 95

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 48.18 E-value: 1.33e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203   1402 PPQSPHVTlsATTTDALTVKLKPHEGDTAPLHGYTLHYKPEFGEWETSEVSVDSQKH--NIEGLLCGSRYQVYATGFNNI 1479
Cdd:pfam00041    2 APSNLTVT--DVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPWNEITVPGTTTsvTLTGLKPGTEYEVRVQAVNGG 79


                   ....*.
gi 24586203   1480 GAGEAS 1485
Cdd:pfam00041   80 GEGPPS 85

Immunoglobulin (Ig) constant domain of the complement receptor of the immunoglobulin superfamily (CRIg); The members here are composed of the Immunoglobulin (Ig) constant domain of the complement receptor of the immunoglobulin superfamily (CRIg). The N-terminal domain of CRIg (also referred to as Z39Ig and V-set and Ig domain-containing 4 (VSIG4)) belongs to the IgV family of immunoglobulin-like domains while the C-terminal domain of CRIg belongs to the IgC family of immunoglobulin-like domains. CRIg plays a role in the complement system, an inhibitor of the alternative pathway convertases, and a negative regulator of T cell activation. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond.

Pssm-ID: 409504 Cd Length: 86 Bit Score: 47.83 E-value: 1.61e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24586203  266 AILCPAQGYPAPSFRWYKfiEGTTRKQAVVLNDRvkqvsGTLIIKDAVVEDSGKYLCVVNNSVGGE 331
Cdd:cd16082   17 SLQCQAWGSPPISYVWYK--EQTNNQEPIKVAAL-----STLLFKPAVVADSGSYFCTAKGRVGSE 75

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 48.32 E-value: 1.80e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24586203   57 AEIECKASGNPMPEIIWIRsDG----TAVGDVPGLRQISSDGKLVFppFRAEDYRQ-EVHAQVYACLARNQFGSIISRD 130
Cdd:cd07693   18 ATLNCKAEGRPTPTIQWLK-NGqpleTDKDDPRSHRIVLPSGSLFF--LRVVHGRKgRSDEGVYVCVAHNSLGEAVSRN 93

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 47.78 E-value: 1.86e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24586203  537 IVAGETLIVTC-PVAGYPIDSIVWERDNRALPI-NRKQKVFPNGTLIIENVERnSDQATYTCVAKNQEG 603
Cdd:cd05724    9 VAVGEMAVLECsPPRGHPEPTVSWRKDGQPLNLdNERVRIVDDGNLLIAEARK-SDEGTYKCVATNMVG 76

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 48.00 E-value: 2.10e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  820 NQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLDpKNDNRYTIREEilstgvMSSLSIKRTERSDSALFTCVATNAFGSD 899
Cdd:cd05730   12 NATANLGQSVTLACDADGFPEPTMTWTKDGEPIE-SGEEKYSFNED------GSEMTILDVDKLDEAEYTCIAENKAGEQ 84


                 ....*...
gi 24586203  900 DASINMIV 907
Cdd:cd05730   85 EAEIHLKV 92

Immunoglobulin-like domain of human nephrin and similar proteins; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin-like domain in human nephrin and similar proteins. Nephrin is an integral component of the slit diaphragm and is a central component of the glomerular ultrafilter. Nephrin plays a structural role and has a role in signaling. Nephrin is a transmembrane protein having a short intracellular portion, an extracellular portion comprised of eight Ig-like domains, and one fibronectin type III-like domain. The extracellular portions of nephrin from neighboring foot processes of separate podocyte cells may interact with each other, and in association with other components of the slit diaphragm form a porous molecular sieve within the slit pore. The intracellular portion of nephrin is associated with linker proteins, which connect nephrin to the actin cytoskeleton. The intracellular portion is tyrosine phosphorylated, and mediates signaling from the slit diaphragm into the podocytes.

Pssm-ID: 143250 Cd Length: 109 Bit Score: 48.39 E-value: 2.13e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  808 VQAPPEFTeklrnQTARRGE---PAVLQCEAKGEKPIGILWNMNNMRLDPKNDnRYTirEEILSTGVM--SSLSIKRTER 882
Cdd:cd05773    7 LQKGPQLR-----KVASRGDgssDANLVCQAQGVPRVQFRWAKNGVPLDLGNP-RYE--ETTEHTGTVhtSILTIINVSA 78

                         90       100       110
                 ....*....|....*....|....*....|.
gi 24586203  883 S-DSALFTCVATNAFGSDDASINMIVQEVPE 912
Cdd:cd05773   79 AlDYALFTCTAHNSLGEDSLDIQLVSTSRPD 109

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 47.54 E-value: 2.22e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  429 PVIRQAFQEETME-PGPSVFLKCVAGGNPTPEISW-ELDGKKIANNDRYQVGqyvtvngdvvSYLNITSVHANDGGLYKC 506
Cdd:cd04968    1 PSIKVRFPADTYAlKGQTVTLECFALGNPVPQIKWrKVDGSPSSQWEITTSE----------PVLEIPNVQFEDEGTYEC 70

                         90
                 ....*....|....*...
gi 24586203  507 IAKSKVGVAEHSAKLNVY 524
Cdd:cd04968   71 EAENSRGKDTVQGRIIVQ 88

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 46.79 E-value: 2.28e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24586203  446 VFLKCVAGGNPTPEISWELDGKKIANNDRYQVGQYvtvngdvvSYLNITSVHANDGGLYKCIAKSKVGVAEHSAKL 521
Cdd:cd05746    1 VQIPCSAQGDPEPTITWNKDGVQVTESGKFHISPE--------GYLAIRDVGVADQGRYECVARNTIGYASVSMVL 68

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 48.03 E-value: 2.29e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1304 VAMPSDQVPAKIAsfddtfTATFkedakmPCLAVGAPQPEITWKIKGVE---FS-----ANDRMRVLPDGSLLIKSVNRQ 1375
Cdd:cd05726    3 VVKPRDQVVALGR------TVTF------QCETKGNPQPAIFWQKEGSQnllFPyqppqPSSRFSVSPTGDLTITNVQRS 70

                         90
                 ....*....|.
gi 24586203 1376 DAGDYSCHAEN 1386
Cdd:cd05726   71 DVGYYICQALN 81

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 47.00 E-value: 2.40e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24586203    346 KIDPPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAI--GHSEPVLRIESvkkEDKGMYQCFVRNDQ 411
Cdd:pfam13895    3 VLTPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAIssSPNFFTLSVSA---EDSGTYTCVARNGR 67

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 47.18 E-value: 2.50e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203    617 PPQVLpFSFGESAADVGDIASANCVVPKGDLPlEIRWSLNSAPIVNGENGFtlVRLNKRTSLLNIDSLNAFHRGVYKCIA 696
Cdd:pfam13927    1 KPVIT-VSPSSVTVREGETVTLTCEATGSPPP-TITWYKNGEPISSGSTRS--RSLSGSNSTLTISNVTRSDAGTYTCVA 76


                   ..
gi 24586203    697 TN 698
Cdd:pfam13927   77 SN 78

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 47.40 E-value: 2.64e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24586203  270 PAQGYPAPSFRWYKfiEGTTrkqAVVLNDRVKQVS-GTLIIKDAVVEDSGKYLCVVNNSVGG-ESVETVLTV 339
Cdd:cd05724   21 PPRGHPEPTVSWRK--DGQP---LNLDNERVRIVDdGNLLIAEARKSDEGTYKCVATNMVGErESRAARLSV 87

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 47.40 E-value: 2.80e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24586203 1331 KMPCLAVGAPQPEITWKIKG--VEFSANDRMRVLPDG--SLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1399
Cdd:cd20990   19 RMDCKVSGLPTPDLSWQLDGkpIRPDSAHKMLVRENGvhSLIIEPVTSRDAGIYTCIATNRAGQNSFNLELVV 91

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

Pssm-ID: 319300 Cd Length: 92 Bit Score: 47.20 E-value: 2.97e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24586203  439 TMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQV----GQYVtvngdvvsYLNITSVHANDGGLYKCIAKSKVG 513
Cdd:cd05737   12 TIMEGKTLNLTCNVWGDPPPEVSWLKNDQALAFLDHCNLkveaGRTV--------YFTINGVSSEDSGKYGLVVKNKYG 82

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

Pssm-ID: 409443 [Multi-domain] Cd Length: 95 Bit Score: 47.54 E-value: 2.97e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24586203  269 CPAQGYPAPSFRWYKfiEGTTRKQavvlNDR-----VKQVSGTLIIKDAVVEDSGKYLCVVNNSVG 329
Cdd:cd05857   26 CPAAGNPTPTMRWLK--NGKEFKQ----EHRiggykVRNQHWSLIMESVVPSDKGNYTCVVENEYG 85

Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2, and similar proteins. Perlecan consists of five domains: domain I has three putative heparan sulfate attachment sites, domain II has four LDL receptor-like repeats, and one Ig-like repeat, domain III resembles the short arm of laminin chains, domain IV has multiple Ig-like repeats (21 repeats in human perlecan), and domain V resembles the globular G domain of the laminin A chain and internal repeats of EGF. Perlecan may participate in a variety of biological functions including cell binding, LDL-metabolism, basement membrane assembly and selective permeability, calcium binding, and growth- and neurite-promoting activities.

Pssm-ID: 143220 Cd Length: 78 Bit Score: 46.71 E-value: 3.02e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24586203  729 GSDAKVECKADGFPKPQVTWKKAVGDTPGEYKDLKKSDNIRveeGTLHVDNIQKTNEGYYLCEAINGIG 797
Cdd:cd05743    1 GETVEFTCVATGVPTPIINWRLNWGHVPDSARVSITSEGGY---GTLTIRDVKESDQGAYTCEAINTRG 66

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 46.79 E-value: 3.07e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203     39 PVFLKEPTNRIDFSNSTgAEIECKASGNPMPEIIWIRSDGTAV-GDVPGLRQISSDGKLVFPPFRAEDyrqevhAQVYAC 117
Cdd:pfam13927    2 PVITVSPSSVTVREGET-VTLTCEATGSPPPTITWYKNGEPISsGSTRSRSLSGSNSTLTISNVTRSD------AGTYTC 74


                   ....
gi 24586203    118 LARN 121
Cdd:pfam13927   75 VASN 78

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 47.01 E-value: 3.12e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  439 TMEPGPSVflkcvagGNPTPEISWELDGKKIA--NNDRYQVGqyvtvNGDVVsylnITSVHANDGGLYKCIAKSKVGVAE 516
Cdd:cd05724   16 VLECSPPR-------GHPEPTVSWRKDGQPLNldNERVRIVD-----DGNLL----IAEARKSDEGTYKCVATNMVGERE 79


                 ....*...
gi 24586203  517 HS-AKLNV 523
Cdd:cd05724   80 SRaARLSV 87

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 47.40 E-value: 3.31e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203   59 IECKASGNPMPEIIWIRsDGT--AVGDVPGLRQISSDGKLV--FPPFRAEDYRQEvhaqvYACLARNQFGSIISRDVHVR 134
Cdd:cd05733   21 IKCEAKGNPQPTFRWTK-DGKffDPAKDPRVSMRRRSGTLVidNHNGGPEDYQGE-----YQCYASNELGTAISNEIRLV 94

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 47.00 E-value: 3.43e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 24586203  269 CPAQGYPAPSFRWYKFIEGTTRKQAVVLNDRvkqvsgTLIIKDAVVEDSGKYLCVVNNSVGGESVETVLTV 339
Cdd:cd05725   19 CEVGGDPVPTVRWRKEDGELPKGRYEILDDH------SLKIRKVTAGDMGSYTCVAENMVGKIEASATLTV 83

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 46.47 E-value: 3.50e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  443 GPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVGQYVTvngdvvsyLNITSVHANDGGLYKCIAKSKVGVAEHSAKLN 522
Cdd:cd05745    2 GQTVDFLCEAQGYPQPVIAWTKGGSQLSVDRRHLVLSSGT--------LRISRVALHDQGQYECQAVNIVGSQRTVAQLT 73


                 .
gi 24586203  523 V 523
Cdd:cd05745   74 V 74

Second immunoglobulin (Ig)-like domain of protein tyrosine kinase (PTK) 7; The members here are composed of the second immunoglobulin (Ig)-like domain in protein tyrosine kinase (PTK) 7, also known as CCK4. PTK7 is a subfamily of the receptor protein tyrosine kinase family, and is referred to as an RPTK-like molecule. RPTKs transduce extracellular signals across the cell membrane and play important roles in regulating cell proliferation, migration, and differentiation. PTK7 is organized as an extracellular portion having seven Ig-like domains, a single transmembrane region, and a cytoplasmic tyrosine kinase-like domain. PTK7 is considered a pseudokinase as it has several unusual residues in some of the highly conserved tyrosine kinase (TK) motifs; it is predicted to lack TK activity. PTK7 may function as a cell-adhesion molecule. PTK7 mRNA is expressed at high levels in placenta, melanocytes, liver, lung, pancreas, and kidney. PTK7 is overexpressed in several cancers, including melanoma and colon cancer lines.

Pssm-ID: 409417 Cd Length: 95 Bit Score: 47.23 E-value: 3.70e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203   39 PVFLKEPTNRIDFSNSTGAEIECKASGNPMPEIIWIRsDGTAVGDVPGLRQISSDGK-LVFPPFRAEdyrqevHAQVYAC 117
Cdd:cd05760    1 PVVLKHPASAAEIQPSSRVTLRCHIDGHPRPTYQWFR-DGTPLSDGQGNYSVSSKERtLTLRSAGPD------DSGLYYC 73

                         90
                 ....*....|...
gi 24586203  118 LARNQFGSIISRD 130
Cdd:cd05760   74 CAHNAFGSVCSSQ 86

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 47.12 E-value: 3.74e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24586203  540 GETLIVTCPVAGYPIDSIVWERD-NRALPINRKQKVFPNGT-LIIENVeRNSDQATYTCVAKNQEGYSARGSLEVQV 614
Cdd:cd20970   17 GENATFMCRAEGSPEPEISWTRNgNLIIEFNTRYIVRENGTtLTIRNI-RRSDMGIYLCIASNGVPGSVEKRITLQV 92

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 47.10 E-value: 3.75e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24586203 1334 CLAVGAPQPEITWKI---KGV-EFSA----NDRMRVLPDGSLLIKSVNRQDAGDYSCHAENSIAKD 1391
Cdd:cd05734   23 CSADGYPPPTIVWKHskgSGVpQFQHivplNGRIQLLSNGSLLIKHVLEEDSGYYLCKVSNDVGAD 88

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 47.03 E-value: 3.80e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  352 QTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAI-GHSEP------------VLRIESVKKEDKGMYQCFVRNDQESAEASA 418
Cdd:cd20951   10 HTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIdPSSIPgkykieseygvhVLHIRRVTVEDSAVYSAVAKNIHGEASSSA 89


                 ..
gi 24586203  419 EL 420
Cdd:cd20951   90 SV 91

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 2 (NCAM-2); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is organized similarly to NCAM, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143278 [Multi-domain] Cd Length: 98 Bit Score: 47.28 E-value: 3.90e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  429 PVIRQAFQEETMEPGpSVFLKCVAGGNPTPEISWE--LDGKKIANNDRYQVGQyVTVNGDV-VSYLNITSVHANDGGLYK 505
Cdd:cd05870    3 PHIIQLKNETTVENG-AATLSCKAEGEPIPEITWKraSDGHTFSEGDKSPDGR-IEVKGQHgESSLHIKDVKLSDSGRYD 80

                         90
                 ....*....|....*...
gi 24586203  506 CIAKSKVGVAEHSAKLNV 523
Cdd:cd05870   81 CEAASRIGGHQKSMYLDI 98

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 46.72 E-value: 4.07e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24586203  820 NQTARRGEPAVLQCEAKGEKPIGILWnMNNMRLDPKNDNRYTIREEilstgvmSSLSIKRTERSDSALFTCVATNAFGS 898
Cdd:cd20952    8 NQTVAVGGTVVLNCQATGEPVPTISW-LKDGVPLLGKDERITTLEN-------GSLQIKGAEKSDTGEYTCVALNLSGE 78

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

Pssm-ID: 409408 [Multi-domain] Cd Length: 92 Bit Score: 46.74 E-value: 4.12e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  817 KLRNQTARRGEPAVLQCEAKGEKP-IGILWNMNNMRLDPKNDNRYTIREEILStgvmSSLSIKRTERSDSALFTCVATNA 895
Cdd:cd05750    5 EMKSQTVQEGSKLVLKCEATSENPsPRYRWFKDGKELNRKRPKNIKIRNKKKN----SELQINKAKLEDSGEYTCVVENI 80

                         90
                 ....*....|..
gi 24586203  896 FGSDDASINMIV 907
Cdd:cd05750   81 LGKDTVTGNVTV 92

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 46.62 E-value: 4.32e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  257 NIVESMASTAIL-CPAQGYPAPSFRWY---KFIEGTtrkqavvlNDRVKQVSGTLIIKDAVVEDSGKYLCVVNNSVGGES 332
Cdd:cd20978   10 NVVVKGGQDVTLpCQVTGVPQPKITWLhngKPLQGP--------MERATVEDGTLTIINVQPEDTGYYGCVATNEIGDIY 81


                 ....*..
gi 24586203  333 VETVLTV 339
Cdd:cd20978   82 TETLLHV 88

Eighth immunoglobulin (Ig)-like domain of human myosin light-chain kinase (MLCK) and similar protein; member of the I-set of IgSF domains; The members here are composed of the eighth immunoglobulin (Ig)-like domain of human myosin light-chain kinase (MLCK) and similar proteins. Myosin light-chain kinase (MLCK) is a key regulator of different forms of cell motility involving actin and myosin II. Agonist stimulation of smooth muscle cells increases cytosolic Ca2+ which binds calmodulin. This Ca2+-calmodulin complex in turn binds to and activates MLCK. Activated MLCK leads to the phosphorylation of the 20 kDa myosin regulatory light chain (RLC) of myosin II and the stimulation of actin-activated myosin MgATPase activity. MLCK is widely present in vertebrate tissues; it phosphorylates the 20 kDa RLC of both smooth and nonmuscle myosin II. Phosphorylation leads to the activation of the myosin motor domain and altered structural properties of myosin II. In smooth muscle MLCK it is involved in initiating contraction. In nonmuscle cells, MLCK may participate in cell division and cell motility; it has been suggested MLCK plays a role in cardiomyocyte differentiation and contraction through regulation of nonmuscle myosin II.

