NCBI Conserved Domain Search

Laminin B domain;

Pssm-ID: 214597 Cd Length: 127 Bit Score: 177.07 E-value: 5.66e-51

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  1578 RGQTLYWKLPEKFLGDKVTSYGGTLEYTFKFSGN--GNSDQSADVILRGNDIALQYKHREPFYADRENKVQIKIIETSWQ 1655
Cdd:smart00281    1 DNEPVYWVAPEQFLGDKVTSYGGKLRYTLSFDGRrgGTHVSAPDVILEGNGLRISHPAEGPPLPDELTTVEVRFREENWQ 80

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*..
gi 1799133945  1656 RVDGQQATREHLLMTLADLDTLLIKSTYNDDCTDSQLLSANLEFAEP 1702
Cdd:smart00281   81 YYGGRPVTREDLMMVLANLTAILIRATYSQQMAGSRLSDVSLEVAVP 127

Laminin B domain;

Pssm-ID: 214597 Cd Length: 127 Bit Score: 168.59 E-value: 4.96e-48

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  1286 DGVAKYWRLPQRFLGDKVTAYGGKMEFEIEFSGS--GHHSSEPMVVLKGNQNILVHRvrnQEHVLRSDSPVRITVETYET 1363
Cdd:smart00281    1 DNEPVYWVAPEQFLGDKVTSYGGKLRYTLSFDGRrgGTHVSAPDVILEGNGLRISHP---AEGPPLPDELTTVEVRFREE 77

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|
gi 1799133945  1364 NYEQLNGAAATREDLLMVLADLDAFLIRATHVAHQTSTSLGDVSWEIAVD 1413
Cdd:smart00281   78 NWQYYGGRPVTREDLMMVLANLTAILIRATYSQQMAGSRLSDVSLEVAVP 127

Laminin B (Domain IV);

Pssm-ID: 459652 Cd Length: 136 Bit Score: 157.43 E-value: 5.32e-44

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1583 YWKLPEKFLGDKVTSYGGTLEYTFKFS---GNGNSDQSADVILRGNDIALQYKHREPFYADR--ENKVQIKIIETSWQRV 1657
Cdd:pfam00052    1 YWSAPEQFLGNKLTSYGGYLTYTVRYEplpGGGSLNSEPDVILEGNGLRLSYSSPDQPPPDPgqEQTYSVRLHEENWRDS 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1799133945 1658 DGQQATREHLLMTLADLDTLLIKSTYNDDCTDSQLLSANLEFAEPYGQGLTAAEVE 1713
Cdd:pfam00052   81 DGAPVSREDFMMVLANLTAILIRATYSTGSGQVSLSNVSLDSAVPGGSGPPASWVE 136

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: 153.80 E-value: 1.66e-43

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1799133945 1075 GTTFSLTCKAVAVPEPYINWRLNWGPVCEPPRCLQTSEGGYGTLTIHDAQPVDQGAYTCEAINVKGRVLATPDCIVRV 1152
Cdd:cd05743      1 GETVEFTCVATGVPTPIINWRLNWGHVPDSARVSITSEGGYGTLTIRDVKESDQGAYTCEAINTRGMVFGIPDGILTV 78

Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of purposes including signal transduction via cell-surface steroid receptors, adhesion, migration and differentiation through mediation of cell adhesion molecules.

Pssm-ID: 238058 [Multi-domain] Cd Length: 151 Bit Score: 151.80 E-value: 8.16e-42

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 3882 AARFDGDAFIELSSDEFPHLTSEkdeiVAFKFKTEQQNGVLLWQGQRPTvqqmEDYISVGIVNGHLHFSYELGGGAAHLI 3961
Cdd:cd00110      1 GVSFSGSSYVRLPTLPAPRTRLS----ISFSFRTTSPNGLLLYAGSQNG----GDFLALELEDGRLVLRYDLGSGSLVLS 72

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1799133945 3962 SEERVDDGKEHSVRFERKGREGQMRIDNYREVDGRSTGILAMLNVDGNIFVGGVPDISKATGGLFSNNFVGCIADVELN 4040
Cdd:cd00110     73 SKTPLNDGQWHSVSVERNGRSVTLSVDGERVVESGSPGGSALLNLDGPLYLGGLPEDLKSPGLPVSPGFVGCIRDLKVN 151

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: 143.85 E-value: 6.00e-40

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  834 VQITVF-PSEKEVRDGRDVSFECRARTSdnSVYPTVRWARVGGPLPSSAHDSGGRLTINPVQLSDAGTYICVSDYNGNTV 912
Cdd:cd05754      1 IQVTVEePRSQEVRPGADVSFICRAKSK--SPAYTLVWTRVNGTLPSRAMDFNGILTIRNVQLSDAGTYVCTGSNMLDTD 78


                   ....*..
gi 1799133945  913 EARATLS 919
Cdd:cd05754     79 EATATLY 85

Laminin B (Domain IV);

Pssm-ID: 459652 Cd Length: 136 Bit Score: 145.11 E-value: 1.14e-39

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1291 YWRLPQRFLGDKVTAYGGKMEFEIEFSGSGHHS---SEPMVVLKGNQNILVHRVRNQEHvLRSDSPVRITVETYETNYEQ 1367
Cdd:pfam00052    1 YWSAPEQFLGNKLTSYGGYLTYTVRYEPLPGGGslnSEPDVILEGNGLRLSYSSPDQPP-PDPGQEQTYSVRLHEENWRD 79

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1799133945 1368 LNGAAATREDLLMVLADLDAFLIRATHVAHQTSTSLGDVSWEIAVDRYTPDgLALEVE 1425
Cdd:pfam00052   80 SDGAPVSREDFMMVLANLTAILIRATYSTGSGQVSLSNVSLDSAVPGGSGP-PASWVE 136

Laminin G domain;

Pssm-ID: 214598 [Multi-domain] Cd Length: 132 Bit Score: 144.02 E-value: 2.14e-39

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  3909 VAFKFKTEQQNGVLLWQGQRPTVqqmeDYISVGIVNGHLHFSYELGGGAAHLISE-ERVDDGKEHSVRFERKGREGQMRI 3987
Cdd:smart00282    2 ISFSFRTTSPNGLLLYAGSKGGG----DYLALELRDGRLVLRYDLGSGPARLTSDpTPLNDGQWHRVAVERNGRSVTLSV 77

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 1799133945  3988 DNYREVDGRSTGILAMLNVDGNIFVGGVPDISKATGGLFSNNFVGCIADVELNGV 4042
Cdd:smart00282   78 DGGNRVSGESPGGLTILNLDGPLYLGGLPEDLKLPPLPVTPGFRGCIRNLKVNGK 132

Laminin G domain; This family includes the Thrombospondin N-terminal-like domain, a Laminin G subfamily.

Pssm-ID: 460494 [Multi-domain] Cd Length: 126 Bit Score: 125.61 E-value: 5.42e-33

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 3913 FKTEQQNGVLLWQGQRPTvqqmeDYISVGIVNGHLHFSYELGGGAAHLIS-EERVDDGKEHSVRFERKGREGQMRIDNYR 3991
Cdd:pfam02210    1 FRTRQPNGLLLYAGGGGS-----DFLALELVNGRLVLRYDLGSGPESLLSsGKNLNDGQWHSVRVERNGNTLTLSVDGQT 75

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1799133945 3992 EVDGRSTGILAMLNVDGNIFVGGVPDISKATGGLFSNNFVGCIADVELNGV 4042
Cdd:pfam02210   76 VVSSLPPGESLLLNLNGPLYLGGLPPLLLLPALPVRAGFVGCIRDVRVNGE 126

Laminin G domain;

Pssm-ID: 395008 [Multi-domain] Cd Length: 131 Bit Score: 118.57 E-value: 1.68e-30

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 3913 FKTEQQNGVLLWQGQRPTvqqmEDYISVGIVNGHLHFSYELGGGAAHLISEERVDDGKEHSVRFERKGREGQMRIDNYRE 3992
Cdd:pfam00054    1 FRTTEPSGLLLYNGTQTE----RDFLALELRDGRLEVSYDLGSGAAVVRSGDKLNDGKWHSVELERNGRSGTLSVDGEAR 76

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1799133945 3993 VDGRS-TGILAMLNVDGNIFVGGVPDISKATGGL-FSNNFVGCIADVELNGVKLD 4045
Cdd:pfam00054   77 PTGESpLGATTDLDVDGPLYVGGLPSLGVKKRRLaISPSFDGCIRDVIVNGKPLD 131

Laminin G domain;

Pssm-ID: 214598 [Multi-domain] Cd Length: 132 Bit Score: 82.00 E-value: 1.33e-17

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  3513 SIKMKLRPQadSDEHILMYFASDygsNTKQYTSLSLIANQVVLTVRRPDKEVQ-KIRSETLEAGELIDVAVRQAGNALVM 3591
Cdd:smart00282    1 SISFSFRTT--SPNGLLLYAGSK---GGGDYLALELRDGRLVLRYDLGSGPARlTSDPTPLNDGQWHRVAVERNGRSVTL 75

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....*..
gi 1799133945  3592 TVDG----NQVSTIETDTLKPGTEIFIGGLPPGLNSPDDVVEQSFQGCVYEILINSQ 3644
Cdd:smart00282   76 SVDGgnrvSGESPGGLTILNLDGPLYLGGLPEDLKLPPLPVTPGFRGCIRNLKVNGK 132

Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of purposes including signal transduction via cell-surface steroid receptors, adhesion, migration and differentiation through mediation of cell adhesion molecules.

