NCBI Conserved Domain Search

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: 191.23 E-value: 9.46e-57

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  422 PPVLLYSFIEQTLQPGPAVSLKCSAAGNPTPQISWTLDGFPLPSNGRFMIGQYITVHGDVISHVNISHVMVEDGGEYACI 501
Cdd:cd20956     1 APVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDGFPIPESPRFRVGDYVTSDGDVVSYVNISSVRVEDGGEYTCT 80

                          90
                  ....*....|....*.
gi 220902488  502 AENRAGRVQHAARLNI 517
Cdd:cd20956    81 ATNDVGSVSHSARINV 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: 181.74 E-value: 2.20e-53

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  707 PPRWIVEPVDANVERNRHIMLHCQAQGVPTPSIVWKKATGSKSGEYEEVRERPFTKLLGNGSLLLQHVKEDREGFYLCQA 786
Cdd:cd20954     1 PPRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKATGSTPGEYKDLLYDPNVRILPNGTLVFGHVQKENEGHYLCEA 80

                          90
                  ....*....|....*.
gi 220902488  787 NNGIGTGIGKVIQLKV 802
Cdd:cd20954    81 KNGIGSGLSKVIFLKV 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: 153.88 E-value: 9.37e-44

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  521 PYIRLIPKVTAVSGETLNLKCPVAGYPIEEIHWERGGRELPDDIRQRVQPDGSLTISPVQKNSDSGVYTCWARNKQGHSA 600
Cdd:cd20958     2 PFIRPMGNLTAVAGQTLRLHCPVAGYPISSITWEKDGRRLPLNHRQRVFPNGTLVIENVQRSSDEGEYTCTARNQQGQSA 81


                  ....*...
gi 220902488  601 RRSGEVTV 608
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: 137.66 E-value: 4.46e-38

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  330 PIQVEISPNVLSVHMGGTAEFRCLVTSNgspvGMQNILWYKDGRQLPSSGRVE----DTLVVPRVSRENRGMYQCVVRRP 405
Cdd:cd20957     1 PLSATIDPPVQTVDFGRTAVFNCSVTGN----PIHTVLWMKDGKPLGHSSRVQilseDVLVIPSVKREDKGMYQCFVRND 76

                          90
                  ....*....|...
gi 220902488  406 eGDTFQATAELQL 418
Cdd:cd20957    77 -GDSAQATAELKL 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: 114.81 E-value: 6.71e-30

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   30 GPGFVMEPPGRVEFSNSSGGWLDCSASGSPQPTVDWVHADGSAVTEIHGVRRVLRNGTLVLMPFAAAAYHQDVHNTIYRC 109
Cdd:cd20955     1 GPVFLKEPTNRIDFSNSTGAEIECKASGNPMPEIIWIRSDGTAVGDVPGLRQISSDGKLVFPPFRAEDYRQEVHAQVYAC 80

                          90
                  ....*....|....*....
gi 220902488  110 IASNSVGRIVSRDVQVRAV 128
Cdd:cd20955    81 LARNQFGSIISRDVHVRAV 99

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: 90.63 E-value: 1.50e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  611 PPKLSPFQTNILQLNMGDRASLTCSVVKGDLPLTINWRKDGRPIDPTQHMSVKQVDQYNSILVIENLGSDHTGNYSCVVR 690
Cdd:cd20959     1 PPRIIPFAFGEGAAQVGMRAQLHCGVPGGDLPLNIRWTLDGQPISDDLGITVSRLGRRSSILSIDSLEASHAGNYTCHAR 80

                          90
                  ....*....|....
gi 220902488  691 NSAAEVENSQALLV 704
Cdd:cd20959    81 NSAGSASYTAPLTV 94

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: 86.01 E-value: 6.14e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  906 PLPPSVLEAAMISSRSVNIKWQPKTLGTGDVTKYIVEFREADPlfvDQWQQIEVKDPPHFNAMIENLKPATRYAFRVIAE 985
Cdd:cd00063     1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGS---GDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRAV 77

                          90
                  ....*....|....*.
gi 220902488  986 GSAGRSAPSQELIVRT 1001
Cdd:cd00063    78 NGGGESPPSESVTVTT 93

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: 82.54 E-value: 1.21e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  707 PPRWIVEPVDANVERNRHIMLHCQAQGVPTPSIVWKKATGSKSGEYEEVRERPF-TKLLGNGSLLLQHVKEDREGFYLCQ 785
Cdd:cd05734     1 PPRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWKHSKGSGVPQFQHIVPLNGrIQLLSNGSLLIKHVLEEDSGYYLCK 80

                          90
                  ....*....|....*..
gi 220902488  786 ANNGIGTGIGKVIQLKV 802
Cdd:cd05734    81 VSNDVGADISKSMYLTV 97

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 85.44 E-value: 1.67e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  904 EPPLPPSVLEAAMISSRSVNIKWQPKTLGtgDVTKYIVEFREADPlfvDQWQQIEVKDPPHFNAMieNLKPATRYAFRVI 983
Cdd:COG3401   231 TPPSAPTGLTATADTPGSVTLSWDPVTES--DATGYRVYRSNSGD---GPFTKVATVTTTSYTDT--GLTNGTTYYYRVT 303

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  984 AEGSAG-RSAPSQELIVRTEPQRPAgPPLSLSARPLSSTELLISWVAPLPElrhgDIQGYNVGYKLSSSGNTAYNFTSVS 1062
Cdd:COG3401   304 AVDAAGnESAPSNVVSVTTDLTPPA-APSGLTATAVGSSSITLSWTASSDA----DVTGYNVYRSTSGGGTYTKIAETVT 378

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488 1063 G----DgdggngelllSGLAKFARYTVVVQAFNQVGP-GPLSEPTAAQTMEDVPS----RPPEDVRCAALSSQSLQVSWQ 1133
Cdd:COG3401   379 TtsytD----------TGLTPGTTYYYKVTAVDAAGNeSAPSEEVSATTASAASGesltASVDAVPLTDVAGATAAASAA 448

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 220902488 1134 PPPIYHTNGLLQGYKLIFEPIIDDIQPSKDEVESRKTTALTMVLTGLRKYTNYSIQV 1190
Cdd:COG3401   449 SNPGVSAAVLADGGDTGNAVPFTTTSSTVTATTTDTTTANLSVTTGSLVGGSGASSV 505

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 73.83 E-value: 1.11e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   432 QTLQPGPAVSLKCSAAGNPTPQISWTLDGFPLPSNGRFMIgqyitVHGDVISHVNISHVMVEDGGEYACIAENRAGRVQH 511
Cdd:pfam07679   10 VEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKV-----TYEGGTYTLTISNVQPDDSGKYTCVATNSAGEAEA 84


                   ....*.
gi 220902488   512 AARLNI 517
Cdd:pfam07679   85 SAELTV 90

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 70.36 E-value: 2.21e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   806 PYFSSTSRSVMVKKGDTALLQCAVSGDKPINIVWMRSGKnTLNPSTNYKISVkqeatpDGVSAELQIRTVDATDSGPYFC 885
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQ-PLRSSDRFKVTY------EGGTYTLTISNVQPDDSGKYTC 73


                   ....*..
gi 220902488   886 RASNLYG 892
Cdd:pfam07679   74 VATNSAG 80

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 68.44 E-value: 8.55e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   521 PYIRLIPKVTAVS-GETLNLKCPVAGYPIEEIHWERGGRELPDDIRQRVQPDG---SLTISPVQKnSDSGVYTCWARNKq 596
Cdd:pfam07679    1 PKFTQKPKDVEVQeGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGgtyTLTISNVQP-DDSGKYTCVATNS- 78

                           90
                   ....*....|....
gi 220902488   597 ghsarrSGEVTVIV 610
Cdd:pfam07679   79 ------AGEAEASA 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: 67.92 E-value: 1.39e-13

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488    527 PKVTAVSGETLNLKCPVAGYPIEEIHWERGGREL---PDDIRQRVQP-DGSLTISPVQKnSDSGVYTCWARNKQGHsarR 602
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLlaeSGRFSVSRSGsTSTLTISNVTP-EDSGTYTCAATNSSGS---A 77


                    ....*...
gi 220902488    603 SGEVTVIV 610
Cdd:smart00410   78 SSGTTLTV 85

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 66.67 E-value: 2.93e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  1216 APADIKVVSSSSQSLYISWLPPNEPNGVITKYSLYTRVVNGREELNNekRSLPSQQAYYEAKGLHPHMEYQFWVTASTRV 1295
Cdd:pfam00041    2 APSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPWNE--ITVPGTTTSVTLTGLKPGTEYEVRVQAVNGG 79


                   ....*.
gi 220902488  1296 GEGKSS 1301
Cdd:pfam00041   80 GEGPPS 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: 66.76 E-value: 3.58e-13

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488    812 SRSVMVKKGDTALLQCAVSGDKPINIVWMRSGKNTLNPSTNYKISvkqeatPDGVSAELQIRTVDATDSGPYFCRASNLY 891
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVS------RSGSTSTLTISNVTPEDSGTYTCAATNSS 74


                    ...
gi 220902488    892 GND 894
Cdd:smart00410   75 GSA 77

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 66.43 E-value: 3.89e-13

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 220902488   521 PYIRLIPK-VTAVSGETLNLKCPVAGYPIEEIHWERGGRELPD---DIRQRVQPDGSLTISPVQKnSDSGVYTCWARN 594
Cdd:pfam13927    2 PVITVSPSsVTVREGETVTLTCEATGSPPPTITWYKNGEPISSgstRSRSLSGSNSTLTISNVTR-SDAGTYTCVASN 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: 66.73 E-value: 4.00e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  707 PPRWIVEPVDANVERNRHIMLHCQAQGVPTPSIVWKkatgsKSGEY--EEVRERpfTKLLGNGSLLLQHVKEDR-----E 779
Cdd:cd05722     1 ELYFLSEPSDIVAMRGGPVVLNCSAESDPPPKIEWK-----KDGVLlnLVSDER--RQQLPNGSLLITSVVHSKhnkpdE 73

                          90       100
                  ....*....|....*....|....
gi 220902488  780 GFYLCQANNG-IGTGIGKVIQLKV 802
Cdd:cd05722    74 GFYQCVAQNEsLGSIVSRTARVTV 97

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: 5.39e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  423 PVLLYSFIEQTLQPGPAVSLKCSAAGNPTPQISWTLDGFPLPSNGRF-MIGQYITVHGDVISHVNishvmVEDGGEYACI 501
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHkMLVRENGRHSLIIEPVT-----KRDAGIYTCI 75

                          90
                  ....*....|....*.
gi 220902488  502 AENRAGRVQHAARLNI 517
Cdd:cd05744    76 ARNRAGENSFNAELVV 91

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 65.66 E-value: 5.92e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   806 PYFSSTSRSVMVKKGDTALLQCAVSGDKPINIVWMRSGKNTLNPSTnykisvkQEATPDGVSAELQIRTVDATDSGPYFC 885
Cdd:pfam13927    2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGST-------RSRSLSGSNSTLTISNVTRSDAGTYTC 74


                   ....
gi 220902488   886 RASN 889
Cdd:pfam13927   75 VASN 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: 65.71 E-value: 6.46e-13

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488    906 PLPPSVLEAAMISSRSVNIKWQPKTLGTGdvTKYIVEFREADPLFVDQWQQIEVKDPPHfNAMIENLKPATRYAFRVIAE 985
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGI--TGYIVGYRVEYREEGSEWKEVNVTPSST-SYTLTGLKPGTEYEFRVRAV 77


                    ....*.
gi 220902488    986 GSAGRS 991
Cdd:smart00060   78 NGAGEG 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: 65.43 E-value: 7.17e-13

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  537 LNLKCPVAGYPIEEIHWERGGRELPDDIRQR---VQPDGSLTISPVQKnSDSGVYTCWARNKQGHSARRS 603
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSrrsELGNGTLTISNVTL-EDSGTYTCVASNSAGGSASAS 69

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 65.28 E-value: 8.58e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   611 PPKLSPFQTNILqLNMGDRASLTCSVVKGDLPlTINWRKDGRPIDPTQHmSVKQVDQYNSILVIENLGSDHTGNYSCVVR 690
Cdd:pfam13927    1 KPVITVSPSSVT-VREGETVTLTCEATGSPPP-TITWYKNGEPISSGST-RSRSLSGSNSTLTISNVTRSDAGTYTCVAS 77


                   .
gi 220902488   691 N 691
Cdd:pfam13927   78 N 78

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: 65.60 E-value: 9.10e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488 1214 PEAPADIKVVSSSSQSLYISWLPPNEPNGVITKYSLYTRVVNGREELNNEKRSLPSQQayYEAKGLHPHMEYQFWVTAST 1293
Cdd:cd00063     1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVEVTPGSETS--YTLTGLKPGTEYEFRVRAVN 78

                          90
                  ....*....|....*
gi 220902488 1294 RVGEGKSSRVSSQIT 1308
Cdd:cd00063    79 GGGESPPSESVTVTT 93

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 65.13 E-value: 1.29e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   908 PPSVLEAAMISSRSVNIKWQPKTLGTGDVTKYIVEFREADPLFVDQWQQIevkDPPHFNAMIENLKPATRYAFRVIAEGS 987
Cdd:pfam00041    2 APSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPWNEITV---PGTTTSVTLTGLKPGTEYEVRVQAVNG 78


                   ....*..
gi 220902488   988 AGRSAPS 994
Cdd:pfam00041   79 GGEGPPS 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 64.51 E-value: 1.40e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   422 PPVLLYSFIEQTLQPGPAVSLKCSAAGNPTPQISWTLDGFPLPSNgrfmiGQYITVHGDVISHVNISHVMVEDGGEYACI 501
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSG-----STRSRSLSGSNSTLTISNVTRSDAGTYTCV 75


                   ...
gi 220902488   502 AEN 504
Cdd:pfam13927   76 ASN 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: 64.73 E-value: 1.94e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  524 RLIPK-VTAVSGETLNLKC-PVAGYPIEEIHWERGGRELP-DDIRQRVQPDGSLTISPVQKnSDSGVYTCWARNKQGHSA 600
Cdd:cd05724     1 RVEPSdTQVAVGEMAVLECsPPRGHPEPTVSWRKDGQPLNlDNERVRIVDDGNLLIAEARK-SDEGTYKCVATNMVGERE 79


                  ....*...
gi 220902488  601 RRSGEVTV 608
Cdd:cd05724    80 SRAARLSV 87

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: 63.89 E-value: 2.22e-12

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 220902488  440 VSLKCSAAGNPTPQISWTLDGFPLPSNGRFmigqyITVHGDVISHVNISHVMVEDGGEYACIAENRAGRVQHA 512
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRD-----SRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASA 68

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 63.59 E-value: 3.63e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  1403 PPTAPVlyVTSATSSSILMHWKCGFTGNAPITGYTLFYRRANGNTD--EMQLSRHASSHELKGLMCGSTYQIHLSAQNKV 1480
Cdd:pfam00041    2 APSNLT--VTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPwnEITVPGTTTSVTLTGLKPGTEYEVRVQAVNGG 79


                   ....*.
gi 220902488  1481 GTSPTS 1486
Cdd:pfam00041   80 GEGPPS 85

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 63.43 E-value: 5.23e-12

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 220902488   627 GDRASLTCSVvKGDLPLTINWRKDGRPIDPTQHMSVKQVDqYNSILVIENLGSDHTGNYSCVVRNSAAEVE 697
Cdd:pfam07679   15 GESARFTCTV-TGTPDPEVSWFKDGQPLRSSDRFKVTYEG-GTYTLTISNVQPDDSGKYTCVATNSAGEAE 83

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 63.43 E-value: 5.38e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   238 PSVVEHTAHVQVSQDEGAVLLCVAQGCPSPEYSWFtHNGAgplPVLSGPRVRLL--GPI--LAIEAVTGEDSGVYKCTAG 313
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWF-KDGQ---PLRSSDRFKVTyeGGTytLTISNVQPDDSGKYTCVAT 76

                           90
                   ....*....|....
gi 220902488   314 NVGGEASAELRLTV 327
Cdd:pfam07679   77 NSAGEAEASAELTV 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: 61.58 E-value: 1.39e-11

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 220902488  630 ASLTCSVvKGDLPLTINWRKDGRPIDPTQHMSVKqVDQYNSILVIENLGSDHTGNYSCVVRNSAAEVENSQA 701
Cdd:cd00096     1 VTLTCSA-SGNPPPTITWYKNGKPLPPSSRDSRR-SELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

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: 62.13 E-value: 1.88e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488 1404 PTAPV-LYVTSATSSSILMHWKCGFTGNAPITGYTLFYRRANGNTDEMQLSRHAS--SHELKGLMCGSTYQIHLSAQNKV 1480
Cdd:cd00063     1 PSPPTnLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVEVTPGSetSYTLTGLKPGTEYEFRVRAVNGG 80

                          90
                  ....*....|...
gi 220902488 1481 GTSPTSTILHVRT 1493
Cdd:cd00063    81 GESPPSESVTVTT 93

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: 60.89 E-value: 3.95e-11

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 220902488  437 GPAVSLKCSAAGNPTPQISWTLDGFPLPsNGRFMIGQYITVhgdvishVNISHVMVEDGGEYACIAENRAGRVQH 511
Cdd:cd05731    10 GGVLLLECIAEGLPTPDIRWIKLGGELP-KGRTKFENFNKT-------LKIENVSEADSGEYQCTASNTMGSARH 76

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 60.89 E-value: 4.15e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  1114 PPEDVRCAALSSQSLQVSWQPPPiyHTNGLLQGYKLIFEPIiDDIQPSKDEVESRktTALTMVLTGLRKYTNYSIQVLAH 1193
Cdd:pfam00041    2 APSNLTVTDVTSTSLTVSWTPPP--DGNGPITGYEVEYRPK-NSGEPWNEITVPG--TTTSVTLTGLKPGTEYEVRVQAV 76


                   ....*.
gi 220902488  1194 TRMGDG 1199
Cdd:pfam00041   77 NGGGEG 82

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: 60.97 E-value: 4.48e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488 1114 PPEDVRCAALSSQSLQVSWQPPPiyHTNGLLQGYKLIFEPIIDDiqpSKDEVESRKTTALTMVLTGLRKYTNYSIQVLAH 1193
Cdd:cd00063     3 PPTNLRVTDVTSTSVTLSWTPPE--DDGGPITGYVVEYREKGSG---DWKEVEVTPGSETSYTLTGLKPGTEYEFRVRAV 77

                          90
                  ....*....|.
gi 220902488 1194 TRMGDGVVSKP 1204
Cdd:cd00063    78 NGGGESPPSES 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: 60.73 E-value: 4.65e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  437 GPAVSLKCSAAGNPTPQISWTLDGFPLpsngrfmigQYITVHGDV---ISHVNISHVMVEDGGEYACIAENRAGRVQHAA 513
Cdd:cd20976    16 GQDFVAQCSARGKPVPRITWIRNAQPL---------QYAADRSTCeagVGELHIQDVLPEDHGTYTCLAKNAAGQVSCSA 86


                  ....
gi 220902488  514 RLNI 517
Cdd:cd20976    87 WVTV 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: 60.60 E-value: 5.13e-11

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488    432 QTLQPGPAVSLKCSAAGNPTPQISWTLDGF-PLPSNGRFMIgqyitVHGDVISHVNISHVMVEDGGEYACIAENRAGRVQ 510
Cdd:smart00410    4 VTVKEGESVTLSCEASGSPPPEVTWYKQGGkLLAESGRFSV-----SRSGSTSTLTISNVTPEDSGTYTCAATNSSGSAS 78


                    ....*..
gi 220902488    511 HAARLNI 517
Cdd:smart00410   79 SGTTLTV 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: 60.20 E-value: 9.23e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488 1008 GPPLSLSARPLSSTELLISWVAPLPElrHGDIQGYNVGYKLSSSGNTaynftSVSGDGDGGNGELLLSGLAKFARYTVVV 1087
Cdd:cd00063     2 SPPTNLRVTDVTSTSVTLSWTPPEDD--GGPITGYVVEYREKGSGDW-----KEVEVTPGSETSYTLTGLKPGTEYEFRV 74

                          90
                  ....*....|....*....
gi 220902488 1088 QAFNQVGPGPLSEPTAAQT 1106
Cdd:cd00063    75 RAVNGGGESPPSESVTVTT 93

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: 59.48 E-value: 1.46e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  437 GPAVSLKCSAAGNPTPQISW-TLDGFPLPSngrfmigQYITVHGDVIshvNISHVMVEDGGEYACIAENRAGRVQHAARL 515
Cdd:cd04968    16 GQTVTLECFALGNPVPQIKWrKVDGSPSSQ-------WEITTSEPVL---EIPNVQFEDEGTYECEAENSRGKDTVQGRI 85


                  ...
gi 220902488  516 NIY 518
Cdd:cd04968    86 IVQ 88

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 58.73 E-value: 1.62e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   707 PPRWIVEPVDANVERNRHIMLHCQAQGVPTPSIVWKKatgsKSGEYEEVRERPFTKLLGNGSLLLQHVKEDREGFYLCQA 786
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYK----NGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVA 76


                   ..
gi 220902488   787 NN 788
Cdd:pfam13927   77 SN 78

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: 58.94 E-value: 1.94e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 220902488  522 YIRLIPKVTAVS-GETLNLKCPVAGYPIEEIHWERGGRELPDDIRQRVQPDGSLTISPVQKnSDSGVYTCWARNKQG 597
Cdd:cd20978     3 FIQKPEKNVVVKgGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVEDGTLTIINVQP-EDTGYYGCVATNEIG 78

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: 58.29 E-value: 3.54e-10

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488    246 HVQVSQDEGAVLLCVAQGCPSPEYSWFTHngaGPLPVLSGPRVRLLGP----ILAIEAVTGEDSGVYKCTAGNVGGEASA 321
Cdd:smart00410    3 SVTVKEGESVTLSCEASGSPPPEVTWYKQ---GGKLLAESGRFSVSRSgstsTLTISNVTPEDSGTYTCAATNSSGSASS 79