Pssm-ID: 409419 Cd Length: 99 Bit Score: 46.87 E-value: 4.74e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  811 PPEFTEKLRNQTARRGEPAVLQCEAKGEKPIGILWnmnnMRLdpkndnRYTIRE----EILSTGVMSSLSIKRTERSDSA 886
Cdd:cd05762    1 PPQIIQFPEDMKVRAGESVELFCKVTGTQPITCTW----MKF------RKQIQEgegiKIENTENSSKLTITEGQQEHCG 70

                         90       100
                 ....*....|....*....|....*...
gi 24586203  887 LFTCVATNAFGSDDASINMIVQEVPEMP 914
Cdd:cd05762   71 CYTLEVENKLGSRQAQVNLTVVDKPDPP 98

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 46.87 E-value: 4.86e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  812 PEFTEKLRNQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLDPKNDNRYTireeILSTGvmSSLSIKRTERSDSALFTCV 891
Cdd:cd05736    1 PVIRVYPEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMDINPKLSKQLT----LIANG--SELHISNVRYEDTGAYTCI 74

                         90
                 ....*....|....*...
gi 24586203  892 ATNAFGSDDASINMIVQE 909
Cdd:cd05736   75 AKNEGGVDEDISSLFVED 92

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 46.43 E-value: 4.94e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 24586203 1328 EDAKMPCLAVGAPQPEITWKIKG--VEFSANDRMRVLPDGSLLIKSVNRQDAGDYSCHAEN 1386
Cdd:cd05867   15 ETARLDCQVEGIPTPNITWSINGapIEGTDPDPRRHVSSGALILTDVQPSDTAVYQCEARN 75

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 46.42 E-value: 5.22e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  714 PPRWILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKavgdtpgEYKDLKKSDNIRV-EEGTLHVDNIQKTNE---GYYL 789
Cdd:cd20972    1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFC-------EGKELQNSPDIQIhQEGDLHSLIIAEAFEedtGRYS 73


                 ....*....
gi 24586203  790 CEAINGIGS 798
Cdd:cd20972   74 CLATNSVGS 82

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (IgSF) domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 46.31 E-value: 6.85e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  429 PVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISW-ELDGKKIANNDRYQVGQyvtvNGDvvsyLNITSVHANDGGLYKCI 507
Cdd:cd05764    1 PLITRHTHELRVLEGQRATLRCKARGDPEPAIHWiSPEGKLISNSSRTLVYD----NGT----LDILITTVKDTGAFTCI 72

                         90
                 ....*....|....*.
gi 24586203  508 AKSKVGVAEHSAKLNV 523
Cdd:cd05764   73 ASNPAGEATARVELHI 88

First immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409547 Cd Length: 99 Bit Score: 46.63 E-value: 6.90e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  715 PRWILEPTDKA-FAQGSDAKVECKADGFPKPQVTWKK----AVGDTPGEYKdlKKSDNIRVEEGTLHVDNIQKTNEGYYL 789
Cdd:cd20955    2 PVFLKEPTNRIdFSNSTGAEIECKASGNPMPEIIWIRsdgtAVGDVPGLRQ--ISSDGKLVFPPFRAEDYRQEVHAQVYA 79

                         90
                 ....*....|..
gi 24586203  790 CEAINGIGSGLS 801
Cdd:cd20955   80 CLARNQFGSIIS 91

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409435 Cd Length: 96 Bit Score: 46.47 E-value: 7.15e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1312 PAKIASFDDTFTATFKEDAK--MPCLAVGAPQPEITWKIKGVEFSANDRMRV-LPDGSLLIKSVNR-QDAGDYSCHAENS 1387
Cdd:cd05848    2 PVFVQEPDDAIFPTDSDEKKviLNCEARGNPVPTYRWLRNGTEIDTESDYRYsLIDGNLIISNPSEvKDSGRYQCLATNS 81


                 .
gi 24586203 1388 I 1388
Cdd:cd05848   82 I 82

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 45.70 E-value: 7.38e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24586203  540 GETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVFPNGTLIIENVERNsDQATYTCVAKNQEG 603
Cdd:cd05745    2 GQTVDFLCEAQGYPQPVIAWTKGGSQLSVDRRHLVLSSGTLRISRVALH-DQGQYECQAVNIVG 64

Fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule); The members here are composed of the fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six IG-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409454 Cd Length: 89 Bit Score: 46.13 E-value: 7.59e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  717 WILEPTDKAFAQGSDAKVECKADGFPKPQVTWKkavgdTPGEYKDLKKSDNIRVEEG-TLHVDNIQKTNEGYYLCEAING 795
Cdd:cd05868    2 WITAPTNLVLSPGEDGTLICRANGNPKPSISWL-----TNGVPIEIAPTDPSRKVDGdTIIFSKVQERSSAVYQCNASNE 76


                 ..
gi 24586203  796 IG 797
Cdd:cd05868   77 YG 78

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 45.96 E-value: 7.78e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  258 IVESMASTAILCPAQGYPAPSFRWYKfiEGTTRkQAVVLNDRVKQVSGTLIIKDAVVEDSGKYLCVVNNSVGGeSVETVL 337
Cdd:cd20970   13 TAREGENATFMCRAEGSPEPEISWTR--NGNLI-IEFNTRYIVRENGTTLTIRNIRRSDMGIYLCIASNGVPG-SVEKRI 88


                 ..
gi 24586203  338 TV 339
Cdd:cd20970   89 TL 90

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 46.26 E-value: 7.89e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  429 PVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDryQVGQYVTVNGDVVSYLNITSVHANDGGLYKCIA 508
Cdd:cd20951    1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSS--IPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVA 78

                         90
                 ....*....|....*
gi 24586203  509 KSKVGVAEHSAKLNV 523
Cdd:cd20951   79 KNIHGEASSSASVVV 93

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409359 Cd Length: 102 Bit Score: 46.39 E-value: 7.91e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  427 DPPVIRQAFQEETMEPGPSVFLKCVAGGNPTPEIS--WELDGKKI---ANNDRYQVGQYVTVNGDvvsyLNITSVHANDG 501
Cdd:cd04970    1 DATRITLAPSNADITVGENATLQCHASHDPTLDLTftWSFNGVPIdleKIEGHYRRRYGKDSNGD----LEIVNAQLKHA 76

                         90       100
                 ....*....|....*....|....*.
gi 24586203  502 GLYKCIAKSKVGVAEHSAKLNVYGLP 527
Cdd:cd04970   77 GRYTCTAQTVVDSDSASATLVVRGPP 102

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 45.90 E-value: 8.05e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203   42 LKEPTNrIDFSNSTGAEIECKASGNPMPEIIWiRSDGTAVGDVPGLRQISSDGK-LVFPPFraedyrQEVHAQVYACLAR 120
Cdd:cd04978    3 IIEPPS-LVLSPGETGELICEAEGNPQPTITW-RLNGVPIEPAPEDMRRTVDGRtLIFSNL------QPNDTAVYQCNAS 74

                         90
                 ....*....|....*
gi 24586203  121 NQFGSIISRD-VHVR 134
Cdd:cd04978   75 NVHGYLLANAfLHVL 89

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 46.49 E-value: 8.05e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  436 QEETMEPGPSVFLKCVAGGNPTPEISWELDGKKI--------ANNDRYQVGQyvtvNGDvvsyLNITSVHANDGGLYKCI 507
Cdd:cd05726    7 RDQVVALGRTVTFQCETKGNPQPAIFWQKEGSQNllfpyqppQPSSRFSVSP----TGD----LTITNVQRSDVGYYICQ 78

                         90
                 ....*....|....*...
gi 24586203  508 AKSKVGVAEHSAKLNVYG 525
Cdd:cd05726   79 ALNVAGSILAKAQLEVTD 96

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and similar proteins; member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and related proteins. The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members: VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1) and VEGFR-3 (Flt-4). VEGF-A interacts with both VEGFR-1 and VEGFR-2. VEGFR-1 binds strongest to VEGF; VEGF-2 binds more weakly. VEGFR-3 appears not to bind VEGF, but binds other members of the VEGF family (VEGF-C and -D). VEGFRs bind VEGFs with high affinity with the IG-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic, and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth. This group also contains alpha-type platelet-derived growth factor receptor precursor (PDGFR)-alpha (CD140a), and PDGFR-beta (CD140b). PDGFRs alpha and beta have an extracellular component with five Ig-like domains, a transmembrane segment, and a cytoplasmic portion that has protein tyrosine kinase activity.

Pssm-ID: 409404 Cd Length: 102 Bit Score: 46.38 E-value: 9.13e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  819 RNQTARRGEPAVLQCEAKGEKPIGIlwNMNNMRLDPKNDNRYTIREEIL-----STGVMSSLSIKRTERSDSALFTCVAT 893
Cdd:cd05742   10 EPTVLPQGETLVLNCTANVNLNEVV--DFQWTYPSEKEGKLALLKPDIKvdwsePGEFVSTLTIPEATLKDSGTYTCAAR 87

                         90
                 ....*....|....
gi 24586203  894 NAFGSDDASINMIV 907
Cdd:cd05742   88 SGVMKKEKQTSVSV 101

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409359 Cd Length: 102 Bit Score: 46.39 E-value: 9.33e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1312 PAKIASFDDTFTATFKEDAKMPCLAVGAPQPEIT--WKIKGVEFSAND------RMRVLPD-GSLLIKSVNRQDAGDYSC 1382
Cdd:cd04970    2 ATRITLAPSNADITVGENATLQCHASHDPTLDLTftWSFNGVPIDLEKieghyrRRYGKDSnGDLEIVNAQLKHAGRYTC 81

                         90       100
                 ....*....|....*....|.
gi 24586203 1383 HAENSIAKDSITHKLIVLAPP 1403
Cdd:cd04970   82 TAQTVVDSDSASATLVVRGPP 102

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 45.46 E-value: 9.44e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203    718 ILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKavGDTPgeykdLKKSDNirveegtLHVDNIQKTNEGYYLCEAINGIG 797
Cdd:pfam13895    3 VLTPSPTVVTEGEPVTLTCSAPGNPPPSYTWYK--DGSA-----ISSSPN-------FFTLSVSAEDSGTYTCVARNGRG 68

                           90
                   ....*....|.
gi 24586203    798 SGLSAVIMISV 808
Cdd:pfam13895   69 GKVSNPVELTV 79

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 45.66 E-value: 9.77e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  822 TARRGEPAVLQCEAKGEKPIGILWNMNNMRLdpKNDNRYTIReeilSTGVMSSLSIKRTERSDSALFTCVATNAFGSDDA 901
Cdd:cd05748    3 VVRAGESLRLDIPIKGRPTPTVTWSKDGQPL--KETGRVQIE----TTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSA 76


                 ....*.
gi 24586203  902 SINMIV 907
Cdd:cd05748   77 TINVKV 82

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 45.91 E-value: 9.99e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 24586203  357 GRPAVFTCQYTGNPIKTVSWMKDGKAIGHSEPV-------LRIESVKKEDKGMYQCFVRNDQESAEASAEL 420
Cdd:cd04969   17 GGDVIIECKPKASPKPTISWSKGTELLTNSSRIcilpdgsLKIKNVTKSDEGKYTCFAVNFFGKANSTGSL 87

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 45.63 E-value: 1.12e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  811 PPEFTEKLRNQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLdPKNDnRYTIREEILSTG-VMSSLSIKRTERSDSALFT 889
Cdd:cd20956    1 APVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDGFPI-PESP-RFRVGDYVTSDGdVVSYVNISSVRVEDGGEYT 78


                 ....*....
gi 24586203  890 CVATNAFGS 898
Cdd:cd20956   79 CTATNDVGS 87

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 45.46 E-value: 1.15e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  812 PEFTEKLRNQTARR-GEPAVLQCEAKGEKPIGILWNMNNMRLDpKNDNRYTIREeilstgvmSSLSIKRTERSDSALFTC 890
Cdd:cd20978    1 PKFIQKPEKNVVVKgGQDVTLPCQVTGVPQPKITWLHNGKPLQ-GPMERATVED--------GTLTIINVQPEDTGYYGC 71


                 ....*..
gi 24586203  891 VATNAFG 897
Cdd:cd20978   72 VATNEIG 78

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 45.62 E-value: 1.29e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  715 PRWILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKAvGDTPGEYKDLKKSDNIRVEEGTLHVDNI-----QKTNEGYYL 789
Cdd:cd07693    1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKN-GQPLETDKDDPRSHRIVLPSGSLFFLRVvhgrkGRSDEGVYV 79

                         90
                 ....*....|...
gi 24586203  790 CEAINGIGSGLSA 802
Cdd:cd07693   80 CVAHNSLGEAVSR 92

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 45.33 E-value: 1.35e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24586203  346 KIDPPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIGHSEP----------VLRIESVKKEDKGMYQCFVRND 410
Cdd:cd05736    4 RVYPEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMDINPKLSkqltliangsELHISNVRYEDTGAYTCIAKNE 78

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

Pssm-ID: 409443 [Multi-domain] Cd Length: 95 Bit Score: 45.61 E-value: 1.40e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  531 QMEKK--AIVAGETLIVTCPVAGYPIDSIVWERDNRalPINRKQKV------FPNGTLIIENVERnSDQATYTCVAKNQE 602
Cdd:cd05857    8 KMEKKlhAVPAANTVKFRCPAAGNPTPTMRWLKNGK--EFKQEHRIggykvrNQHWSLIMESVVP-SDKGNYTCVVENEY 84


                 .
gi 24586203  603 G 603
Cdd:cd05857   85 G 85

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 45.69 E-value: 1.42e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24586203  529 IRQMEKKAIV-AGETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVF--PNGTLIIENVERNsDQATYTCVAKNQEG 603
Cdd:cd05730    6 ARQSEVNATAnLGQSVTLACDADGFPEPTMTWTKDGEPIESGEEKYSFneDGSEMTILDVDKL-DEAEYTCIAENKAG 82

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 45.28 E-value: 1.47e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 24586203  269 CPAQGYPAPSFRWYKfiegttRKQAVVLNDRVKQVSGTLIIKDAVVEDSGKYLCVVNNSVG 329
Cdd:cd05728   21 CKASGNPRPAYRWLK------NGQPLASENRIEVEAGDLRITKLSLSDSGMYQCVAENKHG 75

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 45.62 E-value: 1.51e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  527 PYIRQMEKKAIVA-GETLIVTCPVAGYPIDSIVWERDNRALPINRKQK-----VFPNGTL----IIENVERNSDQATYTC 596
Cdd:cd07693    1 PRIVEHPSDLIVSkGDPATLNCKAEGRPTPTIQWLKNGQPLETDKDDPrshriVLPSGSLfflrVVHGRKGRSDEGVYVC 80

                         90
                 ....*....|....*...
gi 24586203  597 VAKNQ--EGYSARGSLEV 612
Cdd:cd07693   81 VAHNSlgEAVSRNASLEV 98

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 45.19 E-value: 1.51e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  817 KLRNQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLDPKNDnrytiREEILSTGVMssLSIKRTERSDSALFTCVATN-A 895
Cdd:cd20970    8 PSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNT-----RYIVRENGTT--LTIRNIRRSDMGIYLCIASNgV 80

                         90
                 ....*....|..
gi 24586203  896 FGSDDASINMIV 907
Cdd:cd20970   81 PGSVEKRITLQV 92

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.