Pssm-ID: 238058 [Multi-domain] Cd Length: 151 Bit Score: 78.61 E-value: 3.13e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 3493 PLGFTSdTSFLAVKRPV---KFESIKMKLRPqaDSDEHILMYFASDygsNTKQYTSLSLIANQVVLTVRRPDKEVqKIRS 3569
Cdd:cd00110      1 GVSFSG-SSYVRLPTLPaprTRLSISFSFRT--TSPNGLLLYAGSQ---NGGDFLALELEDGRLVLRYDLGSGSL-VLSS 73

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1799133945 3570 ET-LEAGELIDVAVRQAGNALVMTVDGNQV----STIETDTLKPGTEIFIGGLPPGLNSPDDVVEQSFQGCVYEILIN 3642
Cdd:cd00110     74 KTpLNDGQWHSVSVERNGRSVTLSVDGERVvesgSPGGSALLNLDGPLYLGGLPEDLKSPGLPVSPGFVGCIRDLKVN 151

Laminin G domain;

Pssm-ID: 214598 [Multi-domain] Cd Length: 132 Bit Score: 75.84 E-value: 1.74e-15

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  3257 DIEITLNTANPKGIIFETKRINSGDllatpydtiHHEAKITDyGTVLYEFDIGNGRQIVE-TTNPINPNEWNVIKIKNDK 3335
Cdd:smart00282    1 SISFSFRTTSPNGLLLYAGSKGGGD---------YLALELRD-GRLVLRYDLGSGPARLTsDPTPLNDGQWHRVAVERNG 70

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1799133945  3336 NQVTIQLNDESATIRQHTNPLPSLSTgvNRPVFIGG-----RHEPTNEANDFRGIISQVVLSGH 3394
Cdd:smart00282   71 RSVTLSVDGGNRVSGESPGGLTILNL--DGPLYLGGlpedlKLPPLPVTPGFRGCIRNLKVNGK 132

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 65.66 E-value: 1.51e-12

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1799133945 1060 PTVVDPPqTNLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPVCEPPRCLQTSEGGYGTLTIHDAQPVDQGAYTCEAIN 1137
Cdd:pfam13927    2 PVITVSP-SSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of purposes including signal transduction via cell-surface steroid receptors, adhesion, migration and differentiation through mediation of cell adhesion molecules.

Pssm-ID: 238058 [Multi-domain] Cd Length: 151 Bit Score: 67.06 E-value: 3.64e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 3243 IELPPLSDEEiVNLDIEITLNTANPKGIIFETKRINSGDLLAtpydtihheAKITDyGTVLYEFDIGNGRQIVETTNPIN 3322
Cdd:cd00110     10 VRLPTLPAPR-TRLSISFSFRTTSPNGLLLYAGSQNGGDFLA---------LELED-GRLVLRYDLGSGSLVLSSKTPLN 78

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1799133945 3323 PNEWNVIKIKNDKNQVTIQLNDESATirQHTNPLPSLSTGVNRPVFIGG-----RHEPTNEANDFRGIISQVVL 3391
Cdd:cd00110     79 DGQWHSVSVERNGRSVTLSVDGERVV--ESGSPGGSALLNLDGPLYLGGlpedlKSPGLPVSPGFVGCIRDLKV 150

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 64.83 E-value: 3.73e-12

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1799133945  1069 NLQVPRGTTFSLTCKAVAVPEPYINWRLNWG-PVCEPPRCLQTSEGGYGTLTIHDAQPVDQGAYTCEAINVKG 1140
Cdd:smart00410    3 SVTVKEGESVTLSCEASGSPPPEVTWYKQGGkLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSG 75

Laminin G domain; This family includes the Thrombospondin N-terminal-like domain, a Laminin G subfamily.

Pssm-ID: 460494 [Multi-domain] Cd Length: 126 Bit Score: 65.13 E-value: 7.67e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 3528 ILMYFasdyGSNTKQYTSLSLIANQVVLTVRRPDKEVQKIRSET-LEAGELIDVAVRQAGNALVMTVDGNQVSTI----E 3602
Cdd:pfam02210    9 LLLYA----GGGGSDFLALELVNGRLVLRYDLGSGPESLLSSGKnLNDGQWHSVRVERNGNTLTLSVDGQTVVSSlppgE 84

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1799133945 3603 TDTLKPGTEIFIGGLPPGLNSPDDVVEQSFQGCVYEILINSQ 3644
Cdd:pfam02210   85 SLLLNLNGPLYLGGLPPLLLLPALPVRAGFVGCIRDVRVNGE 126

Laminin EGF domain; This family is like pfam00008 but has 8 conserved cysteines instead of six.

Pssm-ID: 395007 Cd Length: 49 Bit Score: 61.22 E-value: 2.27e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1799133945 1748 CECNGHAS---QCDKEYGYCLdCQHNTEGDQCERCKPGFVGDaRRGTPNDC 1795
Cdd:pfam00053    1 CDCNPHGSlsdTCDPETGQCL-CKPGVTGRHCDRCKPGYYGL-PSDPPQGC 49

Low-density lipoprotein receptor domain class A;

Pssm-ID: 395011 Cd Length: 37 Bit Score: 60.73 E-value: 2.61e-11

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 1799133945 1020 SDCKPTEFQCHDRRqCVPSSFHCDGTNDCHDGSDEVGC 1057
Cdd:pfam00057    1 STCSPNEFQCGSGE-CIPRSWVCDGDPDCGDGSDEENC 37

Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation; the laminin-type epidermal growth factor-like module occurs in tandem arrays; the domain contains 4 disulfide bonds (loops a-d) the first three resemble epidermal growth factor (EGF); the number of copies of this domain in the different forms of laminins is highly variable ranging from 3 up to 22 copies

Pssm-ID: 238012 Cd Length: 50 Bit Score: 60.45 E-value: 4.22e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1799133945 1748 CECNGHAS---QCDKEYGYCLdCQHNTEGDQCERCKPGFVGDARRgtPNDCQ 1796
Cdd:cd00055      2 CDCNGHGSlsgQCDPGTGQCE-CKPNTTGRRCDRCAPGYYGLPSQ--GGGCQ 50

Low-density lipoprotein receptor domain class A;

Pssm-ID: 395011 Cd Length: 37 Bit Score: 59.95 E-value: 4.73e-11

                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 1799133945  937 QCMADEKACGNNECVKNDYVCDGEPDCRDRSDEANC 972
Cdd:pfam00057    2 TCSPNEFQCGSGECIPRSWVCDGDPDCGDGSDEENC 37

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 60.66 E-value: 8.77e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1799133945  835 QITVFPSEKEVRDGRDVSFECRARTSDNsvyPTVRWARVGGPLPSSAH------DSGGRLTINPVQLSDAGTYICV 904
Cdd:pfam13927    3 VITVSPSSVTVREGETVTLTCEATGSPP---PTITWYKNGEPISSGSTrsrslsGSNSTLTISNVTRSDAGTYTCV 75

Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about 40 amino acids are present in the N-terminal of this multidomain membrane protein; other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement; the binding of calcium is required for in vitro formation of the native disulfide isomer and is necessary in establishing and maintaining the modular structure

Pssm-ID: 238060 Cd Length: 35 Bit Score: 58.76 E-value: 1.37e-10

                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 1799133945 1022 CKPTEFQCHDRRqCVPSSFHCDGTNDCHDGSDEVGC 1057
Cdd:cd00112      1 CPPNEFRCANGR-CIPSSWVCDGEDDCGDGSDEENC 35

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 60.35 E-value: 1.56e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1060 PTVVDPPQtNLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPVCEPPRCLQTSEGGYGTLTIHDAQPVDQGAYTCEAINVK 1139
Cdd:pfam07679    1 PKFTQKPK-DVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSA 79


                   ....*.
gi 1799133945 1140 GRVLAT 1145
Cdd:pfam07679   80 GEAEAS 85

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 59.58 E-value: 3.06e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  835 QITVFPSEKEVRDGRDVSFECRAR-TSDnsvyPTVRWARVGGPLPSSAH------DSGGRLTINPVQLSDAGTYICVSDY 907
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTgTPD----PEVSWFKDGQPLRSSDRfkvtyeGGTYTLTISNVQPDDSGKYTCVATN 77

                           90
                   ....*....|...
gi 1799133945  908 NGNTVEARATLSV 920
Cdd:pfam07679   78 SAGEAEASAELTV 90

Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about 40 amino acids are present in the N-terminal of this multidomain membrane protein; other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement; the binding of calcium is required for in vitro formation of the native disulfide isomer and is necessary in establishing and maintaining the modular structure

Pssm-ID: 238060 Cd Length: 35 Bit Score: 57.60 E-value: 3.34e-10

                           10        20        30
                   ....*....|....*....|....*....|....*
gi 1799133945  416 CLEGQFKCGTGQCIEESLKCNRKYDCADGSDEITC 450
Cdd:cd00112      1 CPPNEFRCANGRCIPSSWVCDGEDDCGDGSDEENC 35

Low-density lipoprotein receptor domain class A; Cysteine-rich repeat in the low-density lipoprotein (LDL) receptor that plays a central role in mammalian cholesterol metabolism. The N-terminal type A repeats in LDL receptor bind the lipoproteins. Other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement. Mutations in the LDL receptor gene cause familial hypercholesterolemia.

Pssm-ID: 197566 Cd Length: 33 Bit Score: 56.87 E-value: 5.00e-10

                            10        20        30
                    ....*....|....*....|....*....|...
gi 1799133945  1022 CKPTEFQCHDRRqCVPSSFHCDGTNDCHDGSDE 1054
Cdd:smart00192    2 CPPGEFQCDNGR-CIPSSWVCDGVDDCGDGSDE 33

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

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 58.11 E-value: 5.17e-10

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1799133945 1078 FSLTCKAVAVPEPYINWRLNWGPVCEPPRCLQTSEGGYGTLTIHDAQPVDQGAYTCEAINVKGR 1141
Cdd:cd00096      1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGG 64

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 57.90 E-value: 9.06e-10

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945   840 PSEKEVRDGRDVSFECRARTSDNsvyPTVRWARVGGPLPS-------SAHDSGGRLTINPVQLSDAGTYICVSDYNGNTV 912
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPP---PEVTWYKQGGKLLAesgrfsvSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSA 77


                    ....*...
gi 1799133945   913 EARATLSV 920
Cdd:smart00410   78 SSGTTLTV 85

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: 57.79 E-value: 9.76e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1799133945 3067 GDRAWFDCKVTGDPSAVISWTKEGN--DDLPPNAQVTGGRLLFTDLKEDNAGVYRCVAKTKAGPLQTRTVLNV 3137
Cdd:cd20978     16 GQDVTLPCQVTGVPQPKITWLHNGKplQGPMERATVEDGTLTIINVQPEDTGYYGCVATNEIGDIYTETLLHV 88

Laminin EGF domain; This family is like pfam00008 but has 8 conserved cysteines instead of six.