                    ....*.
gi 220902488    322 ELRLTV 327
Cdd:smart00410   80 GTTLTV 85

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: 57.72 E-value: 5.58e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  422 PPVLLYSFIEQTLQPGPAVSLKCSAAGNPTPQISWTLDGFPLPSNGRfmigqyITVHGDVISHVNISHvmvEDGGEYACI 501
Cdd:cd05851     1 PADINVKFKDTYALKGQNVTLECFALGNPVPVIRWRKILEPMPATAE------ISMSGAVLKIFNIQP---EDEGTYECE 71

                          90
                  ....*....|....
gi 220902488  502 AENRAGRVQHAARL 515
Cdd:cd05851    72 AENIKGKDKHQARV 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: 57.61 E-value: 6.41e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  431 EQTLQPGPA---VSLKCSAAGNPTPQISWTLDGFPLPSNGRFMIGQYITVHGDVIshvnISHVMVEDGGEYACIAENRAG 507
Cdd:cd05729    10 EEREHALPAankVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEKGWSLI----IERAIPRDKGKYTCIVENEYG 85

                          90
                  ....*....|
gi 220902488  508 RVQHAARLNI 517
Cdd:cd05729    86 SINHTYDVDV 95

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: 8.28e-10

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 220902488    627 GDRASLTCSVvKGDLPLTINWRKDG-RPIDPTQHMSVKQvDQYNSILVIENLGSDHTGNYSCVVRNSAAEVENSQALLV 704
Cdd:smart00410    9 GESVTLSCEA-SGSPPPEVTWYKQGgKLLAESGRFSVSR-SGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTLTV 85

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 63.48 E-value: 9.69e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488 1008 GPPLSLSARPLSSTELLISWVAPLPELRHGDIQGYNVGYKLSSSGNTAYNFTSVSGDGDGGNGELLLSGlakfARYTVVV 1087
Cdd:COG3401   134 GAATAGTYALGAGLYGVDGANASGTTASSVAGAGVVVSPDTSATAAVATTSLTVTSTTLVDGGGDIEPG----TTYYYRV 209

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488 1088 QAFNQVGPGPLSEPTAAQTMEDVPSrPPEDVRCAALSSQSLQVSWQPppiyHTNGLLQGYKlIFepiiddIQPSKDEVES 1167
Cdd:COG3401   210 AATDTGGESAPSNEVSVTTPTTPPS-APTGLTATADTPGSVTLSWDP----VTESDATGYR-VY------RSNSGDGPFT 277

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488 1168 R--KTTALTMVLTGLRKYTNYSIQVLAHTrmGDGVVSKPlfchSEE-------DVPEAPADIKVVSSSSQSLYISWLPPn 1238
Cdd:COG3401   278 KvaTVTTTSYTDTGLTNGTTYYYRVTAVD--AAGNESAP----SNVvsvttdlTPPAAPSGLTATAVGSSSITLSWTAS- 350

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488 1239 ePNGVITKYSLYtrvVNGREELNNEKRSLPSQQAYYEAKGLHPHMEYQFWVTA----------STRVGEGKSSRVSSQIT 1308
Cdd:COG3401   351 -SDADVTGYNVY---RSTSGGGTYTKIAETVTTTSYTDTGLTPGTTYYYKVTAvdaagnesapSEEVSATTASAASGESL 426

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488 1309 TNRIPAR---IISFGGPVVRPWRSTVTLPCTAVGKPKREWFKSDVALRQggLHNSQLLDSGDLIISSLQLADGGNYSCQV 1385
Cdd:COG3401   427 TASVDAVpltDVAGATAAASAASNPGVSAAVLADGGDTGNAVPFTTTSS--TVTATTTDTTTANLSVTTGSLVGGSGASS 504

                         410       420       430       440       450
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 220902488 1386 DNGIGTDRLTHTLIVQVPPTAPVLYVTSATSSSILMHWKCGFTGNAPITGYTLFY 1440
Cdd:COG3401   505 VTNSVSVIGASAAAAVGGAPDGTPNVTGASPVTVGASTGDVLITDLVSLTTSASS 559

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: 56.47 E-value: 1.15e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   1214 PEAPADIKVVSSSSQSLYISWLPPNEPNGviTKYSLYTRVVNGREELNNEKRSLPSQQAYYEAKGLHPHMEYQFWVTAST 1293
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGI--TGYIVGYRVEYREEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVN 78


                    ....*
gi 220902488   1294 RVGEG 1298
Cdd:smart00060   79 GAGEG 83

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: 56.47 E-value: 1.44e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   1114 PPEDVRCAALSSQSLQVSWQPPPIYHTNGLLQGYKLIFEPIIDDIQpskdeVESRKTTALTMVLTGLRKYTNYSIQVLAH 1193
Cdd:smart00060    3 PPSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYREEGSEWK-----EVNVTPSSTSYTLTGLKPGTEYEFRVRAV 77


                    ....*.
gi 220902488   1194 TRMGDG 1199
Cdd:smart00060   78 NGAGEG 83

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: 56.45 E-value: 1.45e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 220902488  444 CSAAGNPTPQISWTLDGFPLPSNGRFMIgqyitVHGDVIshvnISHVMVEDGGEYACIAENRAGRVQHAARLNI 517
Cdd:cd05728    21 CKASGNPRPAYRWLKNGQPLASENRIEV-----EAGDLR----ITKLSLSDSGMYQCVAENKHGTIYASAELAV 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: 56.35 E-value: 1.46e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 220902488  529 VTAVSGETLNLKCPVAGYPIEEIHWERGGRELP-DDIRQRVQPDGSLTISPVQKNsDSGVYTCWARNKQGHSA 600
Cdd:cd20952     9 QTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLgKDERITTLENGSLQIKGAEKS-DTGEYTCVALNLSGEAT 80

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: 56.35 E-value: 1.61e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  424 VLLYSFIEQTLQPGPAVSLKCSAAGNPTPQISWTLDGFPLP-SNGRFMIGQYITVHgdvishvnISHVMVEDGGEYACIA 502
Cdd:cd20952     1 IILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLgKDERITTLENGSLQ--------IKGAEKSDTGEYTCVA 72

                          90
                  ....*....|....*
gi 220902488  503 ENRAGRVQHAARLNI 517
Cdd:cd20952    73 LNLSGEATWSAVLDV 87

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: 55.96 E-value: 2.35e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  422 PPVLLYSFIEQTLQPGPAVSLKCSAAGNPTP-QISWTLDGFPLPSNGRF---MIGQYITVHgdVISHVNISHvmvedGGE 497
Cdd:cd20959     2 PRIIPFAFGEGAAQVGMRAQLHCGVPGGDLPlNIRWTLDGQPISDDLGItvsRLGRRSSIL--SIDSLEASH-----AGN 74

                          90       100
                  ....*....|....*....|
gi 220902488  498 YACIAENRAGRVQHAARLNI 517
Cdd:cd20959    75 YTCHARNSAGSASYTAPLTV 94

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: 56.00 E-value: 2.41e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  525 LIPKVTAVS-GETLNLKCPVAGYPIEEIHWERGGRELPDDIRQRVQPDGSLTISPVQKNsDSGVYTCWARNkQGHSARRS 603
Cdd:cd20957     6 IDPPVQTVDfGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSEDVLVIPSVKRE-DKGMYQCFVRN-DGDSAQAT 83


                  ...
gi 220902488  604 GEV 606
Cdd:cd20957    84 AEL 86

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: 55.86 E-value: 2.71e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 220902488  440 VSLKCSAAGNPTPQISWTLDGFPLPSN-GRFMIGQyitvHGDVISHVNIshvmvEDGGEYACIAENRAGRVQHAARLNI 517
Cdd:cd20978    19 VTLPCQVTGVPQPKITWLHNGKPLQGPmERATVED----GTLTIINVQP-----EDTGYYGCVATNEIGDIYTETLLHV 88

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 55.26 E-value: 2.78e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 220902488   238 PSVVEHTAHVQVSQDEGAVLLCVAQGCPSPEYSWFtHNGAGPLPVLSGPRVRLLG-PILAIEAVTGEDSGVYKCTAGN 314
Cdd:pfam13927    2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWY-KNGEPISSGSTRSRSLSGSnSTLTISNVTRSDAGTYTCVASN 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: 55.63 E-value: 3.50e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  430 IEQTLQPGPA---VSLKCSAAGNPTPQISWTLDGFPLPSNGRfmIGQYITVHgdviSHVNIS--HVMVEDGGEYACIAEN 504
Cdd:cd05857     9 MEKKLHAVPAantVKFRCPAAGNPTPTMRWLKNGKEFKQEHR--IGGYKVRN----QHWSLImeSVVPSDKGNYTCVVEN 82

                          90
                  ....*....|...
gi 220902488  505 RAGRVQHAARLNI 517
Cdd:cd05857    83 EYGSINHTYHLDV 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: 55.32 E-value: 3.60e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  433 TLQPGPAVSLKCSAAGNPTPQISWTLDG---FPLPSNGRFmigqYITVHGDVIShvnISHVMVEDGGEYACIAENRAGRV 509
Cdd:cd05763    10 TIRAGSTARLECAATGHPTPQIAWQKDGgtdFPAARERRM----HVMPEDDVFF---IVDVKIEDTGVYSCTAQNSAGSI 82


                  ....*...
gi 220902488  510 QHAARLNI 517
Cdd:cd05763    83 SANATLTV 90

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: 54.50 E-value: 4.85e-09

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 220902488  440 VSLKCSAAGNPTPQISWTLDGFPLPSNGRFMIGQyitvHGdvisHVNISHVMVEDGGEYACIAENRAG 507
Cdd:cd05746     1 VQIPCSAQGDPEPTITWNKDGVQVTESGKFHISP----EG----YLAIRDVGVADQGRYECVARNTIG 60

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: 54.71 E-value: 4.86e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  529 VTAVSGETLNLKCPVAGYPIEEIHWERGGRELPDDiRQRVQPDGSLTISPVQKnSDSGVYTCWARNKQGhSARRSGEVTV 608
Cdd:cd05725     7 QVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKG-RYEILDDHSLKIRKVTA-GDMGSYTCVAENMVG-KIEASATLTV 83

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 54.73 E-value: 5.26e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  1008 GPPLSLSARPLSSTELLISWVAPLPelRHGDIQGYNVGYKLSSSGNTAYNFTSvsgdgDGGNGELLLSGLAKFARYTVVV 1087
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPPPD--GNGPITGYEVEYRPKNSGEPWNEITV-----PGTTTSVTLTGLKPGTEYEVRV 73

                           90
                   ....*....|..
gi 220902488  1088 QAFNQVGPGPLS 1099
Cdd:pfam00041   74 QAVNGGGEGPPS 85

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: 54.87 E-value: 5.45e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 220902488  437 GPAVSLKCSAAGNPTPQISWTLDGFPL--PSNGRFMIGQYItvhgdvishVNISHVMVEDGGEYACIAENRAGRV 509
Cdd:cd05856    19 GSSVRLKCVASGNPRPDITWLKDNKPLtpPEIGENKKKKWT---------LSLKNLKPEDSGKYTCHVSNRAGEI 84

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: 54.71 E-value: 6.12e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  623 QLNMGDRASLTCSVVKGDLPLTINWRKDGRPIDpTQHMSVKQVDQYNsiLVIENLGSDHTGNYSCVVRNSAAEVENSQAL 702
Cdd:cd05724     8 QVAVGEMAVLECSPPRGHPEPTVSWRKDGQPLN-LDNERVRIVDDGN--LLIAEARKSDEGTYKCVATNMVGERESRAAR 84


                  .
gi 220902488  703 L 703
Cdd:cd05724    85 L 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: 54.94 E-value: 6.43e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  433 TLQPGPAVSLKCSAAGNPTPQISWTLDGFPLPSngrfmiGQYITVHGDVISHVNISHVMVEDGGEYACIAENRAGRVQHA 512
Cdd:cd05730    14 TANLGQSVTLACDADGFPEPTMTWTKDGEPIES------GEEKYSFNEDGSEMTILDVDKLDEAEYTCIAENKAGEQEAE 87


                  ....*.
gi 220902488  513 ARLNIY 518
Cdd:cd05730    88 IHLKVF 93

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: 54.71 E-value: 6.45e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  708 PRWIVEPVDANVERNRH-IMLHCQAQGVPTPSIVWkkatgSKSGEyeEVRERPFTKLLGNGSLLLQHVKEDREGFYLCQA 786
Cdd:cd20978     1 PKFIQKPEKNVVVKGGQdVTLPCQVTGVPQPKITW-----LHNGK--PLQGPMERATVEDGTLTIINVQPEDTGYYGCVA 73


                  ....*.
gi 220902488  787 NNGIGT 792
Cdd:cd20978    74 TNEIGD 79

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: 53.87 E-value: 7.56e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  255 AVLLCVAQGCPSPEYSWFTHNGAGPLPVLSGPRVRLLGPILAIEAVTGEDSGVYKCTAGN-VGGEASAEL 323
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNsAGGSASASV 70

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 54.11 E-value: 7.69e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 220902488   332 QVEISPNVLSVHMGGTAEFRCLVTSNGSPvgmqNILWYKDGRQLPSSGRVED-------TLVVPRVSRENRGMYQCVVR 403
Cdd:pfam13927    3 VITVSPSSVTVREGETVTLTCEATGSPPP----TITWYKNGEPISSGSTRSRslsgsnsTLTISNVTRSDAGTYTCVAS 77

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: 54.56 E-value: 7.78e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  522 YIRLIPKVTAVSGETLNLKCPVAGYPIEEIHWERGGRELPDDiRQRVQPD---GSLTISPVQKNsDSGVYTCWARNKQGh 598
Cdd:cd20976     4 FSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYA-ADRSTCEagvGELHIQDVLPE-DHGTYTCLAKNAAG- 80

                          90
                  ....*....|
gi 220902488  599 SARRSGEVTV 608
Cdd:cd20976    81 QVSCSAWVTV 90

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: 54.05 E-value: 1.05e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  247 VQVSQDEGAVLLCVAQGCPSPEYSWFtHNGAGPLPVLSGPRVRLLGPILAIEAVTGEDSGVYKCTAGN-VGGEASAELRL 325
Cdd:cd20970    12 VTAREGENATFMCRAEGSPEPEISWT-RNGNLIIEFNTRYIVRENGTTLTIRNIRRSDMGIYLCIASNgVPGSVEKRITL 90


                  ..
gi 220902488  326 TV 327
Cdd:cd20970    91 QV 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: 53.95 E-value: 1.08e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  423 PVLLYSFIEQTLQPGPAVSLKCSAAGNPTPQISWTLDGFPL-PSNGRFMIGQYITVHGDVISHVNishvmVEDGGEYACI 501
Cdd:cd20990     1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIrPDSAHKMLVRENGVHSLIIEPVT-----SRDAGIYTCI 75


                  ....*..
gi 220902488  502 AENRAGR 508
Cdd:cd20990    76 ATNRAGQ 82

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: 54.19 E-value: 1.10e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  431 EQTLQPGPAVSLKCSAAGNPTPQISWTLDGF--------PLPSNGRFMIGQyitvHGDvishVNISHVMVEDGGEYACIA 502
Cdd:cd05726     8 DQVVALGRTVTFQCETKGNPQPAIFWQKEGSqnllfpyqPPQPSSRFSVSP----TGD----LTITNVQRSDVGYYICQA 79

                          90
                  ....*....|....*..
gi 220902488  503 ENRAGRVQHAARLNIYG 519
Cdd:cd05726    80 LNVAGSILAKAQLEVTD 96

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: 53.49 E-value: 1.13e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 220902488  725 IMLHCQAQGVPTPSIVWKKATGSKSGEYEEVRERpftkLLGNGSLLLQHVKEDREGFYLCQANNGIGTGIGKVI 798
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRS----ELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

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: 53.99 E-value: 1.14e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  433 TLQPGPAVSLKCSAAGNPTPQISWTLDGFPL---PSNGRfmigqyITVHGDVISHVNISHvmvEDGGEYACIAENRAGRV 509
Cdd:cd04978    10 VLSPGETGELICEAEGNPQPTITWRLNGVPIepaPEDMR------RTVDGRTLIFSNLQP---NDTAVYQCNASNVHGYL 80


                  ....*...
gi 220902488  510 QHAARLNI 517
Cdd:cd04978    81 LANAFLHV 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: 53.62 E-value: 1.30e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 220902488  719 VERNRHIMLHCQAQGVPTPSIVWKKATgsksgeyEEVRERPFTKLLGNGSLLLQHVKEDREGFYLCQANNGIGTG 793
Cdd:cd04969    14 AAKGGDVIIECKPKASPKPTISWSKGT-------ELLTNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKA 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: 53.10 E-value: 1.50e-08

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 220902488 1331 VTLPCTAVGKPKRE--WFKSDVALRQGGLHNSQL-LDSGDLIISSLQLADGGNYSCQVDNGIGT 1391
Cdd:cd00096     1 VTLTCSASGNPPPTitWYKNGKPLPPSSRDSRRSeLGNGTLTISNVTLEDSGTYTCVASNSAGG 64

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 52.95 E-value: 1.68e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 220902488  1315 RIISFGGPVVRPWRSTVTLPCTAVG--KPKREWFKSDVALRQG-GLHNSQLLDSGDLIISSLQLADGGNYSCQVDN 1387
Cdd:pfam13927    3 VITVSPSSVTVREGETVTLTCEATGspPPTITWYKNGEPISSGsTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 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: 53.27 E-value: 1.76e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  245 AHVQVSQDEGAVLLCVAQGCPSPEYSWFthNGAGPLPVlSGPRVRLL-GPILAIEAVTGEDSGVYKCTAGNVGGEASAEL 323
Cdd:cd20952     7 QNQTVAVGGTVVLNCQATGEPVPTISWL--KDGVPLLG-KDERITTLeNGSLQIKGAEKSDTGEYTCVALNLSGEATWSA 83


                  ....
gi 220902488  324 RLTV 327
Cdd:cd20952    84 VLDV 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: 53.72 E-value: 1.79e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  530 TAVSGETLNLKCPVAGYPIEEIHWERGGRELPDDIRQR----VQPDG----SLTISPVQKNsDSGVYTCWARNKQG---H 598
Cdd:cd20956    12 TLQPGPSVSLKCVASGNPLPQITWTLDGFPIPESPRFRvgdyVTSDGdvvsYVNISSVRVE-DGGEYTCTATNDVGsvsH 90


                  ...
gi 220902488  599 SAR 601
Cdd:cd20956    91 SAR 93

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 53.03 E-value: 2.27e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 220902488  1329 STVTLPCTAVGKPKRE--WFKSDVALRQGGLHnsQLLDSGD---LIISSLQLADGGNYSCQVDNGIGTDrlTHTLIVQV 1402
Cdd:pfam07679   16 ESARFTCTVTGTPDPEvsWFKDGQPLRSSDRF--KVTYEGGtytLTISNVQPDDSGKYTCVATNSAGEA--EASAELTV 90

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: 53.03 E-value: 2.47e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 220902488  432 QTLQPGPAVSLKCSAAGNPTPQISWTLDGFPLPSNgrfmIGQYITVHGDViSHVNISHVMVEDGGEYACIAENRAG 507
Cdd:cd05736    10 QAKEPGVEASLRCHAEGIPLPRVQWLKNGMDINPK----LSKQLTLIANG-SELHISNVRYEDTGAYTCIAKNEGG 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: 52.97 E-value: 2.64e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 220902488   622 LQLNMGDRASLTCSVVKGDLPLTINWRKDGRPIDPTQHMSVKQVDQYNSILVIENLGSDHTGNYSCVVRNS 692
Cdd:pfam00047    6 VTVLEGDSATLTCSASTGSPGPDVTWSKEGGTLIESLKVKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNP 76

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: 52.90 E-value: 2.70e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  529 VTAVSGETLNLKCPVAGYPIEEIHWER-GGRELPDDIRQRVQPDGS-LTISPVQkNSDSGVYTCWARNKQGHSARRSGEV 606
Cdd:cd20970    12 VTAREGENATFMCRAEGSPEPEISWTRnGNLIIEFNTRYIVRENGTtLTIRNIR-RSDMGIYLCIASNGVPGSVEKRITL 90


                  ..
gi 220902488  607 TV 608
Cdd:cd20970    91 QV 92

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: 52.33 E-value: 2.86e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  823 ALLQCAVSGDKPINIVWMRSGKNTLNpstnykiSVKQEATPDGVSAELQIRTVDATDSGPYFCRASNLYG 892
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPP-------SSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAG 63

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 52.64 E-value: 3.39e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   332 QVEISPNVLSVHMGGTAEFRCLVTSNGSPVgmqnILWYKDGRQLPSSGRV-------EDTLVVPRVSRENRGMYQCVVRR 404
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTGTPDPE----VSWFKDGQPLRSSDRFkvtyeggTYTLTISNVQPDDSGKYTCVATN 77

                           90
                   ....*....|....
gi 220902488   405 PEGdtfQATAELQL 418
Cdd:pfam07679   78 SAG---EAEASAEL 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: 52.59 E-value: 3.62e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  422 PPVLLYSFIEQTLQPGPAVSLKCSAAGNPTPQISWTLDGFPLPSNGRFMIGQyitvHGDVISHVnISHVMVEDGGEYACI 501
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQ----EGDLHSLI-IAEAFEEDTGRYSCL 75

                          90
                  ....*....|....*.
gi 220902488  502 AENRAGRVQHAARLNI 517
Cdd:cd20972    76 ATNSVGSDTTSAEIFV 91

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: 52.03 E-value: 4.64e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 220902488  256 VLLCVAQGCPSPEYSWFTHNGagPLPVlSGPRVRLLGPILAIEAVTGEDSGVYKCTAGNVGGEASAELRLTV 327
Cdd:cd05731    14 LLECIAEGLPTPDIRWIKLGG--ELPK-GRTKFENFNKTLKIENVSEADSGEYQCTASNTMGSARHTISVTV 82

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 51.63 E-value: 5.27e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   332 QVEISPNVLSVHMGGTAEFRCLVTSNGSPvgmqNILWYKDGRQLPSSGRvedtLVVPRVSRENRGMYQCVVRRPEGDTFQ 411
Cdd:pfam13895    1 KPVLTPSPTVVTEGEPVTLTCSAPGNPPP----SYTWYKDGSAISSSPN----FFTLSVSAEDSGTYTCVARNGRGGKVS 72