Pssm-ID: 143299 Cd Length: 92 Bit Score: 45.29 E-value: 1.52e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  256 PNIVESM--ASTAILCPAQGYPAPSFRWYKfiegttRKQAVVLNDR--VKQVSG---TLIIKDAVVEDSGKYLCVVNNSV 328
Cdd:cd05891    8 PDVVTIMegKTLNLTCTVFGNPDPEVIWFK------NDQDIELSEHysVKLEQGkyaSLTIKGVTSEDSGKYSINVKNKY 81

                         90
                 ....*....|.
gi 24586203  329 GGESVETVLTV 339
Cdd:cd05891   82 GGETVDVTVSV 92

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

Pssm-ID: 409408 [Multi-domain] Cd Length: 92 Bit Score: 45.19 E-value: 1.63e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24586203  351 TQTVDFGRPAVFTCQYTG-NPIKTVSWMKDGKAIGHSEPV------------LRIESVKKEDKGMYQCFVRN 409
Cdd:cd05750    8 SQTVQEGSKLVLKCEATSeNPSPRYRWFKDGKELNRKRPKnikirnkkknseLQINKAKLEDSGEYTCVVEN 79

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 44.92 E-value: 2.00e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203   41 FLKEPTNrIDFSNSTGAEIECKASGNPMPEIIWIRSDGTavgDVPGLRQ-----ISSDGKLVFPPFRAEDyrqevhAQVY 115
Cdd:cd05763    2 FTKTPHD-ITIRAGSTARLECAATGHPTPQIAWQKDGGT---DFPAARErrmhvMPEDDVFFIVDVKIED------TGVY 71

                         90
                 ....*....|.
gi 24586203  116 ACLARNQFGSI 126
Cdd:cd05763   72 SCTAQNSAGSI 82

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 44.88 E-value: 2.13e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24586203 1331 KMPCLAVGAPQPEITWKIKGVEFSANDRMRVLPDG---SLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1399
Cdd:cd20972   20 RLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEGdlhSLIIAEAFEEDTGRYSCLATNSVGSDTTSAEIFV 91

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 45.00 E-value: 2.19e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  238 ITEPVSSSppkinaltykpniVESMASTAILCPAQGYPAPSFRWYKFIeGTT--RKQAVVLNDRVKQVS-GTLIIKDAVV 314
Cdd:cd20954    5 IVEPVDAN-------------VAAGQDVMLHCQADGFPTPTVTWKKAT-GSTpgEYKDLLYDPNVRILPnGTLVFGHVQK 70

                         90
                 ....*....|....*
gi 24586203  315 EDSGKYLCVVNNSVG 329
Cdd:cd20954   71 ENEGHYLCEAKNGIG 85

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 44.63 E-value: 2.22e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  814 FTEKLRNQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLdpKNDNRYTIREEILSTGvmssLSIKRTERSDSALFTCVAT 893
Cdd:cd20949    2 FTENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQPI--SASVADMSKYRILADG----LLINKVTQDDTGEYTCRAY 75


                 ....
gi 24586203  894 NAFG 897
Cdd:cd20949   76 QVNS 79

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 44.76 E-value: 2.24e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  715 PRWILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKAvgdtpgeykdlKKSDNIRVEEGTLHVDN-------IQ---KTN 784
Cdd:cd05892    1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKN-----------NEMLQYNTDRISLYQDNcgricllIQnanKKD 69

                         90
                 ....*....|...
gi 24586203  785 EGYYLCEAINGIG 797
Cdd:cd05892   70 AGWYTVSAVNEAG 82

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 44.90 E-value: 2.56e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  344 SAKIDPPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGK---AIGHSEP--------VLRIESVKKEDKGMYQCFVRNDQE 412
Cdd:cd05729    6 TEKMEEREHALPAANKVRLECGAGGNPMPNITWLKDGKefkKEHRIGGtkveekgwSLIIERAIPRDKGKYTCIVENEYG 85

                         90
                 ....*....|
gi 24586203  413 SAEASAELKL 422
Cdd:cd05729   86 SINHTYDVDV 95

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 44.53 E-value: 2.63e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  439 TMEPGPSVFLKCVAGGNPTPEISWELDGKK---IANNDRYQVgqyvtVNGDVVSYlnITSVHANDGGLYKCIAKSKVGVA 515
Cdd:cd05763   10 TIRAGSTARLECAATGHPTPQIAWQKDGGTdfpAARERRMHV-----MPEDDVFF--IVDVKIEDTGVYSCTAQNSAGSI 82


                 ....*...
gi 24586203  516 EHSAKLNV 523
Cdd:cd05763   83 SANATLTV 90

Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2, and similar proteins. Perlecan consists of five domains: domain I has three putative heparan sulfate attachment sites, domain II has four LDL receptor-like repeats, and one Ig-like repeat, domain III resembles the short arm of laminin chains, domain IV has multiple Ig-like repeats (21 repeats in human perlecan), and domain V resembles the globular G domain of the laminin A chain and internal repeats of EGF. Perlecan may participate in a variety of biological functions including cell binding, LDL-metabolism, basement membrane assembly and selective permeability, calcium binding, and growth- and neurite-promoting activities.

Pssm-ID: 143220 Cd Length: 78 Bit Score: 44.02 E-value: 2.66e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24586203  540 GETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVFPN---GTLIIENVeRNSDQATYTCVAKNQEGY 604
Cdd:cd05743    1 GETVEFTCVATGVPTPIINWRLNWGHVPDSARVSITSEggyGTLTIRDV-KESDQGAYTCEAINTRGM 67

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 44.54 E-value: 2.75e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1323 TATFKEDAKMPCLAVGAPQPEITWKIKGVEF-SANDRMRVLPDGS-LLIKSVNRQDAGDYSCHAENSIAKDSITHKLIVL 1400
Cdd:cd05730   14 TANLGQSVTLACDADGFPEPTMTWTKDGEPIeSGEEKYSFNEDGSeMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKVF 93


                 .
gi 24586203 1401 A 1401
Cdd:cd05730   94 A 94

Fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 protein (also known as Neph2). This protein has five Ig-like domains, one transmembrane domain, and a cytoplasmic tail. Included in this group is mammalian Kirrel (Neph1). These proteins contain multiple Ig domains, have properties of cell adhesion molecules, and are important in organ development. Neph1 and 2 may mediate axonal guidance and synapse formation in certain areas of the CNS. In the kidney they participate in the formation of the slit diaphragm.

Pssm-ID: 409479 Cd Length: 98 Bit Score: 44.94 E-value: 2.76e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  821 QTARRGEPAVLQCE-AKGEKPIGILWNMNNMRLDPKNDNRYTIREEILSTGVMSSLSIKRTERSD-SALFTCVATNAFGS 898
Cdd:cd05898   11 QYAVRGERGKVKCFiGSTPPPDRIAWAWKENVLESGTLERYTVERTSTGSGVLSTLTINNIMEADfQTHYNCTAWNSFGS 90


                 ....*..
gi 24586203  899 DDASINM 905
Cdd:cd05898   91 GTAIIQL 97

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 44.36 E-value: 2.89e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24586203  540 GETLIVTCPVAGYPIDSIVWERDNR---ALPINRKQKVFPnGTLIIENVERNsDQATYTCVAKNQEGY 604
Cdd:cd04978   14 GETGELICEAEGNPQPTITWRLNGVpiePAPEDMRRTVDG-RTLIFSNLQPN-DTAVYQCNASNVHGY 79

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 44.78 E-value: 2.96e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  714 PPRWILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKAvgdtpGEYKDLKKSDNIRV-EEGTLHVDNIQ-----KTNEGY 787
Cdd:cd05722    1 ELYFLSEPSDIVAMRGGPVVLNCSAESDPPPKIEWKKD-----GVLLNLVSDERRQQlPNGSLLITSVVhskhnKPDEGF 75

                         90
                 ....*....|....*
gi 24586203  788 YLCEAING-IGSGLS 801
Cdd:cd05722   76 YQCVAQNEsLGSIVS 90

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 44.41 E-value: 2.96e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  720 EPTDKAFAQGSDAKVECKADGFPKPQVTWKKAVGDTPGEYKDLKKSDNirveeGTLHVDNIQKTNEGYYLCEAINGIGSG 799
Cdd:cd20952    5 GPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLEN-----GSLQIKGAEKSDTGEYTCVALNLSGEA 79


                 ....*.
gi 24586203  800 L-SAVI 804
Cdd:cd20952   80 TwSAVL 85

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 44.44 E-value: 3.05e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  612 VQVMVPPQVLpfsfgesAADVGDIASANCVVpKGDLPLEIRWSLNSAPIVNGENGFTLVRlnkrtSLLNIDSLNAFHRGV 691
Cdd:cd20957    2 LSATIDPPVQ-------TVDFGRTAVFNCSV-TGNPIHTVLWMKDGKPLGHSSRVQILSE-----DVLVIPSVKREDKGM 68

                         90       100
                 ....*....|....*....|
gi 24586203  692 YKCIATNPAGTSEYVAELQV 711
Cdd:cd20957   69 YQCFVRNDGDSAQATAELKL 88

First immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-1, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-1. NCAM-1 plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-nonNCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves the Ig1, Ig2, and Ig3 domains. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409366 Cd Length: 95 Bit Score: 44.55 E-value: 3.13e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  439 TMEPGPSVFLKCVAGGNPTpEISW-ELDGKKIANNDryqvGQYVTVN-GDVVSYLNITSVHANDGGLYKCIAKSKVGV-A 515
Cdd:cd04977   11 EISVGESKFFLCKVSGDAK-NINWvSPNGEKVLTKH----GNLKVVNhGSVLSSLTIYNANINDAGIYKCVATNGKGTeS 85


                 ....*....
gi 24586203  516 EHSAKLNVY 524
Cdd:cd04977   86 EATVKLDII 94

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 143259 Cd Length: 88 Bit Score: 44.24 E-value: 3.15e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  714 PPRWILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKAVGDTPGeykdlkkSDNIRVEEGTLHVDNIQKTNEGYYLCEAI 793
Cdd:cd05851    1 PADINVKFKDTYALKGQNVTLECFALGNPVPVIRWRKILEPMPA-------TAEISMSGAVLKIFNIQPEDEGTYECEAE 73


                 .
gi 24586203  794 N 794
Cdd:cd05851   74 N 74

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 44.13 E-value: 3.30e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 24586203  728 QGSDAKVECKADGFPKPQVTWKKAVGDTPGEykDLKKSDNIRveegTLHVDNIQKTNEGYYLCEAINGIGS 798
Cdd:cd05876    9 RGQSLVLECIAEGLPTPTVKWLRPSGPLPPD--RVKYQNHNK----TLQLLNVGESDDGEYVCLAENSLGS 73

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 44.31 E-value: 3.33e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  439 TMEPGPSVFLKCVAGGNPTPEISWELDGKKI-ANNDRYQVGQyvtvngdvvSYLNITSVHANDGGLYKCIAKSKVGVAEH 517
Cdd:cd20978   12 VVKGGQDVTLPCQVTGVPQPKITWLHNGKPLqGPMERATVED---------GTLTIINVQPEDTGYYGCVATNEIGDIYT 82


                 ....*.
gi 24586203  518 SAKLNV 523
Cdd:cd20978   83 ETLLHV 88

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 44.16 E-value: 3.38e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24586203  443 GPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVGQyvtvNGDvvsyLNITSVHANDGGLYKCIAKSKVGVA 515
Cdd:cd20968   14 GLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRIAVLE----SGS----LRIHNVQKEDAGQYRCVAKNSLGIA 78

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 44.17 E-value: 3.42e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203    632 VGDIASANCVVpKGDLPLEIRWSLNSAPIVNGENgFTLVRLNKRTSLLnIDSLNAFHRGVYKCIATNPAGTSEYVAELQV 711
Cdd:pfam07679   14 EGESARFTCTV-TGTPDPEVSWFKDGQPLRSSDR-FKVTYEGGTYTLT-ISNVQPDDSGKYTCVATNSAGEAEASAELTV 90

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 44.23 E-value: 3.61e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203   39 PVFLKEPTnriDFSNSTGAEI--ECKASGNPMPEIIWIRSDGTAVGDVPGLR-----QISSDGKLVFppfraeDYRQEVH 111
Cdd:cd20954    2 PRWIVEPV---DANVAAGQDVmlHCQADGFPTPTVTWKKATGSTPGEYKDLLydpnvRILPNGTLVF------GHVQKEN 72

                         90
                 ....*....|....*...
gi 24586203  112 AQVYACLARNQFGSIISR 129
Cdd:cd20954   73 EGHYLCEAKNGIGSGLSK 90

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409438 Cd Length: 89 Bit Score: 44.22 E-value: 3.83e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  715 PRWILEPTDKAF--AQGSDAKVECKADGFPKPQVTWKKAVgdtpgeyKDLKKSDNIRV-EEGTLHVDNIQKTNEGYYLCE 791
Cdd:cd05852    1 PTFEFNPMKKKIlaAKGGRVIIECKPKAAPKPKFSWSKGT-------ELLVNNSRISIwDDGSLEILNITKLDEGSYTCF 73

                         90
                 ....*....|....
gi 24586203  792 AINGIGSGLSAVIM 805
Cdd:cd05852   74 AENNRGKANSTGVL 87

Third immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F (also known as LAR), type IIa; member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains. Included in this group is Drosophila LAR (DLAR).

Pssm-ID: 409401 Cd Length: 82 Bit Score: 43.74 E-value: 3.98e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  437 EETMePGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVGQyvtvngDVVSYLNITSvHANdgglYKCIAKSKVGVAE 516
Cdd:cd05739    7 HEVM-PGGSVNLTCVAVGAPMPYVKWMKGGEELTKEDEMPVGR------NVLELTNIYE-SAN----YTCVAISSLGMIE 74


                 ....*..
gi 24586203  517 HSAKLNV 523
Cdd:cd05739   75 ATAQVTV 81

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 43.99 E-value: 4.27e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24586203 1328 EDAKMPCLAVGAPQPEITWKIKGVEFSAN-DRMRVLPDGS----LLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1399
Cdd:cd05892   16 DPVRLECQISAIPPPQIFWKKNNEMLQYNtDRISLYQDNCgricLLIQNANKKDAGWYTVSAVNEAGVVSCNARLDV 92

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 44.17 E-value: 4.50e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24586203 1327 KEDAKMPCLAVGAPQPEITWKIKGVEFSAN--DRMRVLPDGS-LLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1399
Cdd:cd05736   15 GVEASLRCHAEGIPLPRVQWLKNGMDINPKlsKQLTLIANGSeLHISNVRYEDTGAYTCIAKNEGGVDEDISSLFV 90

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 43.72 E-value: 4.56e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  723 DKAFAQGSDAKVECKADGFPKPQVTWKKavgdtpgEYKDLKKSDNIRV---EEG--TLHVDNIQKTNEGYYLCEAINGIG 797
Cdd:cd20973    6 DKEVVEGSAARFDCKVEGYPDPEVKWMK-------DDNPIVESRRFQIdqdEDGlcSLIISDVCGDDSGKYTCKAVNSLG 78

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 43.69 E-value: 4.65e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 24586203  364 CQYTGNPIKTVSWMK-DG-----KAIGHSEPVLRIESVKKEDKGMYQCFVRN 409
Cdd:cd04968   23 CFALGNPVPQIKWRKvDGspssqWEITTSEPVLEIPNVQFEDEGTYECEAEN 74

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 43.76 E-value: 4.67e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  264 STAIL-CPAQGYPAPSFRWYK-----FIEGTTRKQAVVLNDRVkqvsgtLIIKDAVVEDSGKYLCVVNNSVGGESVETVL 337
Cdd:cd05763   15 STARLeCAATGHPTPQIAWQKdggtdFPAARERRMHVMPEDDV------FFIVDVKIEDTGVYSCTAQNSAGSISANATL 88


                 ..
gi 24586203  338 TV 339
Cdd:cd05763   89 TV 90

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 43.78 E-value: 4.73e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  349 PPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIGHS------EP---VLRIESVKKEDKGMYQCFVRNDQESAEASAE 419
Cdd:cd20976    8 PKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAadrstcEAgvgELHIQDVLPEDHGTYTCLAKNAAGQVSCSAW 87


                 .
gi 24586203  420 L 420
Cdd:cd20976   88 V 88

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 43.75 E-value: 4.83e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  443 GPSVFLKCVAGGNPTPEISW-ELDGKKIANNDRYQVGQyvtvngdvvSYLNITSVHANDGGLYKCIAKSKVGVAEHSAKL 521
Cdd:cd05876   10 GQSLVLECIAEGLPTPTVKWlRPSGPLPPDRVKYQNHN---------KTLQLLNVGESDDGEYVCLAENSLGSARHAYYV 80


                 ..
gi 24586203  522 NV 523
Cdd:cd05876   81 TV 82

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 43.72 E-value: 5.15e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203    819 RNQTARRGEPAVLQCEAK-GEKPIGILWNMNNMRLD-----PKNDNRYTIreeilstgvmSSLSIKRTERSDSALFTCVA 892
Cdd:pfam00047    4 PTVTVLEGDSATLTCSAStGSPGPDVTWSKEGGTLIeslkvKHDNGRTTQ----------SSLLISNVTKEDAGTYTCVV 73

                           90
                   ....*....|...
gi 24586203    893 TNAFGSDDASINM 905
Cdd:pfam00047   74 NNPGGSATLSTSL 86

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 43.09 E-value: 5.32e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24586203  639 NCVVPkGDLPLEIRWSLNSAPIVNGENGFtlVRLNKRTSLLNIDSLNAFHRGVYKCIATNPAGTSE 704
Cdd:cd00096    4 TCSAS-GNPPPTITWYKNGKPLPPSSRDS--RRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSA 66

Immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409398 Cd Length: 101 Bit Score: 44.02 E-value: 5.53e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1310 QVPAKIASFDDTFTATFKEDAKMPCLAVGAPQPEITWKiKGVEFSANDRM-------RVLPD---GSLLIKSVNRQDAGD 1379
Cdd:cd05735    1 KIPAMITSYPNTTLATKGQKKEMSCTAHGEKPIIVRWE-KEDTIINPSEMsrylvttKEVGDeviSTLQILPTVREDSGF 79

                         90       100
                 ....*....|....*....|
gi 24586203 1380 YSCHAENSIAKDSITHKLIV 1399
Cdd:cd05735   80 FSCHAINSYGEDRGIIQLTV 99

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 43.00 E-value: 5.61e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 24586203  728 QGSDAKVECKADGFPKPQVTWKKAVGDTPGEYKDLKKSdnirveEGTLHVDNIQKTNEGYYLCEAINGIGS 798
Cdd:cd05745    1 EGQTVDFLCEAQGYPQPVIAWTKGGSQLSVDRRHLVLS------SGTLRISRVALHDQGQYECQAVNIVGS 65

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 43.35 E-value: 5.69e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  537 IVAGETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVFP---NGTLIIENVERnSDQATYTCVAKNQEGySARGSLEVQ 613
Cdd:cd05748    4 VRAGESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQIETtasSTSLVIKNAKR-SDSGKYTLTLKNSAG-EKSATINVK 81