Pssm-ID: 395007 Cd Length: 49 Bit Score: 56.59 E-value: 1.10e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1799133945 1804 CHCNNHSPRG--CDSF-GRCLlCEHNTEGTHCERCKKGYYGDAtKGSPYDC 1851
Cdd:pfam00053    1 CDCNPHGSLSdtCDPEtGQCL-CKPGVTGRHCDRCKPGYYGLP-SDPPQGC 49

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: 57.79 E-value: 1.22e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1060 PTVVDPPQTNLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPVCEPPRCLQTSEggyGTLTIHDAQPVDQGAYTCEAINVK 1139
Cdd:cd20978      1 PKFIQKPEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVED---GTLTIINVQPEDTGYYGCVATNEI 77


                   ...
gi 1799133945 1140 GRV 1142
Cdd:cd20978     78 GDI 80

Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about 40 amino acids are present in the N-terminal of this multidomain membrane protein; other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement; the binding of calcium is required for in vitro formation of the native disulfide isomer and is necessary in establishing and maintaining the modular structure

Pssm-ID: 238060 Cd Length: 35 Bit Score: 56.06 E-value: 1.25e-09

                           10        20        30
                   ....*....|....*....|....*....|....*
gi 1799133945  752 CLEHEFQCAIGECIDKRRVCDTRPDCLDASDEQNC 786
Cdd:cd00112      1 CPPNEFRCANGRCIPSSWVCDGEDDCGDGSDEENC 35

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: 57.57 E-value: 1.39e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2598 KPGERHQFRCITTGSPTPKITWTgPNGSPLPHD--------VTPLEP-----NIldfSNGRSELNGDYTCTASNPIGEAS 2664
Cdd:cd20956     14 QPGPSVSLKCVASGNPLPQITWT-LDGFPIPESprfrvgdyVTSDGDvvsyvNI---SSVRVEDGGEYTCTATNDVGSVS 89


                   ....*..
gi 1799133945 2665 DHGNVNI 2671
Cdd:cd20956     90 HSARINV 96

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: 1.66e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  1932 PPHLVVNEGEPAAFRCWVPGIPDCQITWHREQLGGPLPHGVYQ-----TGNALKIPQSQLHHAGRYICSAANQYGTGQSp 2006
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSvsrsgSTSTLTISNVTPEDSGTYTCAATNSSGSASS- 79


                    ....*.
gi 1799133945  2007 PAVLEV 2012
Cdd:smart00410   80 GTTLTV 85

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

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 56.39 E-value: 4.02e-09

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1799133945 2118 IDPPNQTVNVNDPAQFRCWVPGQPRAQLKWsRKDGRPLPNG----ILERDgFLRIDKSQLHDAGEYEC 2181
Cdd:cd20957      6 IDPPVQTVDFGRTAVFNCSVTGNPIHTVLW-MKDGKPLGHSsrvqILSED-VLVIPSVKREDKGMYQC 71

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: 55.97 E-value: 4.04e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  2120 PPNQTVNVNDPAQFRCWVPGQPRAQLKWSRKDGRPL---PNGILERDGF---LRIDKSQLHDAGEYECTSTepDGSTQLS 2193
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLaesGRFSVSRSGStstLTISNVTPEDSGTYTCAAT--NSSGSAS 78


                    ....*..
gi 1799133945  2194 PPARLNV 2200
Cdd:smart00410   79 SGTTLTV 85

Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about 40 amino acids are present in the N-terminal of this multidomain membrane protein; other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement; the binding of calcium is required for in vitro formation of the native disulfide isomer and is necessary in establishing and maintaining the modular structure

Pssm-ID: 238060 Cd Length: 35 Bit Score: 54.52 E-value: 4.24e-09

                           10        20        30
                   ....*....|....*....|....*....|..
gi 1799133945  125 CATTEFTCLDKSCIPADQRCDGRRNCPDGSDE 156
Cdd:cd00112      1 CPPNEFRCANGRCIPSSWVCDGEDDCGDGSDE 32

Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation; the laminin-type epidermal growth factor-like module occurs in tandem arrays; the domain contains 4 disulfide bonds (loops a-d) the first three resemble epidermal growth factor (EGF); the number of copies of this domain in the different forms of laminins is highly variable ranging from 3 up to 22 copies

Pssm-ID: 238012 Cd Length: 50 Bit Score: 54.67 E-value: 4.85e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1799133945 1803 PCHCNNHSPRG--CDSF-GRCLlCEHNTEGTHCERCKKGYYGDATKG 1846
Cdd:cd00055      1 PCDCNGHGSLSgqCDPGtGQCE-CKPNTTGRRCDRCAPGYYGLPSQG 46

Laminin-type epidermal growth factor-like domai;

Pssm-ID: 214543 Cd Length: 46 Bit Score: 54.62 E-value: 5.04e-09

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|.
gi 1799133945  1748 CECN--GHAS-QCDKEYGYCLdCQHNTEGDQCERCKPGFVGDarrgTPNDC 1795
Cdd:smart00180    1 CDCDpgGSASgTCDPDTGQCE-CKPNVTGRRCDRCAPGYYGD----GPPGC 46

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: 55.59 E-value: 6.32e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  2212 PPVQTVNEGEPSRIRCWVPGHPNIQLQFVKRGRRPLPAHARFS------QGNLEIPRTLKSDEDEYICIATDpttNRPVE 2285
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSvsrsgsTSTLTISNVTPEDSGTYTCAATN---SSGSA 77


                    ....*...
gi 1799133945  2286 SNPARVIV 2293
Cdd:smart00410   78 SSGTTLTV 85

Low-density lipoprotein receptor domain class A; Cysteine-rich repeat in the low-density lipoprotein (LDL) receptor that plays a central role in mammalian cholesterol metabolism. The N-terminal type A repeats in LDL receptor bind the lipoproteins. Other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement. Mutations in the LDL receptor gene cause familial hypercholesterolemia.

Pssm-ID: 197566 Cd Length: 33 Bit Score: 53.79 E-value: 6.86e-09

                            10        20        30
                    ....*....|....*....|....*....|...
gi 1799133945   415 ECLEGQFKCGTGQCIEESLKCNRKYDCADGSDE 447
Cdd:smart00192    1 TCPPGEFQCDNGRCIPSSWVCDGVDDCGDGSDE 33

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: 55.20 E-value: 8.64e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  3060 SSESPQIGDRAWFDCKVTGDPSAVISWTKEGNDDL--PPNAQVTG----GRLLFTDLKEDNAGVYRCVAKTKAGPLQTRT 3133
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLaeSGRFSVSRsgstSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                    ....
gi 1799133945  3134 VLNV 3137
Cdd:smart00410   82 TLTV 85

Low-density lipoprotein receptor domain class A; Cysteine-rich repeat in the low-density lipoprotein (LDL) receptor that plays a central role in mammalian cholesterol metabolism. The N-terminal type A repeats in LDL receptor bind the lipoproteins. Other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement. Mutations in the LDL receptor gene cause familial hypercholesterolemia.

Pssm-ID: 197566 Cd Length: 33 Bit Score: 53.41 E-value: 9.57e-09

                            10        20        30
                    ....*....|....*....|....*....|..
gi 1799133945   125 CATTEFTCLDKSCIPADQRCDGRRNCPDGSDE 156
Cdd:smart00192    2 CPPGEFQCDNGRCIPSSWVCDGVDDCGDGSDE 33

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

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 55.09 E-value: 9.83e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2120 PPNQTVNVNDPAQFRCWVPGQPRAQLKWSRKDGRpLPNG---ILErDGFLRIDKSQLHDAGEYECTSTEPDGSTQLSppA 2196
Cdd:cd05725      4 PQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGE-LPKGryeILD-DHSLKIRKVTAGDMGSYTCVAENMVGKIEAS--A 79


                   ....
gi 1799133945 2197 RLNV 2200
Cdd:cd05725     80 TLTV 83

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 54.57 E-value: 1.49e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1799133945 3065 QIGDRAWFDCKVTGDPSAVISWTKeGNDDLPPNA----QVTGGR--LLFTDLKEDNAGVYRCVAKTKAGPLQTRTVLNV 3137
Cdd:pfam07679   13 QEGESARFTCTVTGTPDPEVSWFK-DGQPLRSSDrfkvTYEGGTytLTISNVQPDDSGKYTCVATNSAGEAEASAELTV 90

Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about 40 amino acids are present in the N-terminal of this multidomain membrane protein; other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement; the binding of calcium is required for in vitro formation of the native disulfide isomer and is necessary in establishing and maintaining the modular structure

Pssm-ID: 238060 Cd Length: 35 Bit Score: 52.98 E-value: 1.59e-08

                           10        20        30
                   ....*....|....*....|....*....|....*
gi 1799133945  938 CMADEKACGNNECVKNDYVCDGEPDCRDRSDEANC 972
Cdd:cd00112      1 CPPNEFRCANGRCIPSSWVCDGEDDCGDGSDEENC 35

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: 54.09 E-value: 2.44e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  836 ITVFPSEKEVRDGRDVSFECRARtsDNSVyPTVRWARVGGPLPSSA--HDSGGRLTINPVQLSDAGTYICVSD--YNGNT 911
Cdd:cd04968      4 KVRFPADTYALKGQTVTLECFAL--GNPV-PQIKWRKVDGSPSSQWeiTTSEPVLEIPNVQFEDEGTYECEAEnsRGKDT 80


                   ....*.
gi 1799133945  912 VEARAT 917
Cdd:cd04968     81 VQGRII 86

Low-density lipoprotein receptor domain class A;

Pssm-ID: 395011 Cd Length: 37 Bit Score: 52.25 E-value: 2.62e-08

                           10        20        30
                   ....*....|....*....|....*....|....*
gi 1799133945  752 CLEHEFQCAIGECIDKRRVCDTRPDCLDASDEQNC 786
Cdd:pfam00057    3 CSPNEFQCGSGECIPRSWVCDGDPDCGDGSDEENC 37