                   ....*.
gi 220902488   412 ATAELQ 417
Cdd:pfam13895   73 NPVELT 78

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: 51.64 E-value: 6.73e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  529 VTAVSGETLNLKCPVAGYPIEEIHWERGGRELPDDIRQRVQPDGSLTISPVQKnSDSGVYTCWARNKQGhSARrsGEVTV 608
Cdd:cd05731     5 TMVLRGGVLLLECIAEGLPTPDIRWIKLGGELPKGRTKFENFNKTLKIENVSE-ADSGEYQCTASNTMG-SAR--HTISV 80


                  ..
gi 220902488  609 IV 610
Cdd:cd05731    81 TV 82

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 57.32 E-value: 7.19e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488 1402 VPPTAPV-LYVTSATSSSILMHWKCgfTGNAPITGYTLfYRRANGNTDEMQLSR-HASSHELKGLMCGSTYQIHLSAQNK 1479
Cdd:COG3401   231 TPPSAPTgLTATADTPGSVTLSWDP--VTESDATGYRV-YRSNSGDGPFTKVATvTTTSYTDTGLTNGTTYYYRVTAVDA 307

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488 1480 VGT-SPTSTILHVRTQGQSPGHPASTALLAPNSTSllVRLhSW--PDNGCPLLYFVlqYRAVTddPDAEWVLVSNALKpQ 1556
Cdd:COG3401   308 AGNeSAPSNVVSVTTDLTPPAAPSGLTATAVGSSS--ITL-SWtaSSDADVTGYNV--YRSTS--GGGTYTKIAETVT-T 379

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 220902488 1557 RRIVINNLQPSTLYQLRMEAHNVAGISQAEFNFVTLTKDGDPPPP 1601
Cdd:COG3401   380 TSYTDTGLTPGTTYYYKVTAVDAAGNESAPSEEVSATTASAASGE 424

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: 51.35 E-value: 7.84e-08

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488    337 PNVLSVHMGGTAEFRCLVTSNGSPvgmqNILWYKDGRQ-LPSSGRVE-------DTLVVPRVSRENRGMYQCVVRRPEGD 408
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPP----EVTWYKQGGKlLAESGRFSvsrsgstSTLTISNVTPEDSGTYTCAATNSSGS 76


                    ....*....
gi 220902488    409 TFqATAELQ 417
Cdd:smart00410   77 AS-SGTTLT 84

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: 51.24 E-value: 8.34e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  432 QTLQPGPAVSLKCSAAGNPTPQISWTLDGFPLPsNGRFMIGQYITvhgdvishVNISHVMVEDGGEYACIAENRAGRVQH 511
Cdd:cd05725     7 QVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELP-KGRYEILDDHS--------LKIRKVTAGDMGSYTCVAENMVGKIEA 77


                  ....
gi 220902488  512 AARL 515
Cdd:cd05725    78 SATL 81

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: 51.71 E-value: 8.59e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  529 VTAVSGETLNLKCPVAGYPIEEIHWERGGRELPDDIRQRVQ--PDGSLTISPVQK----NSDSGVYTCWARNKQ-GHSAR 601
Cdd:cd05722    11 IVAMRGGPVVLNCSAESDPPPKIEWKKDGVLLNLVSDERRQqlPNGSLLITSVVHskhnKPDEGFYQCVAQNESlGSIVS 90


                  ....*..
gi 220902488  602 RSGEVTV 608
Cdd:cd05722    91 RTARVTV 97

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: 51.05 E-value: 9.36e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  529 VTAVSGETLNLKCPVAGYPIEEIHWERGGRELPDDIRQRVQP---DGSLTISPVQKnSDSGVYTCWARNKQGhsaRRSGE 605
Cdd:cd05748     2 IVVRAGESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQIETtasSTSLVIKNAKR-SDSGKYTLTLKNSAG---EKSAT 77


                  ....*
gi 220902488  606 VTVIV 610
Cdd:cd05748    78 INVKV 82

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: 51.03 E-value: 1.11e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 220902488  345 GGTAEFRCLVTsnGSPVgmQNILWYKDGRQLPSSGRVE----DTLVVPRVSR-ENRGMYQCVVRRPEGDTFQATAELQ 417
Cdd:cd20958    15 GQTLRLHCPVA--GYPI--SSITWEKDGRRLPLNHRQRvfpnGTLVIENVQRsSDEGEYTCTARNQQGQSASRSVFVK 88

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: 51.08 E-value: 1.18e-07

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   1008 GPPLSLSARPLSSTELLISWVAPLPELRHGDIQGYNVGYKLSSSGNTAYNFTSVSgdgdggnGELLLSGLAKFARYTVVV 1087
Cdd:smart00060    2 SPPSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYREEGSEWKEVNVTPSS-------TSYTLTGLKPGTEYEFRV 74


                    ....*....
gi 220902488   1088 QAFNQVGPG 1096
Cdd:smart00060   75 RAVNGAGEG 83

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: 51.34 E-value: 1.18e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 220902488 1510 NSTSLLVRLHSWPDNGCPLLYFVLQYRAVTDDpdaEWVLVSNALKPQRRIVINNLQPSTLYQLRMEAHNVAGIS 1583
Cdd:cd00063    13 TSTSVTLSWTPPEDDGGPITGYVVEYREKGSG---DWKEVEVTPGSETSYTLTGLKPGTEYEFRVRAVNGGGES 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: 50.86 E-value: 1.22e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 220902488  252 DEGAVLLCVAQGCPSPEYSWFTHNGAGPLPvlsgpRVRLLGP-ILAIEAVTGEDSGVYKCTAGNVGGEASAELRLTV 327
Cdd:cd05725    12 DDSAEFQCEVGGDPVPTVRWRKEDGELPKG-----RYEILDDhSLKIRKVTAGDMGSYTCVAENMVGKIEASATLTV 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: 50.71 E-value: 1.23e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  437 GPAVSLKCSAAGNPTPQISWTLDGFPLPSNGRFMIGQYITVHgdvishvnISHVMVEDGGEYACIAENRAGRVQHAARLN 516
Cdd:cd05745     2 GQTVDFLCEAQGYPQPVIAWTKGGSQLSVDRRHLVLSSGTLR--------ISRVALHDQGQYECQAVNIVGSQRTVAQLT 73


                  .
gi 220902488  517 I 517
Cdd:cd05745    74 V 74

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: 51.40 E-value: 1.36e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  708 PRWIVEPVDANVERNRHIMLHCQAQGVPTPSIVWKKATGSKSGEYEEVRERPFtkLLGNGSLLLQHVKEDR-----EGFY 782
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDKDDPRSHRI--VLPSGSLFFLRVVHGRkgrsdEGVY 78

                          90       100
                  ....*....|....*....|
gi 220902488  783 LCQANNGIGTGIGKVIQLKV 802
Cdd:cd07693    79 VCVAHNSLGEAVSRNASLEV 98

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: 50.65 E-value: 1.41e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  523 IRLIPKVTAVSGETLNLKCPVAGYPIEEIHWERGGRELPDDIRQRVQPDG----SLTISPVQkNSDSGVYTCWARNKQGH 598
Cdd:cd20973     1 IQTLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEdglcSLIISDVC-GDDSGKYTCKAVNSLGE 79

                          90
                  ....*....|
gi 220902488  599 sARRSGEVTV 608
Cdd:cd20973    80 -ATCSAELTV 88

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: 50.86 E-value: 1.45e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  247 VQVSQDEGAVLLCVA-QGCPSPEYSWfTHNGAgPLpVLSGPRVRLL-GPILAIEAVTGEDSGVYKCTAGNVGGE-ASAEL 323
Cdd:cd05724     7 TQVAVGEMAVLECSPpRGHPEPTVSW-RKDGQ-PL-NLDNERVRIVdDGNLLIAEARKSDEGTYKCVATNMVGErESRAA 83


                  ....
gi 220902488  324 RLTV 327
Cdd:cd05724    84 RLSV 87

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: 50.88 E-value: 1.68e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  423 PVLLYSFIEQTLQPGPAVSLKCSAAGNPTPQISWTLDGFPLpsNGRFMIGQYITVHGDVISHVNISHVMVEDGGEYACIA 502
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPI--DPSSIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVA 78

                          90
                  ....*....|....*
gi 220902488  503 ENRAGRVQHAARLNI 517
Cdd:cd20951    79 KNIHGEASSSASVVV 93

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: 50.32 E-value: 1.70e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 220902488  534 GETLNLKCPVAGYPIEEIHWERGGRELPDDIRQRVQPDGSLTISPVQKNsDSGVYTCWARNKQGhSARRSGEVTV 608
Cdd:cd05745     2 GQTVDFLCEAQGYPQPVIAWTKGGSQLSVDRRHLVLSSGTLRISRVALH-DQGQYECQAVNIVG-SQRTVAQLTV 74

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: 50.61 E-value: 1.70e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  613 KLSPfqtNILQLNMGDRASLTCSVvKGDLPLTINWRKDGRPIDPTQHMSVKQVDqynsILVIENLGSDHTGNYSCVVRNs 692
Cdd:cd20957     5 TIDP---PVQTVDFGRTAVFNCSV-TGNPIHTVLWMKDGKPLGHSSRVQILSED----VLVIPSVKREDKGMYQCFVRN- 75


                  ....*....
gi 220902488  693 aaEVENSQA 701
Cdd:cd20957    76 --DGDSAQA 82

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: 50.09 E-value: 2.50e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  437 GPAVSLKCSAA-GNPTPQISWTLDGFPLPSNGrfmIGQYITVHGDVIshvnISHVMVEDGGEYACIAENRAG-RVQHAAR 514
Cdd:cd05724    12 GEMAVLECSPPrGHPEPTVSWRKDGQPLNLDN---ERVRIVDDGNLL----IAEARKSDEGTYKCVATNMVGeRESRAAR 84


                  ...
gi 220902488  515 LNI 517
Cdd:cd05724    85 LSV 87

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: 50.11 E-value: 2.56e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  238 PSVVEHTAHVQVSQDEGAVLLCVAQGCPSPEYSWFtHNGAgPLPVLSGPRVRLLGP-----ILAIEAVTGEDSGVYKCTA 312
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWY-KNGV-PIDPSSIPGKYKIESeygvhVLHIRRVTVEDSAVYSAVA 78

                          90
                  ....*....|....*
gi 220902488  313 GNVGGEASAELRLTV 327
Cdd:cd20951    79 KNIHGEASSSASVVV 93

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: 49.64 E-value: 2.61e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 220902488  348 AEFRCLVTSNGSPvgmqNILWYKDGRQLPSSGRVED-------TLVVPRVSRENRGMYQCVVRRPEGDTFQATA 414
Cdd:cd00096     1 VTLTCSASGNPPP----TITWYKNGKPLPPSSRDSRrselgngTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

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: 49.81 E-value: 2.71e-07

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 220902488   1329 STVTLPCTAVGKPKRE--WFKSDVAL--RQGGLHNSQLLDSGDLIISSLQLADGGNYSCQVDNGIGTDRLTHTLIV 1400
Cdd:smart00410   10 ESVTLSCEASGSPPPEvtWYKQGGKLlaESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTLTV 85

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: 49.91 E-value: 2.94e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 220902488  259 CVAQGCPSPEYSWFtHNGAgPLPvlSGPRVRLLGPILAIEAVTGEDSGVYKCTAGNVGGE--ASAELRL 325
Cdd:cd05728    21 CKASGNPRPAYRWL-KNGQ-PLA--SENRIEVEAGDLRITKLSLSDSGMYQCVAENKHGTiyASAELAV 85

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: 49.93 E-value: 3.23e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  246 HVQVSQDEGAVLLCVAQGCPSPEYSWfTHNGAGPLPVLSGPRVRLL--GPILAIEAVTGEDSGVYKCTAGNVGGEASAEL 323
Cdd:cd05763     8 DITIRAGSTARLECAATGHPTPQIAW-QKDGGTDFPAARERRMHVMpeDDVFFIVDVKIEDTGVYSCTAQNSAGSISANA 86


                  ....
gi 220902488  324 RLTV 327
Cdd:cd05763    87 TLTV 90

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: 49.84 E-value: 3.43e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  245 AHVQVSQDEGAVLLCVAQGCPSPEYSWFtHNGAgplPVLSGPRVRLLG-PILAIEAVTGEDSGVYKCTAGNVG--GEASA 321
Cdd:cd20957     9 PVQTVDFGRTAVFNCSVTGNPIHTVLWM-KDGK---PLGHSSRVQILSeDVLVIPSVKREDKGMYQCFVRNDGdsAQATA 84


                  ....
gi 220902488  322 ELRL 325
Cdd:cd20957    85 ELKL 88

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: 49.42 E-value: 4.45e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 220902488  530 TAVSGETLNLKCPVAGYPIEEIHWERGGRELPDDIRQR--VQPDG--SLTISPVQKnSDSGVYTCWARNKQGHSA 600
Cdd:cd05744    11 EVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKmlVRENGrhSLIIEPVTK-RDAGIYTCIARNRAGENS 84

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: 49.66 E-value: 4.51e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 220902488  433 TLQPGPAVSLKCSAAGNPTPQISWTLDGFPLPSNGRFMI--GQYitvhgdvISHVNISHVMVEDGGEYACIAENRAGR 508
Cdd:cd05747    14 TVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQItsTEY-------KSTFEISKVQMSDEGNYTVVVENSEGK 84

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: 48.93 E-value: 4.89e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  713 EPVDANVERNRHIMLHCQAQGVPTPSIVWKKATGS-KSGEYEevrerpftkLLGNGSLLLQHVKEDREGFYLCQANNGIG 791
Cdd:cd05725     3 RPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGElPKGRYE---------ILDDHSLKIRKVTAGDMGSYTCVAENMVG 73


                  .
gi 220902488  792 T 792
Cdd:cd05725    74 K 74

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: 49.16 E-value: 5.83e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 220902488 1329 STVTLPCTAVGKPKRE--WFKSDVALRQgglhNSQL--LDSGDLIISSLQLADGGNYSCQVDNGIGT 1391
Cdd:cd20968    15 LKAVLPCTTMGNPKPSvsWIKGDDLIKE----NNRIavLESGSLRIHNVQKEDAGQYRCVAKNSLGI 77

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: 49.11 E-value: 6.23e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 220902488  627 GDRASLTCsVVKGDLPLTINWRKDGRPIDPTQHMSVKQVDQYNSILVIENLGSDHTGNYSCVVRNSAAEVENSQALLV 704
Cdd:cd20973    12 GSAARFDC-KVEGYPDPEVKWMKDDNPIVESRRFQIDQDEDGLCSLIISDVCGDDSGKYTCKAVNSLGEATCSAELTV 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: 49.00 E-value: 6.66e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  521 PYIRLIPkvTAVSGETLnLKCPVAGYPIEEIHWERGGRELPDDIRQRVQPDGSLTISPVQKnSDSGVYTCWARNKQGhSA 600
Cdd:cd04969     7 PVKKKIL--AAKGGDVI-IECKPKASPKPTISWSKGTELLTNSSRICILPDGSLKIKNVTK-SDEGKYTCFAVNFFG-KA 81


                  ....*...
gi 220902488  601 RRSGEVTV 608
Cdd:cd04969    82 NSTGSLSV 89

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: 48.94 E-value: 6.71e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  712 VEPVDANVERNRHIMLHCQA-QGVPTPSIVWKKaTGSksgEYEEVRERpfTKLLGNGSLLLQHVKEDREGFYLCQANNGI 790
Cdd:cd05724     2 VEPSDTQVAVGEMAVLECSPpRGHPEPTVSWRK-DGQ---PLNLDNER--VRIVDDGNLLIAEARKSDEGTYKCVATNMV 75

                          90
                  ....*....|..
gi 220902488  791 GTGIGKVIQLKV 802
Cdd:cd05724    76 GERESRAARLSV 87

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: 6.92e-07

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   1403 PPTAPVLYVTSATSSSILMHWKCGFTGNA--PITGYTLFYRRANGNTDEMQLSRHASSHELKGLMCGSTYQIHLSAQNKV 1480
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGItgYIVGYRVEYREEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNGA 80


                    ...
gi 220902488   1481 GTS 1483
Cdd:smart00060   81 GEG 83

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: 49.06 E-value: 7.86e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 220902488  722 NRHIMLHCQAQGVPTPSIVWKKATGSKSGEYE------EVRERpftklLGNGSLLLQHVKEDREGFYLCQANNGIG 791
Cdd:cd05732    16 LEQITLTCEAEGDPIPEITWRRATRGISFEEGdldgriVVRGH-----ARVSSLTLKDVQLTDAGRYDCEASNRIG 86

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: 48.93 E-value: 8.30e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  815 VMVKKGDTALLQCAVSGDKPINIVWMRSGKNTLNPSTNYKISVkqeaTPDGVsaeLQIRTVDATDSGPYFCRASNLYGND 894
Cdd:cd20969    12 VFVDEGHTVQFVCRADGDPPPAILWLSPRKHLVSAKSNGRLTV----FPDGT---LEVRYAQVQDNGTYLCIAANAGGND 84

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: 48.37 E-value: 8.40e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 220902488  437 GPAVSLKCSAAGNPTPQISWTLDGFPLPSNGrfmigqyiTVHGDVISHVNISHVMVEDGGEYACIAENRAGRVQHA 512
Cdd:cd05876    10 GQSLVLECIAEGLPTPTVKWLRPSGPLPPDR--------VKYQNHNKTLQLLNVGESDDGEYVCLAENSLGSARHA 77

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: 48.37 E-value: 8.48e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 220902488  531 AVSGETLNLKCPVAGYPIEEIHWERGGRELPDDIRQRVQPDGSLTISPVQKnSDSGVYTCWARNKQGhSARRSGEVTV 608
Cdd:cd05876     7 ALRGQSLVLECIAEGLPTPTVKWLRPSGPLPPDRVKYQNHNKTLQLLNVGE-SDDGEYVCLAENSLG-SARHAYYVTV 82

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: 1.00e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 220902488   51 LDCSASGSPQPTVDWVHADGS-AVTEIHGVRRVLRNGTLVLMPFaaaayhQDVHNTIYRCIASNSVGRIVSRDV 123
Cdd:cd00096     3 LTCSASGNPPPTITWYKNGKPlPPSSRDSRRSELGNGTLTISNV------TLEDSGTYTCVASNSAGGSASASV 70

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: 48.46 E-value: 1.04e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   31 PGFVMEPpgrvEFSNSSGG---WLDCSASGSPQPTVDWVHADGSAVTEIHGVR-----RVLRNGTLVLMPFaaaayhQDV 102
Cdd:cd20954     2 PRWIVEP----VDANVAAGqdvMLHCQADGFPTPTVTWKKATGSTPGEYKDLLydpnvRILPNGTLVFGHV------QKE 71

                          90       100
                  ....*....|....*....|...
gi 220902488  103 HNTIYRCIASNSVGRIVSRDVQV 125
Cdd:cd20954    72 NEGHYLCEAKNGIGSGLSKVIFL 94

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: 48.41 E-value: 1.13e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  521 PYIRLIPKVTAVS-GETLNLKCPVAGYPIEEIHWERGGRELPDDIRQR--VQPDGS-LTISPVqKNSDSGVYTCWARNKQ 596
Cdd:cd05736     1 PVIRVYPEFQAKEpGVEASLRCHAEGIPLPRVQWLKNGMDINPKLSKQltLIANGSeLHISNV-RYEDTGAYTCIAKNEG 79


                  .
gi 220902488  597 G 597
Cdd:cd05736    80 G 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: 48.38 E-value: 1.23e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 220902488  526 IPK-VTAVSGETLNLKCPVAGYPIEEIHWER-GGRELPDdIRQR---VQP-DGSLTISPVqKNSDSGVYTCWARNKQG 597
Cdd:cd05763     5 TPHdITIRAGSTARLECAATGHPTPQIAWQKdGGTDFPA-ARERrmhVMPeDDVFFIVDV-KIEDTGVYSCTAQNSAG 80

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: 48.27 E-value: 1.30e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  809 SSTSRSVMVKKGDTALLQCAVSGDKPINIVWMRSGKNTLNPSTNYkiSVKQEATpdgvsaELQIRTVDATDSGPYFCRAS 888
Cdd:cd20970     6 PQPSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRY--IVRENGT------TLTIRNIRRSDMGIYLCIAS 77


                  .
gi 220902488  889 N 889
Cdd:cd20970    78 N 78

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: 48.21 E-value: 1.32e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  249 VSQDEGAVLLCVAQGCPSPEYSWFThNGAgPLPVLSGPRVRLL-GPILAIEAVTGEDSGVYKCTAGNVGGEASAELRLTV 327
Cdd:cd04978    11 LSPGETGELICEAEGNPQPTITWRL-NGV-PIEPAPEDMRRTVdGRTLIFSNLQPNDTAVYQCNASNVHGYLLANAFLHV 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: 48.02 E-value: 1.42e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 220902488  256 VLLCVAQGCPSPEYSWFTHngAGPLPVlSGPRVR---LLGpILAIEAVTGEDSGVYKCTAGNVGGEASAELRLTV 327
Cdd:cd20976    20 VAQCSARGKPVPRITWIRN--AQPLQY-AADRSTceaGVG-ELHIQDVLPEDHGTYTCLAKNAAGQVSCSAWVTV 90

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: 48.29 E-value: 1.47e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  432 QTLQPGPAVSLKCSAAGNPTPQISW--TLDGFplpSNGRFMIGQYITVHGDV-ISHVNISHVMVEDGGEYACIAENRAGR 508
Cdd:cd05732    11 QTAVELEQITLTCEAEGDPIPEITWrrATRGI---SFEEGDLDGRIVVRGHArVSSLTLKDVQLTDAGRYDCEASNRIGG 87


                  ....*....
gi 220902488  509 VQHAARLNI 517
Cdd:cd05732    88 DQQSMYLEV 96

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: 48.02 E-value: 1.65e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   30 GPGFVMEPPGRVeFSNSSGG---WLDCSASGSPQPTVDWVHaDGSAVTEIHGVRRVLRNGTLVLM-PFAAAAYHQdvhnt 105
Cdd:cd05848     1 GPVFVQEPDDAI-FPTDSDEkkvILNCEARGNPVPTYRWLR-NGTEIDTESDYRYSLIDGNLIISnPSEVKDSGR----- 73

                          90       100
                  ....*....|....*....|....*...
gi 220902488  106 iYRCIASNSVGRIVSRDvqvrAVVAQAY 133
Cdd:cd05848    74 -YQCLATNSIGSILSRE----ALLQFAY 96