                 .
gi 24586203  614 V 614
Cdd:cd05748   82 V 82

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 143259 Cd Length: 88 Bit Score: 43.47 E-value: 5.71e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1312 PAKI-ASFDDTFtATFKEDAKMPCLAVGAPQPEITWK--IKGVEFSANDRMrvlpDGSLL-IKSVNRQDAGDYSCHAENS 1387
Cdd:cd05851    1 PADInVKFKDTY-ALKGQNVTLECFALGNPVPVIRWRkiLEPMPATAEISM----SGAVLkIFNIQPEDEGTYECEAENI 75


                 ....*....
gi 24586203 1388 IAKDsiTHK 1396
Cdd:cd05851   76 KGKD--KHQ 82

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 43.72 E-value: 5.82e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24586203 1330 AKMPCLAVGAPQPEITWKIKGVEFSANDRMRVLPDG----SLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1399
Cdd:cd20973   15 ARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEdglcSLIISDVCGDDSGKYTCKAVNSLGEATCSAELTV 88

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 43.69 E-value: 6.02e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  448 LKCVAGGNPTPEISWELDGKKIANNDRYQVGQYVTVNGDVVSYLNItsVHA----NDGGLYKCIAKSKVGVA-EHSAKLN 522
Cdd:cd07693   20 LNCKAEGRPTPTIQWLKNGQPLETDKDDPRSHRIVLPSGSLFFLRV--VHGrkgrSDEGVYVCVAHNSLGEAvSRNASLE 97


                 .
gi 24586203  523 V 523
Cdd:cd07693   98 V 98

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409435 Cd Length: 96 Bit Score: 43.78 E-value: 6.36e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24586203  269 CPAQGYPAPSFRWykFIEGTtrKQAVVLNDRVKQVSGTLIIKDAV-VEDSGKYLCVVNNSVG 329
Cdd:cd05848   26 CEARGNPVPTYRW--LRNGT--EIDTESDYRYSLIDGNLIISNPSeVKDSGRYQCLATNSIG 83

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 43.75 E-value: 6.52e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  527 PYIRQMEK-----KAIVAGETLIVTCPVAGYPIDSIVWERDNRAL-PINR------KQKVFpngTLIIENVeRNSDQATY 594
Cdd:cd05729    1 PRFTDTEKmeereHALPAANKVRLECGAGGNPMPNITWLKDGKEFkKEHRiggtkvEEKGW---SLIIERA-IPRDKGKY 76


                 ....*....
gi 24586203  595 TCVAKNQEG 603
Cdd:cd05729   77 TCIVENEYG 85

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 43.34 E-value: 6.61e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  349 PPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIgHSEPVLRIES-----------VKKEDKGMYQCFVRNDQESAEAS 417
Cdd:cd20972    8 LRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKEL-QNSPDIQIHQegdlhsliiaeAFEEDTGRYSCLATNSVGSDTTS 86


                 ...
gi 24586203  418 AEL 420
Cdd:cd20972   87 AEI 89

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 43.34 E-value: 6.68e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  435 FQEETMEpgpsVFLKCVAGGNPTPEISWELDGKKIANNDRYQVgqyvtVNGdvvSYLNITSVHANDGGLYKCIAKSKVGV 514
Cdd:cd05723    8 YAHESMD----IVFECEVTGKPTPTVKWVKNGDVVIPSDYFKI-----VKE---HNLQVLGLVKSDEGFYQCIAENDVGN 75


                 ....*..
gi 24586203  515 AEHSAKL 521
Cdd:cd05723   76 AQASAQL 82

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 43.00 E-value: 6.76e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24586203  268 LCPAQGYPAPSFRWykfiegtTRKQAVVLNDRVKQV--SGTLIIKDAVVEDSGKYLCVVNNSVGGESVETVLTV 339
Cdd:cd05745    8 LCEAQGYPQPVIAW-------TKGGSQLSVDRRHLVlsSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 43.38 E-value: 7.09e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24586203  736 CKADGFPKPQVTWKKavGDTPGEYKDLKKSDNirvEEGT-LHVDNIQKTNEGYYLCEAINGIG 797
Cdd:cd05730   25 CDADGFPEPTMTWTK--DGEPIESGEEKYSFN---EDGSeMTILDVDKLDEAEYTCIAENKAG 82

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 43.32 E-value: 7.13e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24586203   61 CKASGNPMPEIIWIRsDGTAVGDVPGLRQ---ISSDGKLV----FPPFRAEDyrqevhAQVYACLARNQFGSI 126
Cdd:cd20956   23 CVASGNPLPQITWTL-DGFPIPESPRFRVgdyVTSDGDVVsyvnISSVRVED------GGEYTCTATNDVGSV 88

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 43.32 E-value: 7.39e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24586203  269 CPAQGYPAPSFRWYKfiEG----TTRKQAVVLNdrvkqvsGTLIIKDAV-VEDSGKYLCVVNNSVG 329
Cdd:cd20958   22 CPVAGYPISSITWEK--DGrrlpLNHRQRVFPN-------GTLVIENVQrSSDEGEYTCTARNQQG 78

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 43.25 E-value: 7.67e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  528 YIRQMEKKAIVAGETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVFPNG----TLIIENVERnSDQATYTCVAKNQEG 603
Cdd:cd05744    3 FLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVREngrhSLIIEPVTK-RDAGIYTCIARNRAG 81

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 43.64 E-value: 7.77e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  811 PPEFTEKLRNQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLDPKNDNRYTI--REEILSTGvmsSLSIKRTERSDSALF 888
Cdd:cd05734    1 PPRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWKHSKGSGVPQFQHIVPLngRIQLLSNG---SLLIKHVLEEDSGYY 77

                         90
                 ....*....|.
gi 24586203  889 TCVATNAFGSD 899
Cdd:cd05734   78 LCKVSNDVGAD 88

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 43.22 E-value: 7.78e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24586203  267 ILCPAQGYPAPSFRWYKfieGTtrkQAVVLNDRVKQV-SGTLIIKDAVVEDSGKYLCVVNNSVGGESVETVLTV 339
Cdd:cd04969   22 IECKPKASPKPTISWSK---GT---ELLTNSSRICILpDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 43.31 E-value: 7.91e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  349 PPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDG------KAIGHSEPV---------LRIESVKK--EDKGMYQCFVRN-- 409
Cdd:cd07693    7 PSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGqpletdKDDPRSHRIvlpsgslffLRVVHGRKgrSDEGVYVCVAHNsl 86

                         90
                 ....*....|..
gi 24586203  410 -DQESAEASAEL 420
Cdd:cd07693   87 gEAVSRNASLEV 98

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 43.21 E-value: 8.15e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  346 KIDPPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIgHSEP----------VLRIESVKKEDKGMYQCFVRNDQESAE 415
Cdd:cd04978    3 IIEPPSLVLSPGETGELICEAEGNPQPTITWRLNGVPI-EPAPedmrrtvdgrTLIFSNLQPNDTAVYQCNASNVHGYLL 81


                 ....*
gi 24586203  416 ASAEL 420
Cdd:cd04978   82 ANAFL 86

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 42.88 E-value: 8.21e-05

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203     630 ADVGDIASANCVVpKGDLPLEIRWSLNSAPIVNGENGFTLVRlNKRTSLLNIDSLNAFHRGVYKCIATNPAGTSEYVAEL 709
Cdd:smart00410    6 VKEGESVTLSCEA-SGSPPPEVTWYKQGGKLLAESGRFSVSR-SGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTL 83


                    ..
gi 24586203     710 QV 711
Cdd:smart00410   84 TV 85

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 43.01 E-value: 8.26e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  811 PPEFTEKLRNQTARRGEPAVLQCEAKGeKPIG-ILWNMNNMRLDpKNDNRYTIREEIlstgvmSSLSIKRTERSDSALFT 889
Cdd:cd20976    1 APSFSSVPKDLEAVEGQDFVAQCSARG-KPVPrITWIRNAQPLQ-YAADRSTCEAGV------GELHIQDVLPEDHGTYT 72

                         90
                 ....*....|....*...
gi 24586203  890 CVATNAFGSDDASINMIV 907
Cdd:cd20976   73 CLAKNAAGQVSCSAWVTV 90

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 43.38 E-value: 8.45e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24586203  353 TVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIGHSE---------PVLRIESVKKEDKGMYQCFVRNDQESAEASAELKL 422
Cdd:cd05730   14 TANLGQSVTLACDADGFPEPTMTWTKDGEPIESGEekysfnedgSEMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKV 92

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 43.16 E-value: 8.58e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  346 KIDPPTQTVDFGRPAVFTCQY-TGNPIKTVSWMKDGKAIGHSEPVLR--------IESVKKEDKGMYQCFVRN---DQES 413
Cdd:cd05724    1 RVEPSDTQVAVGEMAVLECSPpRGHPEPTVSWRKDGQPLNLDNERVRivddgnllIAEARKSDEGTYKCVATNmvgERES 80


                 ...
gi 24586203  414 AEA 416
Cdd:cd05724   81 RAA 83

Fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule); The members here are composed of the fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six IG-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409454 Cd Length: 89 Bit Score: 43.05 E-value: 8.65e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  440 MEPGPSVFLKCVAGGNPTPEISWELDGK--KIANNDRYQvgqyvTVNGDVVSYlniTSVHANDGGLYKCIAKSKVGVAEH 517
Cdd:cd05868   11 LSPGEDGTLICRANGNPKPSISWLTNGVpiEIAPTDPSR-----KVDGDTIIF---SKVQERSSAVYQCNASNEYGYLLA 82


                 ....*.
gi 24586203  518 SAKLNV 523
Cdd:cd05868   83 NAFVNV 88

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 43.24 E-value: 8.74e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24586203  538 VAGETLIVTCPVAGYPIDSIVWERDNR--ALPINRKQKVFPNGTLIIENVER----NSDQATYTCVAKN 600
Cdd:cd05722   14 MRGGPVVLNCSAESDPPPKIEWKKDGVllNLVSDERRQQLPNGSLLITSVVHskhnKPDEGFYQCVAQN 82

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 43.15 E-value: 8.86e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24586203  269 CPAQGYPAPSFRWYkfiegTTRKQAVVL--NDRVKQVS-GTLIIKDAVVEDSGKYLCVVNNSVGGESVETVLTV 339
Cdd:cd20969   24 CRADGDPPPAILWL-----SPRKHLVSAksNGRLTVFPdGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLHV 92

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 42.77 E-value: 8.93e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24586203  826 GEPAVLQCEA-KGEKPIGILWNMNNMRLDPKNdNRYTIREEilstgvmSSLSIKRTERSDSALFTCVATNAFG 897
Cdd:cd05724   12 GEMAVLECSPpRGHPEPTVSWRKDGQPLNLDN-ERVRIVDD-------GNLLIAEARKSDEGTYKCVATNMVG 76

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 42.96 E-value: 9.36e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24586203  442 PGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQvgQYVTVNGDVVsylnITSVHANDGGLYKCIAKSKVG 513
Cdd:cd05867   13 PGETARLDCQVEGIPTPNITWSINGAPIEGTDPDP--RRHVSSGALI----LTDVQPSDTAVYQCEARNRHG 78

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 42.95 E-value: 9.68e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  353 TVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIGHSEPV-----------LRIESVKKEDKGMYQCFVRNDQESAEASAELK 421
Cdd:cd20973    8 EVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFqidqdedglcsLIISDVCGDDSGKYTCKAVNSLGEATCSAELT 87


                 .
gi 24586203  422 L 422
Cdd:cd20973   88 V 88

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 42.88 E-value: 9.79e-05

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203      57 AEIECKASGNPMPEIIWIRSDGTAVGDVPGLRQISSDGK--LVFPPFRAEDyrqevhAQVYACLARNQFGSIISR-DVHV 133
Cdd:smart00410   12 VTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTstLTISNVTPED------SGTYTCAATNSSGSASSGtTLTV 85

Immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409458 Cd Length: 95 Bit Score: 43.05 E-value: 1.11e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24586203   59 IECKASGNPMPEIIWIRsDGTA--VGDVPGLRQISSDGKLVFPPFRAEdyRQEVHAQVYACLARNQFGSIISRDVHVR 134
Cdd:cd05874   21 IQCEAKGKPPPSFSWTR-NGTHfdIDKDPKVTMKPNTGTLVINIMNGE--KAEAYEGVYQCTARNERGAAVSNNIVIR 95

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 42.73 E-value: 1.12e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1311 VPAKIASFDDTFTATFKEDAKMPCLAVGAPQPEITWKIKGVEFSANDRMRVLP---DGSLLIKSVNRQDAGDYSCHAENS 1387
Cdd:cd05747    2 LPATILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSteyKSTFEISKVQMSDEGNYTVVVENS 81


                 ...
gi 24586203 1388 IAK 1390
Cdd:cd05747   82 EGK 84

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 42.76 E-value: 1.14e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203   39 PVFLKEPTNRIDFSNSTGAEIECKASGNPMPEIIWIRsDGTAVGDVPGLRQIsSDGKLVFPPFRAEDYRqevhaqVYACL 118
Cdd:cd20978    1 PKFIQKPEKNVVVKGGQDVTLPCQVTGVPQPKITWLH-NGKPLQGPMERATV-EDGTLTIINVQPEDTG------YYGCV 72

                         90
                 ....*....|
gi 24586203  119 ARNQFGSIIS 128
Cdd:cd20978   73 ATNEIGDIYT 82

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 43.04 E-value: 1.16e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24586203  736 CKADGFPKPQVTWKKAVGDTPGEYKDLK-----KSDnIRVEEGTLhvDNIQKTNEGYYLCEAINGIGSGLSAV 803
Cdd:cd05869   24 CEASGDPIPSITWRTSTRNISSEEKTLDghivvRSH-ARVSSLTL--KYIQYTDAGEYLCTASNTIGQDSQSM 93

Fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule); The members here are composed of the fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six IG-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409454 Cd Length: 89 Bit Score: 42.66 E-value: 1.23e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 24586203 1328 EDAKMPCLAVGAPQPEITWKIKGV--EFSANDRMRVLPDGSLLIKSVNRQDAGDYSCHAEN 1386
Cdd:cd05868   15 EDGTLICRANGNPKPSISWLTNGVpiEIAPTDPSRKVDGDTIIFSKVQERSSAVYQCNASN 75

Immunoglobulin (Ig)-like domain of human neurofascin (NF); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of human neurofascin (NF). NF belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and a cytoplasmic domain. NF has many alternatively spliced isoforms having different temporal expression patterns during development. NF participates in axon subcellular targeting and synapse formation, however little is known of the functions of the different isoforms. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409459 Cd Length: 95 Bit Score: 42.66 E-value: 1.28e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  428 PPVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGK--KIANNDRYQVGQYvtvNGDVVSYLNITSVHANDGGLYK 505
Cdd:cd05875    1 PTITKQSAKDYIVDPRDNILIECEAKGNPVPTFHWTRNGKffNVAKDPRVSMRRR---SGTLVIDFRGGGRPEDYEGEYQ 77

                         90
                 ....*....|
gi 24586203  506 CIAKSKVGVA 515
Cdd:cd05875   78 CFARNKFGTA 87

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 43.00 E-value: 1.29e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24586203  831 LQCEAKGEKPIGILWNMNNMRLDPKNDNRYTIreeILSTGVMSSLSikrtERSDSALFTCVATNAFGS 898
Cdd:cd04967   24 LNCRARANPVPSYRWLMNGTEIDLESDYRYSL---VDGTLVISNPS----KAKDAGHYQCLATNTVGS 84

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 2 (NCAM-2); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is organized similarly to NCAM, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143278 [Multi-domain] Cd Length: 98 Bit Score: 43.04 E-value: 1.31e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24586203 1330 AKMPCLAVGAPQPEITWK--IKGVEFSANDRMrvlPDG-----------SLLIKSVNRQDAGDYSCHAENSI 1388
Cdd:cd05870   19 ATLSCKAEGEPIPEITWKraSDGHTFSEGDKS---PDGrievkgqhgesSLHIKDVKLSDSGRYDCEAASRI 87

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 42.61 E-value: 1.39e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24586203  264 STAIL-CPAQGYPAPSFRWykfIEGTTrkqAVVLNDRVKQV-SGTLIIKDAVVEDSGKYLCVVNNSVG 329
Cdd:cd20968   15 LKAVLpCTTMGNPKPSVSW---IKGDD---LIKENNRIAVLeSGSLRIHNVQKEDAGQYRCVAKNSLG 76

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 41.78 E-value: 1.40e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24586203  545 VTCPVAGYPIDSIVWERDNRALPINRKQKVFPNGTLIIENVErNSDQATYTCVAKNQEGYSA 606
Cdd:cd05746    3 IPCSAQGDPEPTITWNKDGVQVTESGKFHISPEGYLAIRDVG-VADQGRYECVARNTIGYAS 63

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 42.40 E-value: 1.41e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  261 SMASTAIL--------CPAQGYPAPSFRWYKfIEGTTRKQAVVLNDRVKqvsgTLIIKDAVVEDSGKYLCVVNNSVGgeS 332
Cdd:cd05731    1 SESSTMVLrggvllleCIAEGLPTPDIRWIK-LGGELPKGRTKFENFNK----TLKIENVSEADSGEYQCTASNTMG--S 73


                 ....*...
gi 24586203  333 VETVLTVT 340
Cdd:cd05731   74 ARHTISVT 81

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 42.39 E-value: 1.42e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  812 PEFTEKLRNQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLDPKNDNRYTIREeilsTGVmSSLSIKRTERSDSALFTCV 891
Cdd:cd20990    1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVRE----NGV-HSLIIEPVTSRDAGIYTCI 75