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: 53.61 E-value: 3.20e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 3054 QVLLEVSSESPQIGDRAWFDCKVTGDPSAVISWTKEGN--DDLPPNAQ--VTGGRLLFTDLKEDNAGVYRCVAKTKAGPL 3129
Cdd:cd04978      1 YWIIEPPSLVLSPGETGELICEAEGNPQPTITWRLNGVpiEPAPEDMRrtVDGRTLIFSNLQPNDTAVYQCNASNVHGYL 80


                   ....*...
gi 1799133945 3130 QTRTVLNV 3137
Cdd:cd04978     81 LANAFLHV 88

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

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 53.55 E-value: 3.33e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  840 PSEKEVRDGRDVSFECRARtsdNSVYPTVRWARVGGPLPSSA----HDSGgrLTINPVQLSDAGTYICVSDYNGNTVEAR 915
Cdd:cd05725      4 PQNQVVLVDDSAEFQCEVG---GDPVPTVRWRKEDGELPKGRyeilDDHS--LKIRKVTAGDMGSYTCVAENMVGKIEAS 78


                   ....*
gi 1799133945  916 ATLSV 920
Cdd:cd05725     79 ATLTV 83

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 53.34 E-value: 3.53e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1799133945 2400 PVIT--PQTQTIPEGDPARIQCTVPGNPSAA---QHLSFERVDGKGLPFGSSDDRGVLTIPSTQLQDAGEYVCLYS 2470
Cdd:pfam13927    2 PVITvsPSSVTVREGETVTLTCEATGSPPPTitwYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVAS 77

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: 53.61 E-value: 3.57e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1062 VVDPPQtNLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPVCE-PPRCLQTSEGgyGTLTIHDAQPVDQGAYTCEAINVKG 1140
Cdd:cd04978      2 WIIEPP-SLVLSPGETGELICEAEGNPQPTITWRLNGVPIEPaPEDMRRTVDG--RTLIFSNLQPNDTAVYQCNASNVHG 78


                   ....
gi 1799133945 1141 RVLA 1144
Cdd:cd04978     79 YLLA 82

Laminin-type epidermal growth factor-like domai;

Pssm-ID: 214543 Cd Length: 46 Bit Score: 51.93 E-value: 3.75e-08

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*...
gi 1799133945  1172 SCDTRGAVTPYPN-NYGTCECKSQVTGPNCDQCKPGAFHlseKSPEGC 1218
Cdd:smart00180    2 DCDPGGSASGTCDpDTGQCECKPNVTGRRCDRCAPGYYG---DGPPGC 46

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: 52.99 E-value: 4.56e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  840 PSEKEVRDGRDVSFECRARTSDNsvyPTVRWARVGGPLPSSA--HDSGGRLTINPVQLSDAGTYICVSDYNGNTVEARAT 917
Cdd:cd05728      6 ISDTEADIGSSLRWECKASGNPR---PAYRWLKNGQPLASENriEVEAGDLRITKLSLSDSGMYQCVAENKHGTIYASAE 82


                   ...
gi 1799133945  918 LSV 920
Cdd:cd05728     83 LAV 85

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: 4.61e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2118 IDPPNQTVNVNDPAQFRCWV-PGQPRAQLKWSRKDGRpLPNGILERDGFLRIDKSQLH-------DAGEYECTSTEPDGS 2189
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSAsTGSPGPDVTWSKEGGT-LIESLKVKHDNGRTTQSSLLisnvtkeDAGTYTCVVNNPGGS 79


                   ....
gi 1799133945 2190 TQLS 2193
Cdd:pfam00047   80 ATLS 83

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: 52.89 E-value: 4.73e-08

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  2404 PQTQTIPEGDPARIQCTVPGNPSAaqHLSFERVDGKGLPFGS------SDDRGVLTIPSTQLQDAGEYVClySPENSPPV 2477
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPP--EVTWYKQGGKLLAESGrfsvsrSGSTSTLTISNVTPEDSGTYTC--AATNSSGS 76


                    ....*....
gi 1799133945  2478 KTNPSTLNV 2486
Cdd:smart00410   77 ASSGTTLTV 85

Laminin EGF domain; This family is like pfam00008 but has 8 conserved cysteines instead of six.

Pssm-ID: 395007 Cd Length: 49 Bit Score: 51.59 E-value: 5.21e-08

                           10        20        30
                   ....*....|....*....|....*....|....*
gi 1799133945 1477 PAQGQCQCKASVIGPNCDRCAPNSFGLAPTNPQGC 1511
Cdd:pfam00053   15 PETGQCLCKPGVTGRHCDRCKPGYYGLPSDPPQGC 49

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 52.57 E-value: 5.65e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1799133945 2585 PPTAVVEPRTWNGKPGERHQFRCITTGSPTPKITWTgPNGSPLPHDVTPLEPN-----ILDFSNGRSELNGDYTCTASN 2658
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWY-KNGEPISSGSTRSRSLsgsnsTLTISNVTRSDAGTYTCVASN 78

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: 53.02 E-value: 6.56e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1059 QPTVVDPPqTNLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPVcEPPRCLQTSEGGYGTLTIHDAQPVDQGAYTCEAINV 1138
Cdd:cd20976      1 APSFSSVP-KDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPL-QYAADRSTCEAGVGELHIQDVLPEDHGTYTCLAKNA 78

                           90
                   ....*....|....
gi 1799133945 1139 KGRVlatpDCIVRV 1152
Cdd:cd20976     79 AGQV----SCSAWV 88

Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about 40 amino acids are present in the N-terminal of this multidomain membrane protein; other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement; the binding of calcium is required for in vitro formation of the native disulfide isomer and is necessary in establishing and maintaining the modular structure

Pssm-ID: 238060 Cd Length: 35 Bit Score: 51.05 E-value: 7.04e-08

                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 1799133945  564 CSSVQFECKrDGKCIDKALECNHKYDCEDGSDETEC 599
Cdd:cd00112      1 CPPNEFRCA-NGRCIPSSWVCDGEDDCGDGSDEENC 35

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 52.64 E-value: 7.59e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2586 PTAVVEPRTWNGKPGERHQFRCITTGSPTPKITWTgPNGSPLP----HDVTPlEPNI--LDFSNGRSELNGDYTCTASNP 2659
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWF-KDGQPLRssdrFKVTY-EGGTytLTISNVQPDDSGKYTCVATNS 78

                           90
                   ....*....|..
gi 1799133945 2660 IGEASDHGNVNI 2671
Cdd:pfam07679   79 AGEAEASAELTV 90

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 52.01 E-value: 8.26e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2298 RPIIDPAEQTVPEGSPFKIRCYVPGHPSVQLTFRRVSGQLNEDADennglLAVQRAELTDEGDYICTARDPDTGapIDST 2377
Cdd:pfam13895    1 KPVLTPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAISSSPN-----FFTLSVSAEDSGTYTCVARNGRGG--KVSN 73


                   ....*.
gi 1799133945 2378 PATVHV 2383
Cdd:pfam13895   74 PVELTV 79

Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about 40 amino acids are present in the N-terminal of this multidomain membrane protein; other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement; the binding of calcium is required for in vitro formation of the native disulfide isomer and is necessary in establishing and maintaining the modular structure

Pssm-ID: 238060 Cd Length: 35 Bit Score: 50.67 E-value: 8.39e-08

                           10        20        30
                   ....*....|....*....|....*....|....*
gi 1799133945  275 CPSGERACKSGHCLPVAQFCDRRVQCPDGDDEEHC 309
Cdd:cd00112      1 CPPNEFRCANGRCIPSSWVCDGEDDCGDGSDEENC 35

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 52.18 E-value: 9.12e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1799133945 3054 QVLLEVSSESPQIGDRAWFDCKVTGDPSAVISWTKEG-----NDDLPPNAQVTGGRLLFTDLKEDNAGVYRCVAK 3123
Cdd:pfam13927    3 VITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGepissGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVAS 77

Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about 40 amino acids are present in the N-terminal of this multidomain membrane protein; other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement; the binding of calcium is required for in vitro formation of the native disulfide isomer and is necessary in establishing and maintaining the modular structure

Pssm-ID: 238060 Cd Length: 35 Bit Score: 50.28 E-value: 1.08e-07

                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 1799133945  314 CKSNEFRCEStNVCVPTVVVCDGWKDCHDGSDEKKC 349
Cdd:cd00112      1 CPPNEFRCAN-GRCIPSSWVCDGEDDCGDGSDEENC 35

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 51.63 E-value: 1.14e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1927 QPVIDPPHLVVNEGEPAAFRCWVPGIPDCQITWHREqlGGPLPhgvyQTGNALkIPQSQLHHAGRYICSAANQYGTGQSP 2006
Cdd:pfam13895    1 KPVLTPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKD--GSAIS----SSPNFF-TLSVSAEDSGTYTCVARNGRGGKVSN 73


                   ....*.
gi 1799133945 2007 PAVLEV 2012
Cdd:pfam13895   74 PVELTV 79

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 51.80 E-value: 1.15e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1925 PPQPVIDPPHLVVNEGEPAAFRCWVPGIPDCQITWHREqlGGPLPHG------VYQTGNALKIPQSQLHHAGRYICSAAN 1998
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKN--GEPISSGstrsrsLSGSNSTLTISNVTRSDAGTYTCVASN 78

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: 52.20 E-value: 1.20e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1066 PQTNLQVPrGTTFSLTCKAVAVPEPYINWRLNWGPV----CEPPRCLQTseggyGTLTIHDAQPVDQGAYTCEAINVKGR 1141
Cdd:cd05867      6 PQSHLYGP-GETARLDCQVEGIPTPNITWSINGAPIegtdPDPRRHVSS-----GALILTDVQPSDTAVYQCEARNRHGN 79


                   ...
gi 1799133945 1142 VLA 1144
Cdd:cd05867     80 LLA 82

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

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 52.13 E-value: 1.23e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1928 PVIDPPH----LVVNEGEPAAFRCWVPGIPDCQITWHREqlgGPLP------HGVYQTGNALKIPQSQLHHAGRYICSAA 1997
Cdd:cd20970      1 PVISTPQpsftVTAREGENATFMCRAEGSPEPEISWTRN---GNLIiefntrYIVRENGTTLTIRNIRRSDMGIYLCIAS 77

                           90
                   ....*....|....*
gi 1799133945 1998 NQYGTGQSPPAVLEV 2012
Cdd:cd20970     78 NGVPGSVEKRITLQV 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: 51.56 E-value: 1.27e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1799133945 3072 FDCKVTGDPSAVISWTKEGNDDLPPNA-----QVTGGRLLFTDLKEDNAGVYRCVAKTKAGPLQTRTV 3134
Cdd:cd00096      3 LTCSASGNPPPTITWYKNGKPLPPSSRdsrrsELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Low-density lipoprotein receptor domain class A; Cysteine-rich repeat in the low-density lipoprotein (LDL) receptor that plays a central role in mammalian cholesterol metabolism. The N-terminal type A repeats in LDL receptor bind the lipoproteins. Other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement. Mutations in the LDL receptor gene cause familial hypercholesterolemia.