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: 47.86 E-value: 1.66e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  524 RLIPKVTAVSGETLNLKCPVAGYPIEEIHW-ERGGRELPDDIRQRVQPDGSLTISpVQKNSDSGVYTCWARNKQGHSARR 602
Cdd:cd05764     5 RHTHELRVLEGQRATLRCKARGDPEPAIHWiSPEGKLISNSSRTLVYDNGTLDIL-ITTVKDTGAFTCIASNPAGEATAR 83

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: 47.87 E-value: 1.84e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  809 SSTSRSVMVKKGDTALLQCAVSGDKPINIVWMRsGKNTLNPSTNYKISVKQEATPDGVSAELQIRTVDATDSGPYFCRAS 888
Cdd:cd05735     7 TSYPNTTLATKGQKKEMSCTAHGEKPIIVRWEK-EDTIINPSEMSRYLVTTKEVGDEVISTLQILPTVREDSGFFSCHAI 85

                          90
                  ....*....|....*.
gi 220902488  889 NLYGNDQQLVQLQVQE 904
Cdd:cd05735    86 NSYGEDRGIIQLTVQE 101

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: 47.21 E-value: 2.18e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 220902488  344 MGGTAEFRCLVTSNGSPvgmqNILWYKDGRQLPSSGRVE---DTLVVPRVSRENRGMYQCVVRRPEGdTFQATAELQL 418
Cdd:cd05728    13 IGSSLRWECKASGNPRP----AYRWLKNGQPLASENRIEveaGDLRITKLSLSDSGMYQCVAENKHG-TIYASAELAV 85

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: 47.54 E-value: 2.19e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 220902488  257 LLCVAQGCPSPEYSW--FTHNGAGPLPVLSGPRVRLLGPILAIEAVTGEDSGVYKCTAGN-VGGEaSAELRLTV 327
Cdd:cd20953    23 LLCPAQGYPAPSFRWykFIEGTTRKQAVVLNDRVKQVSGTLIIKDAVVEDSGKYLCVVNNsVGGE-SVETVLTV 95

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: 47.39 E-value: 2.28e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  247 VQVSQDEGAVLLCVAQGCPSPEYSWFtHNGAgplpVLSGPRVRLL--GPILAIEAVTGEDSGVYKCTAGNVGGEASAELR 324
Cdd:cd20978    11 VVVKGGQDVTLPCQVTGVPQPKITWL-HNGK----PLQGPMERATveDGTLTIINVQPEDTGYYGCVATNEIGDIYTETL 85


                  ...
gi 220902488  325 LTV 327
Cdd:cd20978    86 LHV 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: 47.20 E-value: 2.66e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 220902488  534 GETLNLKCPVAGYPIEEIHWERGG---RELPDDIRQRVQpDGSLTISPVQKnSDSGVYTCWARNKQG 597
Cdd:cd05867    14 GETARLDCQVEGIPTPNITWSINGapiEGTDPDPRRHVS-SGALILTDVQP-SDTAVYQCEARNRHG 78

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: 47.00 E-value: 3.16e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  248 QVSQDEG--AVLLCVAQGCPSPEYSWFtHNGAGPLPVLSGPRVRLL-GPILAIEAVTGEDSGVYKCTAGNVGGEASAELR 324
Cdd:cd20969    11 QVFVDEGhtVQFVCRADGDPPPAILWL-SPRKHLVSAKSNGRLTVFpDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAH 89


                  ...
gi 220902488  325 LTV 327
Cdd:cd20969    90 LHV 92

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: 47.16 E-value: 3.22e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  521 PYIRLIPKVTAVS-GETLNLKCPVAGYPIEEIHWERGGREL---PDDIRQR--VQPDGSLTISPV----QKNSDSGVYTC 590
Cdd:cd07693     1 PRIVEHPSDLIVSkGDPATLNCKAEGRPTPTIQWLKNGQPLetdKDDPRSHriVLPSGSLFFLRVvhgrKGRSDEGVYVC 80

                          90
                  ....*....|....*...
gi 220902488  591 WARNKQGHSARRSGEVTV 608
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: 47.12 E-value: 3.29e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  714 PVDANVERNRHIMLHCQAQGVPTPSIVWKKatgsKSGEYEEVRERpfTKLLGNGSLL-LQHVKEDREGFYLCQANNGIGT 792
Cdd:cd20970     9 SFTVTAREGENATFMCRAEGSPEPEISWTR----NGNLIIEFNTR--YIVRENGTTLtIRNIRRSDMGIYLCIASNGVPG 82

                          90
                  ....*....|
gi 220902488  793 GIGKVIQLKV 802
Cdd:cd20970    83 SVEKRITLQV 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: 47.12 E-value: 3.62e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  432 QTLQPGPAVSLKCSAAG-NPTPQISWTLDGFPL----PSNGRFMIGQYItvhgdviSHVNISHVMVEDGGEYACIAENRA 506
Cdd:cd05750     9 QTVQEGSKLVLKCEATSeNPSPRYRWFKDGKELnrkrPKNIKIRNKKKN-------SELQINKAKLEDSGEYTCVVENIL 81

                          90
                  ....*....|.
gi 220902488  507 GRVQHAARLNI 517
Cdd:cd05750    82 GKDTVTGNVTV 92

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: 46.81 E-value: 3.87e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 220902488  440 VSLKCSAAGNPTPQISWTLDG-FPLPSNgrfmigqYITVHGDviSHVNISHVMVEDGGEYACIAENRAGRVQHAARLNI 517
Cdd:cd05723    15 IVFECEVTGKPTPTVKWVKNGdVVIPSD-------YFKIVKE--HNLQVLGLVKSDEGFYQCIAENDVGNAQASAQLII 84

Sixth immunoglobulin (Ig) domain of contactin-2; The members here are composed of the sixth 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 (AC) in the developing chick retina, corresponding to the period of formation and maturation of AC processes.

Pssm-ID: 409440 Cd Length: 102 Bit Score: 46.96 E-value: 4.60e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  614 LSPFQTNIlqlNMGDRASLTCSVVKG-DLPLTINWRKDGRPID---PTQHMSVKQVDQYNSILVIENLGSDHTGNYSCVV 689
Cdd:cd05854     7 LAPSSADI---NQGENLTLQCHASHDpTMDLTFTWSLDDFPIDldkPNGHYRRMEVKETIGDLVIVNAQLSHAGTYTCTA 83

                          90
                  ....*....|....*....
gi 220902488  690 RNSAAEVENSQALLVNVPP 708
Cdd:cd05854    84 QTVVDSASASATLVVRGPP 102

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: 46.73 E-value: 4.67e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  437 GPAVSLKCSAAGNPTPQISWTLDG-FPLPSNGRFMI---GQYITVHgDVISHvnishvmveDGGEYACIAENRA-GRVQH 511
Cdd:cd20970    17 GENATFMCRAEGSPEPEISWTRNGnLIIEFNTRYIVrenGTTLTIR-NIRRS---------DMGIYLCIASNGVpGSVEK 86


                  ....*.
gi 220902488  512 AARLNI 517
Cdd:cd20970    87 RITLQV 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: 46.85 E-value: 4.83e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 220902488  252 DEGAVLLCVAQGCPSPEYSWfTHNGAgplPVLSGPRVRLL---GPILAIEAVTGEDSGVYKCTAGNVGGEASAELRLTV 327
Cdd:cd05730    18 GQSVTLACDADGFPEPTMTW-TKDGE---PIESGEEKYSFnedGSEMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKV 92

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 46.23 E-value: 4.89e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 220902488  1328 RSTVTLPCTAVGKPKrewfkSDVALRQGGLHNSQlldSGDLIISSLQLADGGNYSCQVDNG-IGTDRLTHTLIV 1400
Cdd:pfam13895   14 GEPVTLTCSAPGNPP-----PSYTWYKDGSAISS---SPNFFTLSVSAEDSGTYTCVARNGrGGKVSNPVELTV 79

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: 46.34 E-value: 5.14e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488    714 PVDANVERNRHIMLHCQAQGVPTPSIVWKKATGSKSGEYEEVRerpFTKLLGNGSLLLQHVKEDREGFYLCQANNGIGTG 793
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFS---VSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSA 77


                    ....*....
gi 220902488    794 IGKViQLKV 802
Cdd:smart00410   78 SSGT-TLTV 85

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: 46.15 E-value: 5.69e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  528 KVTAVSGETLNLKCPVAGYPIEEIHWERGGRELPDDIRQRVQPDGSLTISPVQKNsDSGVYTCWARNKQG 597
Cdd:cd05852    11 KILAAKGGRVIIECKPKAAPKPKFSWSKGTELLVNNSRISIWDDGSLEILNITKL-DEGSYTCFAENNRG 79

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: 46.35 E-value: 5.85e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 220902488   51 LDCSASGSPQPTVDWvHADGSAVTEIHGVRRVLRNGTLVLMPFAaaayhQDVHNTIYRCIASNSVGRIVSR 121
Cdd:cd20970    22 FMCRAEGSPEPEISW-TRNGNLIIEFNTRYIVRENGTTLTIRNI-----RRSDMGIYLCIASNGVPGSVEK 86

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: 45.85 E-value: 6.22e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 220902488  820 GDTALLQCAVSGDKPINIVWMRSGKNTlnPSTNYKIsvkqeaTPDgvsAELQIRTVDATDSGPYFCRASNLYG 892
Cdd:cd05725    12 DDSAEFQCEVGGDPVPTVRWRKEDGEL--PKGRYEI------LDD---HSLKIRKVTAGDMGSYTCVAENMVG 73

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: 46.36 E-value: 6.33e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  521 PYIRLIPKVTAVSGETLNLKCPVAGYPIEEIHWERGGR-----ELPDDIRQRVQPD---GSLTISPVQKnSDSGVYTCWA 592
Cdd:cd05732     3 PKITYLENQTAVELEQITLTCEAEGDPIPEITWRRATRgisfeEGDLDGRIVVRGHarvSSLTLKDVQL-TDAGRYDCEA 81


                  ....*
gi 220902488  593 RNKQG 597
Cdd:cd05732    82 SNRIG 86

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 45.85 E-value: 6.49e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   612 PKLSPFQTNIlqlNMGDRASLTCSVvKGDLPLTINWRKDGRPIDPTQHMSVKQVDqynsilvienlgSDHTGNYSCVVRN 691
Cdd:pfam13895    2 PVLTPSPTVV---TEGEPVTLTCSA-PGNPPPSYTWYKDGSAISSSPNFFTLSVS------------AEDSGTYTCVARN 65


                   ..
gi 220902488   692 SA 693
Cdd:pfam13895   66 GR 67

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: 46.33 E-value: 6.59e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 220902488  259 CVAQGCPSPEYSW------FTHNGAGPLPVLSGPRVRLLgpilaIEAVTGEDSGVYKCTAGNVGGEASAELRLTV 327
Cdd:cd05744    22 CKVSGLPTPDLFWqlngkpVRPDSAHKMLVRENGRHSLI-----IEPVTKRDAGIYTCIARNRAGENSFNAELVV 91

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 45.85 E-value: 6.62e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   521 PYIRLIPKVTAVsGETLNLKCPVAGYPIEEIHWERGGRELPDdiRQRVQpdgSLTISPvqknSDSGVYTCWARNkqGHSA 600
Cdd:pfam13895    2 PVLTPSPTVVTE-GEPVTLTCSAPGNPPPSYTWYKDGSAISS--SPNFF---TLSVSA----EDSGTYTCVARN--GRGG 69

                           90
                   ....*....|
gi 220902488   601 RRSGEVTVIV 610
Cdd:pfam13895   70 KVSNPVELTV 79

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: 46.51 E-value: 6.71e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 220902488  440 VSLKCSAAGNPTPQISWTLDGFPLPSNGRFMIGQYITVHGDVISHVNISHVMVEDGGEYACIAENRAGRVQHAARLNI 517
Cdd:cd05869    20 ITLTCEASGDPIPSITWRTSTRNISSEEKTLDGHIVVRSHARVSSLTLKYIQYTDAGEYLCTASNTIGQDSQSMYLEV 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: 46.32 E-value: 6.77e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 220902488   51 LDCSASGSPQPTVDWvHADGSAVTEIHGVRRV-LRNGTLVLMPFAAAAYHQDvHNTIYRCIASN-SVGRIVSRDVQVRA 127
Cdd:cd05722    21 LNCSAESDPPPKIEW-KKDGVLLNLVSDERRQqLPNGSLLITSVVHSKHNKP-DEGFYQCVAQNeSLGSIVSRTARVTV 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: 45.90 E-value: 8.26e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 220902488  534 GETLNLKCPVAGYPIEEIHWERGGR---ELPDDIRQRVQPDgSLTISPVQKNsDSGVYTCWARNKQG 597
Cdd:cd04978    14 GETGELICEAEGNPQPTITWRLNGVpiePAPEDMRRTVDGR-TLIFSNLQPN-DTAVYQCNASNVHG 78

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: 45.85 E-value: 8.79e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   31 PGFVMEPPGRVEFSNSSGGWLDCSASGSPQPTVDWVHaDGSAVTEIHGvRRVLRNGTLVLMPFaaaayhQDVHNTIYRCI 110
Cdd:cd20978     1 PKFIQKPEKNVVVKGGQDVTLPCQVTGVPQPKITWLH-NGKPLQGPME-RATVEDGTLTIINV------QPEDTGYYGCV 72

                          90
                  ....*....|
gi 220902488  111 ASNSVGRIVS 120
Cdd:cd20978    73 ATNEIGDIYT 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: 45.78 E-value: 8.93e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  233 RGIISPSVVEhtahvqVSQDEGAVLLCVAQGCPSPEYSWftHNGAGPLP--VLSGPRVRLLGPILAIEAVTGEDSGVYKC 310
Cdd:cd20949     1 TFTENAYVTT------VKEGQSATILCEVKGEPQPNVTW--HFNGQPISasVADMSKYRILADGLLINKVTQDDTGEYTC 72

                          90
                  ....*....|....*..
gi 220902488  311 TAGNVGGEASAELRLTV 327
Cdd:cd20949    73 RAYQVNSIASDMQERTV 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: 45.72 E-value: 1.02e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  709 RWIVEPVDANVERNRHIMLHCQAQGVPTPSIVWKKaTGSKSGEYEEVRERPFTKLL--GNGSLLLQHVKEDREGFYLCQA 786
Cdd:cd05726     1 QFVVKPRDQVVALGRTVTFQCETKGNPQPAIFWQK-EGSQNLLFPYQPPQPSSRFSvsPTGDLTITNVQRSDVGYYICQA 79

                          90
                  ....*....|....*.
gi 220902488  787 NNGIGTGIGKViQLKV 802
Cdd:cd05726    80 LNVAGSILAKA-QLEV 94

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: 1.11e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  520 LPYIRL---IPKVTAVSGETLNLKCPVAGYPIEEIHWERGGRELPD-DIRQRVQPDGS-LTISPVQKNsDSGVYTCWARN 594
Cdd:cd05730     1 PPTIRArqsEVNATANLGQSVTLACDADGFPEPTMTWTKDGEPIESgEEKYSFNEDGSeMTILDVDKL-DEAEYTCIAEN 79


                  ....*
gi 220902488  595 KQGHS 599
Cdd:cd05730    80 KAGEQ 84

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: 45.36 E-value: 1.11e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  434 LQPGPAVSLKCSAAGNPTPQISWTLDGFPL------PSNgrfmigqyiTVHGDVISHVNishvmVEDGGE--YACIAENR 505
Cdd:cd05868    11 LSPGEDGTLICRANGNPKPSISWLTNGVPIeiaptdPSR---------KVDGDTIIFSK-----VQERSSavYQCNASNE 76

                          90
                  ....*....|..
gi 220902488  506 AGRVQHAARLNI 517
Cdd:cd05868    77 YGYLLANAFVNV 88

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: 45.70 E-value: 1.16e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  440 VSLKCSAAGNPTPQISWTLDGFPLPSNGRFmigQYITVHGDVISHvNISHvmVEDGGEYACIAENRAGRV 509
Cdd:cd05848    22 VILNCEARGNPVPTYRWLRNGTEIDTESDY---RYSLIDGNLIIS-NPSE--VKDSGRYQCLATNSIGSI 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: 45.18 E-value: 1.30e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  712 VEPVDANVERNRHIMLHCQAQGVPTPSIVWkkatgSKSGEYEEVRERPFTkLLGNGSLLLQHVKEDREGFYLCQANNGIG 791
Cdd:cd20952     4 QGPQNQTVAVGGTVVLNCQATGEPVPTISW-----LKDGVPLLGKDERIT-TLENGSLQIKGAEKSDTGEYTCVALNLSG 77


                  .
gi 220902488  792 T 792
Cdd:cd20952    78 E 78

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: 45.37 E-value: 1.30e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  817 VKKGDTALLQCAVSGDKP-INIVWMRSGK--NTLNPSTNYKISVKQEatpdgvSAELQIRTVDATDSGPYFCRASNLYGN 893
Cdd:cd05895    11 VAAGSKLVLRCETSSEYPsLRFKWFKNGKeiNRKNKPENIKIQKKKK------KSELRINKASLADSGEYMCKVSSKLGN 84


                  .
gi 220902488  894 D 894
Cdd:cd05895    85 D 85

First immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR). 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 all FGFs.

Pssm-ID: 409362 Cd Length: 94 Bit Score: 45.27 E-value: 1.33e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  328 ATPIQVEISPNVLSVHMGGTAEFRCLVTSNgspvgMQNILWYKDGRQLPSSGRVEDT---LVVPRVSRENRGMYQCVVRR 404
Cdd:cd04973     7 APPTYQISEVESYSAHPGDLLQLRCRLRDD-----VQSINWTKDGVQLGENNRTRITgeeVQIKDAVPRDSGLYACVTSS 81


                  ...
gi 220902488  405 PEG 407
Cdd:cd04973    82 PSG 84

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: 44.91 E-value: 1.39e-05

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   1498 PGHPASTALLAPNSTSLLVrlhSW--PDNGCPLLYfVLQYRAVTDDPDAEWVLVSNAlKPQRRIVINNLQPSTLYQLRME 1575
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTL---SWepPPDDGITGY-IVGYRVEYREEGSEWKEVNVT-PSSTSYTLTGLKPGTEYEFRVR 75


                    ....*...
gi 220902488   1576 AHNVAGIS 1583
Cdd:smart00060   76 AVNGAGEG 83

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: 45.62 E-value: 1.41e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  614 LSPFQTNIlqlNMGDRASLTCSVVKGD-LPLTINWRKDGRPID---PTQHMSVKQVDQYNSILVIENLGSDHTGNYSCVV 689
Cdd:cd04970     7 LAPSNADI---TVGENATLQCHASHDPtLDLTFTWSFNGVPIDlekIEGHYRRRYGKDSNGDLEIVNAQLKHAGRYTCTA 83

                          90
                  ....*....|....*....
gi 220902488  690 RNSAAEVENSQALLVNVPP 708
Cdd:cd04970    84 QTVVDSDSASATLVVRGPP 102

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: 45.14 E-value: 1.44e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 220902488 1331 VTLPCT--AVGKPKREWFKSDVALRQGGlhNSQLLDSGDLIISSLQLADGGNYSCQVDNGIGTDRLTHTLIV 1400
Cdd:cd04969    20 VIIECKpkASPKPTISWSKGTELLTNSS--RICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

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: 45.26 E-value: 1.46e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  437 GPAVSLKCSAAGNPTPQISWTLDGFPLPSNGRFMIGQyitvHGDVISHVNISHVMVEDGGEYACIAENRAGRVQHAARLN 516
Cdd:cd20973    12 GSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQ----DEDGLCSLIISDVCGDDSGKYTCKAVNSLGEATCSAELT 87


                  .
gi 220902488  517 I 517
Cdd:cd20973    88 V 88

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: 45.08 E-value: 1.66e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  622 LQLNMGDRASLTCSVvKGDLPLTINWRKDGRPIDptQHMSVKQVDQynSILVIENLGSDHTGNYSCVVRNSAAEVENSQA 701
Cdd:cd20978    11 VVVKGGQDVTLPCQV-TGVPQPKITWLHNGKPLQ--GPMERATVED--GTLTIINVQPEDTGYYGCVATNEIGDIYTETL 85


                  ...
gi 220902488  702 LLV 704
Cdd:cd20978    86 LHV 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: 44.92 E-value: 1.70e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  808 FSSTSRSVMVKKGDTALLQCAVSGDKPINIVWMRSGKNTLNPSTNYKISVKQEatpdgvSAELQIRTVDATDSGPYFCRA 887
Cdd:cd05763     2 FTKTPHDITIRAGSTARLECAATGHPTPQIAWQKDGGTDFPAARERRMHVMPE------DDVFFIVDVKIEDTGVYSCTA 75


                  ....*
gi 220902488  888 SNLYG 892
Cdd:cd05763    76 QNSAG 80

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: 44.50 E-value: 1.72e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 220902488  637 VKGDLPLTINWRKDGRPIDPTQHMSVKQVDqYNSILVIENLGSDHTGNYSCVVRNSAAEVENS 699
Cdd:cd05748    16 IKGRPTPTVTWSKDGQPLKETGRVQIETTA-SSTSLVIKNAKRSDSGKYTLTLKNSAGEKSAT 77

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: 44.97 E-value: 1.82e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 220902488  719 VERNRHIMLHCQAQGVPTPSIVWKKATGSKSGEYEEVRERPFTKLLGN-GSLLLQHVKEDREGFYLCQANNGIG 791
Cdd:cd05869    14 MELEEQITLTCEASGDPIPSITWRTSTRNISSEEKTLDGHIVVRSHARvSSLTLKYIQYTDAGEYLCTASNTIG 87

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: 44.94 E-value: 1.90e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  611 PPKLSPFQTNiLQLNMGDRASLTCSVVkGDLPLTINWRKDGRPIDPTQHMSVKQVDQyNSILVIENLGSDHTGNYSCVVR 690
Cdd:cd05762     1 PPQIIQFPED-MKVRAGESVELFCKVT-GTQPITCTWMKFRKQIQEGEGIKIENTEN-SSKLTITEGQQEHCGCYTLEVE 77