                         90
                 ....*....|....*.
gi 24586203  892 ATNAFGSDDASINMIV 907
Cdd:cd20990   76 ATNRAGQNSFNLELVV 91

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 42.63 E-value: 1.42e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24586203  721 PTDKAFAQGSDAKVECKADGFPKPQVTWKKAVGD-TPgeykDLKKSDNIRVEEGTLHVDNIQKTNEGYYLCEAINGIG 797
Cdd:cd05736    7 PEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMDiNP----KLSKQLTLIANGSELHISNVRYEDTGAYTCIAKNEGG 80

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 42.38 E-value: 1.46e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24586203  728 QGSDAKVECKADGFPKPQVTWKkavgdTPGEYK-DLKKSDNIRV-EEGTLHVDNIQKTNEGYYLCEAINGIG 797
Cdd:cd20969   16 EGHTVQFVCRADGDPPPAILWL-----SPRKHLvSAKSNGRLTVfPDGTLEVRYAQVQDNGTYLCIAANAGG 82

First immunoglobulin (Ig) domain of contactin-2; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module by contacts between IG domains 1 and 4, and domains 2 and 3. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-2 is also expressed in retinal amacrine cells in the developing chick retina, corresponding to the period of formation and maturation of AC processes. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409437 [Multi-domain] Cd Length: 97 Bit Score: 42.60 E-value: 1.50e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203   38 GPVFLKEPTNRIDFSNSTGAEI--ECKASGNPMPEIIWiRSDGTAVGDVPGLRQISSDGKLVFP-PFRAEDyrqevhAQV 114
Cdd:cd05850    2 GPVFEEQPSSTLFPEGSAEEKVtlACRARASPPATYRW-KMNGTELKMEPDSRYRLVAGNLVISnPVKAKD------AGS 74

                         90       100
                 ....*....|....*....|
gi 24586203  115 YACLARNQFGSIISRDVHVR 134
Cdd:cd05850   75 YQCLASNRRGTVVSREASLR 94

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 42.31 E-value: 1.54e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24586203  542 TLIVTCPVAGYPIDSIVWERDnrALPI-----NRKQKVFPNGTLIIENVERnSDQATYTCVAKNQEG--YSARGSLEVQ 613
Cdd:cd05738   16 TATMLCAASGNPDPEISWFKD--FLPVdtatsNGRIKQLRSGALQIENSEE-SDQGKYECVATNSAGtrYSAPANLYVR 91

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 42.62 E-value: 1.58e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  266 AILCPAQGYPAPSFRWykFIEGTTRKqaVVLNDRVKQVSGTLIIKDAV-VEDSGKYLCVVNNSVGgesveTVLTVTAPLS 344
Cdd:cd04967   23 ALNCRARANPVPSYRW--LMNGTEID--LESDYRYSLVDGTLVISNPSkAKDAGHYQCLATNTVG-----SVLSREATLQ 93

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 42.59 E-value: 1.62e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24586203 1331 KMPCLAVGAPQPEITWKIKGVEFSANDRMRVLPDG----SLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1399
Cdd:cd05729   23 RLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEekgwSLIIERAIPRDKGKYTCIVENEYGSINHTYDVDV 95

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 42.66 E-value: 1.63e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  810 APPEFTeKLRNQTARRGEPAV-LQCEAKGEKPIGILWNMN--NMRLDPKN-DNRYTIREEILstgvMSSLSIKRTERSDS 885
Cdd:cd05869    1 AKPKIT-YVENQTAMELEEQItLTCEASGDPIPSITWRTStrNISSEEKTlDGHIVVRSHAR----VSSLTLKYIQYTDA 75

                         90
                 ....*....|....*...
gi 24586203  886 ALFTCVATNAFGSDDASI 903
Cdd:cd05869   76 GEYLCTASNTIGQDSQSM 93

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 42.39 E-value: 1.67e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  247 PKINALTYKPNIVESMASTAILCPAQGYPAPSFRWYKfiEGTTRKQAVVLNDRVKQVSGTLII--KDAVVED-SGKYLCV 323
Cdd:cd05733    1 PTITEQSPKDYIVDPRDNITIKCEAKGNPQPTFRWTK--DGKFFDPAKDPRVSMRRRSGTLVIdnHNGGPEDyQGEYQCY 78


                 ....*.
gi 24586203  324 VNNSVG 329
Cdd:cd05733   79 ASNELG 84

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 42.00 E-value: 1.70e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203    531 QMEKKAIVAGETLIVTCPVAGYPIDSIVWERDNRALPinrkqkvfPNGTLIIENVErNSDQATYTCVAKNQEGYSARGSL 610
Cdd:pfam13895    5 TPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAIS--------SSPNFFTLSVS-AEDSGTYTCVARNGRGGKVSNPV 75


                   ....
gi 24586203    611 EVQV 614
Cdd:pfam13895   76 ELTV 79

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 42.18 E-value: 1.70e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24586203    264 STAIL-CPA-QGYPAPSFRWYKfiEGTTRKQAVVLNDRVKQVSG-TLIIKDAVVEDSGKYLCVVNNSVGGESVETVL 337
Cdd:pfam00047   12 DSATLtCSAsTGSPGPDVTWSK--EGGTLIESLKVKHDNGRTTQsSLLISNVTKEDAGTYTCVVNNPGGSATLSTSL 86

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 42.34 E-value: 1.80e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  428 PPVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVgqyvtVNGDVVSYLNITSVHANDGGLYKCI 507
Cdd:cd05747    3 PATILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQI-----TSTEYKSTFEISKVQMSDEGNYTVV 77


                 ....*....
gi 24586203  508 AKSKVGVAE 516
Cdd:cd05747   78 VENSEGKQE 86

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 42.24 E-value: 1.86e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  246 PPKINALTYKPNIVESMASTAiLCPAQGYPAPSFRWYKfiegtTRKQAVVLNDRVKQVSGT--LIIKDAVVEDSGKYLCV 323
Cdd:cd20976    1 APSFSSVPKDLEAVEGQDFVA-QCSARGKPVPRITWIR-----NAQPLQYAADRSTCEAGVgeLHIQDVLPEDHGTYTCL 74

                         90
                 ....*....|....*.
gi 24586203  324 VNNSVGGESVETVLTV 339
Cdd:cd20976   75 AKNAAGQVSCSAWVTV 90

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 41.82 E-value: 1.91e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 24586203 1334 CLAVGAPQPEITWKIKGVEFSANDRMRVLpDGSLLIKSVNRQDAGDYSCHAEN 1386
Cdd:cd05728   21 CKASGNPRPAYRWLKNGQPLASENRIEVE-AGDLRITKLSLSDSGMYQCVAEN 72

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 41.81 E-value: 1.91e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24586203  270 PAQGYPAPSFRWYKfiEGTTRKQAVVLNDRVKQVSGTLIIKDAVVEDSGKY-LCVVNNSvgGESVETV 336
Cdd:cd05748   15 PIKGRPTPTVTWSK--DGQPLKETGRVQIETTASSTSLVIKNAKRSDSGKYtLTLKNSA--GEKSATI 78

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 41.81 E-value: 1.95e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  454 GNPTPEISWELDGKKIANNDRYQVGqyvtvNGDVVSYLNITSVHANDGGLYKCIAKSKVGvaEHSAKLNV 523
Cdd:cd05748   18 GRPTPTVTWSKDGQPLKETGRVQIE-----TTASSTSLVIKNAKRSDSGKYTLTLKNSAG--EKSATINV 80

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 42.22 E-value: 1.96e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  349 PPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDG--------KAIGHSEP---VLRIESVKKEDKGMYQCFVRNDQESAEAS 417
Cdd:cd05763    6 PHDITIRAGSTARLECAATGHPTPQIAWQKDGgtdfpaarERRMHVMPeddVFFIVDVKIEDTGVYSCTAQNSAGSISAN 85


                 ...
gi 24586203  418 AEL 420
Cdd:cd05763   86 ATL 88

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 42.54 E-value: 1.99e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1303 IVAMPSDQVPAKiasfddtftatfKEDAKMPCLAVGAPQPEITWKIKGVEF-----SANDRMRVLPDGSLLIKSV----- 1372
Cdd:cd07693    3 IVEHPSDLIVSK------------GDPATLNCKAEGRPTPTIQWLKNGQPLetdkdDPRSHRIVLPSGSLFFLRVvhgrk 70

                         90
                 ....*....|....*.
gi 24586203 1373 NRQDAGDYSCHAENSI 1388
Cdd:cd07693   71 GRSDEGVYVCVAHNSL 86

First immunoglobulin (Ig)-like domain of neural cell adhesion molecule (NCAM-1); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of neural cell adhesion molecule (NCAM-1). NCAM-1 plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-nonNCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves the Ig1, Ig2, and Ig3 domains. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409451 Cd Length: 97 Bit Score: 42.33 E-value: 2.02e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  443 GPSVFLKC-VAGGNPTPEISW-ELDGKKIANNDryqvgQYVTV--NGDVVSYLNITSVHANDGGLYKCIAKSKVGvAEHS 518
Cdd:cd05865   15 GESKFFLCqVAGEAKDKDISWfSPNGEKLTPNQ-----QRISVvrNDDYSSTLTIYNANIDDAGIYKCVVSNEDE-GESE 88


                 ....*
gi 24586203  519 AKLNV 523
Cdd:cd05865   89 ATVNV 93

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 42.00 E-value: 2.03e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24586203   57 AEIECKAS-GNPMPEIIWIRsDGTAVGDVPGLRQISSDGKLVFPPFRAEDyrqevhAQVYACLARNQFGSIISRD 130
Cdd:cd05724   15 AVLECSPPrGHPEPTVSWRK-DGQPLNLDNERVRIVDDGNLLIAEARKSD------EGTYKCVATNMVGERESRA 82

Immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1; The members here are composed of the immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. NRG-1 belongs to the neuregulin gene family which is comprised of four genes. This group represents NRG-1. NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, and heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. The NRG-1 protein binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. NRG-1 has multiple functions, for example, in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival.

Pssm-ID: 409476 Cd Length: 93 Bit Score: 41.90 E-value: 2.22e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  812 PEFTEkLRNQTARRGEPAVLQCEAKGEKP-IGILWNMNNMRLDPKNDNRYTireEILSTGVMSSLSIKRTERSDSALFTC 890
Cdd:cd05895    1 PKLKE-MKSQEVAAGSKLVLRCETSSEYPsLRFKWFKNGKEINRKNKPENI---KIQKKKKKSELRINKASLADSGEYMC 76

                         90
                 ....*....|....*..
gi 24586203  891 VATNAFGSDDASINMIV 907
Cdd:cd05895   77 KVSSKLGNDSASANVTI 93

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 41.85 E-value: 2.35e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  536 AIVAGETLIVTCPVAGYPIDSIVWERDNRAL--PINRKQKVFPNGTLIIENVeRNSDQATYTCVAKNQEGySARGSLEVQ 613
Cdd:cd20976   12 EAVEGQDFVAQCSARGKPVPRITWIRNAQPLqyAADRSTCEAGVGELHIQDV-LPEDHGTYTCLAKNAAG-QVSCSAWVT 89


                 .
gi 24586203  614 V 614
Cdd:cd20976   90 V 90

Immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG); The members here are composed of the immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG). MOG, a minor component of the myelin sheath, is an important CNS-specific autoantigen, linked to the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). It is a transmembrane protein having an extracellular Ig domain. MOG is expressed in the CNS on the outermost lamellae of the myelin sheath, and on the surface of oligodendrocytes, and may participate in the completion, compaction, and/or maintenance of myelin. This group also includes butyrophilin (BTN). BTN is the most abundant protein in bovine milk-fat globule membrane (MFGM).

Pssm-ID: 409378 Cd Length: 114 Bit Score: 42.56 E-value: 2.35e-04

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 24586203  376 WMKDgkAIGHSEPVLRIESVKKEDKGMYQCFVRNDQESAEASAELK 421
Cdd:cd05713   69 LLKD--AIAEGSVALRIHNVRPSDEGQYTCFFRSGSFYEEATLELK 112

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 45.76 E-value: 2.78e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1402 PPQSPH-VTLSATTTDALTVKLKPHEGDTAPlhGYTLHYKP-EFGEWE----TSEVS-VDSqkhnieGLLCGSRYQVYAT 1474
Cdd:COG3401  232 PPSAPTgLTATADTPGSVTLSWDPVTESDAT--GYRVYRSNsGDGPFTkvatVTTTSyTDT------GLTNGTTYYYRVT 303

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1475 GFNNIG-AGEASDILNTRTKGQKPKLPEKPRFIEVSSNSVSLhfkAWKD-GGCPMSHFVVESKKRDQIEWNQISNNVKpD 1552
Cdd:COG3401  304 AVDAAGnESAPSNVVSVTTDLTPPAAPSGLTATAVGSSSITL---SWTAsSDADVTGYNVYRSTSGGGTYTKIAETVT-T 379

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24586203 1553 NNYVVLDLEPATWYNLRITAHNSAGFTVAEydFATLTVTGGTIAPSRDLPELSAEDTIRIILSN 1616
Cdd:COG3401  380 TSYTDTGLTPGTTYYYKVTAVDAAGNESAP--SEEVSATTASAASGESLTASVDAVPLTDVAGA 441

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

Pssm-ID: 409443 [Multi-domain] Cd Length: 95 Bit Score: 41.76 E-value: 2.80e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24586203 1331 KMPCLAVGAPQPEITWKIKGVEFSANDRM---RV-LPDGSLLIKSVNRQDAGDYSCHAENSIAkdSITH 1395
Cdd:cd05857   23 KFRCPAAGNPTPTMRWLKNGKEFKQEHRIggyKVrNQHWSLIMESVVPSDKGNYTCVVENEYG--SINH 89

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

Pssm-ID: 409443 [Multi-domain] Cd Length: 95 Bit Score: 41.76 E-value: 2.94e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  362 FTCQYTGNPIKTVSWMKDGKA------IG-----HSEPVLRIESVKKEDKGMYQCFVRNDQESAEASAEL 420
Cdd:cd05857   24 FRCPAAGNPTPTMRWLKNGKEfkqehrIGgykvrNQHWSLIMESVVPSDKGNYTCVVENEYGSINHTYHL 93

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 41.74 E-value: 2.96e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  247 PKInalTYKPNIVESMASTAIL-CPAQGYPAPSFRW------YKFIEGTTRKQAVVlndRVKQVSGTLIIKDAVVEDSGK 319
Cdd:cd05732    3 PKI---TYLENQTAVELEQITLtCEAEGDPIPEITWrratrgISFEEGDLDGRIVV---RGHARVSSLTLKDVQLTDAGR 76

                         90
                 ....*....|...
gi 24586203  320 YLCVVNNSVGGES 332
Cdd:cd05732   77 YDCEASNRIGGDQ 89

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 41.84 E-value: 3.09e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  246 PPKINALTYKPNIVESMA-STAILCPAQGYPAPSFRWykfiegtTRKQAVVLNDRVKQV----SGTLIIKDAVVEDSGKY 320
Cdd:cd05730    1 PPTIRARQSEVNATANLGqSVTLACDADGFPEPTMTW-------TKDGEPIESGEEKYSfnedGSEMTILDVDKLDEAEY 73

                         90       100
                 ....*....|....*....|.
gi 24586203  321 LCVVNNSVGGESVETVLTVTA 341
Cdd:cd05730   74 TCIAENKAGEQEAEIHLKVFA 94

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 41.41 E-value: 3.32e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  257 NIVESMASTAIL-CPAQGYPAPSFRWYKfiegttRKQAVVLNDRVKQVSG-----TLIIKDAVVEDSGKYLCVVNNSVGG 330
Cdd:cd20973    6 DKEVVEGSAARFdCKVEGYPDPEVKWMK------DDNPIVESRRFQIDQDedglcSLIISDVCGDDSGKYTCKAVNSLGE 79


                 ....*....
gi 24586203  331 ESVETVLTV 339
Cdd:cd20973   80 ATCSAELTV 88

Phage-related protein, tail protein J [Mobilome: prophages, transposons];

Pssm-ID: 443767 [Multi-domain] Cd Length: 978 Bit Score: 45.71 E-value: 3.46e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  926 SVQLSWAQPYDGNSpldrYIIEFKRSRASWSEIDRVivpgHTTEAQVQKLsPATTYNIRIVAENAIGTSQ--SSEAVTII 1003
Cdd:COG4733  553 TLTVSWDAPAGAVA----YEVEWRRDDGNWVSVPRT----SGTSFEVPGI-YAGDYEVRVRAINALGVSSawAASSETTV 623

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1004 TAEEAPSGKPQNIKVEPVNqTTMRVTWKPPPrtewNGEILGYYVGYklSNTNSsyvFETINFITEEGKEHNLELQNLRVY 1083
Cdd:COG4733  624 TGKTAPPPAPTGLTATGGL-GGITLSWSFPV----DADTLRTEIRY--STTGD---WASATVAQALYPGNTYTLAGLKAG 693

                        170
                 ....*....|....
gi 24586203 1084 TQYSVVIQAFNKIG 1097
Cdd:COG4733  694 QTYYYRARAVDRSG 707

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 41.25 E-value: 3.84e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24586203  728 QGSDAKVECKADGFPKPQVTWKK-----AVGDTPGEYKDLKKSDnirveEGTLHVDNIQKTNEGYYLCEAINGIG 797
Cdd:cd20951   14 EKSDAKLRVEVQGKPDPEVKWYKngvpiDPSSIPGKYKIESEYG-----VHVLHIRRVTVEDSAVYSAVAKNIHG 83