Pssm-ID: 197566 Cd Length: 33 Bit Score: 50.32 E-value: 1.29e-07

                            10        20        30
                    ....*....|....*....|....*....|..
gi 1799133945   752 CLEHEFQCAIGECIDKRRVCDTRPDCLDASDE 783
Cdd:smart00192    2 CPPGEFQCDNGRCIPSSWVCDGVDDCGDGSDE 33

Laminin-type epidermal growth factor-like domai;

Pssm-ID: 214543 Cd Length: 46 Bit Score: 50.39 E-value: 1.48e-07

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*.
gi 1799133945  1804 CHCN--NHSPRGCDSF-GRCLlCEHNTEGTHCERCKKGYYGDATKG 1846
Cdd:smart00180    1 CDCDpgGSASGTCDPDtGQCE-CKPNVTGRRCDRCAPGYYGDGPPG 45

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: 1.82e-07

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1799133945  2592 PRTWNGKPGERHQFRCITTGSPTPKITWTGPNGSPLPHD----VTPLEPN-ILDFSNGRSELNGDYTCTASNPIGEAS 2664
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESgrfsVSRSGSTsTLTISNVTPEDSGTYTCAATNSSGSAS 78

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 51.03 E-value: 1.88e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1799133945 2116 PQI--DPPNQTVNVNDPAQFRCWVPGQPRAQLKWsRKDGRPLPNGILERDGF------LRIDKSQLHDAGEYECT 2182
Cdd:pfam13927    2 PVItvSPSSVTVREGETVTLTCEATGSPPPTITW-YKNGEPISSGSTRSRSLsgsnstLTISNVTRSDAGTYTCV 75

Low-density lipoprotein receptor domain class A; Cysteine-rich repeat in the low-density lipoprotein (LDL) receptor that plays a central role in mammalian cholesterol metabolism. The N-terminal type A repeats in LDL receptor bind the lipoproteins. Other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement. Mutations in the LDL receptor gene cause familial hypercholesterolemia.

Pssm-ID: 197566 Cd Length: 33 Bit Score: 49.55 E-value: 2.30e-07

                            10        20        30
                    ....*....|....*....|....*....|....
gi 1799133945   313 QCKSNEFRCeSTNVCVPTVVVCDGWKDCHDGSDE 346
Cdd:smart00192    1 TCPPGEFQC-DNGRCIPSSWVCDGVDDCGDGSDE 33

Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about 40 amino acids are present in the N-terminal of this multidomain membrane protein; other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement; the binding of calcium is required for in vitro formation of the native disulfide isomer and is necessary in establishing and maintaining the modular structure

Pssm-ID: 238060 Cd Length: 35 Bit Score: 49.51 E-value: 2.32e-07

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 1799133945  498 CNDQEFRCPYlaeTRCFHYDRLCDGTDDCGDGSDETNC 535
Cdd:cd00112      1 CPPNEFRCAN---GRCIPSSWVCDGEDDCGDGSDEENC 35

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: 50.85 E-value: 3.09e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2583 QEPPTAVVEprtwngKPGERHQFRCITTGSPTPKITWTGpNGSPL--PHDVTPLEPNILDFSNGRSELNGDYTCTASNPI 2660
Cdd:cd20978      5 QKPEKNVVV------KGGQDVTLPCQVTGVPQPKITWLH-NGKPLqgPMERATVEDGTLTIINVQPEDTGYYGCVATNEI 77


                   ..
gi 1799133945 2661 GE 2662
Cdd:cd20978     78 GD 79

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: 50.63 E-value: 3.55e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2401 VITPQTQTIPEGDPARIQCTVPGNpSAAQHLSFERVDGKgLPFGSSDDRGVLTIPSTQLQDAGEYVCLYS 2470
Cdd:cd05754      5 VEEPRSQEVRPGADVSFICRAKSK-SPAYTLVWTRVNGT-LPSRAMDFNGILTIRNVQLSDAGTYVCTGS 72

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: 50.58 E-value: 3.94e-07

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  2880 PRVRVVSQGDNIVLKCSVQGAENGE------HFKWALLRGGSLVRQLGTEPTLEITKADPSnDFGVYRCNVEDNNGLVIG 2953
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEvtwykqGGKLLAESGRFSVSRSGSTSTLTISNVTPE-DSGTYTCAATNSSGSASS 79


                    ..
gi 1799133945  2954 SA 2955
Cdd:smart00410   80 GT 81

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: 4.03e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1925 PPQPVIDPPHLVVNEGEPAAFRCWVPGIPDCQITWHREqlGGPLPHG---VYQTGNALKIPQSQLHHAGRYICSAANQYG 2001
Cdd:cd20957      1 PLSATIDPPVQTVDFGRTAVFNCSVTGNPIHTVLWMKD--GKPLGHSsrvQILSEDVLVIPSVKREDKGMYQCFVRNDGD 78


                   ....
gi 1799133945 2002 TGQS 2005
Cdd:cd20957     79 SAQA 82

Low-density lipoprotein receptor domain class A; Cysteine-rich repeat in the low-density lipoprotein (LDL) receptor that plays a central role in mammalian cholesterol metabolism. The N-terminal type A repeats in LDL receptor bind the lipoproteins. Other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement. Mutations in the LDL receptor gene cause familial hypercholesterolemia.

Pssm-ID: 197566 Cd Length: 33 Bit Score: 48.40 E-value: 4.75e-07

                            10        20        30
                    ....*....|....*....|....*....|...
gi 1799133945   937 QCMADEKACGNNECVKNDYVCDGEPDCRDRSDE 969
Cdd:smart00192    1 TCPPGEFQCDNGRCIPSSWVCDGVDDCGDGSDE 33

Low-density lipoprotein receptor domain class A;

Pssm-ID: 395011 Cd Length: 37 Bit Score: 48.78 E-value: 4.85e-07

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 1799133945  312 VQCKSNEFRCEStNVCVPTVVVCDGWKDCHDGSDEKKC 349
Cdd:pfam00057    1 STCSPNEFQCGS-GECIPRSWVCDGDPDCGDGSDEENC 37

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: 50.27 E-value: 5.09e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1066 PQTNLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPVCEPPRC-LQTSEGGYGTLTIHDAQPVDQGAYTCEAINVKGRvlA 1144
Cdd:cd20973      3 TLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFqIDQDEDGLCSLIISDVCGDDSGKYTCKAVNSLGE--A 80


                   ....*...
gi 1799133945 1145 TPDCIVRV 1152
Cdd:cd20973     81 TCSAELTV 88

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 50.33 E-value: 5.67e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2116 PQID--PPNQTVNVNDPAQFRCWVPGQPRAQLKWsRKDGRPLPNG----ILERDG--FLRIDKSQLHDAGEYECTSTEPD 2187
Cdd:pfam07679    1 PKFTqkPKDVEVQEGESARFTCTVTGTPDPEVSW-FKDGQPLRSSdrfkVTYEGGtyTLTISNVQPDDSGKYTCVATNSA 79

                           90
                   ....*....|...
gi 1799133945 2188 GSTQLSppARLNV 2200
Cdd:pfam07679   80 GEAEAS--AELTV 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: 49.81 E-value: 5.88e-07

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  2303 PAEQTVPEGSPFKIRCYVPGHPSVQLTFRRVSGQL-------NEDADENNGLLAVQRAELTDEGDYICTARDpdtGAPID 2375
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLlaesgrfSVSRSGSTSTLTISNVTPEDSGTYTCAATN---SSGSA 77


                    ....*...
gi 1799133945  2376 STPATVHV 2383
Cdd:smart00410   78 SSGTTLTV 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: 49.81 E-value: 5.94e-07

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  2684 PKLIVTVGEPLQVKCEAfgaPGDPEPEVEWLHDpGPERGDLPDDFKPVTISEQF-IRHPNVGLGNAGVYTCKGSSAHATA 2762
Cdd:smart00410    2 PSVTVKEGESVTLSCEA---SGSPPPEVTWYKQ-GGKLLAESGRFSVSRSGSTStLTISNVTPEDSGTYTCAATNSSGSA 77


                    ....*...
gi 1799133945  2763 TKNIYIEV 2770
Cdd:smart00410   78 SSGTTLTV 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: 49.80 E-value: 6.36e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2119 DPPNQTVNVNDPAQFRCWVPGQPRAQLKWsRKDGRPLPnGILER-----DGFLRIDKSQLHDAGEYECTSTEPDGSTQLS 2193
Cdd:cd20952      5 GPQNQTVAVGGTVVLNCQATGEPVPTISW-LKDGVPLL-GKDERittleNGSLQIKGAEKSDTGEYTCVALNLSGEATWS 82

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: 6.76e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1799133945 2206 IQPQVDPPVQTVNEGEPSRIRCWVPGHPNIQLQFVKRGrRPLPAHAR---FSQGNLEIPRTLKSDEDEYICIATDP 2278
Cdd:cd20957      2 LSATIDPPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDG-KPLGHSSRvqiLSEDVLVIPSVKREDKGMYQCFVRND 76

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

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 49.25 E-value: 7.07e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  851 VSFECRARTSDNsvyPTVRWARVGGPLPSSAHDS------GGRLTINPVQLSDAGTYICV 904
Cdd:cd00096      1 VTLTCSASGNPP---PTITWYKNGKPLPPSSRDSrrselgNGTLTISNVTLEDSGTYTCV 57

Low-density lipoprotein receptor domain class A; Cysteine-rich repeat in the low-density lipoprotein (LDL) receptor that plays a central role in mammalian cholesterol metabolism. The N-terminal type A repeats in LDL receptor bind the lipoproteins. Other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement. Mutations in the LDL receptor gene cause familial hypercholesterolemia.