                  ..
gi 220902488  691 NS 692
Cdd:cd05762    78 NK 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: 44.88 E-value: 1.93e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   810 STSRSVMVKKGDTALLQCAVS-GDKPINIVWMRSGKNTLNPSTnykisvKQEATPDGVSAELQIRTVDATDSGPYFCRAS 888
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSAStGSPGPDVTWSKEGGTLIESLK------VKHDNGRTTQSSLLISNVTKEDAGTYTCVVN 74


                   ....*.
gi 220902488   889 NLYGND 894
Cdd:pfam00047   75 NPGGSA 80

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: 44.79 E-value: 2.06e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 220902488  256 VLLCVAQGCPSPEYSWFTHNGAG----PLPVLSGPRVRLLG-PILAIEAVTGEDSGVYKCTAGN-VGGEASAELRLTV 327
Cdd:cd05734    20 VLNCSADGYPPPTIVWKHSKGSGvpqfQHIVPLNGRIQLLSnGSLLIKHVLEEDSGYYLCKVSNdVGADISKSMYLTV 97

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: 44.81 E-value: 2.14e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  521 PYIRLIPKVTAVSGETLNLKC-PVAGYPIEEIHWERGGRELPDDIRQRVQPDGSLTISPVQKNS----DSGVYTCWARNK 595
Cdd:cd05750     1 PKLKEMKSQTVQEGSKLVLKCeATSENPSPRYRWFKDGKELNRKRPKNIKIRNKKKNSELQINKakleDSGEYTCVVENI 80

                          90
                  ....*....|....*
gi 220902488  596 QGHSarrSGEVTVIV 610
Cdd:cd05750    81 LGKD---TVTGNVTV 92

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: 44.41 E-value: 2.44e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  708 PRWIVEPVDANVERNRHIMLHCQAQGVPTPSIVWKKATgsksgeyEEVRERPFTKLL----GNGSLLLQHVKEDREGFYL 783
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNG-------KPVRPDSAHKMLvrenGRHSLIIEPVTKRDAGIYT 73


                  ....*...
gi 220902488  784 CQANNGIG 791
Cdd:cd05744    74 CIARNRAG 81

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: 2.50e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 220902488  727 LHCQAQGVPTPSIVWKKATGSksgeyeeVRERPFTKLL---GNGSLLLQHVKEDREGFYLCQANNGIGTGIG 795
Cdd:cd05743     6 FTCVATGVPTPIINWRLNWGH-------VPDSARVSITsegGYGTLTIRDVKESDQGAYTCEAINTRGMVFG 70

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 44.56 E-value: 2.62e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   708 PRWIVEPVDANVERNRHIMLHCQAQGVPTPSIVWKKAtGS--KSGEYEEVRERPftkllGNGSLLLQHVKEDREGFYLCQ 785
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKD-GQplRSSDRFKVTYEG-----GTYTLTISNVQPDDSGKYTCV 74


                   ....*..
gi 220902488   786 ANNGIGT 792
Cdd:pfam07679   75 ATNSAGE 81

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: 2.89e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  710 WIVEPVDANVERNRHIMLHCQAQGVPTPSIVWKKATGSksgEYEEVRERPFTKLLGNGSLLLQHVKEDREGFYLCQANNG 789
Cdd:cd05763     2 FTKTPHDITIRAGSTARLECAATGHPTPQIAWQKDGGT---DFPAARERRMHVMPEDDVFFIVDVKIEDTGVYSCTAQNS 78


                  ...
gi 220902488  790 IGT 792
Cdd:cd05763    79 AGS 81

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: 44.11 E-value: 2.91e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 220902488   534 GETLNLKCPV-AGYPIEEIHWERGGRELPDDIRQRVQPDG----SLTISPVQKNsDSGVYTCWARNKQGHSARRS 603
Cdd:pfam00047   11 GDSATLTCSAsTGSPGPDVTWSKEGGTLIESLKVKHDNGRttqsSLLISNVTKE-DAGTYTCVVNNPGGSATLST 84

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: 44.27 E-value: 3.11e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  806 PYFSSTSRSVMVKKGDTALLQCAVSGDKPINIVWMRSGKNT-LNPSTNYKISvkqeaTPDGvSAELQIRTVDATDSGPYF 884
Cdd:cd20974     1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVIsTSTLPGVQIS-----FSDG-RAKLSIPAVTKANSGRYS 74


                  ....*...
gi 220902488  885 CRASNLYG 892
Cdd:cd20974    75 LTATNGSG 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: 44.08 E-value: 3.48e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 220902488  534 GETLNLKCPVAGYPIEEIHWERGGREL-PDDIRQRVQPDGSLTISPVqKNSDSGVYTCWARNKQGH 598
Cdd:cd05856    19 GSSVRLKCVASGNPRPDITWLKDNKPLtPPEIGENKKKKWTLSLKNL-KPEDSGKYTCHVSNRAGE 83

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: 44.44 E-value: 3.49e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 220902488  819 KGDTALLQCAVSGDKPINIVWMRSGKNTLNPSTNY--KISVKQEAtpdGVSAeLQIRTVDATDSGPYFCRASNLYGND 894
Cdd:cd05732    15 ELEQITLTCEAEGDPIPEITWRRATRGISFEEGDLdgRIVVRGHA---RVSS-LTLKDVQLTDAGRYDCEASNRIGGD 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: 43.86 E-value: 3.53e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 220902488  252 DEGAVLLCVAQGCPSPEYSWFTHNGAGPlpvlSGPRVRLLGPILAIEAVTGEDSGVYKCTAGNVGGEASAELRLTV 327
Cdd:cd05851    16 GQNVTLECFALGNPVPVIRWRKILEPMP----ATAEISMSGAVLKIFNIQPEDEGTYECEAENIKGKDKHQARVYV 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: 43.77 E-value: 4.01e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  529 VTAVSGETLNLKCPVAGYPIEEIHWERGGRELPDDIRQRVQPDGSLTISPVQKnSDSGVYTCWARNKQGHSARRSGEVTV 608
Cdd:cd20968     9 VTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRIAVLESGSLRIHNVQK-EDAGQYRCVAKNSLGIAYSKPVTIEV 87

Sixth immunoglobulin (Ig) domain of contactin-2; The members here are composed of the sixth 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 (AC) in the developing chick retina, corresponding to the period of formation and maturation of AC processes.

Pssm-ID: 409440 Cd Length: 102 Bit Score: 44.26 E-value: 4.08e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  433 TLQP-------GPAVSLKCSAAGNPTPQIS--WTLDGFPL---PSNGRFMIGQYITVHGD-VISHVNISHvmvedGGEYA 499
Cdd:cd05854     6 TLAPssadinqGENLTLQCHASHDPTMDLTftWSLDDFPIdldKPNGHYRRMEVKETIGDlVIVNAQLSH-----AGTYT 80

                          90       100
                  ....*....|....*....|..
gi 220902488  500 CIAENRAGRVQHAARLNIYGLP 521
Cdd:cd05854    81 CTAQTVVDSASASATLVVRGPP 102

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: 43.86 E-value: 4.10e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 220902488  527 PKVTAV-SGETLNLKCPVAGYPIEEIHWERGGRELP----DDIRQRVQPDGsLTISPVqKNSDSGVYTCWARNKQG 597
Cdd:cd20949     6 AYVTTVkEGQSATILCEVKGEPQPNVTWHFNGQPISasvaDMSKYRILADG-LLINKV-TQDDTGEYTCRAYQVNS 79

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: 43.55 E-value: 4.19e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 220902488  725 IMLHCQAQGVPTPSIVWKKATGSKSGEYEEVRErpFTKllgngSLLLQHVKEDREGFYLCQANNGIGT 792
Cdd:cd05731    13 LLLECIAEGLPTPDIRWIKLGGELPKGRTKFEN--FNK-----TLKIENVSEADSGEYQCTASNTMGS 73

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: 43.85 E-value: 4.22e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 220902488  444 CSAAGNPTPQISWTLDGFPL---PSNGRfmIGQYITvhgdviSHVNISHVMVEDGGEYACIAENRAGrVQHAARLNIY 518
Cdd:cd05738    21 CAASGNPDPEISWFKDFLPVdtaTSNGR--IKQLRS------GALQIENSEESDQGKYECVATNSAG-TRYSAPANLY 89

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: 43.92 E-value: 4.24e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  806 PYFSSTSRSVMVKK-GDTALLQCAVSGDKPINIVWMRSGKNTLNPSTNYKISvkqeatpDGVsaeLQIRTVDATDSGPYF 884
Cdd:cd20978     1 PKFIQKPEKNVVVKgGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVE-------DGT---LTIINVQPEDTGYYG 70


                  ....*...
gi 220902488  885 CRASNLYG 892
Cdd:cd20978    71 CVATNEIG 78

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: 43.81 E-value: 4.38e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  710 WIVEPVDanvernrHIMLHCQAQGVPTPSIVWkkatgSKSGEYEEVRERPFTKLLG-NGSLLLQH----VKEDREGFYLC 784
Cdd:cd05875    11 YIVDPRD-------NILIECEAKGNPVPTFHW-----TRNGKFFNVAKDPRVSMRRrSGTLVIDFrgggRPEDYEGEYQC 78

                          90
                  ....*....|....*..
gi 220902488  785 QANNGIGTGIGKVIQLK 801
Cdd:cd05875    79 FARNKFGTALSNKIRLQ 95

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: 43.86 E-value: 4.39e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  808 FSSTSRSVMVKKGDTALLQCAVSGDKPINIVWMRSGKNTlnpstnyKISVKQEATPDGVSAELQIRTVDATDSGPYFCRA 887
Cdd:cd20949     2 FTENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQPI-------SASVADMSKYRILADGLLINKVTQDDTGEYTCRA 74


                  ....*
gi 220902488  888 SNLYG 892
Cdd:cd20949    75 YQVNS 79

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: 43.62 E-value: 4.41e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  238 PSVVEHTAHVQVSQDEGAVLLCVAQGCPSPEYSWFTHNGAgplpVLSGPRVRLLGP--ILAIEAVTGEDSGVYKCTAGNV 315
Cdd:cd05764     1 PLITRHTHELRVLEGQRATLRCKARGDPEPAIHWISPEGK----LISNSSRTLVYDngTLDILITTVKDTGAFTCIASNP 76

                          90
                  ....*....|..
gi 220902488  316 GGEASAELRLTV 327
Cdd:cd05764    77 AGEATARVELHI 88

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: 43.74 E-value: 4.75e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 220902488  534 GETLNLKCPVAGYPIEEIHWERGGRELPDDIRQRVQpDGSLTISPVQKnSDSGVYTCWARNKQGhSARRSGEVTV 608
Cdd:cd05728    14 GSSLRWECKASGNPRPAYRWLKNGQPLASENRIEVE-AGDLRITKLSL-SDSGMYQCVAENKHG-TIYASAELAV 85

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 43.56 E-value: 4.85e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 220902488  1510 NSTSLLVrlhSW---PDNGCPLLYFVLQYRAVTDDPDAEWVLVSNalkPQRRIVINNLQPSTLYQLRMEAHNVAGISQ 1584
Cdd:pfam00041   12 TSTSLTV---SWtppPDGNGPITGYEVEYRPKNSGEPWNEITVPG---TTTSVTLTGLKPGTEYEVRVQAVNGGGEGP 83

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: 43.55 E-value: 5.07e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 220902488  529 VTAVSGETLNLKCPVAGYPIEEIHWERGGREL-PDDIRQR-VQPDG--SLTISPVqKNSDSGVYTCWARNKQGHSA 600
Cdd:cd20990    10 LTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIrPDSAHKMlVRENGvhSLIIEPV-TSRDAGIYTCIATNRAGQNS 84

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: 43.70 E-value: 5.20e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  257 LLCVAQGCPSPEYSWfTHNGagpLPVLSGPRVRL------LGPI---LAIEAVTGEDSGVYKCTAGNVGGEASAELRLTV 327
Cdd:cd20956    21 LKCVASGNPLPQITW-TLDG---FPIPESPRFRVgdyvtsDGDVvsyVNISSVRVEDGGEYTCTATNDVGSVSHSARINV 96

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: 43.65 E-value: 5.25e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  817 VKKGDTALLQCAVSGDKP-INIVWMRSGKN-TLNPSTNYKISVKQEatpdgvSAELQIRTVDATDSGPYFCRASNLYGND 894
Cdd:cd05750    11 VQEGSKLVLKCEATSENPsPRYRWFKDGKElNRKRPKNIKIRNKKK------NSELQINKAKLEDSGEYTCVVENILGKD 84

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: 43.74 E-value: 5.38e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  517 IYGLPYIrlipkVTAVSGETLNLKCPVAGYPIEEIHWERGGRELPDDIRQRVQPD----GSLTISPVQkNSDSGVYTCWA 592
Cdd:cd05891     4 IGGLPDV-----VTIMEGKTLNLTCTVFGNPDPEVIWFKNDQDIELSEHYSVKLEqgkyASLTIKGVT-SEDSGKYSINV 77


                  ....*
gi 220902488  593 RNKQG 597
Cdd:cd05891    78 KNKYG 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: 43.82 E-value: 5.68e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 220902488  821 DTALLQCAVSGDKPINIVWMRSGKNTLNPSTNY--KISVKQEATpdgVSAeLQIRTVDATDSGPYFCRASNLYGND 894
Cdd:cd05869    18 EQITLTCEASGDPIPSITWRTSTRNISSEEKTLdgHIVVRSHAR---VSS-LTLKYIQYTDAGEYLCTASNTIGQD 89

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: 5.71e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 220902488 1330 TVTLPCTAVGKPKR--EWFKSDVALRQGGLHnsQLLDSGDLIISSLQLADGGNYSCQVDNGIGTDRLTHTLIV 1400
Cdd:cd05745     4 TVDFLCEAQGYPQPviAWTKGGSQLSVDRRH--LVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in Perlecan. Perlecan is a large multi-domain heparin sulfate proteoglycan, important in tissue development and organogenesis. Perlecan can be represented as 5 major portions; its fourth major portion (domain IV) is a tandem repeat of immunoglobulin-like domains (Ig2-Ig15) which can vary in size due to alternative splicing. Perlecan binds many cellular and extracellular ligands. Its domain IV region has many binding sites. Some of these have been mapped at the level of individual Ig-like domains, including a site restricted to the Ig5 domain for heparin/sulfatide, a site restricted to the Ig3 domain for nidogen-1 and nidogen-2, a site restricted to Ig4-5 for fibronectin, and sites restricted to Ig2 and to Ig13-15 for fibulin-2. 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: 409412 Cd Length: 85 Bit Score: 43.31 E-value: 6.12e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  431 EQTLQPGPAVSLKCSA-AGNPTPQISWTLDGFPLPSNGRfmigqyitvhgDVISHVNISHVMVEDGGEYACIAENRAGRV 509
Cdd:cd05754    10 SQEVRPGADVSFICRAkSKSPAYTLVWTRVNGTLPSRAM-----------DFNGILTIRNVQLSDAGTYVCTGSNMLDTD 78


                  ....*.
gi 220902488  510 QHAARL 515
Cdd:cd05754    79 EATATL 84

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: 43.55 E-value: 6.33e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  437 GPAVSLKCSAAGNPTPQISWTLDGFPL-PSNGRFMIGQyiTVHGDVISHVNIShvMVEDGGEYACIAENRAGRVQHAARL 515
Cdd:cd05893    15 GMPVTFTCRVAGNPKPKIYWFKDGKQIsPKSDHYTIQR--DLDGTCSLHTTAS--TLDDDGNYTIMAANPQGRISCTGRL 90


                  ..
gi 220902488  516 NI 517
Cdd:cd05893    91 MV 92

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 47.69 E-value: 6.49e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488 1467 GSTYQIHLSAQNKVGTSPTSTILHVRTQGQSPGHPASTALLAPNSTSllVRLhSWPDNGCPLL--YFVlqYRAvtDDPDA 1544
Cdd:COG3401   202 GTTYYYRVAATDTGGESAPSNEVSVTTPTTPPSAPTGLTATADTPGS--VTL-SWDPVTESDAtgYRV--YRS--NSGDG 274

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 220902488 1545 EWVLVSNAlkPQRRIVINNLQPSTLYQLRMEAHNVAGISQAEFNFVTLTKDGDPPPP 1601
Cdd:COG3401   275 PFTKVATV--TTTSYTDTGLTNGTTYYYRVTAVDAAGNESAPSNVVSVTTDLTPPAA 329

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: 43.17 E-value: 6.84e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  811 TSRSVMVKKGDTALLQCAVSGDKPINIVWMRSGKNTLNPSTNYkisvkqeatpDGVSAELQIRTVDATDSGPYFCRASNL 890
Cdd:cd05731     1 SESSTMVLRGGVLLLECIAEGLPTPDIRWIKLGGELPKGRTKF----------ENFNKTLKIENVSEADSGEYQCTASNT 70


                  ..
gi 220902488  891 YG 892
Cdd:cd05731    71 MG 72

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: 43.08 E-value: 7.22e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  704 VNVPPRWIVepvdanVERNRHIMLHCQAQGVPTPSIVWKK-----ATGSKSGEYEEVRerpftkllgNGSLLLQHVKEDR 778
Cdd:cd05738     2 IDMGPQLKV------VEKARTATMLCAASGNPDPEISWFKdflpvDTATSNGRIKQLR---------SGALQIENSEESD 66

                          90
                  ....*....|....
gi 220902488  779 EGFYLCQANNGIGT 792
Cdd:cd05738    67 QGKYECVATNSAGT 80

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: 43.25 E-value: 7.34e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 220902488  255 AVLLC-VAQGCPSPEYSWfTHNGAgPLPVLSGPRVRLLGP---ILAIEAVTGEDSGVYKCTAGNVGGEASAELRLTV 327
Cdd:cd20959    20 AQLHCgVPGGDLPLNIRW-TLDGQ-PISDDLGITVSRLGRrssILSIDSLEASHAGNYTCHARNSAGSASYTAPLTV 94

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: 43.40 E-value: 7.75e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 220902488 1330 TVTLPCTAVG--KPKREWFKSDVALRQGGLHNSQLLDSG-DLIISSLQLADGGNYSCQVDNGIGTDRLTHTLIVQ 1401
Cdd:cd05736    17 EASLRCHAEGipLPRVQWLKNGMDINPKLSKQLTLIANGsELHISNVRYEDTGAYTCIAKNEGGVDEDISSLFVE 91

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: 9.03e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  238 PSVVEHTAHVQVSQDEGAVLLCVAQGCPSPEYSWFtHNGAGPLPVLSGPRVRLL----GPILAIEAVTG----EDSGVYK 309
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWL-KNGQPLETDKDDPRSHRIvlpsGSLFFLRVVHGrkgrSDEGVYV 79

                          90       100
                  ....*....|....*....|
gi 220902488  310 CTAGNVGGEA-SAELRLTVA 328
Cdd:cd07693    80 CVAHNSLGEAvSRNASLEVA 99

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: 43.00 E-value: 9.12e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  714 PVDANVERNRHIMLHCQAQGVPTPSIVWKKatgsksgEYEEVRERPFTKLLGNGSLLLQHVKEDREGFYLCQANNGIGTG 793
Cdd:cd20968     6 PTNVTIIEGLKAVLPCTTMGNPKPSVSWIK-------GDDLIKENNRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGIA 78


                  ....*....
gi 220902488  794 IGKVIQLKV 802
Cdd:cd20968    79 YSKPVTIEV 87

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: 42.96 E-value: 9.74e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 220902488  433 TLQPGPAVSLKCSAAGNPTPQISWTLDGFPLPSNGRFMI----GQYITvhgdvishVNISHVMVEDGGEYACIAENRAG 507
Cdd:cd05737    12 TIMEGKTLNLTCNVWGDPPPEVSWLKNDQALAFLDHCNLkveaGRTVY--------FTINGVSSEDSGKYGLVVKNKYG 82

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: 42.86 E-value: 1.01e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 220902488  437 GPAVSLKCSAAGNPTPQISWTLD---GFP-----LPSNGRFMigqyITVHGDVIshvnISHVMVEDGGEYACIAENRAG 507
Cdd:cd05734    16 GKAVVLNCSADGYPPPTIVWKHSkgsGVPqfqhiVPLNGRIQ----LLSNGSLL----IKHVLEEDSGYYLCKVSNDVG 86

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: 42.92 E-value: 1.01e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  437 GPAVSLKCSAAGNPTPQISWTLDGFPLPSNGRFMIGQYITVHGDVISHVNISH--VMVEDGGEYACIAENRAGR-VQHAA 513
Cdd:cd07693    15 GDPATLNCKAEGRPTPTIQWLKNGQPLETDKDDPRSHRIVLPSGSLFFLRVVHgrKGRSDEGVYVCVAHNSLGEaVSRNA 94


                  ....
gi 220902488  514 RLNI 517
Cdd:cd07693    95 SLEV 98

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: 1.02e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  432 QTLQPGPAVSLKCSAAGNPTPQISW--TLDGFPLPS-----NGRFMI-GQyitvHGDviSHVNISHVMVEDGGEYACIAE 503
Cdd:cd05870    11 ETTVENGAATLSCKAEGEPIPEITWkrASDGHTFSEgdkspDGRIEVkGQ----HGE--SSLHIKDVKLSDSGRYDCEAA 84

                          90
                  ....*....|....
gi 220902488  504 NRAGRVQHAARLNI 517
Cdd:cd05870    85 SRIGGHQKSMYLDI 98

Second Ig-like domain of Junctional adhesion molecule-1 (JAM1); a member of the I-set of IgSF domains; The members here are composed of the second Ig-like domain of Junctional adhesion molecule-1 (JAM1). JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The 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 second Ig-like domain of JAM1 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, the A strand of the I-set is discontinuous but lacks 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: 409542 Cd Length: 97 Bit Score: 43.07 E-value: 1.02e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  626 MGDRASLTCSVVKGDLPLTINWRKDGRPIdPTQHMSVK-------QVDQYNSILVIENLGSDHTGNYSCVVRNSAAEVEN 698
Cdd:cd20950    11 IGNRAVLTCSEPDGSPPSEYTWFKDGVVM-PTNPKSTRafsnssySLDPTTGELVFDPLSASDTGEYSCEARNGYGTPMR 89