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 41.38 E-value: 3.84e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24586203   59 IECKASGNPMPEIIWIRSDGTAvgdVPGLRQISSDGKLVFPPFRAEDyrqevhAQVYACLARNQFGsiisRDVH 132
Cdd:cd04968   21 LECFALGNPVPQIKWRKVDGSP---SSQWEITTSEPVLEIPNVQFED------EGTYECEAENSRG----KDTV 81

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 40.86 E-value: 3.92e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24586203 1334 CLAVGAPQPEITWKIKGVEfsandrmrvLPDG---------SLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1399
Cdd:cd05731   17 CIAEGLPTPDIRWIKLGGE---------LPKGrtkfenfnkTLKIENVSEADSGEYQCTASNTMGSARHTISVTV 82

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 41.31 E-value: 3.92e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  439 TMEPGPsVFLKCVAGGNPTPEISWELDGKKIA--NNDRYQvgqyVTVNGdvvSYLnITSV-----HANDGGLYKCIAKSK 511
Cdd:cd05722   13 AMRGGP-VVLNCSAESDPPPKIEWKKDGVLLNlvSDERRQ----QLPNG---SLL-ITSVvhskhNKPDEGFYQCVAQNE 83

                         90
                 ....*....|....
gi 24586203  512 -VG-VAEHSAKLNV 523
Cdd:cd05722   84 sLGsIVSRTARVTV 97

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 40.63 E-value: 3.93e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24586203  363 TCQYTGNPIKTVSWMKDGKAIGHS-------EPVLRIESVKKEDKGMYQCFVRNDQESAEASAEL 420
Cdd:cd05746    4 PCSAQGDPEPTITWNKDGVQVTESgkfhispEGYLAIRDVGVADQGRYECVARNTIGYASVSMVL 68

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 41.15 E-value: 4.12e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24586203  450 CVAGGNPTPEISWELDGKKI---ANNDRYQvgqyVTVNGdvvsYLNITSVHANDGGLYKCIAKSKVGvAEHSAKLNVY 524
Cdd:cd05738   21 CAASGNPDPEISWFKDFLPVdtaTSNGRIK----QLRSG----ALQIENSEESDQGKYECVATNSAG-TRYSAPANLY 89

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 41.48 E-value: 4.21e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  813 EFTEKLRNQTARRGEPAVLQCEAKGEKPIGILWNMNNMR--LDPKNDNRYTIREEILSTGvmsSLSIKRTERSDSALFTC 890
Cdd:cd05726    1 QFVVKPRDQVVALGRTVTFQCETKGNPQPAIFWQKEGSQnlLFPYQPPQPSSRFSVSPTG---DLTITNVQRSDVGYYIC 77


                 ....*...
gi 24586203  891 VATNAFGS 898
Cdd:cd05726   78 QALNVAGS 85

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 41.48 E-value: 4.25e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  347 IDPPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKA--IGHSEPV-------------LRIESVKKEDKGMYQCFVRNDQ 411
Cdd:cd05726    4 VKPRDQVVALGRTVTFQCETKGNPQPAIFWQKEGSQnlLFPYQPPqpssrfsvsptgdLTITNVQRSDVGYYICQALNVA 83

                         90
                 ....*....|...
gi 24586203  412 ESAEASAELKLGG 424
Cdd:cd05726   84 GSILAKAQLEVTD 96

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 41.03 E-value: 4.73e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  720 EPTDKAFAQGSDAKVECKADGFPKPQVTWKKAvGDT--PGEYKDLkksdnirVEEGTLHVDNIQKTNEGYYLCEAINGIG 797
Cdd:cd05723    3 KPSNIYAHESMDIVFECEVTGKPTPTVKWVKN-GDVviPSDYFKI-------VKEHNLQVLGLVKSDEGFYQCIAENDVG 74


                 ....*....
gi 24586203  798 SGLSAVIMI 806
Cdd:cd05723   75 NAQASAQLI 83

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409438 Cd Length: 89 Bit Score: 41.14 E-value: 4.77e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  532 MEKKAIVA-GETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVFPNGTLIIENVERNsDQATYTCVAKNQEGYS-ARGS 609
Cdd:cd05852    8 MKKKILAAkGGRVIIECKPKAAPKPKFSWSKGTELLVNNSRISIWDDGSLEILNITKL-DEGSYTCFAENNRGKAnSTGV 86


                 ...
gi 24586203  610 LEV 612
Cdd:cd05852   87 LSV 89

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 40.84 E-value: 4.91e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203   42 LKEPTNRIDFSNSTgAEIECKASGNPMPEIIWIRSDgtavGDVPGLR-QISSDGKLVFPPFRAEDyrqevhAQVYACLAR 120
Cdd:cd05725    1 VKRPQNQVVLVDDS-AEFQCEVGGDPVPTVRWRKED----GELPKGRyEILDDHSLKIRKVTAGD------MGSYTCVAE 69


                 ....*.
gi 24586203  121 NQFGSI 126
Cdd:cd05725   70 NMVGKI 75

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 40.94 E-value: 5.20e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24586203  633 GDIASANCVVpKGDLPLEIRWSLNSAPIVNGENGFTLVRLNKRTSLLnIDSLNAFHRGVYKCIATNPAGTSEYVAELQV 711
Cdd:cd05744   15 GRLCRFDCKV-SGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHSLI-IEPVTKRDAGIYTCIARNRAGENSFNAELVV 91

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 40.64 E-value: 5.55e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203    719 LEPTDKAFAQGSDAKVECKADGF-PKPQVTWKKAVGDTPGEYKDLKKSDNIRVEegTLHVDNIQKTNEGYYLCEAINGIG 797
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSASTGsPGPDVTWSKEGGTLIESLKVKHDNGRTTQS--SLLISNVTKEDAGTYTCVVNNPGG 78


                   ....*...
gi 24586203    798 SGLSAVIM 805
Cdd:pfam00047   79 SATLSTSL 86

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 41.00 E-value: 5.63e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  715 PRWILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKAVgdtPGEYKDLKKSDNIR-----VEEGTLHVDNIQKTNEGYYL 789
Cdd:cd05765    1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEKQV---PGKENLIMRPNHVRgnvvvTNIGQLVIYNAQPQDAGLYT 77


                 ....*....
gi 24586203  790 CEAINGIGS 798
Cdd:cd05765   78 CTARNSGGL 86

Fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule); The members here are composed of the fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six IG-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409454 Cd Length: 89 Bit Score: 40.73 E-value: 5.76e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203   41 FLKEPTNRIDFSNSTGAEIeCKASGNPMPEIIWIrSDGTAVGDVP--GLRQISSDgKLVFPPFraedyrQEVHAQVYACL 118
Cdd:cd05868    2 WITAPTNLVLSPGEDGTLI-CRANGNPKPSISWL-TNGVPIEIAPtdPSRKVDGD-TIIFSKV------QERSSAVYQCN 72

                         90
                 ....*....|
gi 24586203  119 ARNQFGSIIS 128
Cdd:cd05868   73 ASNEYGYLLA 82

First immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409436 [Multi-domain] Cd Length: 95 Bit Score: 40.71 E-value: 6.85e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24586203  269 CPAQGYPAPSFRWYKfiegtTRKQAVVLNDRVKQVSGTLIIKDA-VVEDSGKYLCVVNNSVG 329
Cdd:cd05849   26 CRARANPFPIYKWRK-----NNLDIDLTNDRYSMVGGNLVINNPdKYKDAGRYVCIVSNIYG 82

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409435 Cd Length: 96 Bit Score: 40.70 E-value: 6.86e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  715 PRWILEPTDKAFAQGSDAK---VECKADGFPKPQVTWKKAvgdtpGEYKDLKKSDNIRVEEGTLHVDNIQKTNE-GYYLC 790
Cdd:cd05848    2 PVFVQEPDDAIFPTDSDEKkviLNCEARGNPVPTYRWLRN-----GTEIDTESDYRYSLIDGNLIISNPSEVKDsGRYQC 76

                         90
                 ....*....|.
gi 24586203  791 EAINGIGSGLS 801
Cdd:cd05848   77 LATNSIGSILS 87

First immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409436 [Multi-domain] Cd Length: 95 Bit Score: 40.71 E-value: 7.40e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203   38 GPVFLKEPTNRIDFSNSTGAEIE--CKASGNPMPEIIWIRSDGTAvgDVPGLRQISSDGKLVFP-PFRAEDyrqevhAQV 114
Cdd:cd05849    1 GPVFEEQPIDTIYPEESTEGKVSvnCRARANPFPIYKWRKNNLDI--DLTNDRYSMVGGNLVINnPDKYKD------AGR 72

                         90
                 ....*....|....*.
gi 24586203  115 YACLARNQFGSIISRD 130
Cdd:cd05849   73 YVCIVSNIYGKVRSRE 88

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.

Pssm-ID: 143299 Cd Length: 92 Bit Score: 40.28 E-value: 8.39e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24586203  439 TMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQV----GQYVTvngdvvsyLNITSVHANDGGLYKCIAKSKVG 513
Cdd:cd05891   12 TIMEGKTLNLTCTVFGNPDPEVIWFKNDQDIELSEHYSVkleqGKYAS--------LTIKGVTSEDSGKYSINVKNKYG 82

Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin I-set (IgI) domain of the Human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins. APEG-1 is a novel specific smooth muscle differentiation marker predicted to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the human APEG-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409567 Cd Length: 91 Bit Score: 40.53 E-value: 8.44e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  812 PEFTEKLRNQTARRGEPAVLQCEAKGE-KPIgILWNMNNMRLDPknDNRYTIREeilSTGVMSSLSIKRTERSDSALFTC 890
Cdd:cd20975    1 PTFKVSLMDQSVREGQDVIMSIRVQGEpKPV-VSWLRNRQPVRP--DQRRFAEE---AEGGLCRLRILAAERGDAGFYTC 74


                 ....*...
gi 24586203  891 VATNAFGS 898
Cdd:cd20975   75 KAVNEYGA 82

Third immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F (also known as LAR), type IIa; member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains. Included in this group is Drosophila LAR (DLAR).

Pssm-ID: 409401 Cd Length: 82 Bit Score: 39.88 E-value: 8.87e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 24586203 1334 CLAVGAPQPEITWKIKGVEFSANDRMrvlPDGSLLIKSVNRQDAGDYSCHAENSI 1388
Cdd:cd05739   19 CVAVGAPMPYVKWMKGGEELTKEDEM---PVGRNVLELTNIYESANYTCVAISSL 70

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 40.08 E-value: 9.43e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  632 VGDIASANCVVPKGDLPLEIRWSLNSAPIVNGENGFTLVRLNKrtslLNIDSLNAFHRGVYKCIATNPAGTSEY-VAELQ 710
Cdd:cd05724   11 VGEMAVLECSPPRGHPEPTVSWRKDGQPLNLDNERVRIVDDGN----LLIAEARKSDEGTYKCVATNMVGERESrAARLS 86


                 .
gi 24586203  711 V 711
Cdd:cd05724   87 V 87

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (IgSF) domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 40.15 E-value: 9.63e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 24586203 1330 AKMPCLAVGAPQPEITWKI-KGVEFSANDRMRVLPDGSLLIKSVNRQDAGDYSCHAEN 1386
Cdd:cd05764   18 ATLRCKARGDPEPAIHWISpEGKLISNSSRTLVYDNGTLDILITTVKDTGAFTCIASN 75

Third immunoglobulin domain in Cluster of Differentiation (CD) 22; member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain in Cluster of Differentiation (CD) 22 (also known as Siglec-2). CD22, a sialic-acid binding immunoglobulin type-lectin (Siglec) family member, is an inhibitory co-receptor of the B-cell receptor (BCR). The inhibitory function of CD22 and its restricted expression on B cells makes CD22 an attractive target against dysregulated B cells that cause autoimmune diseases and B-cell-derived cancers. CD22 plays a vital role in establishing a baseline level of B-cell inhibition, and thus is an important determinant of homeostasis in humoral immunity. Siglecs are primarily expressed on immune cells and recognize sialic acid-containing glycan ligands. Siglecs are organized as an extracellular module composed of Ig-like domains (an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains), followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG (Siglec-4, myelin-associated glycoprotein), the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409531 Cd Length: 88 Bit Score: 40.17 E-value: 9.68e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  343 LSAKIDPPTQTVDFGRPAVFTCQYTG-NPI-KTVSWMKDGKAIGHSEPV-LRIESVKKEDKGMYQCFVRNDQeSAEASAE 419
Cdd:cd20937    3 LEIKVTPSDAIVREGDSVTMTCEVSSsNPEyTTVSWLKDGTSLKKQNTFtLNLREVTKDQSGKYCCQVSNDV-GPGRSEE 81


                 ...
gi 24586203  420 LKL 422
Cdd:cd20937   82 VFL 84

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 40.08 E-value: 9.81e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  626 GESAADVGDIASANCVVPKGDLPlEIRWSLNSAPIVNGENGFTLVRLNKRTSLLnIDSLNAFHRGVYKCIATNPAGTSEY 705
Cdd:cd20990    8 GDLTVQEGKLCRMDCKVSGLPTP-DLSWQLDGKPIRPDSAHKMLVRENGVHSLI-IEPVTSRDAGIYTCIATNRAGQNSF 85


                 ....*.
gi 24586203  706 VAELQV 711
Cdd:cd20990   86 NLELVV 91

Immunoglobulin (Ig)-like domain at the C-terminus of semaphorins; The members here are composed of the immunoglobulin (Ig)-like domain in semaphorins. Semaphorins are transmembrane protein that have important roles in a variety of tissues. Functionally, semaphorins were initially characterized for their importance in the development of the nervous system and in axonal guidance. Later they have been found to be important for the formation and functioning of the cardiovascular, endocrine, gastrointestinal, hepatic, immune, musculoskeletal, renal, reproductive, and respiratory systems. Semaphorins function through binding to their receptors and transmembrane semaphorins also serves as receptors themselves. Although molecular mechanism of semaphorins is poorly understood, the Ig-like domains may be involved in ligand binding or dimerization.

Pssm-ID: 409368 Cd Length: 88 Bit Score: 40.14 E-value: 9.93e-04

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 24586203 1344 ITWKIKG--VEFSANDRMRVLPDGSLLIKSVNRQDAGDYSCHAENS 1387
Cdd:cd04979   27 VTWIHNGkkVPRYRSPRLVLKTERGLLIRSAQEADAGVYECHSGER 72

Immunoglobulin-like Ig0 domain of basigin-1 (BSG1) and similar proteins; The members here are composed of the immunoglobulin (Ig) domain of the collagenase stimulatory factor, basigin-1 (BSG1; also known as Cluster of Differentiation 147 (CD147) and Extracellular Matrix Metalloproteinase Inducer (EMMPRIN)) and similar proteins. CD147 is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily. It is expressed in nearly all cells including platelets and fibroblasts and is involved in inflammatory diseases, and cancer progression. CD147 is highly expressed in several cancers and used as a prognostic marker. The two primary isoforms of CD147 that are related to cancer progression have been identified: CD147 Ig1-Ig2 (also called Basigin-2) that is ubiquitously expressed in most tissues and CD147 Ig0-Ig1-Ig2 (also called Basigin-1) that is retinal specific and implicated in retinoblastoma. Studies showed that CD147 Ig0 domain is a potent stimulator of interleukin-6 and suggest that the CD147 Ig0 dimer is the functional unit required for activity.