Pssm-ID: 197566 Cd Length: 33 Bit Score: 47.63 E-value: 9.34e-07

                            10        20        30
                    ....*....|....*....|....*....|....
gi 1799133945   563 RCSSVQFECKrDGKCIDKALECNHKYDCEDGSDE 596
Cdd:smart00192    1 TCPPGEFQCD-NGRCIPSSWVCDGVDDCGDGSDE 33

Low-density lipoprotein receptor domain class A; Cysteine-rich repeat in the low-density lipoprotein (LDL) receptor that plays a central role in mammalian cholesterol metabolism. The N-terminal type A repeats in LDL receptor bind the lipoproteins. Other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement. Mutations in the LDL receptor gene cause familial hypercholesterolemia.

Pssm-ID: 197566 Cd Length: 33 Bit Score: 47.24 E-value: 1.23e-06

                            10        20        30
                    ....*....|....*....|....*....|...
gi 1799133945   274 ECPSGERACKSGHCLPVAQFCDRRVQCPDGDDE 306
Cdd:smart00192    1 TCPPGEFQCDNGRCIPSSWVCDGVDDCGDGSDE 33

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: 48.66 E-value: 1.61e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  2023 PIRQTVDRDQPARFKCWVPGNSNVQLRWSRPGGAPLPSG------VQEQQGILHIPRASDQEVGQYVCTATDPSDNTplq 2096
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESgrfsvsRSGSTSTLTISNVTPEDSGTYTCAATNSSGSA--- 77


                    ....*...
gi 1799133945  2097 SEPVQLNI 2104
Cdd:smart00410   78 SSGTTLTV 85

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 48.55 E-value: 1.68e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2115 APQIDPPNQTVNVNDPAQFRCWVPGQPRAQLKWsRKDGRPLPNGileRDGFlrIDKSQLHDAGEYECTSTEPDGSTQlSP 2194
Cdd:pfam13895    1 KPVLTPSPTVVTEGEPVTLTCSAPGNPPPSYTW-YKDGSAISSS---PNFF--TLSVSAEDSGTYTCVARNGRGGKV-SN 73


                   ....*.
gi 1799133945 2195 PARLNV 2200
Cdd:pfam13895   74 PVELTV 79

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

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 48.65 E-value: 1.81e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1799133945 3067 GDRAWFDCKVTGDPSAVISWtKEGNDDLPPNA-----QVTGGR--LLFTDLKEDNAGVYRCVAKTKAGPLQTRTVLNV 3137
Cdd:cd05744     15 GRLCRFDCKVSGLPTPDLFW-QLNGKPVRPDSahkmlVRENGRhsLIIEPVTKRDAGIYTCIARNRAGENSFNAELVV 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: 48.56 E-value: 1.85e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1799133945 2600 GERHQFRCITTGSPTPKITWTGPNGsPLPHDVTPLEP--NILDFSNGRSELNGDYTCTASNPIGEAS 2664
Cdd:cd05731     10 GGVLLLECIAEGLPTPDIRWIKLGG-ELPKGRTKFENfnKTLKIENVSEADSGEYQCTASNTMGSAR 75

Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation; the laminin-type epidermal growth factor-like module occurs in tandem arrays; the domain contains 4 disulfide bonds (loops a-d) the first three resemble epidermal growth factor (EGF); the number of copies of this domain in the different forms of laminins is highly variable ranging from 3 up to 22 copies

Pssm-ID: 238012 Cd Length: 50 Bit Score: 47.35 E-value: 2.05e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1799133945 1172 SCDTRGAVTPYPNNY-GTCECKSQVTGPNCDQCKPGAFHLSEKsPEGC 1218
Cdd:cd00055      3 DCNGHGSLSGQCDPGtGQCECKPNTTGRRCDRCAPGYYGLPSQ-GGGC 49

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: 48.70 E-value: 2.06e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1799133945 1075 GTTFSLTCKAVAVPEPYINWRLNWGPvcEPPRCLQTSEGGygTLTIHDAQPVDQGAYTCEAINVKGR 1141
Cdd:cd04968     16 GQTVTLECFALGNPVPQIKWRKVDGS--PSSQWEITTSEP--VLEIPNVQFEDEGTYECEAENSRGK 78

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: 48.77 E-value: 2.08e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1799133945 3067 GDRAWFDCKVTGDPSAVISWTKEGNDDLPPNAQ------VTGGRLLFTDLKEDNAGVYRCVAKTKAGPLQTRTVLNV 3137
Cdd:cd05763     14 GSTARLECAATGHPTPQIAWQKDGGTDFPAARErrmhvmPEDDVFFIVDVKIEDTGVYSCTAQNSAGSISANATLTV 90

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

Pssm-ID: 409436 [Multi-domain] Cd Length: 95 Bit Score: 48.80 E-value: 2.19e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  837 TVFPSEKEvrDGRdVSFECRARTSDnsvYPTVRWARVGGPLP-SSAHDS--GGRLTI-NPVQLSDAGTYICVSDYNGNTV 912
Cdd:cd05849     11 TIYPEEST--EGK-VSVNCRARANP---FPIYKWRKNNLDIDlTNDRYSmvGGNLVInNPDKYKDAGRYVCIVSNIYGKV 84


                   ....*...
gi 1799133945  913 EAR-ATLS 919
Cdd:cd05849     85 RSReATLS 92

Laminin G domain;

Pssm-ID: 395008 [Multi-domain] Cd Length: 131 Bit Score: 49.62 E-value: 2.47e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 3264 TANPKGIIFETKRINSGDLLAtpydtihheAKITDyGTVLYEFDIGNGRQIVETTNPINPNEWNVIKIKNDKNQVTIQLN 3343
Cdd:pfam00054    3 TTEPSGLLLYNGTQTERDFLA---------LELRD-GRLEVSYDLGSGAAVVRSGDKLNDGKWHSVELERNGRSGTLSVD 72

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1799133945 3344 DESATIRqhTNPLPSLSTG-VNRPVFIGG--------RHEPTNEAndFRGIISQVVLSGHNVG 3397
Cdd:pfam00054   73 GEARPTG--ESPLGATTDLdVDGPLYVGGlpslgvkkRRLAISPS--FDGCIRDVIVNGKPLD 131

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 47.95 E-value: 2.88e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1799133945 2014 KPVIppKVDPIRQTVDRDQPARFKCWVPGNSNVQLRWSRPGGAPLPS-----GVQEQQGILHIPRASDQEVGQYVCTAT 2087
Cdd:pfam13927    1 KPVI--TVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGstrsrSLSGSNSTLTISNVTRSDAGTYTCVAS 77

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: 47.88 E-value: 3.10e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1799133945 3074 CKVTGDPSAVISWTKEGNDDLPPNAQVT---GGRLLFTDLKEDNAGVYRCVAKTKAGPLQTRTVLNV 3137
Cdd:cd20952     21 CQATGEPVPTISWLKDGVPLLGKDERITtleNGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 87

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 47.56 E-value: 3.12e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2673 PSLTVKTNPPgpklIVTVGEPLQVKCEAFGapgDPEPEVEWLHDpGPERGDLPDDFKPVTISEQFIRHPNVGLGNAGVYT 2752
Cdd:pfam13927    2 PVITVSPSSV----TVREGETVTLTCEATG---SPPPTITWYKN-GEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYT 73


                   ....
gi 1799133945 2753 CKGS 2756
Cdd:pfam13927   74 CVAS 77

Low-density lipoprotein receptor domain class A; Cysteine-rich repeat in the low-density lipoprotein (LDL) receptor that plays a central role in mammalian cholesterol metabolism. The N-terminal type A repeats in LDL receptor bind the lipoproteins. Other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement. Mutations in the LDL receptor gene cause familial hypercholesterolemia.

Pssm-ID: 197566 Cd Length: 33 Bit Score: 46.09 E-value: 3.54e-06

                            10        20        30
                    ....*....|....*....|....*....|....*
gi 1799133945   498 CNDQEFRCPYlaeTRCFHYDRLCDGTDDCGDGSDE 532
Cdd:smart00192    2 CPPGEFQCDN---GRCIPSSWVCDGVDDCGDGSDE 33

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: 47.70 E-value: 5.14e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1929 VID-PPHL-VVNEGEPAAFRCWVPGIPDCQITWHREQLGGPLPHG---VYQT-GNALKIPQSQLHHAGRYICSAANQYGT 2002
Cdd:cd05738      1 IIDmGPQLkVVEKARTATMLCAASGNPDPEISWFKDFLPVDTATSngrIKQLrSGALQIENSEESDQGKYECVATNSAGT 80

                           90
                   ....*....|.
gi 1799133945 2003 GQSPPAVLEVK 2013
Cdd:cd05738     81 RYSAPANLYVR 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: 47.17 E-value: 5.16e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1799133945 2119 DPPNQTVNVNDPAQFRCWVPGQ-PRAQLKWSRKDGrPLPNGILERDGFLRIDKSQLHDAGEYECTST 2184
Cdd:cd05754      7 EPRSQEVRPGADVSFICRAKSKsPAYTLVWTRVNG-TLPSRAMDFNGILTIRNVQLSDAGTYVCTGS 72

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: 47.62 E-value: 5.27e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  837 TVFPSEKevrDGRDVSFECRARTSDnsvYPTVRWARVGGPLPSSAHDS----GGRLTI-NPVQLSDAGTYICVSDYNGNT 911
Cdd:cd04967     11 TIFPEDS---DEKKVALNCRARANP---VPSYRWLMNGTEIDLESDYRyslvDGTLVIsNPSKAKDAGHYQCLATNTVGS 84


                   ....*....
gi 1799133945  912 VEAR-ATLS 919
Cdd:cd04967     85 VLSReATLQ 93

Low-density lipoprotein receptor domain class A;

Pssm-ID: 395011 Cd Length: 37 Bit Score: 45.70 E-value: 5.31e-06

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 1799133945  498 CNDQEFRCpylAETRCFHYDRLCDGTDDCGDGSDETNC 535
Cdd:pfam00057    3 CSPNEFQC---GSGECIPRSWVCDGDPDCGDGSDEENC 37