                  ....
gi 220902488  699 SQAL 702
Cdd:cd20950    90 SNAV 93

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: 42.59 E-value: 1.09e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  815 VMVKKGDTALLQCAVSGDKPINIVWMRSGKNtLNPSTNYKISVKQeatpdGVSAELQIRTVDATDSGPYFCRASNLYGND 894
Cdd:cd05891    11 VTIMEGKTLNLTCTVFGNPDPEVIWFKNDQD-IELSEHYSVKLEQ-----GKYASLTIKGVTSEDSGKYSINVKNKYGGE 84

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: 42.57 E-value: 1.13e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  707 PPRWIVEPVDANVERNRHIMLHCQAQGVPTPSIVWKKatgsksgEYEEVRERPFTKLLGNG---SLLLQHVKEDREGFYL 783
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFC-------EGKELQNSPDIQIHQEGdlhSLIIAEAFEEDTGRYS 73


                  ....*....
gi 220902488  784 CQANNGIGT 792
Cdd:cd20972    74 CLATNSVGS 82

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: 42.86 E-value: 1.18e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 220902488  820 GDTALLQCAVS-GDKPINIVWMRSGKNTlnpSTNYKISVKQeatPDGVSAELQIRTVDATDSGPYFCRASNLYG 892
Cdd:cd20959    17 GMRAQLHCGVPgGDLPLNIRWTLDGQPI---SDDLGITVSR---LGRRSSILSIDSLEASHAGNYTCHARNSAG 84

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 42.63 E-value: 1.20e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 220902488    51 LDCSASGSPQPTVDWVHaDGSAVTEIHGVrRVLRNG---TLVLMPfaaaAYHQDVHntIYRCIASNSVG 116
Cdd:pfam07679   20 FTCTVTGTPDPEVSWFK-DGQPLRSSDRF-KVTYEGgtyTLTISN----VQPDDSG--KYTCVATNSAG 80

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 42.38 E-value: 1.21e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 220902488   432 QTLQPGPAVSLKCSAAGNPTPQISWTLDGFPLPSNGRFMigqyitvhgdvishvnISHVMVEDGGEYACIAENRAG 507
Cdd:pfam13895    9 TVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAISSSPNFF----------------TLSVSAEDSGTYTCVARNGRG 68

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: 42.48 E-value: 1.22e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 220902488  632 LTCSVVKGDLPlTINWRKDGRPIdPTQHMSVKQVDqyNSILVIENLGSDHTGNYSCVVRNSAAEVENSQALLV 704
Cdd:cd20952    19 LNCQATGEPVP-TISWLKDGVPL-LGKDERITTLE--NGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 87

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: 42.58 E-value: 1.27e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  513 ARLnIYGLPYIrlipkVTAVSGETLNLKCPVAGYPIEEIHWERGGRELP--DDIRQRVQPDGSLTISPVQKNS-DSGVYT 589
Cdd:cd05737     1 ARV-LGGLPDV-----VTIMEGKTLNLTCNVWGDPPPEVSWLKNDQALAflDHCNLKVEAGRTVYFTINGVSSeDSGKYG 74

                          90       100
                  ....*....|....*....|.
gi 220902488  590 CWARNKQGhsaRRSGEVTVIV 610
Cdd:cd05737    75 LVVKNKYG---SETSDVTVSV 92

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: 1.39e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  707 PPRWIVEPVDanvernrHIMLHCQAQGVPTPSIVWKkatgsKSGEYEEVRERPFTKLLGN-GSLLLQH---VKEDREGFY 782
Cdd:cd05733     8 PKDYIVDPRD-------NITIKCEAKGNPQPTFRWT-----KDGKFFDPAKDPRVSMRRRsGTLVIDNhngGPEDYQGEY 75

                          90
                  ....*....|....*...
gi 220902488  783 LCQANNGIGTGIGKVIQL 800
Cdd:cd05733    76 QCYASNELGTAISNEIRL 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: 1.39e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 220902488  644 TINWRKDGRPIDPTQHMSVKQVDQYNSILVIENLGSDHTGNYSCVVRNSAAEVENS 699
Cdd:cd05729    35 NITWLKDGKEFKKEHRIGGTKVEEKGWSLIIERAIPRDKGKYTCIVENEYGSINHT 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: 42.09 E-value: 1.42e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 220902488  437 GPAVSLKCSAAGNPTPQISWTLDGFPLPSNGRFMI---GQYITvhgdvishVNISHVMVEDGGEYACIAENRAGRV 509
Cdd:cd05743     1 GETVEFTCVATGVPTPIINWRLNWGHVPDSARVSItseGGYGT--------LTIRDVKESDQGAYTCEAINTRGMV 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: 42.31 E-value: 1.43e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  249 VSQDEGAVLLCVAQGCPSPEYSWFTHNgagpLPV---LSGPRVRLL-GPILAIEAVTGEDSGVYKCTAGN-VGGEASAEL 323
Cdd:cd05738    11 VEKARTATMLCAASGNPDPEISWFKDF----LPVdtaTSNGRIKQLrSGALQIENSEESDQGKYECVATNsAGTRYSAPA 86


                  ....
gi 220902488  324 RLTV 327
Cdd:cd05738    87 NLYV 90

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. 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 structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. 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: 409559 Cd Length: 82 Bit Score: 41.84 E-value: 1.73e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 220902488  345 GGTAEFRCLVTSNGSPVGmqnilWYKDGRQLPSSGRVE-------DTLVVPRVSRENRGMYQCVV 402
Cdd:cd20967    12 GHKIRLTVELADPDAEVK-----WYKDGQELQSSSKVIfesigakRTLTVQQASLADAGEYQCVA 71

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: 41.82 E-value: 1.75e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  245 AHVQVSQDEGAVLLCVAQGCPSPEYSWFTHNGAgplpvLSGPRVRLL--GPILAIEAVTGEDSGVYKCTAGNVGGEASAE 322
Cdd:cd05876     3 SSLVALRGQSLVLECIAEGLPTPTVKWLRPSGP-----LPPDRVKYQnhNKTLQLLNVGESDDGEYVCLAENSLGSARHA 77


                  ....*
gi 220902488  323 LRLTV 327
Cdd:cd05876    78 YYVTV 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: 42.18 E-value: 1.93e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  806 PYFSSTSRSVMVKKGDTALLQCAVSGDKPINIVWMRSGKNtLNPSTNYKISvkqeatPDGVSAELQIRTVDATDSGPYFC 885
Cdd:cd20972     2 PQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKE-LQNSPDIQIH------QEGDLHSLIIAEAFEEDTGRYSC 74


                  ....*....
gi 220902488  886 RASNLYGND 894
Cdd:cd20972    75 LATNSVGSD 83

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: 41.33 E-value: 1.98e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 220902488  442 LKCSAAGNPTPQISWTLDGFPLPSNgrfmigqyitvhgdviSHVNISHVMVEDGGEYACIAENRAG 507
Cdd:cd20948    15 LSCHAASNPPAQYSWTINGTFQTSS----------------QELFLPAITENNEGTYTCSAHNSLT 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: 41.93 E-value: 2.06e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  627 GDRASLTCSVvKGDLPLTINWRKDGRPIDptqhMSVKQVDQYNSI---LVIENLGSDHTGNYSCVVRNSAAEVENSQALL 703
Cdd:cd20949    14 GQSATILCEV-KGEPQPNVTWHFNGQPIS----ASVADMSKYRILadgLLINKVTQDDTGEYTCRAYQVNSIASDMQERT 88


                  .
gi 220902488  704 V 704
Cdd:cd20949    89 V 89

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

Pssm-ID: 462230 Cd Length: 109 Bit Score: 42.45 E-value: 2.07e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   529 VTAVSGETLNLKCPVAGYPIEE---IHWERGGRELPDD--------------IRQRV-------QPDGSLTISPVQKnSD 584
Cdd:pfam07686    6 VTVALGGSVTLPCTYSSSMSEAstsVYWYRQPPGKGPTfliayysngseegvKKGRFsgrgdpsNGDGSLTIQNLTL-SD 84

                           90       100
                   ....*....|....*....|....
gi 220902488   585 SGVYTCWARNKQGHSARRSGEVTV 608
Cdd:pfam07686   85 SGTYTCAVIPSGEGVFGKGTRLTV 108

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: 42.09 E-value: 2.13e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   31 PGFVMEPpgrvefSNSSG-----GWLDCSASGSPQPTVDWVHADGSAV------TEIHGVRRVLRNGTLVLmpfaAAAYH 99
Cdd:cd05734     2 PRFVVQP------NDQDGiygkaVVLNCSADGYPPPTIVWKHSKGSGVpqfqhiVPLNGRIQLLSNGSLLI----KHVLE 71

                          90       100
                  ....*....|....*....|..
gi 220902488  100 QDVHNtiYRCIASNSVGRIVSR 121
Cdd:cd05734    72 EDSGY--YLCKVSNDVGADISK 91

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: 41.92 E-value: 2.27e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 220902488 1330 TVTLPCTAVGKPKRE--WFKS----DVALRQGGLhnsQLLDSGDLIISSLQLADGGNYSCQVDNGIGT 1391
Cdd:cd05738    16 TATMLCAASGNPDPEisWFKDflpvDTATSNGRI---KQLRSGALQIENSEESDQGKYECVATNSAGT 80

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: 41.44 E-value: 2.38e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 220902488  721 RNRHIMLHCQAQGVPTPSIVWKKATGSKSGEyeevrerPFTKLLGNGSLLLQHVKEDREGFYLCQANNGIGT 792
Cdd:cd05876     9 RGQSLVLECIAEGLPTPTVKWLRPSGPLPPD-------RVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGS 73

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: 41.67 E-value: 2.41e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   33 FVMEPPGRVEFSNSSGGWLDCSASGSPQPTVDWVhADGSAVtEIHG--VRRVLRNGTLVLMPFaaaayhQDVHNTIYRCI 110
Cdd:cd04978     1 YWIIEPPSLVLSPGETGELICEAEGNPQPTITWR-LNGVPI-EPAPedMRRTVDGRTLIFSNL------QPNDTAVYQCN 72


                  ....*....
gi 220902488  111 ASNSVGRIV 119
Cdd:cd04978    73 ASNVHGYLL 81

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: 41.08 E-value: 2.46e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 220902488  727 LHCQAQGVPTPSIVWKKATGSKSGEYEEVrerpftkLLGNGSLLLQHVKEDREGFYLCQANNGIGT 792
Cdd:cd05745     7 FLCEAQGYPQPVIAWTKGGSQLSVDRRHL-------VLSSGTLRISRVALHDQGQYECQAVNIVGS 65

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: 41.77 E-value: 2.52e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 220902488  534 GETLNLKCPVAGYPIEEIHWErggRELPDDIRQRVQPD-----------GSLTISPVQKNsDSGVYTCWARNKQG 597
Cdd:cd05765    15 GETASFHCDVTGRPQPEITWE---KQVPGKENLIMRPNhvrgnvvvtniGQLVIYNAQPQ-DAGLYTCTARNSGG 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: 41.87 E-value: 2.58e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  808 FSSTSRSVMVKKGDTALLQCAVSGDKPINIVWMRSG-KNTLNPSTNYKISVKQEATPDGvsaELQIRTVDATDSGPYFCR 886
Cdd:cd05726     2 FVVKPRDQVVALGRTVTFQCETKGNPQPAIFWQKEGsQNLLFPYQPPQPSSRFSVSPTG---DLTITNVQRSDVGYYICQ 78


                  ....*..
gi 220902488  887 ASNLYGN 893
Cdd:cd05726    79 ALNVAGS 85

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: 41.62 E-value: 2.58e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 220902488   51 LDCSAS-GSPQPTVDWVHaDGSAVTEIHGVRRVLRNGTLVLMPfaaaAYHQDVHNtiYRCIASNSVGRIVSRD 122
Cdd:cd05724    17 LECSPPrGHPEPTVSWRK-DGQPLNLDNERVRIVDDGNLLIAE----ARKSDEGT--YKCVATNMVGERESRA 82

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: 41.89 E-value: 2.60e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  714 PVDANVERNRHIMLHCQAQGVPTPSIVWkkatgSKSGEYEEVRERPFTKLL-GNGSLLLQHVKEDR----EGFYLCQANN 788
Cdd:cd05874     8 PKDYIVDPRENIVIQCEAKGKPPPSFSW-----TRNGTHFDIDKDPKVTMKpNTGTLVINIMNGEKaeayEGVYQCTARN 82

                          90
                  ....*....|...
gi 220902488  789 GIGTGIGKVIQLK 801
Cdd:cd05874    83 ERGAAVSNNIVIR 95

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: 41.77 E-value: 2.67e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488 1330 TVTLPCTAVGKPKRE----WFKSDVA--LRQGGLH---NSQLLDSGDLIISSLQLADGGNYSCQVDNGIGTDRLTHTLIV 1400
Cdd:cd04970    19 NATLQCHASHDPTLDltftWSFNGVPidLEKIEGHyrrRYGKDSNGDLEIVNAQLKHAGRYTCTAQTVVDSDSASATLVV 98


                  ....
gi 220902488 1401 QVPP 1404
Cdd:cd04970    99 RGPP 102

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: 2.69e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 220902488  257 LLCVAQGCPSPEYSWFTHNGagplPVLSGPRVRLLGPILAIEAVTGEDSGVYKCTAGNVGGEASAELRLTV 327
Cdd:cd04968    21 LECFALGNPVPQIKWRKVDG----SPSSQWEITTSEPVLEIPNVQFEDEGTYECEAENSRGKDTVQGRIIV 87

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: 41.71 E-value: 2.74e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  531 AVSGETLNLKCPVA-GYPIEEIHWERGGRELPDDI---RQRVQPDGSLTISPVQKNSDSGVYTCWARNKQGHsARRSGEV 606
Cdd:cd20959    14 AQVGMRAQLHCGVPgGDLPLNIRWTLDGQPISDDLgitVSRLGRRSSILSIDSLEASHAGNYTCHARNSAGS-ASYTAPL 92


                  ..
gi 220902488  607 TV 608
Cdd:cd20959    93 TV 94

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: 41.42 E-value: 2.76e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 220902488  436 PGPAVSLKCSAAGNPTPQISWTLDGFPLPSNGRFMiGQYITVHGDVISHVNISHVMVedggeYACIAENRAG 507
Cdd:cd05867    13 PGETARLDCQVEGIPTPNITWSINGAPIEGTDPDP-RRHVSSGALILTDVQPSDTAV-----YQCEARNRHG 78

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: 41.43 E-value: 3.00e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 220902488  433 TLQPGPAVSLKCSAAGNPTPQISWTLDGFPLPSNGRFMI----GQYITvhgdvishVNISHVMVEDGGEYACIAENRAG 507
Cdd:cd05891    12 TIMEGKTLNLTCTVFGNPDPEVIWFKNDQDIELSEHYSVkleqGKYAS--------LTIKGVTSEDSGKYSINVKNKYG 82

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: 41.56 E-value: 3.79e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  617 FQTNIL----QLNMGDRASLTCSVVKGDLPLTINW-RKDGRPIDPTQH-MSVKQVDQYNSILVIENLGSDHTGNYSCVVr 690
Cdd:cd05865     1 LQVDIVpsqgEISVGESKFFLCQVAGEAKDKDISWfSPNGEKLTPNQQrISVVRNDDYSSTLTIYNANIDDAGIYKCVV- 79

                          90
                  ....*....|....*.
gi 220902488  691 nsAAEVENSQALLVNV 706
Cdd:cd05865    80 --SNEDEGESEATVNV 93

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: 41.19 E-value: 3.99e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 220902488  627 GDRASLTCSVvKGDLPLTINWRKDGRPIDPTQHMSVKQVdQYNSILVIENLGSDHTGNYSCVVRNSAAEVE 697
Cdd:cd05747    18 GESARFSCDV-DGEPAPTVTWMREGQIIVSSQRHQITST-EYKSTFEISKVQMSDEGNYTVVVENSEGKQE 86

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: 41.24 E-value: 4.02e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   51 LDCSASGSPQPTVDWVHaDGS--AVTEIHGVRRVLRNGTLVLmpfaaaayhqDVHNT-------IYRCIASNSVGRIVSR 121
Cdd:cd05733    21 IKCEAKGNPQPTFRWTK-DGKffDPAKDPRVSMRRRSGTLVI----------DNHNGgpedyqgEYQCYASNELGTAISN 89


                  ....*
gi 220902488  122 DVQVR 126
Cdd:cd05733    90 EIRLV 94

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: 41.07 E-value: 4.03e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 220902488  442 LKCSAAGNPTPQISWTLDGFPLPSNGRFMIGQYitvhgdviSHVNISHVMVEDGGEYACIAENRAG 507
Cdd:cd20968    19 LPCTTMGNPKPSVSWIKGDDLIKENNRIAVLES--------GSLRIHNVQKEDAGQYRCVAKNSLG 76

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: 41.12 E-value: 4.14e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  521 PYIRLIPKVTAVSGETLNLKCPVAGYPIEEIHWERG--------GRELPDDirqRVQPDG-----SLTISPVqKNSDSGV 587
Cdd:cd05870     3 PHIIQLKNETTVENGAATLSCKAEGEPIPEITWKRAsdghtfseGDKSPDG---RIEVKGqhgesSLHIKDV-KLSDSGR 78

                          90
                  ....*....|
gi 220902488  588 YTCWARNKQG 597
Cdd:cd05870    79 YDCEAASRIG 88

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: 40.55 E-value: 4.33e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 220902488  534 GETLNLKCPVAGYPIEEIHWERGGRELPDDIRQRVQPD---GSLTISPVqKNSDSGVYTCWARNKQG 597
Cdd:cd05743     1 GETVEFTCVATGVPTPIINWRLNWGHVPDSARVSITSEggyGTLTIRDV-KESDQGAYTCEAINTRG 66

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: 41.12 E-value: 4.34e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 220902488  722 NRHIMLHCQAQGVPTPSIVWKKAT-------GSKSGEYE-EVRERpftklLGNGSLLLQHVKEDREGFYLCQANNGIG 791
Cdd:cd05870    16 NGAATLSCKAEGEPIPEITWKRASdghtfseGDKSPDGRiEVKGQ-----HGESSLHIKDVKLSDSGRYDCEAASRIG 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: 41.03 E-value: 4.65e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  522 YIRLIPKVTAVSGETLNLKCPVAGYPIEEIHWERGGRELPDDIRQRVQPDG---SLTISPVQKNsDSGVYTCWARNKQGh 598
Cdd:cd20972     4 FIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEGdlhSLIIAEAFEE-DTGRYSCLATNSVG- 81

                          90
                  ....*....|
gi 220902488  599 SARRSGEVTV 608
Cdd:cd20972    82 SDTTSAEIFV 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: 41.00 E-value: 4.85e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  423 PVLLYSFIEQTLQPGPAVSLKCSAAGNPTPQISWTLDgfpLPSNGRfMIGQYITVHGDV----ISHVNISHVMVEDGGEY 498
Cdd:cd05765     1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEKQ---VPGKEN-LIMRPNHVRGNVvvtnIGQLVIYNAQPQDAGLY 76

                          90
                  ....*....|..
gi 220902488  499 ACIAENRAGRVQ 510
Cdd:cd05765    77 TCTARNSGGLLR 88

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: 41.09 E-value: 4.86e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  806 PYFSSTSRSVMVKKGDTALLQCAVSGDKPINIVWMRSGKNtLNPSTNYKISVKQEATpdgvsaELQIRTVDATDSGPYFC 885
Cdd:cd05736     1 PVIRVYPEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMD-INPKLSKQLTLIANGS------ELHISNVRYEDTGAYTC 73


                  ....*....
gi 220902488  886 RASNLYGND 894
Cdd:cd05736    74 IAKNEGGVD 82

Chitodextrinase [Carbohydrate transport and metabolism];

Pssm-ID: 443178 [Multi-domain] Cd Length: 369 Bit Score: 44.38 E-value: 5.22e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  904 EPPLPPSVLEAAMISSRSVNIKWQPKTLGTGdVTKYIVeFREADplFVDQWQQIEvkdpphfNAMIENLKPATRYAFRVI 983
Cdd:COG3979     1 QAPTAPTGLTASNVTSSSVSLSWDASTDNVG-VTGYDV-YRGGD--QVATVTGLT-------AWTVTGLTPGTEYTFTVG 69

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  984 AEGSAG-RSAPSQELIVRTEPQRPAGPPLSLSA----RPLSSTELLISWVAPLPELRHGDIQGYNVGYKLSSSGNTAYNF 1058
Cdd:COG3979    70 ACDAAGnVSAASGTSTAMFGGSSTTLGSAEGVAdtsgNLAASGAFFGVTTPPTPSSTLVVDGTTTVNAAATANGGTGGSG 149

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 220902488 1059 TSVSGDGDGGNGELLLSGLAKFARYTVVVQAFNQVGPGPLSEPTAAQT 1106
Cdd:COG3979   150 GTTTIITTGVEGGGGSKTAQSLNAITAAGTAALNGGVVGGADEVLTCS 197

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: 40.99 E-value: 5.41e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 220902488  528 KVTAVS-GETLNLKCPVAGYPIEEIHWERGGRELPDD-------IRQRVQpdgSLTISPVQKnSDSGVYTCWARNKQG 597
Cdd:cd05857    12 KLHAVPaANTVKFRCPAAGNPTPTMRWLKNGKEFKQEhriggykVRNQHW---SLIMESVVP-SDKGNYTCVVENEYG 85

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: 40.64 E-value: 5.83e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  249 VSQDEGAVLLCVAQGCPSPEYSWFTHNGagplPVLSGPRVRLL--GP---ILAIEAVTGEDSGVYKCTAGNVGGEASAEL 323
Cdd:cd20973     9 VVEGSAARFDCKVEGYPDPEVKWMKDDN----PIVESRRFQIDqdEDglcSLIISDVCGDDSGKYTCKAVNSLGEATCSA 84


                  ....
gi 220902488  324 RLTV 327
Cdd:cd20973    85 ELTV 88

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 40.24 E-value: 6.08e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 220902488    51 LDCSASGSPQPTVDWVHADGSAVTEIHGVRR-VLRNGTLVLMPFAAAayhqdvHNTIYRCIASN 113
Cdd:pfam13927   21 LTCEATGSPPPTITWYKNGEPISSGSTRSRSlSGSNSTLTISNVTRS------DAGTYTCVASN 78