Pssm-ID: 409534 Cd Length: 116 Bit Score: 40.72 E-value: 9.98e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24586203  443 GPSVFLKCVAGGNPTPEISWELDGKKI----------ANNDRYQVgqYVTVNGDVVSYLNITSVHANDGGLYKCIA 508
Cdd:cd20940   15 GDSVELHCEAVGSPIPEIQWWFEGQEPneicsqlwdgARLDRVHI--NATYHQHATSTISIDNLTEEDTGTYECRA 88

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 39.69 E-value: 1.00e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203    429 PVIRQAFQeeTMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQvgqyvtvngdvvsylnITSVHANDGGLYKCIA 508
Cdd:pfam13895    2 PVLTPSPT--VVTEGEPVTLTCSAPGNPPPSYTWYKDGSAISSSPNFF----------------TLSVSAEDSGTYTCVA 63

                           90
                   ....*....|....*.
gi 24586203    509 K-SKVGVAEHSAKLNV 523
Cdd:pfam13895   64 RnGRGGKVSNPVELTV 79

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 39.69 E-value: 1.00e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24586203    269 CPAQGYPAPSFRWYKfiegttrkqavvlNDRVKQVSGTLIIKDAVVEDSGKYLCVVNNSVGGEsVETVLTVT 340
Cdd:pfam13895   21 CSAPGNPPPSYTWYK-------------DGSAISSSPNFFTLSVSAEDSGTYTCVARNGRGGK-VSNPVELT 78

IL-beta-binding protein; Provisional

Pssm-ID: 165149 [Multi-domain] Cd Length: 326 Bit Score: 43.47 E-value: 1.03e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203   215 YQCRTKHrltgETRLSATKGRLVItepVSSSPPKINALTYkPNIVESMASTAILCP-AQGYPAPSFRWYKFIEGTTRkqa 293
Cdd:PHA02785   97 YICITKN----ETYCDMMSLNLTI---VSVSESNIDLISY-PQIVNERSTGEMVCPnINAFIASNVNADIIWSGHRR--- 165

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203   294 vVLNDRVKQVS-GTLIIKDAVVEDSGKYLCVVNNSVGGESVETVLTVTAPLSAKIDPPTQ------TVDFGRPAVFTCQY 366
Cdd:PHA02785  166 -LRNKRLKQRTpGIITIEDVRKNDAGYYTCVLKYIYGDKTYNVTRIVKLEVRDRIIPPTMqlpegvVTSIGSNLTIACRV 244

                         170
                  ....*....|....*..
gi 24586203   367 TGNPIKT---VSWMKDG 380
Cdd:PHA02785  245 SLRPPTTdadVFWISNG 261

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 40.32 E-value: 1.03e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  527 PYIRQM-EKKAIVAGETLIVTCPVAGYPIDSIVWERDNRAL--PINRKQKVFPNGT-LIIENVeRNSDQATYTCVAKNQE 602
Cdd:cd05736    1 PVIRVYpEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMDInpKLSKQLTLIANGSeLHISNV-RYEDTGAYTCIAKNEG 79


                 .
gi 24586203  603 G 603
Cdd:cd05736   80 G 80

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 39.87 E-value: 1.05e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  529 IRQMEKKAIVAGETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVFPNG----TLIIENVeRNSDQATYTCVAKNQEGy 604
Cdd:cd20973    1 IQTLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEdglcSLIISDV-CGDDSGKYTCKAVNSLG- 78

                         90
                 ....*....|
gi 24586203  605 SARGSLEVQV 614
Cdd:cd20973   79 EATCSAELTV 88

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 39.93 E-value: 1.11e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  714 PPRWILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKAVgdTPGEYKDLKKSDNIRVeeGTLHVDNIQKTNEGYYLCEAI 793
Cdd:cd20976    1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNA--QPLQYAADRSTCEAGV--GELHIQDVLPEDHGTYTCLAK 76


                 ....
gi 24586203  794 NGIG 797
Cdd:cd20976   77 NAAG 80

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 40.07 E-value: 1.17e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  822 TARRGEPAVLQCEAKGEKPIGILWNMNNMRLDPKNDNRytiREEILSTGvmsSLSIKRTERSDSALFTCVATNAFGSDDA 901
Cdd:cd20969   13 FVDEGHTVQFVCRADGDPPPAILWLSPRKHLVSAKSNG---RLTVFPDG---TLEVRYAQVQDNGTYLCIAANAGGNDSM 86


                 ....*.
gi 24586203  902 SINMIV 907
Cdd:cd20969   87 PAHLHV 92

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 40.10 E-value: 1.24e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24586203 1327 KEDAKMPCLAVGAPQPEITWKIKGV--EFSANDR-MRVLPDG---SLLIKSVNRQDAGDYSCHAENS 1387
Cdd:cd20951   15 KSDAKLRVEVQGKPDPEVKWYKNGVpiDPSSIPGkYKIESEYgvhVLHIRRVTVEDSAVYSAVAKNI 81

Third immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The third Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM).

Pssm-ID: 409569 Cd Length: 93 Bit Score: 40.07 E-value: 1.25e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  429 PVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVGQYVTVNGDVVSYLNITSVHAndgGLYKCIA 508
Cdd:cd20977    1 PVPQYVSKDMMAKAGDVTMIYCMYGSNPTAHPNYFKNGKDVNGNPEDRITRHNRTSGKRLLFKTTLPEDE---GVYTCEV 77

                         90
                 ....*....|....*.
gi 24586203  509 KSKVG-VAEHSAKLNV 523
Cdd:cd20977   78 DNGVGkPQKHSLKLTV 93

Third immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F (also known as LAR), type IIa; member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains. Included in this group is Drosophila LAR (DLAR).

Pssm-ID: 409401 Cd Length: 82 Bit Score: 39.50 E-value: 1.35e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  721 PTDKAFAQGSDAKVECKADGFPKPQVTWKKAVgdtpgeyKDLKKSDNIRVEEGTLHVDNIQKTNEgyYLCEAINGIGSgL 800
Cdd:cd05739    4 PSNHEVMPGGSVNLTCVAVGAPMPYVKWMKGG-------EELTKEDEMPVGRNVLELTNIYESAN--YTCVAISSLGM-I 73


                 ....*....
gi 24586203  801 SAVIMISVQ 809
Cdd:cd05739   74 EATAQVTVK 82

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

Pssm-ID: 319300 Cd Length: 92 Bit Score: 39.88 E-value: 1.38e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24586203  349 PPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIGHSE-----------PVLRIESVKKEDKGMYQCFVRN 409
Cdd:cd05737    8 PDVVTIMEGKTLNLTCNVWGDPPPEVSWLKNDQALAFLDhcnlkveagrtVYFTINGVSSEDSGKYGLVVKN 79

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members, VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1), and VEGFR-3 (Flt-4). VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic, and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409365 Cd Length: 90 Bit Score: 39.50 E-value: 1.43e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24586203 1327 KEDAKMPCLAVGAPQPEITWKIKGVEFSANdrMRVLPDGSLLIKSVNRQDAGDYSCHAENSIA--KDSITHKLIV 1399
Cdd:cd04976   18 KRSVRLPMKVKAYPPPEVVWYKDGLPLTEK--ARYLTRHSLIIKEVTEEDTGNYTILLSNKQSnvFKNLTATLVV 90

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (IgSF) domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 39.38 E-value: 1.48e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  527 PYI-RQMEKKAIVAGETLIVTCPVAGYPIDSIVW-ERDNRALPINRKQKVFPNGTLIIeNVERNSDQATYTCVAKNQEGy 604
Cdd:cd05764    1 PLItRHTHELRVLEGQRATLRCKARGDPEPAIHWiSPEGKLISNSSRTLVYDNGTLDI-LITTVKDTGAFTCIASNPAG- 78

                         90
                 ....*....|
gi 24586203  605 SARGSLEVQV 614
Cdd:cd05764   79 EATARVELHI 88

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 39.53 E-value: 1.50e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  536 AIVAGETLIVTCPVAGYPIDSIVWERD---NRALPINRKQKVFP-NGTLIIENVeRNSDQATYTCVAKNQEG-YSARGSL 610
Cdd:cd05763   10 TIRAGSTARLECAATGHPTPQIAWQKDggtDFPAARERRMHVMPeDDVFFIVDV-KIEDTGVYSCTAQNSAGsISANATL 88


                 ..
gi 24586203  611 EV 612
Cdd:cd05763   89 TV 90

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 39.40 E-value: 1.60e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  812 PEFTEKLRNQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLDPKNDNRYTIREeilsTGVMSsLSIKRTERSDSALFTCV 891
Cdd:cd05744    1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRE----NGRHS-LIIEPVTKRDAGIYTCI 75

                         90
                 ....*....|....*.
gi 24586203  892 ATNAFGSDDASINMIV 907
Cdd:cd05744   76 ARNRAGENSFNAELVV 91

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 39.45 E-value: 1.65e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24586203  540 GETLIVTCPVAGYPIDSIVWERDNrALPINRKQKVFPNGTLIIENVERnSDQATYTCVAKNQEGYS-ARGSLEVQ 613
Cdd:cd04968   16 GQTVTLECFALGNPVPQIKWRKVD-GSPSSQWEITTSEPVLEIPNVQF-EDEGTYECEAENSRGKDtVQGRIIVQ 88

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 39.37 E-value: 1.66e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  443 GPSVFLKCVAGGNPTPEISWELDGKKIANNDRYqvgqYVTVNGDvvsyLNITSVHANDGGLYKCIAKSKVGVAEHSAKLN 522
Cdd:cd04969   17 GGDVIIECKPKASPKPTISWSKGTELLTNSSRI----CILPDGS----LKIKNVTKSDEGKYTCFAVNFFGKANSTGSLS 88


                 .
gi 24586203  523 V 523
Cdd:cd04969   89 V 89

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

Pssm-ID: 319300 Cd Length: 92 Bit Score: 39.50 E-value: 1.69e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  256 PNIVESMASTAI--LCPAQGYPAPSFRWYKfiegttRKQAVVLNDR----VKQVS-GTLIIKDAVVEDSGKYLCVVNNSV 328
Cdd:cd05737    8 PDVVTIMEGKTLnlTCNVWGDPPPEVSWLK------NDQALAFLDHcnlkVEAGRtVYFTINGVSSEDSGKYGLVVKNKY 81

                         90
                 ....*....|.
gi 24586203  329 GGESVETVLTV 339
Cdd:cd05737   82 GSETSDVTVSV 92

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 39.12 E-value: 1.71e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24586203   60 ECKASGNPMPEIIWIRsDGTAvgdVPGLRQIS-SDGKLVFPPFRAEDyrqevhAQVYACLARNQFGSI 126
Cdd:cd05728   20 ECKASGNPRPAYRWLK-NGQP---LASENRIEvEAGDLRITKLSLSD------SGMYQCVAENKHGTI 77

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 39.64 E-value: 1.78e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  429 PVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVgQYVTVNGDvvSYLNITSVHANDGGLYKCIA 508
Cdd:cd20974    1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVISTSTLPGV-QISFSDGR--AKLSIPAVTKANSGRYSLTA 77

                         90
                 ....*....|....*
gi 24586203  509 KSKVGVAEHSAKLNV 523
Cdd:cd20974   78 TNGSGQATSTAELLV 92

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 39.15 E-value: 1.81e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203   43 KEPTNrIDFSNSTGAEIECKASGNPMPEIIWIRSDgTAVGDVPGLRQISSdGKLVFPPFRAEDYRQevhaqvYACLARNQ 122
Cdd:cd20968    4 RPPTN-VTIIEGLKAVLPCTTMGNPKPSVSWIKGD-DLIKENNRIAVLES-GSLRIHNVQKEDAGQ------YRCVAKNS 74

                         90
                 ....*....|.
gi 24586203  123 FGSIISRDVHV 133
Cdd:cd20968   75 LGIAYSKPVTI 85

Immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1; The members here are composed of the immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. NRG-1 belongs to the neuregulin gene family which is comprised of four genes. This group represents NRG-1. NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, and heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. The NRG-1 protein binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. NRG-1 has multiple functions, for example, in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival.

Pssm-ID: 409476 Cd Length: 93 Bit Score: 39.59 E-value: 1.84e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24586203  274 YPAPSFRWYKFIEGTTRK-QAVVLNDRVKQVSGTLIIKDAVVEDSGKYLCVVNNSVGGESVETVLTV 339
Cdd:cd05895   27 YPSLRFKWFKNGKEINRKnKPENIKIQKKKKKSELRINKASLADSGEYMCKVSSKLGNDSASANVTI 93

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

Pssm-ID: 409408 [Multi-domain] Cd Length: 92 Bit Score: 39.42 E-value: 1.88e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  438 ETMEPGPSVFLKCVA-GGNPTPEISWELDGKKI----ANNDRYQvgqyvtvNGDVVSYLNITSVHANDGGLYKCIAKSKV 512
Cdd:cd05750    9 QTVQEGSKLVLKCEAtSENPSPRYRWFKDGKELnrkrPKNIKIR-------NKKKNSELQINKAKLEDSGEYTCVVENIL 81

                         90
                 ....*....|.
gi 24586203  513 GVAEHSAKLNV 523
Cdd:cd05750   82 GKDTVTGNVTV 92

Immunoglobulin (Ig)-like domain of human neurofascin (NF); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of human neurofascin (NF). NF belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and a cytoplasmic domain. NF has many alternatively spliced isoforms having different temporal expression patterns during development. NF participates in axon subcellular targeting and synapse formation, however little is known of the functions of the different isoforms. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409459 Cd Length: 95 Bit Score: 39.57 E-value: 1.92e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  247 PKINALTYKPNIVESMASTAILCPAQGYPAPSFRWYKfiegTTRKQAVVLNDRV--KQVSGTLII----KDAVVEDSGKY 320
Cdd:cd05875    1 PTITKQSAKDYIVDPRDNILIECEAKGNPVPTFHWTR----NGKFFNVAKDPRVsmRRRSGTLVIdfrgGGRPEDYEGEY 76


                 ....*....
gi 24586203  321 LCVVNNSVG 329
Cdd:cd05875   77 QCFARNKFG 85

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 39.40 E-value: 1.94e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  540 GETLIVTCPVAGYPIDSIVWERDNRA--------LPINRKQKVFPNGTLIIENVeRNSDQATYTCVAKNQEGYSARGSLE 611
Cdd:cd05734   16 GKAVVLNCSADGYPPPTIVWKHSKGSgvpqfqhiVPLNGRIQLLSNGSLLIKHV-LEEDSGYYLCKVSNDVGADISKSMY 94


                 ...
gi 24586203  612 VQV 614
Cdd:cd05734   95 LTV 97

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 39.49 E-value: 1.96e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24586203  269 CPAQGYPAPSFRWYKfiEGTTRKQAvvLNDRVKQVSG--TLIIKDAVVEDSGKYLCVVNNSVGGES 332
Cdd:cd20972   23 CRVTGNPTPVVRWFC--EGKELQNS--PDIQIHQEGDlhSLIIAEAFEEDTGRYSCLATNSVGSDT 84

Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2, and similar proteins. Perlecan consists of five domains: domain I has three putative heparan sulfate attachment sites, domain II has four LDL receptor-like repeats, and one Ig-like repeat, domain III resembles the short arm of laminin chains, domain IV has multiple Ig-like repeats (21 repeats in human perlecan), and domain V resembles the globular G domain of the laminin A chain and internal repeats of EGF. Perlecan may participate in a variety of biological functions including cell binding, LDL-metabolism, basement membrane assembly and selective permeability, calcium binding, and growth- and neurite-promoting activities.

Pssm-ID: 143220 Cd Length: 78 Bit Score: 39.01 E-value: 2.00e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 24586203 1334 CLAVGAPQPEITWKIKGVEFSANDRMRVLPD---GSLLIKSVNRQDAGDYSCHAENS 1387
Cdd:cd05743    8 CVATGVPTPIINWRLNWGHVPDSARVSITSEggyGTLTIRDVKESDQGAYTCEAINT 64

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 39.24 E-value: 2.03e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  439 TMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVGQYVTVNGdvvsyLNITSVHANDGGLYKCIAKSKVGVAEHS 518
Cdd:cd20949   10 TVKEGQSATILCEVKGEPQPNVTWHFNGQPISASVADMSKYRILADG-----LLINKVTQDDTGEYTCRAYQVNSIASDM 84


                 ....*
gi 24586203  519 AKLNV 523
Cdd:cd20949   85 QERTV 89

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 39.07 E-value: 2.07e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24586203  729 GSDAKVECKADGFPKPQVTWKK----AVGDTPGEYKDLKksdnirveeGTLHVDNIQKTNEGYYLCEAINGIG 797
Cdd:cd05856   19 GSSVRLKCVASGNPRPDITWLKdnkpLTPPEIGENKKKK---------WTLSLKNLKPEDSGKYTCHVSNRAG 82

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 39.07 E-value: 2.13e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24586203  263 ASTAILCPAQGYPAPSFRWYKFIEGTTRKQAvvlnDRVKQVSGTLIIKDAVVEDSGKYLCVVNNSVG 329
Cdd:cd05856   20 SSVRLKCVASGNPRPDITWLKDNKPLTPPEI----GENKKKKWTLSLKNLKPEDSGKYTCHVSNRAG 82

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 39.31 E-value: 2.14e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  714 PPRWILEPTDkafaqgsDAKVECKADGFPKPQVTWKKAvgdtpGEYKDLKKSDNIRVEE--GTLHVDN---IQKTNEGYY 788
Cdd:cd05733    8 PKDYIVDPRD-------NITIKCEAKGNPQPTFRWTKD-----GKFFDPAKDPRVSMRRrsGTLVIDNhngGPEDYQGEY 75

                         90
                 ....*....|....*...
gi 24586203  789 LCEAINGIGSGLSAVIMI 806
Cdd:cd05733   76 QCYASNELGTAISNEIRL 93

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 39.07 E-value: 2.18e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 24586203  364 CQYTGNPIKTVSWMKDGKAIGHSEP--------VLRIESVKKEDKGMYQCFVRN 409
Cdd:cd05856   26 CVASGNPRPDITWLKDNKPLTPPEIgenkkkkwTLSLKNLKPEDSGKYTCHVSN 79

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 38.77 E-value: 2.18e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24586203  352 QTVDFgrpavfTCQYTGNPIKTVSWMKDGKAIG----H---SEPVLRIESVKKEDKGMYQCFVRNDQESAEASAEL 420
Cdd:cd05745    3 QTVDF------LCEAQGYPQPVIAWTKGGSQLSvdrrHlvlSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQL 72

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (IgSF) domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 39.00 E-value: 2.30e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  812 PEFTEKLRNQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLDPkNDNRYTIREEilstgvmSSLSIKRTERSDSALFTCV 891
Cdd:cd05764    1 PLITRHTHELRVLEGQRATLRCKARGDPEPAIHWISPEGKLIS-NSSRTLVYDN-------GTLDILITTVKDTGAFTCI 72

                         90
                 ....*....|....*.
gi 24586203  892 ATNAFGSDDASINMIV 907
Cdd:cd05764   73 ASNPAGEATARVELHI 88

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 39.15 E-value: 2.31e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  435 FQEETMEPgpSVFLKCVAGGNPTPEISWELDGK--KIANNDRYQVgqyvtVNGDVVsylnITS-VHANDGGLYKCIAKSK 511
Cdd:cd04967   13 FPEDSDEK--KVALNCRARANPVPSYRWLMNGTeiDLESDYRYSL-----VDGTLV----ISNpSKAKDAGHYQCLATNT 81