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: 47.64 E-value: 5.64e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2586 PTAVVEPRTWNGKPGERHQFRCITTGSPTPKITWTgPNGSplphDVTPLEPNILDF---------SNGRSELNGDYTCTA 2656
Cdd:cd05736      1 PVIRVYPEFQAKEPGVEASLRCHAEGIPLPRVQWL-KNGM----DINPKLSKQLTLiangselhiSNVRYEDTGAYTCIA 75


                   ....*....
gi 1799133945 2657 SNPIGEASD 2665
Cdd:cd05736     76 KNEGGVDED 84

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: 47.32 E-value: 5.75e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1065 PPQTNLQVP-----RGTTFSLTCKAVAVPEPYINWRlnwgPVCEP-PRCLQTSEGGyGTLTIHDAQPVDQGAYTCEAINV 1138
Cdd:cd05851      1 PADINVKFKdtyalKGQNVTLECFALGNPVPVIRWR----KILEPmPATAEISMSG-AVLKIFNIQPEDEGTYECEAENI 75


                   ...
gi 1799133945 1139 KGR 1141
Cdd:cd05851     76 KGK 78

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: 6.04e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1799133945 3066 IGDRAWFDCKVTGDPSAVISWTKEGnDDLPPNA--QVTGGRLLFTDLKEDNAGVYRCVAKTKAGPLQTRTVLNV 3137
Cdd:cd05728     13 IGSSLRWECKASGNPRPAYRWLKNG-QPLASENriEVEAGDLRITKLSLSDSGMYQCVAENKHGTIYASAELAV 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: 47.11 E-value: 6.14e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  2499 PPLLSVAPGSPARFNCVAHSDTPARIRWgFREENGPLPE----HVNQDGDD--IVISEAGDRNVGEYVCSATNDFGTGVA 2572
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTW-YKQGGKLLAEsgrfSVSRSGSTstLTISNVTPEDSGTYTCAATNSSGSASS 79


                    ....*..
gi 1799133945  2573 dPVRLEV 2579
Cdd:smart00410   80 -GTTLTV 85

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: 46.55 E-value: 6.87e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1799133945 2604 QFRCITTGSPTPKITWTGpNGSPLPHDVTPLEPNI-----LDFSNGRSELNGDYTCTASNPIGEAS 2664
Cdd:cd00096      2 TLTCSASGNPPPTITWYK-NGKPLPPSSRDSRRSElgngtLTISNVTLEDSGTYTCVASNSAGGSA 66

Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation; the laminin-type epidermal growth factor-like module occurs in tandem arrays; the domain contains 4 disulfide bonds (loops a-d) the first three resemble epidermal growth factor (EGF); the number of copies of this domain in the different forms of laminins is highly variable ranging from 3 up to 22 copies

Pssm-ID: 238012 Cd Length: 50 Bit Score: 45.81 E-value: 7.47e-06

                           10        20        30
                   ....*....|....*....|....*....|....*
gi 1799133945 1477 PAQGQCQCKASVIGPNCDRCAPNSFGLaPTNPQGC 1511
Cdd:cd00055     16 PGTGQCECKPNTTGRRCDRCAPGYYGL-PSQGGGC 49

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: 46.73 E-value: 7.54e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  3154 PVVYTVGQPAYLSCigKTETKPNQSVVWTKEEGDLPSGS-RVE------QGVLMLPSVHRDDEGSYTCEIVKEENPVFST 3226
Cdd:smart00410    3 SVTVKEGESVTLSC--EASGSPPPEVTWYKQGGKLLAESgRFSvsrsgsTSTLTISNVTPEDSGTYTCAATNSSGSASSG 80


                    ....*
gi 1799133945  3227 VDLQI 3231
Cdd:smart00410   81 TTLTV 85

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: 46.78 E-value: 8.02e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1799133945 2970 QIVKFDDKSDASFTC-PIYSVPGSKVDWTYENGDLPSKAVPNGNKIEIKEFDDASAGTYVCKVSFDGNVVEGFVT 3043
Cdd:cd05754      9 RSQEVRPGADVSFICrAKSKSPAYTLVWTRVNGTLPSRAMDFNGILTIRNVQLSDAGTYVCTGSNMLDTDEATAT 83

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: 8.11e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2203 PQAIQPQVDPPVqTVNEGEPSRIRCWVPGHPNIQLQFVKRGRRPLPA-----HARFSQGNLEIPRTLKSDEDEYICIATD 2277
Cdd:cd20969      1 RAAIRDRKAQQV-FVDEGHTVQFVCRADGDPPPAILWLSPRKHLVSAksngrLTVFPDGTLEVRYAQVQDNGTYLCIAAN 79

                           90
                   ....*....|....*.
gi 1799133945 2278 PTTNrpvESNPARVIV 2293
Cdd:cd20969     80 AGGN---DSMPAHLHV 92

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: 46.63 E-value: 9.21e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1799133945 2122 NQTVNVNDPAQFRCWVPGQPRAQLKWSRKDGrPLPNGILERDGF---LRIDKSQLHDAGEYECTSTEPDGSTQ 2191
Cdd:cd05731      4 STMVLRGGVLLLECIAEGLPTPDIRWIKLGG-ELPKGRTKFENFnktLKIENVSEADSGEYQCTASNTMGSAR 75

Low-density lipoprotein receptor domain class A;

Pssm-ID: 395011 Cd Length: 37 Bit Score: 44.93 E-value: 9.56e-06

                           10        20        30
                   ....*....|....*....|....*....|..
gi 1799133945  125 CATTEFTCLDKSCIPADQRCDGRRNCPDGSDE 156
Cdd:pfam00057    3 CSPNEFQCGSGECIPRSWVCDGDPDCGDGSDE 34

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: 9.85e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  840 PSEKEVRDGRDVSFECRARTSDNsvyPTVRWARVGGPLPSSAH-----DSGGRLTINPVQLSDAGTYICV-SDYNGNTVE 913
Cdd:cd20970      9 SFTVTAREGENATFMCRAEGSPE---PEISWTRNGNLIIEFNTryivrENGTTLTIRNIRRSDMGIYLCIaSNGVPGSVE 85


                   ....*..
gi 1799133945  914 ARATLSV 920
Cdd:cd20970     86 KRITLQV 92

Low-density lipoprotein receptor domain class A;

Pssm-ID: 395011 Cd Length: 37 Bit Score: 44.93 E-value: 9.94e-06

                           10        20        30
                   ....*....|....*....|....*....|....*
gi 1799133945  416 CLEGQFKCGTGQCIEESLKCNRKYDCADGSDEITC 450
Cdd:pfam00057    3 CSPNEFQCGSGECIPRSWVCDGDPDCGDGSDEENC 37

Laminin EGF domain; This family is like pfam00008 but has 8 conserved cysteines instead of six.

Pssm-ID: 395007 Cd Length: 49 Bit Score: 45.04 E-value: 1.06e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1799133945 1173 CDTRGAVTPYPN-NYGTCECKSQVTGPNCDQCKPGAFHLSEKSPEGC 1218
Cdd:pfam00053    3 CNPHGSLSDTCDpETGQCLCKPGVTGRHCDRCKPGYYGLPSDPPQGC 49

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: 1.11e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1062 VVDPPQ--TNLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPVCEPPRCLQTSEGGyGTLTIHDAQPVDQGAYTCEAIN-V 1138
Cdd:cd20970      2 VISTPQpsFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVRENG-TTLTIRNIRRSDMGIYLCIASNgV 80


                   ....
gi 1799133945 1139 KGRV 1142
Cdd:cd20970     81 PGSV 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: 46.44 E-value: 1.12e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1799133945 2607 CITTGSPTPKITWTGPNGSPLPHDVTPLEPN-ILDFSNGRSELNGDYTCTASNPIGEASDHGNVNI 2671
Cdd:cd05876     17 CIAEGLPTPTVKWLRPSGPLPPDRVKYQNHNkTLQLLNVGESDDGEYVCLAENSLGSARHAYYVTV 82

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 46.48 E-value: 1.28e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1928 PVID--PPHLVVNEGEPAAFRCWVPGIPDCQITWHREqlGGPLPHG-----VYQTGNA-LKIPQSQLHHAGRYICSAANQ 1999
Cdd:pfam07679    1 PKFTqkPKDVEVQEGESARFTCTVTGTPDPEVSWFKD--GQPLRSSdrfkvTYEGGTYtLTISNVQPDDSGKYTCVATNS 78


                   ...
gi 1799133945 2000 YGT 2002
Cdd:pfam07679   79 AGE 81

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: 46.37 E-value: 1.28e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 3154 PVVYTV--GQPAYLSCIgkTETKPNQSVVWTKEEGDLPSGSRVE---QGVLMLPSVHRDDEGSYTCEIVKEENPVFSTVD 3228
Cdd:cd20957      8 PPVQTVdfGRTAVFNCS--VTGNPIHTVLWMKDGKPLGHSSRVQilsEDVLVIPSVKREDKGMYQCFVRNDGDSAQATAE 85


                   ...
gi 1799133945 3229 LQI 3231
Cdd:cd20957     86 LKL 88

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: 46.29 E-value: 1.49e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2584 EPPTAVVEPrtwngkpGERHQFRCITTGSPTPKITWTgPNGSPL----PHDVTPLEPNILDFSNGRSELNGDYTCTASNP 2659
Cdd:cd04978      5 EPPSLVLSP-------GETGELICEAEGNPQPTITWR-LNGVPIepapEDMRRTVDGRTLIFSNLQPNDTAVYQCNASNV 76

                           90
                   ....*....|..
gi 1799133945 2660 IGEASDHGNVNI 2671
Cdd:cd04978     77 HGYLLANAFLHV 88

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: 45.65 E-value: 2.13e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1799133945 3066 IGDRAWFDCKV-TGDPSAVISWTKEGN------DDLPPNAQVTGGRLLFTDLKEDNAGVYRCVAKTKAGPLQTRTVL 3135
Cdd:pfam00047   10 EGDSATLTCSAsTGSPGPDVTWSKEGGtlieslKVKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGSATLSTSL 86