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: 40.69 E-value: 6.08e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   34 VMEPPGRVEFSNSSGGWLDCSASGSPQPTVDWVHADgSAVTEIHGVrRVLRNGTLVLMPFAAAAYHQdvhntiYRCIASN 113
Cdd:cd20968     2 ITRPPTNVTIIEGLKAVLPCTTMGNPKPSVSWIKGD-DLIKENNRI-AVLESGSLRIHNVQKEDAGQ------YRCVAKN 73

                          90
                  ....*....|..
gi 220902488  114 SVGRIVSRDVQV 125
Cdd:cd20968    74 SLGIAYSKPVTI 85

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: 40.84 E-value: 6.16e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  423 PVLLYSFIEQ--TLQPGPAVSLKCSAAGNPTPQISWTLDG---FPLPSNGRfmigqyITVHGDviSHVNISHVMVEDGGE 497
Cdd:cd20969     1 RAAIRDRKAQqvFVDEGHTVQFVCRADGDPPPAILWLSPRkhlVSAKSNGR------LTVFPD--GTLEVRYAQVQDNGT 72

                          90       100
                  ....*....|....*....|
gi 220902488  498 YACIAENRAGRVQHAARLNI 517
Cdd:cd20969    73 YLCIAANAGGNDSMPAHLHV 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: 40.57 E-value: 6.39e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488 1329 STVTLPCTAVGK---PKREWFKSDVALR---------QGGLHNSQLLdsgdliISSLQLADGGNYSCQVDNGIGTDRLTH 1396
Cdd:cd05750    15 SKLVLKCEATSEnpsPRYRWFKDGKELNrkrpknikiRNKKKNSELQ------INKAKLEDSGEYTCVVENILGKDTVTG 88


                  ....
gi 220902488 1397 TLIV 1400
Cdd:cd05750    89 NVTV 92

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: 40.56 E-value: 6.62e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  808 FSSTSRSVMVKKGDTALLQCAVSGDKPINIVWMRSGkNTLnPSTNYKISVKQEATpdgvsaeLQIRTVDATDSGPYFCRA 887
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDG-VPL-LGKDERITTLENGS-------LQIKGAEKSDTGEYTCVA 72


                  ....*
gi 220902488  888 SNLYG 892
Cdd:cd20952    73 LNLSG 77

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: 40.35 E-value: 6.85e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 220902488  249 VSQDEGAVLLCVAQGCPSPEYSWFThNGAGPLPVLSGPRVRLLGPILAIEAVTGEDSGVYKCTAGN 314
Cdd:cd05868    11 LSPGEDGTLICRANGNPKPSISWLT-NGVPIEIAPTDPSRKVDGDTIIFSKVQERSSAVYQCNASN 75

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: 40.62 E-value: 6.96e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 220902488   51 LDCSASGSPQPTVDWVhADGSAVTEIHGVR---RVLRNGTLVlmpfaaaaYHQDVHNT------IYRCIASNSVGRIV 119
Cdd:cd20956    21 LKCVASGNPLPQITWT-LDGFPIPESPRFRvgdYVTSDGDVV--------SYVNISSVrvedggEYTCTATNDVGSVS 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: 40.61 E-value: 7.04e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 220902488  637 VKGDLPLTINWRKDGRPIDPTQHMSVKQVDQYNSILVIENLGSDHTGNYSCVVRNSAAEVENSQALLV 704
Cdd:cd05857    28 AAGNPTPTMRWLKNGKEFKQEHRIGGYKVRNQHWSLIMESVVPSDKGNYTCVVENEYGSINHTYHLDV 95

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: 7.48e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  423 PVLLYSFIEQTLQPGPAVSLKCSAAGNPTPQISWTLDGFPLPSNGRfmigQYITVHGDVISHVNISHVMVEDGGEYACIA 502
Cdd:cd20975     1 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQR----RFAEEAEGGLCRLRILAAERGDAGFYTCKA 76

                          90
                  ....*....|....*
gi 220902488  503 ENRAGRVQHAARLNI 517
Cdd:cd20975    77 VNEYGARQCEARLEV 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: 40.30 E-value: 7.58e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   30 GPGFVMEPPGRV--EFSNSSGGWLDCSASGSPQPTVDWVHaDGSAVTEIHGVRRVLRNGTLVLM-PFAAAayhqdvHNTI 106
Cdd:cd04967     1 GPVFEEQPDDTIfpEDSDEKKVALNCRARANPVPSYRWLM-NGTEIDLESDYRYSLVDGTLVISnPSKAK------DAGH 73

                          90       100
                  ....*....|....*....|
gi 220902488  107 YRCIASNSVGRIVSRDVQVR 126
Cdd:cd04967    74 YQCLATNTVGSVLSREATLQ 93

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: 40.31 E-value: 7.88e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  331 IQVEISPNVLSVHMGGTAEFRCLVTSNGspvgmQNILWYK-DGRQLPSS---------GRVEDTLVVPRVSRENRGMYQC 400
Cdd:cd04977     1 LQVKIIPSYAEISVGESKFFLCKVSGDA-----KNINWVSpNGEKVLTKhgnlkvvnhGSVLSSLTIYNANINDAGIYKC 75

                          90
                  ....*....|....*...
gi 220902488  401 VVRRPEGDTFQATAELQL 418
Cdd:cd04977    76 VATNGKGTESEATVKLDI 93

Immunoglobulin (Ig)-like domain of human cartilage link protein (LP), and similar domains; The members here are composed of the immunoglobulin (Ig)-like domain similar to that found in human cartilage link protein (LP; also called hyaluronan and proteoglycan link protein). In cartilage, chondroitin-keratan sulfate proteoglycan (CSPG), aggrecan, forms cartilage link protein stabilized aggregates with hyaluronan (HA). These aggregates contribute to the tissue's load bearing properties. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. Members of the vertebrate HPLN (hyaluronan/HA and proteoglycan binding link) protein family are physically linked adjacent to CSPG genes.

Pssm-ID: 409461 Cd Length: 117 Bit Score: 40.77 E-value: 8.01e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488 1313 PARIISFGGpvvrpwrSTVTLPCTAVGKPKRE--------WFK--------SDVALRQGGLHNS--------QLLDSGD- 1367
Cdd:cd05877     4 QAKVFSHRG-------GNVTLPCRYHYEPELSaprkirvkWTKlevdyakeEDVLVAIGTRHKSygsyqgrvFLRRADDl 76

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 220902488 1368 ---LIISSLQLADGGNYSCQVDNGIGTDRLTHTLIVQ 1401
Cdd:cd05877    77 dasLVITDLRLEDYGRYRCEVIDGLEDESVVVALRLR 113

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: 40.23 E-value: 8.91e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   34 VMEPPGRVEFSNSSGGWLDCSASGSPQPTVDWVHaDGSAV---TEIHGVRR-VLRNGTLVLMPFAAAAYHQDvHNTIYRC 109
Cdd:cd07693     3 IVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLK-NGQPLetdKDDPRSHRiVLPSGSLFFLRVVHGRKGRS-DEGVYVC 80

                          90
                  ....*....|...
gi 220902488  110 IASNSVGRIVSRD 122
Cdd:cd07693    81 VAHNSLGEAVSRN 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: 40.08 E-value: 9.39e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  238 PSVVEHT-AHVQVSQDEGAVLLCVAQGCPSPEYSWfTHNGAgPLPVLSGPRV--RLLGPILAIEAVTG--ED-SGVYKCT 311
Cdd:cd05733     1 PTITEQSpKDYIVDPRDNITIKCEAKGNPQPTFRW-TKDGK-FFDPAKDPRVsmRRRSGTLVIDNHNGgpEDyQGEYQCY 78

                          90
                  ....*....|....*
gi 220902488  312 AGNVGGEA-SAELRL 325
Cdd:cd05733    79 ASNELGTAiSNEIRL 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: 39.69 E-value: 1.01e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 220902488 1330 TVTLPCTA-VGKPKRE--WFKSDVALRQGGLHnSQLLDSGDLIISSLQLADGGNYSCQVDNGIGT 1391
Cdd:cd05724    14 MAVLECSPpRGHPEPTvsWRKDGQPLNLDNER-VRIVDDGNLLIAEARKSDEGTYKCVATNMVGE 77

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: 39.09 E-value: 1.07e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 220902488  539 LKCPVAGYPIEEIHWERGGRELPDDIRQRVQPDGSLTISPVQKnSDSGVYTCWARNKQGHSA 600
Cdd:cd05746     3 IPCSAQGDPEPTITWNKDGVQVTESGKFHISPEGYLAIRDVGV-ADQGRYECVARNTIGYAS 63

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: 39.74 E-value: 1.12e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 220902488  257 LLCVAQGCPSPEYSWFTHNGAGPLPVlsgpRVRLLGPILAIEAVTGeDSGVYKCTA-GNVGGE 318
Cdd:cd16082    18 LQCQAWGSPPISYVWYKEQTNNQEPI----KVAALSTLLFKPAVVA-DSGSYFCTAkGRVGSE 75

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: 39.62 E-value: 1.13e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  428 SFIEQ----TLQPGPAVSLKCSAAGNPTPQISWTLDGFPLPSNGRFMIGQYITVHGdvishVNISHVMVEDGGEYACIAE 503
Cdd:cd20949     1 TFTENayvtTVKEGQSATILCEVKGEPQPNVTWHFNGQPISASVADMSKYRILADG-----LLINKVTQDDTGEYTCRAY 75

                          90
                  ....*....|....
gi 220902488  504 NRAGRVQHAARLNI 517
Cdd:cd20949    76 QVNSIASDMQERTV 89

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: 39.91 E-value: 1.13e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  422 PPVLLYSFIEQTLQPGPAVSLKCSAAGNPTPQISWTLDGFPLPSNGrfmiGQYITVHGDviSHVNISHVMVEDGGEYACI 501
Cdd:cd05760     1 PVVLKHPASAAEIQPSSRVTLRCHIDGHPRPTYQWFRDGTPLSDGQ----GNYSVSSKE--RTLTLRSAGPDDSGLYYCC 74


                  ....*...
gi 220902488  502 AENRAGRV 509
Cdd:cd05760    75 AHNAFGSV 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: 39.90 E-value: 1.17e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488 1325 RPWRSTVTLPCTAVGKPKRE--WFKSDVALRQ----GGLHNSQllDSGDLIISSLQLADGGNYSCQVDNGIGTdrLTHTL 1398
Cdd:cd05729    16 LPAANKVRLECGAGGNPMPNitWLKDGKEFKKehriGGTKVEE--KGWSLIIERAIPRDKGKYTCIVENEYGS--INHTY 91


                  ....
gi 220902488 1399 IVQV 1402
Cdd:cd05729    92 DVDV 95

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: 39.54 E-value: 1.27e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  806 PYFSSTSRSVMVKKGDTALLQCAVSGdKPI-NIVWMRSGKNtlnpsTNYKISvkqEATPDGVSAELQIRTVDATDSGPYF 884
Cdd:cd20976     2 PSFSSVPKDLEAVEGQDFVAQCSARG-KPVpRITWIRNAQP-----LQYAAD---RSTCEAGVGELHIQDVLPEDHGTYT 72


                  ....*...
gi 220902488  885 CRASNLYG 892
Cdd:cd20976    73 CLAKNAAG 80

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: 39.70 E-value: 1.35e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 220902488  528 KVTAVSGETLNLKCPVAGYPIEEIHWERGGRE--LPDDIRQRVQPD-GSLTISPVQKNSDS--GVYTCWARNKQG 597
Cdd:cd05733    10 DYIVDPRDNITIKCEAKGNPQPTFRWTKDGKFfdPAKDPRVSMRRRsGTLVIDNHNGGPEDyqGEYQCYASNELG 84

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: 1.36e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  711 IVEPVDANVERNRHIMLHCQAQGVPTPSIVWKKATGSKSGEYEEVRerpftkllGNGSLLLQHVKEDREGFYLCQANNGI 790
Cdd:cd04968     5 VRFPADTYALKGQTVTLECFALGNPVPQIKWRKVDGSPSSQWEITT--------SEPVLEIPNVQFEDEGTYECEAENSR 76


                  .
gi 220902488  791 G 791
Cdd:cd04968    77 G 77

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: 39.49 E-value: 1.37e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 220902488  1329 STVTLPCTAVGKPKR---EWFKSDVALRQGGLHNSQLLDSGD--LIISSLQLADGGNYSCQVDNGIG 1390
Cdd:pfam00047   12 DSATLTCSASTGSPGpdvTWSKEGGTLIESLKVKHDNGRTTQssLLISNVTKEDAGTYTCVVNNPGG 78

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 39.30 E-value: 1.38e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 220902488   817 VKKGDTALLQCAVSGDKPINIVWMRSGKnTLNPSTNYkisvkqeatpdgvsaelQIRTVDATDSGPYFCRASN 889
Cdd:pfam13895   11 VTEGEPVTLTCSAPGNPPPSYTWYKDGS-AISSSPNF-----------------FTLSVSAEDSGTYTCVARN 65

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: 1.40e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  815 VMVKKGDTALLQCAVSGDKPINIVWMRSGKNtLNPSTNYKISVKQeatpdGVSAELQIRTVDATDSGPYFCRASNLYGND 894
Cdd:cd05737    11 VTIMEGKTLNLTCNVWGDPPPEVSWLKNDQA-LAFLDHCNLKVEA-----GRTVYFTINGVSSEDSGKYGLVVKNKYGSE 84

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: 39.09 E-value: 1.41e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 220902488  632 LTCSVvKGDLPLTINWRKDGRPIDPTQHMSVKQvdqyNSILVIENLGSDHTGNYSCVVRNS 692
Cdd:cd05746     3 IPCSA-QGDPEPTITWNKDGVQVTESGKFHISP----EGYLAIRDVGVADQGRYECVARNT 58

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: 39.46 E-value: 1.45e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  709 RWIVEPVDANVErnrhimLHCQAQGVPTPSIVW-KKATGSKSGEYEEVRERPFTkllgngsLLLQHVKEDREGFYLCQAN 787
Cdd:cd05856    12 RVIARPVGSSVR------LKCVASGNPRPDITWlKDNKPLTPPEIGENKKKKWT-------LSLKNLKPEDSGKYTCHVS 78


                  ....
gi 220902488  788 NGIG 791
Cdd:cd05856    79 NRAG 82

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: 39.40 E-value: 1.46e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   51 LDCSASGSPQPTVDWVHaDGSAVTEIHGVRRVLRNGTLVLMpfaaaaYHQDVHNTIYRCIASNSVGrivsrDVQVRAVVA 130
Cdd:cd20952    19 LNCQATGEPVPTISWLK-DGVPLLGKDERITTLENGSLQIK------GAEKSDTGEYTCVALNLSG-----EATWSAVLD 86

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: 39.78 E-value: 1.47e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488 1311 RIPARIISFGGPVVRPWRSTVTLPCTAVG-KP-KREWFKSDVALRQGGL--HNSQLLDSGDLIISSLQL-----ADGGNY 1381
Cdd:cd05735     1 KIPAMITSYPNTTLATKGQKKEMSCTAHGeKPiIVRWEKEDTIINPSEMsrYLVTTKEVGDEVISTLQIlptvrEDSGFF 80

                          90       100
                  ....*....|....*....|
gi 220902488 1382 SCQVDNGIGTDRLTHTLIVQ 1401
Cdd:cd05735    81 SCHAINSYGEDRGIIQLTVQ 100

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: 39.53 E-value: 1.52e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  240 VVEHTAHVQVSQDEGAVLLCVAQGCPSPEYSWFTHNGAgplpVLSGPRVRLL-GPILAIEAVTGEDSGVYKCTAGNVGGE 318
Cdd:cd20968     2 ITRPPTNVTIIEGLKAVLPCTTMGNPKPSVSWIKGDDL----IKENNRIAVLeSGSLRIHNVQKEDAGQYRCVAKNSLGI 77


                  ....*
gi 220902488  319 ASAEL 323
Cdd:cd20968    78 AYSKP 82

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: 39.51 E-value: 1.55e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 220902488 1330 TVTLPCTAVGKPKRE--WFKSDVALrQGGLHNSQLLDSG---DLIISSLQLADGGNYSCQVDNGIGTDRLTHTLIV 1400
Cdd:cd05891    18 TLNLTCTVFGNPDPEviWFKNDQDI-ELSEHYSVKLEQGkyaSLTIKGVTSEDSGKYSINVKNKYGGETVDVTVSV 92

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: 1.67e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 220902488  440 VSLKCSAAGNPTPQISWTLDG--FPLPSNGRfmigqyITVHGD----VISHVNIshVMVEDGGEYACIAENRAG 507
Cdd:cd05733    19 ITIKCEAKGNPQPTFRWTKDGkfFDPAKDPR------VSMRRRsgtlVIDNHNG--GPEDYQGEYQCYASNELG 84

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 38.92 E-value: 1.70e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 220902488   257 LLCVAQGCPSPEYSWFThngaGPLPVLSGPRVRLLgpilaieAVTGEDSGVYKCTAGN-VGGEASAELRLTV 327
Cdd:pfam13895   19 LTCSAPGNPPPSYTWYK----DGSAISSSPNFFTL-------SVSAEDSGTYTCVARNgRGGKVSNPVELTV 79

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: 39.07 E-value: 1.73e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 220902488 1329 STVTLPCTAVGKP--KREWFKSDVAL-RQGGLHNSqlldSGDLIISSLQLADGGNYSCQVDNGIGTDRLTHTLIVQ 1401
Cdd:cd04968    17 QTVTLECFALGNPvpQIKWRKVDGSPsSQWEITTS----EPVLEIPNVQFEDEGTYECEAENSRGKDTVQGRIIVQ 88

First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domain A168 within the A-band segment of human cardiac titin. 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 structures of the titin-A168169 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: 409563 Cd Length: 93 Bit Score: 39.38 E-value: 1.80e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 220902488  534 GETLNLKCPVAGYPIEEIHWERGGRELPDDiRQRVQPDGS-----LTISPVQKNSDSGVYTCWARNKQGHSA 600
Cdd:cd20971    16 QSNATLVCKVTGHPKPIVKWYRQGKEIIAD-GLKYRIQEFkggyhQLIIASVTDDDATVYQVRATNQGGSVS 86

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: 1.84e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  612 PKLSPFQTNILQlnMGDRASLTCSVVKGDLPLTINWRKDGRPIDPTQHMSVK-QVDQYNSILVIENLGSDHTGNYSCVVR 690
Cdd:cd05750     1 PKLKEMKSQTVQ--EGSKLVLKCEATSENPSPRYRWFKDGKELNRKRPKNIKiRNKKKNSELQINKAKLEDSGEYTCVVE 78


                  .
gi 220902488  691 N 691
Cdd:cd05750    79 N 79

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: 2.05e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 220902488  535 ETLNLKCPVAGYPIEEIHWERGGREL---PDDIRQRVqpDGSLTISPVQKNSDSGVYTCWARNKQGhsARRSGEVTV 608
Cdd:cd04967    20 KKVALNCRARANPVPSYRWLMNGTEIdleSDYRYSLV--DGTLVISNPSKAKDAGHYQCLATNTVG--SVLSREATL 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: 38.32 E-value: 2.06e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 220902488 1331 VTLPCTAVGKPKR--EWFKSDVALRQGG-LHNSQlldSGDLIISSLQLADGGNYSCQVDNGIG 1390
Cdd:cd05746     1 VQIPCSAQGDPEPtiTWNKDGVQVTESGkFHISP---EGYLAIRDVGVADQGRYECVARNTIG 60

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: 39.31 E-value: 2.08e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  708 PRWIVEPVDANVERNRHIMLHCQAQGVPTPSIVWK---KATGSKSGEYEEVRERpftkllGNGSLLLQHVKEDREGFYLC 784
Cdd:cd20990     1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQldgKPIRPDSAHKMLVREN------GVHSLIIEPVTSRDAGIYTC 74


                  ....*..
gi 220902488  785 QANNGIG 791
Cdd:cd20990    75 IATNRAG 81

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: 39.11 E-value: 2.11e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  632 LTCsVVKGDLPLTINWRKDGRPIDPTQHMSVKQVDQYNSILVIENLGSDHTGNYSCVVRN 691
Cdd:cd05737    21 LTC-NVWGDPPPEVSWLKNDQALAFLDHCNLKVEAGRTVYFTINGVSSEDSGKYGLVVKN 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: 39.14 E-value: 2.12e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  622 LQLNMGDRASLTCSVVKGDLPlTINWRKDGR---PIDPTQHMSVKQVDqynSILVIENLGSDHTGNYSCVVRNSAAEVEN 698
Cdd:cd05763     9 ITIRAGSTARLECAATGHPTP-QIAWQKDGGtdfPAARERRMHVMPED---DVFFIVDVKIEDTGVYSCTAQNSAGSISA 84


                  ....*.
gi 220902488  699 SQALLV 704
Cdd:cd05763    85 NATLTV 90

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: 2.13e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  238 PSVVEHTAHVQVSQD--EGAVLL-CVAQGCPSPEYSWFTHNGAgpLPVLSGPRVRLLGPILAIE-AVTGEDSGVYKCTAG 313
Cdd:cd04967     2 PVFEEQPDDTIFPEDsdEKKVALnCRARANPVPSYRWLMNGTE--IDLESDYRYSLVDGTLVISnPSKAKDAGHYQCLAT 79

                          90
                  ....*....|....*.
gi 220902488  314 N-VGGEASAELRLTVA 328
Cdd:cd04967    80 NtVGSVLSREATLQFG 95

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: 2.27e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  437 GPAVSLKCSAAGNPTPQISWTL-DGFPLPSNGRFMIGQYITvhgdvishVNISHVMVEDGGEYACIAENRAGRVQHAARL 515
Cdd:cd05764    15 GQRATLRCKARGDPEPAIHWISpEGKLISNSSRTLVYDNGT--------LDILITTVKDTGAFTCIASNPAGEATARVEL 86


                  ..
gi 220902488  516 NI 517
Cdd:cd05764    87 HI 88

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: 39.14 E-value: 2.32e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  625 NMGDRASLTCSVVKGDLPlTINWRKDGRPIDPTQHMSVKQVDqyNSILVIENLGSDHTGNYSCVVRNSAAEVENSQALLV 704
Cdd:cd05730    16 NLGQSVTLACDADGFPEP-TMTWTKDGEPIESGEEKYSFNED--GSEMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKV 92

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: 2.41e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 220902488  437 GPAVSLKCSAAGNPTPQISWTLDGFPLPSNGRFMigqyITVHgDVISHVNISHVMVEDGGEYACIAENRAG 507
Cdd:cd05748     7 GESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQ----IETT-ASSTSLVIKNAKRSDSGKYTLTLKNSAG 72

First immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR). 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 all FGFs.