                 ..
gi 24586203  512 VG 513
Cdd:cd04967   82 VG 83

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 39.22 E-value: 2.32e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  349 PPTQTVDFGRPAVFTCQYTGNPIKTVSWMKD----------GKAIGHSEPVLRIESVKKEDKGMYQCFVRND---QESAE 415
Cdd:cd05738    6 PQLKVVEKARTATMLCAASGNPDPEISWFKDflpvdtatsnGRIKQLRSGALQIENSEESDQGKYECVATNSagtRYSAP 85


                 ....*.
gi 24586203  416 ASAELK 421
Cdd:cd05738   86 ANLYVR 91

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 39.07 E-value: 2.39e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  429 PVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWE--LDGK-KIANNDRYQVGQYVTVNgdvVSYLNITSVHANDGGLYK 505
Cdd:cd05765    1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEkqVPGKeNLIMRPNHVRGNVVVTN---IGQLVIYNAQPQDAGLYT 77

                         90
                 ....*....|....*...
gi 24586203  506 CIAKSKVGVAEHSAKLNV 523
Cdd:cd05765   78 CTARNSGGLLRANFPLSV 95

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 39.07 E-value: 2.43e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24586203  535 KAIVAGETLIVTCPVAGYPIDSIVWER--DNRALPINRKQKVFPN------GTLIIENVeRNSDQATYTCVAKNQEG 603
Cdd:cd05765   10 QTVKVGETASFHCDVTGRPQPEITWEKqvPGKENLIMRPNHVRGNvvvtniGQLVIYNA-QPQDAGLYTCTARNSGG 85

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 39.07 E-value: 2.55e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24586203 1328 EDAKMPCLAVGAPQPEITWKiKGVEFSANDRMR---------VLPDGSLLIKSVNRQDAGDYSCHAENS 1387
Cdd:cd05765   16 ETASFHCDVTGRPQPEITWE-KQVPGKENLIMRpnhvrgnvvVTNIGQLVIYNAQPQDAGLYTCTARNS 83

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 38.72 E-value: 2.64e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24586203  366 YTGNPIKTVSWMKDGKAIGHSEPV----------LRIESVKKEDKGMYQCFVRNDQESAEASAELK 421
Cdd:cd05748   16 IKGRPTPTVTWSKDGQPLKETGRVqiettasstsLVIKNAKRSDSGKYTLTLKNSAGEKSATINVK 81

C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C); The members here are composed of the C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C). MyBP-C consists of repeated domains, Ig and fibronectin type 3, and various linkers. Three isoforms of MYBP-C exist: slow-skeletal (ssMyBP-C), fast-skeletal (fsMyBP-C), and cardiac (cMyBP-C). cMYBP-C has insertions between and inside domains and an additional cardiac-specific Ig domain at the N-terminus. For cMYBP_C an interaction has been demonstrated between this C5 domain and the Ig C8 domain.

Pssm-ID: 409475 Cd Length: 86 Bit Score: 38.67 E-value: 2.66e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24586203  367 TGNPIKTVSWMKDGKAIGHSEPVLRIESVK-----------KEDKGMYQCFVRNdqESAEASAELKL 422
Cdd:cd05894   20 SGEPAPTVTWSRGDKAFTATEGRVRVESYKdlssfviegaeREDEGVYTITVTN--PVGEDHASLFV 84

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 38.64 E-value: 2.92e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  339 VTAPLSakidPPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAI-----GHS----EPVLRIESVKKEDKGMYQCFVRN 409
Cdd:cd20970    3 ISTPQP----SFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIiefntRYIvrenGTTLTIRNIRRSDMGIYLCIASN 78

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 38.78 E-value: 3.02e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24586203  264 STAILCPAQGYPAPSFRWYKFIEGTTRKQAVVLNdrvKQVSGT-LIIKDAVVEDSGKYLCVVNNSVG 329
Cdd:cd05736   17 EASLRCHAEGIPLPRVQWLKNGMDINPKLSKQLT---LIANGSeLHISNVRYEDTGAYTCIAKNEGG 80

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 38.72 E-value: 3.07e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24586203   1328 EDAKMPCLAV-GAPQPEITWKIKG-------VEFSANDRMRVLpdgSLLIKSVNRQDAGDYSCHAENSIAKDSIT 1394
Cdd:pfam00047   12 DSATLTCSAStGSPGPDVTWSKEGgtlieslKVKHDNGRTTQS---SLLISNVTKEDAGTYTCVVNNPGGSATLS 83

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 38.54 E-value: 3.38e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 24586203  351 TQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIGHSEP-------VLRIESVKKEDKGMYQCFVRNDQESA 414
Cdd:cd05731    4 STMVLRGGVLLLECIAEGLPTPDIRWIKLGGELPKGRTkfenfnkTLKIENVSEADSGEYQCTASNTMGSA 74

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 38.58 E-value: 3.45e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24586203  826 GEPAVLQCEAKGE-KPIgILWNMNNMRLDP------KNDNRYTIREEILStgvmsslsikrteRSDSALFTCVATNAFG 897
Cdd:cd04978   14 GETGELICEAEGNpQPT-ITWRLNGVPIEPapedmrRTVDGRTLIFSNLQ-------------PNDTAVYQCNASNVHG 78

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 38.69 E-value: 3.58e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24586203 1331 KMPCLAVGAPQPEITWKIKG---VEFSANDRMRvlPDGSLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1399
Cdd:cd05856   23 RLKCVASGNPRPDITWLKDNkplTPPEIGENKK--KKWTLSLKNLKPEDSGKYTCHVSNRAGEINATYKVDV 92

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor 2 (FGFR2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of human fibroblast growth factor receptor 2 (FGFR2). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. FGFR2 is required for male sex determination. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409444 Cd Length: 105 Bit Score: 38.79 E-value: 3.62e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1323 TATFKEDAKMPCLAVGAPQPEITWkIKGVEFSANdrmRVLPDGS--------------------LLIKSVNRQDAGDYSC 1382
Cdd:cd05858   12 SVVVGTDAEFVCKVYSDAQPHIQW-LKHVEKNGS---KYGPDGLpyvevlktagvnttdkeievLYLRNVTFEDAGEYTC 87

                         90
                 ....*....|....*...
gi 24586203 1383 HAENSIAKDSITHKLIVL 1400
Cdd:cd05858   88 LAGNSIGISHHSAWLTVL 105

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 38.60 E-value: 3.73e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  823 ARRGEPAVLQCEAKGEKPIGILWNMNNMRLdpKNDNRYTIREEilstgvmSSLSIKRTERSDSALFTCVATNAFGSDDAS 902
Cdd:cd04969   14 AAKGGDVIIECKPKASPKPTISWSKGTELL--TNSSRICILPD-------GSLKIKNVTKSDEGKYTCFAVNFFGKANST 84


                 ....*
gi 24586203  903 INMIV 907
Cdd:cd04969   85 GSLSV 89

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 38.47 E-value: 3.84e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  716 RWILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKAVGDTPGEYKDLKKsdnIRVEEGTLHVDNIQKTNEGYYLCEA--I 793
Cdd:cd20949    1 TFTENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQPISASVADMSK---YRILADGLLINKVTQDDTGEYTCRAyqV 77


                 ....*
gi 24586203  794 NGIGS 798
Cdd:cd20949   78 NSIAS 82

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 38.54 E-value: 3.95e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  429 PVI-RQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGK--KIANNDRyqvgqyVTVNGDVVSYlnitSVHANDG---- 501
Cdd:cd05733    1 PTItEQSPKDYIVDPRDNITIKCEAKGNPQPTFRWTKDGKffDPAKDPR------VSMRRRSGTL----VIDNHNGgped 70

                         90
                 ....*....|....*.
gi 24586203  502 --GLYKCIAKSKVGVA 515
Cdd:cd05733   71 yqGEYQCYASNELGTA 86

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 38.42 E-value: 4.08e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  247 PKInalTYKPN--IVESMASTAILCPAQGYPAPSFRWYKFI-----EGTTRKQAVVLNDRVKQVSGTLiiKDAVVEDSGK 319
Cdd:cd05869    3 PKI---TYVENqtAMELEEQITLTCEASGDPIPSITWRTSTrnissEEKTLDGHIVVRSHARVSSLTL--KYIQYTDAGE 77

                         90       100
                 ....*....|....*....|
gi 24586203  320 YLCVVNNSVGGESVETVLTV 339
Cdd:cd05869   78 YLCTASNTIGQDSQSMYLEV 97

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 38.34 E-value: 4.32e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203   41 FLKEPTNRIdFSNSTGAEIECKASGNPMPEIIWiRSDGTAV-GDVPGLRQISSDGKLVFPPFRAEDyrqevhAQVYACLA 119
Cdd:cd05867    2 WTRRPQSHL-YGPGETARLDCQVEGIPTPNITW-SINGAPIeGTDPDPRRHVSSGALILTDVQPSD------TAVYQCEA 73

                         90
                 ....*....|....*
gi 24586203  120 RNQFGSI-ISRDVHV 133
Cdd:cd05867   74 RNRHGNLlANAHVHV 88

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 37.76 E-value: 4.71e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24586203   1327 KEDAKMPCLAVGAPQPEITWKIKGVEFSandrmrvlPDGSLLIKSVNRQDAGDYSCHAENS-IAKDSITHKLIV 1399
Cdd:pfam13895   14 GEPVTLTCSAPGNPPPSYTWYKDGSAIS--------SSPNFFTLSVSAEDSGTYTCVARNGrGGKVSNPVELTV 79

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.

Pssm-ID: 143299 Cd Length: 92 Bit Score: 37.97 E-value: 5.11e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203 1315 IASFDDTFTATFKEDAKMPCLAVGAPQPEITWKIKGVEFSANDRMRVLPD----GSLLIKSVNRQDAGDYSCHAENSIAK 1390
Cdd:cd05891    4 IGGLPDVVTIMEGKTLNLTCTVFGNPDPEVIWFKNDQDIELSEHYSVKLEqgkyASLTIKGVTSEDSGKYSINVKNKYGG 83


                 ...
gi 24586203 1391 DSI 1393
Cdd:cd05891   84 ETV 86

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 38.30 E-value: 5.19e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  531 QMEKKAIV--AGETLIVTCPVAGYPIDSIVWERDNRALPI-----NRKQKVfpngTLIIENVeRNSDQATYTCVAKNQEG 603
Cdd:cd05856    8 KMRRRVIArpVGSSVRLKCVASGNPRPDITWLKDNKPLTPpeigeNKKKKW----TLSLKNL-KPEDSGKYTCHVSNRAG 82

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 38.08 E-value: 5.20e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  347 IDPPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIGHSEPV----------LRIESVKKEDKGMYQCFVRNDQESAEA 416
Cdd:cd20949    4 ENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQPISASVADmskyriladgLLINKVTQDDTGEYTCRAYQVNSIASD 83


                 ....
gi 24586203  417 SAEL 420
Cdd:cd20949   84 MQER 87

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 37.90 E-value: 5.44e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24586203   57 AEIECKASGNPMPEIIWiRSDGTAVGDvPGLRQISSDGKLVFPPFRAEDyrqevhAQVYACLARN 121
Cdd:cd20957   19 AVFNCSVTGNPIHTVLW-MKDGKPLGH-SSRVQILSEDVLVIPSVKRED------KGMYQCFVRN 75

Fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains; member of the C2-set IgSF domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains. The CEA family is a group of anchored or secreted glycoproteins, expressed by epithelial cells, leukocytes, endothelial cells and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), also known as CD66e (Cluster of Differentiation 66e), is a cell surface glycoprotein that plays a role in cell adhesion, intracellular signaling and tumor progression. Diseases associated with CEACAM5 include lung cancer and rectum cancer. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409540 Cd Length: 76 Bit Score: 37.48 E-value: 5.63e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24586203  269 CPAQGYPAPSFRWYkfiegttrkqavvLNDRVKQVSGTLIIKDAVVEDSGKYLCVVNNSVGGESVETVLTVT 340
Cdd:cd20948   17 CHAASNPPAQYSWT-------------INGTFQTSSQELFLPAITENNEGTYTCSAHNSLTGKNISLVLSVT 75

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 37.75 E-value: 6.32e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  436 QEETMEPGPSVFLKCVAGGNPTPEISWELDGK---KIANNDRYQVGQYVTvngdvvsyLNITSVHANDGGLYKCIAKSKV 512
Cdd:cd20969   10 QQVFVDEGHTVQFVCRADGDPPPAILWLSPRKhlvSAKSNGRLTVFPDGT--------LEVRYAQVQDNGTYLCIAANAG 81

                         90
                 ....*....|.
gi 24586203  513 GVAEHSAKLNV 523
Cdd:cd20969   82 GNDSMPAHLHV 92

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409474 Cd Length: 92 Bit Score: 37.77 E-value: 6.57e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  429 PVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIA-NNDRYQVGQYVtvngDVVSYLNITSVHANDGGLYKCI 507
Cdd:cd05893    1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQISpKSDHYTIQRDL----DGTCSLHTTASTLDDDGNYTIM 76

                         90
                 ....*....|....*.
gi 24586203  508 AKSKVGVAEHSAKLNV 523
Cdd:cd05893   77 AANPQGRISCTGRLMV 92

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 37.99 E-value: 6.88e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24586203  650 EIRWSLNSAPIVNGENGFTLvrlNKRTSLLNIDSLNAFHRGVYKCIATNPAGTSEYVAELQV 711
Cdd:cd05730   34 TMTWTKDGEPIESGEEKYSF---NEDGSEMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKV 92

First immunoglobulin (Ig) domain of contactin-2; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module by contacts between IG domains 1 and 4, and domains 2 and 3. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-2 is also expressed in retinal amacrine cells in the developing chick retina, corresponding to the period of formation and maturation of AC processes. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409437 [Multi-domain] Cd Length: 97 Bit Score: 37.98 E-value: 7.31e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24586203  269 CPAQGYPAPSFRWYkfIEGTTRKQAVvlNDRVKQVSGTLIIKDAV-VEDSGKYLCVVNNSVG 329
Cdd:cd05850   27 CRARASPPATYRWK--MNGTELKMEP--DSRYRLVAGNLVISNPVkAKDAGSYQCLASNRRG 84

T-cell surface glycoprotein CD3 delta chain; This is an immunoglobulin-like domain. It is found on the T-cell surface glycoprotein CD3 delta chain. CD3delta and CD3epsilon complex together as part of the T-cell receptor complex.

Pssm-ID: 465231 Cd Length: 63 Bit Score: 36.84 E-value: 7.78e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 24586203    361 VF-TCQYTGNPIKtvsWMKDGKAI-GHSEPVLRIESVKKEDKGMYQCFVRNDQES 413
Cdd:pfam16680    4 VLlTCNSSSKSIT---WLKDGKGIkSTNTKTLDLGKFSEDPRGLYQCQGEKKKSS 55

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (IgSF) domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 37.46 E-value: 7.89e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  247 PKINALTYKPNIVESMASTaILCPAQGYPAPSFRWY----KFIEGTTRkqAVVLNDrvkqvsGTLIIKDAVVEDSGKYLC 322
Cdd:cd05764    1 PLITRHTHELRVLEGQRAT-LRCKARGDPEPAIHWIspegKLISNSSR--TLVYDN------GTLDILITTVKDTGAFTC 71

                         90
                 ....*....|....
gi 24586203  323 VVNNSvGGESVETV 336
Cdd:cd05764   72 IASNP-AGEATARV 84

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 37.18 E-value: 7.92e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24586203  740 GFPKPQVTWKKavGDTPgeykdLKKSDNIRVEEG----TLHVDNIQKTNEGYYLCEAINGIGS 798
Cdd:cd05748   18 GRPTPTVTWSK--DGQP-----LKETGRVQIETTasstSLVIKNAKRSDSGKYTLTLKNSAGE 73

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 37.40 E-value: 8.30e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  528 YIRQMEKKAIVAGETLIVTCPVAGYPIDSIVWERDNRAL---PINRKQKVFPNG---TLIIENVERNsDQATYTCVAKNQ 601
Cdd:cd20951    3 FIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIdpsSIPGKYKIESEYgvhVLHIRRVTVE-DSAVYSAVAKNI 81

                         90
                 ....*....|...
gi 24586203  602 EGY-SARGSLEVQ 613
Cdd:cd20951   82 HGEaSSSASVVVE 94

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 2 (NCAM-2); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is organized similarly to NCAM, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143278 [Multi-domain] Cd Length: 98 Bit Score: 37.65 E-value: 8.51e-03

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24586203  817 KLRNQTARRGEPAVLQCEAKGEKPIGILWN-----MNNMRLDPKNDNRYTIREEILStgvmSSLSIKRTERSDSALFTCV 891
Cdd:cd05870    7 QLKNETTVENGAATLSCKAEGEPIPEITWKrasdgHTFSEGDKSPDGRIEVKGQHGE----SSLHIKDVKLSDSGRYDCE 82

                         90
                 ....*....|..
gi 24586203  892 ATNAFGSDDASI 903
Cdd:cd05870   83 AASRIGGHQKSM 94

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 37.54 E-value: 8.73e-03

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gi 24586203  269 CPAQGYPAPSFRWykfiegTTRKQAVVLNDRVKQ-----VSGTLI----IKDAVVEDSGKYLCVVNNSVG 329
Cdd:cd20956   23 CVASGNPLPQITW------TLDGFPIPESPRFRVgdyvtSDGDVVsyvnISSVRVEDGGEYTCTATNDVG 86

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409474 Cd Length: 92 Bit Score: 37.38 E-value: 8.81e-03

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gi 24586203  357 GRPAVFTCQYTGNPIKTVSWMKDGKAI 383
Cdd:cd05893   15 GMPVTFTCRVAGNPKPKIYWFKDGKQI 41