Pssm-ID: 409362 Cd Length: 94 Bit Score: 39.11 E-value: 2.45e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  420 DAPPVLLYSFIE-QTLQPGPAVSLKCSAAgNPTPQISWTLDGFPLPSNGR-FMIGQYITVHGDVishvnishvmVEDGGE 497
Cdd:cd04973     6 EAPPTYQISEVEsYSAHPGDLLQLRCRLR-DDVQSINWTKDGVQLGENNRtRITGEEVQIKDAV----------PRDSGL 74


                  ....*
gi 220902488  498 YACIA 502
Cdd:cd04973    75 YACVT 79

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: 2.48e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 220902488  253 EGAVLLCVAQGCPSPEYSWFThNGAGPLPVLSgPRVRLL--GPILAIEAVTGEDSGVYKCTAGNVGG 317
Cdd:cd05736    16 VEASLRCHAEGIPLPRVQWLK-NGMDINPKLS-KQLTLIanGSELHISNVRYEDTGAYTCIAKNEGG 80

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: 38.98 E-value: 2.52e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  708 PRWIVEPVDANVERNRHIMLHCQAQGVPTPSIVWKKatGSKSGEYEEVRERPFTKLLGNGSLLLQHVKEDREGFYLCQAN 787
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKK--NNEMLQYNTDRISLYQDNCGRICLLIQNANKKDAGWYTVSAV 78


                  ....
gi 220902488  788 NGIG 791
Cdd:cd05892    79 NEAG 82

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: 39.17 E-value: 2.57e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 220902488  534 GETLNLKCPVAGYPIEEIHWERGGRE--------LPDDIRQRVQPDGSLTISPVQKnSDSGVYTCWARNKQG 597
Cdd:cd05726    14 GRTVTFQCETKGNPQPAIFWQKEGSQnllfpyqpPQPSSRFSVSPTGDLTITNVQR-SDVGYYICQALNVAG 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: 38.53 E-value: 2.58e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488 1323 VVRPWRSTVTLPCTAVG--KPKREWFKSDVALrQGGLHNSQLLDSGdLIISSLQLADGGNYSCQVDNGIGTDRLTHTLIV 1400
Cdd:cd20978    11 VVVKGGQDVTLPCQVTGvpQPKITWLHNGKPL-QGPMERATVEDGT-LTIINVQPEDTGYYGCVATNEIGDIYTETLLHV 88

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: 39.07 E-value: 2.60e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  437 GPAVSLKCSAAGNPTPQIS--WTLDGFPL---PSNGRFMIGQYITVHGDVIshvnISHVMVEDGGEYACIAENRAGRVQH 511
Cdd:cd04970    17 GENATLQCHASHDPTLDLTftWSFNGVPIdleKIEGHYRRRYGKDSNGDLE----IVNAQLKHAGRYTCTAQTVVDSDSA 92

                          90
                  ....*....|
gi 220902488  512 AARLNIYGLP 521
Cdd:cd04970    93 SATLVVRGPP 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: 38.58 E-value: 2.61e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  709 RWIVEPVDANVERNRHIMLHCQAQGVPTPSIVWkkatgSKSGEYEEVRERPFTKLLGNGSLLLQHVKEDREGFYLCQANN 788
Cdd:cd04978     1 YWIIEPPSLVLSPGETGELICEAEGNPQPTITW-----RLNGVPIEPAPEDMRRTVDGRTLIFSNLQPNDTAVYQCNASN 75


                  ....
gi 220902488  789 GIGT 792
Cdd:cd04978    76 VHGY 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: 38.74 E-value: 2.62e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  806 PYFSSTS----RSVMVKKGDTALLQCAVSGDKPINIVWMRSGKntlnpstnykiSVKQEATPDGVSAE-----LQIRTVD 876
Cdd:cd05729     1 PRFTDTEkmeeREHALPAANKVRLECGAGGNPMPNITWLKDGK-----------EFKKEHRIGGTKVEekgwsLIIERAI 69

                          90
                  ....*....|....*.
gi 220902488  877 ATDSGPYFCRASNLYG 892
Cdd:cd05729    70 PRDKGKYTCIVENEYG 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: 2.67e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  238 PSVVEHTAHVQVSQDEGAVLLCVAQGCPSPEYSWFTHNGAGPLPVLSGPRVRllGPI-------LAIEAVTGEDSGVYKC 310
Cdd:cd05765     1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEKQVPGKENLIMRPNHVR--GNVvvtnigqLVIYNAQPQDAGLYTC 78

                          90
                  ....*....|....*..
gi 220902488  311 TAGNVGGEASAELRLTV 327
Cdd:cd05765    79 TARNSGGLLRANFPLSV 95

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: 39.00 E-value: 2.69e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  807 YFSSTSRSVMVKKGDTALLQCAVSGDKPINIVWMRSGKnTLNPSTNYkisvKQEATPDG---VSAELQIRTvDATDSGPY 883
Cdd:cd05722     3 YFLSEPSDIVAMRGGPVVLNCSAESDPPPKIEWKKDGV-LLNLVSDE----RRQQLPNGsllITSVVHSKH-NKPDEGFY 76


                  ....*.
gi 220902488  884 FCRASN 889
Cdd:cd05722    77 QCVAQN 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: 39.00 E-value: 2.72e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488 1313 PARIISF-GGPVVrpwrstvtLPCTAVGK--PKREWFKSDVALRQGGLHNSQLLDSGDLIISSLQLA-----DGGNYSCQ 1384
Cdd:cd05722     8 PSDIVAMrGGPVV--------LNCSAESDppPKIEWKKDGVLLNLVSDERRQQLPNGSLLITSVVHSkhnkpDEGFYQCV 79


                  ....
gi 220902488 1385 VDNG 1388
Cdd:cd05722    80 AQNE 83

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: 38.68 E-value: 2.79e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488 1326 PWRSTVTLPCTAVG--KPKREWFKSDVALRQ----GGLHNSQLLDSgdLIISSLQLADGGNYSCQVDNGIGTDRLTHTLI 1399
Cdd:cd05857    17 PAANTVKFRCPAAGnpTPTMRWLKNGKEFKQehriGGYKVRNQHWS--LIMESVVPSDKGNYTCVVENEYGSINHTYHLD 94


                  .
gi 220902488 1400 V 1400
Cdd:cd05857    95 V 95

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: 38.74 E-value: 2.98e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 220902488  257 LLCVAQGCPSPEYSWFTHNGA-GPLPVLSGPRVRLLGPILAIEAVTGEDSGVYKCTAGNVGGEASAELRLTV 327
Cdd:cd05729    24 LECGAGGNPMPNITWLKDGKEfKKEHRIGGTKVEEKGWSLIIERAIPRDKGKYTCIVENEYGSINHTYDVDV 95

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: 38.54 E-value: 3.07e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  806 PYFSSTSRSVMVKKGDTALLQCAVSGDKPINIVWMRSGKnTLNPSTNYKISVKQeatpDGVSAeLQIRTVDATDSGPYFC 885
Cdd:cd20990     1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGK-PIRPDSAHKMLVRE----NGVHS-LIIEPVTSRDAGIYTC 74


                  ....*....
gi 220902488  886 RASNLYGND 894
Cdd:cd20990    75 IATNRAGQN 83

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: 38.76 E-value: 3.34e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 220902488  536 TLNLKCPVAGYPIEEIHWERGGRELPDDirqrvqpDGSLTISPVQKN--------SDSGVYTCWARNKQGH 598
Cdd:cd05760    18 RVTLRCHIDGHPRPTYQWFRDGTPLSDG-------QGNYSVSSKERTltlrsagpDDSGLYYCCAHNAFGS 81

IL-1 receptor-like protein; Provisional

Pssm-ID: 165173 [Multi-domain] Cd Length: 227 Bit Score: 41.05 E-value: 3.35e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  573 SLTISPVqKNSDSGVYTCWARNKQghsarRSGEVTVIVPPKLSPFQtniLQLNMGDRASLTCSVVKGDLPL----TINWR 648
Cdd:PHA02826   99 NLWIGNV-INIDEGIYICTISSGN-----ICEESTIRLTFDSGTIN---YQFNSGKDSKLHCYGTDGISSTfkdyTLTWY 169

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 220902488  649 KDGRPIDPTQHMsvkQVDQYNSILVIENLGSDHTGNYSCVVR 690
Cdd:PHA02826  170 KNGNIVLYTDRI---QLRNNNSTLVIKSATHDDSGIYTCNLR 208

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: 38.33 E-value: 3.38e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 220902488   340 LSVHMGGTAEFRCLVTSNGSPVgmqNILWYKDGRQLPSSGRVED--------TLVVPRVSRENRGMYQCVVR 403
Cdd:pfam00047    6 VTVLEGDSATLTCSASTGSPGP---DVTWSKEGGTLIESLKVKHdngrttqsSLLISNVTKEDAGTYTCVVN 74

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: 38.74 E-value: 3.51e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 220902488  533 SGETLNLKCPVAGYPIEEIHWERGGRELPDDIRQ---RVQPDGSLTISPVQKNSDSGVYTCWARNKQG 597
Cdd:cd05729    18 AANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIggtKVEEKGWSLIIERAIPRDKGKYTCIVENEYG 85

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: 38.40 E-value: 3.63e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 220902488  727 LHCQAQGVPTPSIVWkkatgSKSGEYEEVRERPFTKLLGNGS-LLLQHVKEDREGFYLCQANNGIG 791
Cdd:cd05736    20 LRCHAEGIPLPRVQW-----LKNGMDINPKLSKQLTLIANGSeLHISNVRYEDTGAYTCIAKNEGG 80

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: 38.21 E-value: 3.88e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  423 PVLLYSFIEQTLQPGPAVSLKCSAAGNPTPQISWTLDGFPLPSNgrfmiGQYITVHGDVISHVN--ISHVMVEDGGEYAC 500
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYN-----TDRISLYQDNCGRICllIQNANKKDAGWYTV 75

                          90
                  ....*....|....*..
gi 220902488  501 IAENRAGRVQHAARLNI 517
Cdd:cd05892    76 SAVNEAGVVSCNARLDV 92

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: 38.16 E-value: 4.14e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 220902488  628 DRASLTCSVvKGDLPLTINWRKDGRPIDPTQHMSVkQVDQYNSILVIENLGS---DHTGNYSCVVRN 691
Cdd:cd05733    17 DNITIKCEA-KGNPQPTFRWTKDGKFFDPAKDPRV-SMRRRSGTLVIDNHNGgpeDYQGEYQCYASN 81

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: 37.94 E-value: 4.40e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 220902488   431 EQTLQPGPAVSLKCSA-AGNPTPQISWTLDGfplpsnGRFMIGQYITVHGDVISH--VNISHVMVEDGGEYACIAENR 505
Cdd:pfam00047    5 TVTVLEGDSATLTCSAsTGSPGPDVTWSKEG------GTLIESLKVKHDNGRTTQssLLISNVTKEDAGTYTCVVNNP 76

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: 38.16 E-value: 4.86e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  238 PSVVEHTAHVQVSQDEGAVLLCVAQGCPSPEYSWftHNGAGPLPVLSGPR--VRLLG-PILAIEAVTGEDSGVYKCTAGN 314
Cdd:cd20990     1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSW--QLDGKPIRPDSAHKmlVRENGvHSLIIEPVTSRDAGIYTCIATN 78

                          90
                  ....*....|...
gi 220902488  315 VGGEASAELRLTV 327
Cdd:cd20990    79 RAGQNSFNLELVV 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: 38.00 E-value: 4.94e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  707 PPRWIVEPVDANVERNRHIMLHCQAQGVPTPSIVWkkatgSKSGEYEEVRERPFTKLLGNGSLLLQHVKEDREGFYLCQA 786
Cdd:cd20976     1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITW-----IRNAQPLQYAADRSTCEAGVGELHIQDVLPEDHGTYTCLA 75


                  ....*.
gi 220902488  787 NNGIGT 792
Cdd:cd20976    76 KNAAGQ 81

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: 37.86 E-value: 5.36e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  621 ILQLNMGDRASLTCSVvKGDLPLTINWRKDGRPIDPTQHMSVKQVDQYNSILVIENLGSDHTGNYSCVVRNSAAEVENSQ 700
Cdd:cd05744     9 DLEVQEGRLCRFDCKV-SGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRAGENSFNA 87


                  ....
gi 220902488  701 ALLV 704
Cdd:cd05744    88 ELVV 91

Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in Perlecan. Perlecan is a large multi-domain heparin sulfate proteoglycan, important in tissue development and organogenesis. Perlecan can be represented as 5 major portions; its fourth major portion (domain IV) is a tandem repeat of immunoglobulin-like domains (Ig2-Ig15) which can vary in size due to alternative splicing. Perlecan binds many cellular and extracellular ligands. Its domain IV region has many binding sites. Some of these have been mapped at the level of individual Ig-like domains, including a site restricted to the Ig5 domain for heparin/sulfatide, a site restricted to the Ig3 domain for nidogen-1 and nidogen-2, a site restricted to Ig4-5 for fibronectin, and sites restricted to Ig2 and to Ig13-15 for fibulin-2. 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: 409412 Cd Length: 85 Bit Score: 37.54 E-value: 5.69e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 220902488 1324 VRPWRsTVTLPCTAVGK---PKREWFKSDvalrqGGLHNSQLLDSGDLIISSLQLADGGNYSCQVDNGIGTDRLTHTLI 1399
Cdd:cd05754    13 VRPGA-DVSFICRAKSKspaYTLVWTRVN-----GTLPSRAMDFNGILTIRNVQLSDAGTYVCTGSNMLDTDEATATLY 85

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: 37.55 E-value: 5.71e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  722 NRHIMLHCQAQGVPTPSIVWKKATgsksgeyeevRERPFT---KLLGNGSLLLQHV-KEDREGFYLCQANNGIGTGIGKV 797
Cdd:cd20958    15 GQTLRLHCPVAGYPISSITWEKDG----------RRLPLNhrqRVFPNGTLVIENVqRSSDEGEYTCTARNQQGQSASRS 84


                  ....*
gi 220902488  798 IQLKV 802
Cdd:cd20958    85 VFVKV 89

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: 37.84 E-value: 5.92e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 220902488   51 LDCSASGSPQPTVDWVHADGSAVTEiHGVRRVLRNGTLVLMPFAAAAYhqdvhnTIYRCIASNSVG 116
Cdd:cd05764    20 LRCKARGDPEPAIHWISPEGKLISN-SSRTLVYDNGTLDILITTVKDT------GAFTCIASNPAG 78

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: 37.81 E-value: 5.94e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 220902488  624 LNMGDRASLTCSVvKGDLPLTINWRKDGRPIDPTQHMSVKQVDQynSILVIENLGSDHTGNYSCVVRN 691
Cdd:cd04978    11 LSPGETGELICEA-EGNPQPTITWRLNGVPIEPAPEDMRRTVDG--RTLIFSNLQPNDTAVYQCNASN 75

Immunoglobulin (Ig)-like domain of semaphorin 4D (Sema4D) and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of semaphorin 4D (Sema4D) and similar proteins. Sema4D is a Class IV semaphorin. Semaphorins are classified based on structural features additional to the Sema domain. Sema4D has extracellular Sema and Ig domains, a transmembrane domain, and a short cytoplasmic domain. Sema4D plays a part in the development of GABAergic synapses. Sema4D in addition is an immune semaphorin. It is abundant on resting T cells; its expression is weak on resting B cells and antigen presenting cells (APCs), but is upregulated by various stimuli. The receptor used by Sema4D in the immune system is CD72. Sem4D enhances the activation of B cells and DCs through binding CD72, perhaps by reducing CD72s inhibitory signals. The receptor used by Sema4D in the non-lymphatic tissues is plexin-B1. Sem4D is anchored to the cell surface but its extracellular domain can be released from the cell surface by a metalloprotease-dependent process. Sem4D may mediate its effects in its membrane-bound form and/or its cleaved form.

Pssm-ID: 409457 Cd Length: 87 Bit Score: 37.49 E-value: 6.01e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 220902488  431 EQTLQPGPAVSLKCSAAGNpTPQISWTLDGFPLP-SNGRFmigqyiTVHGDVIShvnISHVMVEDGGEYACIAENRA 506
Cdd:cd05873     5 QRTFKLGGNAELKCSPKSN-LARVVWKFQGKVLKaESPKY------GLYGDGLL---IFNASEADAGRYQCLSVEKS 71

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: 6.14e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 220902488  251 QDEGAVLLCVAQGCPSPEYSWFThngagplpvlsGPRVRLLGPILAIEAVTGEDSGVYKCTAGNVGGEASAELRLTV 327
Cdd:cd20948     9 SGENLNLSCHAASNPPAQYSWTI-----------NGTFQTSSQELFLPAITENNEGTYTCSAHNSLTGKNISLVLSV 74

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

Pssm-ID: 462230 Cd Length: 109 Bit Score: 38.21 E-value: 6.31e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488   138 EVLSAARGCTAILRCVVPTFVKELVRVVSW-------VHEPAIYIYPSLQG----DGKFHLLPT-----GELLIHNLQES 201
Cdd:pfam07686    4 REVTVALGGSVTLPCTYSSSMSEASTSVYWyrqppgkGPTFLIAYYSNGSEegvkKGRFSGRGDpsngdGSLTIQNLTLS 83


                   ..
gi 220902488   202 DE 203
Cdd:pfam07686   84 DS 85

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: 37.68 E-value: 6.38e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  240 VVEHTAHvQVSQDEGAVLLCVAQGCPSPEYSWftHNGAGPLP-----VLSGPRVRLLGP-ILAIEAVTGEDSGVYKCTAG 313
Cdd:cd20954     5 IVEPVDA-NVAAGQDVMLHCQADGFPTPTVTW--KKATGSTPgeykdLLYDPNVRILPNgTLVFGHVQKENEGHYLCEAK 81

                          90
                  ....*....|....*
gi 220902488  314 N-VGGEASAELRLTV 327
Cdd:cd20954    82 NgIGSGLSKVIFLKV 96

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: 37.48 E-value: 6.78e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  806 PYFSSTSRSVMVKKGDTALLQCAVSGDKPINIVWMRSGKnTLNPSTNYKISVKqeatpDGVSAELQIRTVDATDSGPYFC 885
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGK-PVRPDSAHKMLVR-----ENGRHSLIIEPVTKRDAGIYTC 74


                  ....*..
gi 220902488  886 RASNLYG 892
Cdd:cd05744    75 IARNRAG 81

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: 36.84 E-value: 7.66e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 220902488  257 LLCVAQGCPSPEYSWftHNGAGPLPVlSGPRVRLLGPILAIEAVTGEDSGVYKCTAGNVGGEASAELRLTV 327
Cdd:cd05745     7 FLCEAQGYPQPVIAW--TKGGSQLSV-DRRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in Perlecan. Perlecan is a large multi-domain heparin sulfate proteoglycan, important in tissue development and organogenesis. Perlecan can be represented as 5 major portions; its fourth major portion (domain IV) is a tandem repeat of immunoglobulin-like domains (Ig2-Ig15) which can vary in size due to alternative splicing. Perlecan binds many cellular and extracellular ligands. Its domain IV region has many binding sites. Some of these have been mapped at the level of individual Ig-like domains, including a site restricted to the Ig5 domain for heparin/sulfatide, a site restricted to the Ig3 domain for nidogen-1 and nidogen-2, a site restricted to Ig4-5 for fibronectin, and sites restricted to Ig2 and to Ig13-15 for fibulin-2. 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: 409412 Cd Length: 85 Bit Score: 37.15 E-value: 7.94e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  240 VVEHTAHVQVSQDEGAVLLCVAQG-CPSPEYSWFTHNGagPLPvlsgPRVRLLGPILAIEAVTGEDSGVYKCTAGNVGG- 317
Cdd:cd05754     4 TVEEPRSQEVRPGADVSFICRAKSkSPAYTLVWTRVNG--TLP----SRAMDFNGILTIRNVQLSDAGTYVCTGSNMLDt 77


                  ....*..
gi 220902488  318 -EASAEL 323
Cdd:cd05754    78 dEATATL 84

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: 37.53 E-value: 8.15e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  806 PYFSSTSRsvMVKK------GDTALLQCAVSGDKPINIVWMRSGKntlnpstnykiSVKQEATPDGVSAELQ-----IRT 874
Cdd:cd05857     1 PYWTNPEK--MEKKlhavpaANTVKFRCPAAGNPTPTMRWLKNGK-----------EFKQEHRIGGYKVRNQhwsliMES 67

                          90
                  ....*....|....*....
gi 220902488  875 VDATDSGPYFCRASNLYGN 893
Cdd:cd05857    68 VVPSDKGNYTCVVENEYGS 86

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: 37.60 E-value: 8.19e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 220902488   51 LDCSASGSPQPTVDWvHADGSAVTEIHGVRRVLRNGTLVLM-PFAAaayhQDVhnTIYRCIASNSVGRIVSRDVQVR 126
Cdd:cd05850    25 LACRARASPPATYRW-KMNGTELKMEPDSRYRLVAGNLVISnPVKA----KDA--GSYQCLASNRRGTVVSREASLR 94

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: 37.18 E-value: 8.49e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 220902488  711 IVEPVDANVERNRHIMLHCQAQGVPTPSIVWkkatgSKSGEYeeVRERPFTKLLGNGSL-LLQHVKEDrEGFYLCQANNG 789
Cdd:cd05723     1 LKKPSNIYAHESMDIVFECEVTGKPTPTVKW-----VKNGDV--VIPSDYFKIVKEHNLqVLGLVKSD-EGFYQCIAEND 72


                  ..
gi 220902488  790 IG 791
Cdd:cd05723    73 VG 74

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: 37.37 E-value: 8.70e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 220902488   51 LDCSASGSPQPTVDWVHADGSAVT-EIHGVRRVLRNGTLVLMpfaaaaYHQDVHNTIYRCIASNSVGRiVSRDVQVR 126
Cdd:cd20969    22 FVCRADGDPPPAILWLSPRKHLVSaKSNGRLTVFPDGTLEVR------YAQVQDNGTYLCIAANAGGN-DSMPAHLH 91