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: 45.65 E-value: 2.18e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  840 PSEKEVRDGRDVSFECRARTSdnSVYPTVRWARVGGPLPSSAHDSGGR-------LTINPVQLSDAGTYICVSDYNGNTV 912
Cdd:pfam00047    3 PPTVTVLEGDSATLTCSASTG--SPGPDVTWSKEGGTLIESLKVKHDNgrttqssLLISNVTKEDAGTYTCVVNNPGGSA 80


                   ....*.
gi 1799133945  913 EARATL 918
Cdd:pfam00047   81 TLSTSL 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: 45.46 E-value: 2.29e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1799133945 1932 PPHLVVNEGEPAAFRCWVPGIPDCQITWHREqlGGPLPHGVYQT--GNALKIPQSQLHHAGRYICSAANQYGT 2002
Cdd:cd05725      4 PQNQVVLVDDSAEFQCEVGGDPVPTVRWRKE--DGELPKGRYEIldDHSLKIRKVTAGDMGSYTCVAENMVGK 74

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: 45.57 E-value: 2.36e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1799133945 2606 RCITTGSPTPKITWTgPNGSPLP---HDVTPLEPNILDFSNGRSELNGDYTCTASNPIGEASDH 2666
Cdd:cd20952     20 NCQATGEPVPTISWL-KDGVPLLgkdERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEATWS 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: 45.72 E-value: 2.48e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  835 QITVFPSEKEVRDGRDVSFECRARTSDNsvyPTVRWARVGG--------PLPSSAHDS---GGRLTINPVQLSDAGTYIC 903
Cdd:cd05726      1 QFVVKPRDQVVALGRTVTFQCETKGNPQ---PAIFWQKEGSqnllfpyqPPQPSSRFSvspTGDLTITNVQRSDVGYYIC 77

                           90
                   ....*....|....*..
gi 1799133945  904 VSDYNGNTVEARATLSV 920
Cdd:cd05726     78 QALNVAGSILAKAQLEV 94

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: 45.52 E-value: 2.55e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2677 VKTNPPgpKLIVTVGEPLQVKCEAfgaPGDPEPEVEW------LHDPGPERGDLPDdfkpvtisEQFIRHPNVGLGNAGV 2750
Cdd:cd04978      2 WIIEPP--SLVLSPGETGELICEA---EGNPQPTITWrlngvpIEPAPEDMRRTVD--------GRTLIFSNLQPNDTAV 68

                           90       100
                   ....*....|....*....|.
gi 1799133945 2751 YTCKGSSAHATATKNIYIEVV 2771
Cdd:cd04978     69 YQCNASNVHGYLLANAFLHVL 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: 45.22 E-value: 2.66e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1799133945 2585 PPTAVVEPRTWNGKPGERHQFRCITTGSPTPKITWTgPNGSPLPHD--VTPLEPNILDFSNGRSELNGDYTCTASNP 2659
Cdd:cd20957      1 PLSATIDPPVQTVDFGRTAVFNCSVTGNPIHTVLWM-KDGKPLGHSsrVQILSEDVLVIPSVKREDKGMYQCFVRND 76

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

Pssm-ID: 238011 Cd Length: 38 Bit Score: 43.78 E-value: 2.98e-05

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 1799133945 3411 DACASTNLCLNGANCRNANNhhGFSCECAEEFHGEYCQ 3448
Cdd:cd00054      3 DECASGNPCQNGGTCVNTVG--SYRCSCPPGYTGRNCE 38

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: 44.93 E-value: 3.01e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2123 QTVNvndpaqFRCWVPGQPRAQLKWSrKDGRPLP---NGILERDGFLRIDKSQLHDAGEYECTSTEPDGSTQLSppARLN 2199
Cdd:cd05745      3 QTVD------FLCEAQGYPQPVIAWT-KGGSQLSvdrRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTV--AQLT 73


                   .
gi 1799133945 2200 V 2200
Cdd:cd05745     74 V 74

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: 45.18 E-value: 3.04e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  840 PSEKEVRDGRDVSFECraRTSDNSvYPTVRWARVGGPL-PSSAH----DSGGR--LTINPVQLSDAGTYICVSDYNGNTV 912
Cdd:cd05744      7 PGDLEVQEGRLCRFDC--KVSGLP-TPDLFWQLNGKPVrPDSAHkmlvRENGRhsLIIEPVTKRDAGIYTCIARNRAGEN 83


                   ....*...
gi 1799133945  913 EARATLSV 920
Cdd:cd05744     84 SFNAELVV 91

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 44.86 E-value: 3.11e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1799133945 2492 PPRPVATPPLLSVAPGSPARFNCVAHSDTPARIRW----GFREENGPLPEHVNQDGDDIVISEAGDRNVGEYVCSATN 2565
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWykngEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 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: 45.31 E-value: 3.24e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1799133945 3067 GDRAWFDCKVTGDPSAVISWTKeGNDDLPPNAQVT---GGRLLFTDLKEDNAGVYRCVAKTKAGPLQTRTV 3134
Cdd:cd20968     14 GLKAVLPCTTMGNPKPSVSWIK-GDDLIKENNRIAvleSGSLRIHNVQKEDAGQYRCVAKNSLGIAYSKPV 83

Laminin-type epidermal growth factor-like domai;

Pssm-ID: 214543 Cd Length: 46 Bit Score: 43.84 E-value: 3.32e-05

                            10        20        30
                    ....*....|....*....|....*....|....*
gi 1799133945  1477 PAQGQCQCKASVIGPNCDRCAPNSFGlapTNPQGC 1511
Cdd:smart00180   15 PDTGQCECKPNVTGRRCDRCAPGYYG---DGPPGC 46

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: 3.63e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2581 EDQEPPT-AVVEPRTWNGKPGERHQFRCITTGSPTpKITWTgPNGSPL-PHDVTPLEPNILDFSNGRSELNGDYTCTASN 2658
Cdd:cd04973      4 PPEAPPTyQISEVESYSAHPGDLLQLRCRLRDDVQ-SINWT-KDGVQLgENNRTRITGEEVQIKDAVPRDSGLYACVTSS 81

                           90
                   ....*....|...
gi 1799133945 2659 PIGEASDHGNVNI 2671
Cdd:cd04973     82 PSGSDTTYFSVNV 94

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

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 44.69 E-value: 4.51e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  840 PSEKEVRDGRDVSFECRARtsdNSVYPTVRWARVGGPL---PSSAHDSGGRLTINPVQLSDAGTYICVSDYNGNTVEARA 916
Cdd:cd20978      8 EKNVVVKGGQDVTLPCQVT---GVPQPKITWLHNGKPLqgpMERATVEDGTLTIINVQPEDTGYYGCVATNEIGDIYTET 84


                   ....
gi 1799133945  917 TLSV 920
Cdd:cd20978     85 LLHV 88

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 44.09 E-value: 5.18e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1799133945 2300 IIDPAEQTVPEGSPFKIRCYVPGHPSVQLTFRRVSGQLNE------DADENNGLLAVQRAELTDEGDYICTAR 2366
Cdd:pfam13927    5 TVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSgstrsrSLSGSNSTLTISNVTRSDAGTYTCVAS 77

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: 44.31 E-value: 5.26e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1799133945 3066 IGDRAWFDCKV-TGDPSAVISWTKEG---NDDLPPNAQVTGGRLLFTDLKEDNAGVYRCVAKTKAG 3127
Cdd:cd05724     11 VGEMAVLECSPpRGHPEPTVSWRKDGqplNLDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVG 76

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

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 44.36 E-value: 5.41e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1929 VIDPPHLVVNEGEPAAFRCWVPGIPDCQITWhreQLGG----PLPHGVYQTGN--ALKIPQSQLHHAGRYICSAANQYGT 2002
Cdd:cd04978      3 IIEPPSLVLSPGETGELICEAEGNPQPTITW---RLNGvpiePAPEDMRRTVDgrTLIFSNLQPNDTAVYQCNASNVHGY 79

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

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 44.44 E-value: 6.29e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1799133945 2402 ITPQTQTIPEGDPARIQCTVPGNPsaAQHLSFeRVDGKGLPFGSS---DDRGVLTIPSTQLQDAGEYVC 2467
Cdd:cd20957      6 IDPPVQTVDFGRTAVFNCSVTGNP--IHTVLW-MKDGKPLGHSSRvqiLSEDVLVIPSVKREDKGMYQC 71

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: 44.08 E-value: 6.67e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1799133945 2135 CWVPGQPRAQLKWSRKDGRPLPNGILER-DGFLRIDKSQLHDAGEYEC 2181
Cdd:cd04968     23 CFALGNPVPQIKWRKVDGSPSSQWEITTsEPVLEIPNVQFEDEGTYEC 70

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

Pssm-ID: 143259 Cd Length: 88 Bit Score: 44.24 E-value: 6.94e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1799133945  848 GRDVSFECRARtsDNSVyPTVRWARVGGPLPSSAH--DSGGRLTINPVQLSDAGTYIC 903
Cdd:cd05851     16 GQNVTLECFAL--GNPV-PVIRWRKILEPMPATAEisMSGAVLKIFNIQPEDEGTYEC 70

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: 44.00 E-value: 7.08e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1799133945 2600 GERHQFRCITTGSPTPKITWTGPNGSPLPHDV-TPLEPN-ILDFSNGRSELNGDYTCTASNPIGEAS 2664
Cdd:cd05764     15 GQRATLRCKARGDPEPAIHWISPEGKLISNSSrTLVYDNgTLDILITTVKDTGAFTCIASNPAGEAT 81

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

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 44.11 E-value: 7.44e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2492 PPRPVATPPLLSVAPGSPARFNCVAHSDTPARIRWgFRE----ENGP-LPEHVNQDGDDIVISEAGDRNVGEYVCSATND 2566
Cdd:cd20972      1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRW-FCEgkelQNSPdIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNS 79


                   ...
gi 1799133945 2567 FGT 2569
Cdd:cd20972     80 VGS 82

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 43.92 E-value: 7.57e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2207 QPQVDPPVQTVNEGEPSRIRCWVPGHPNIQLQFVKRGrRPLPaharfSQGNLEIPRTLKSDEDEYICIATDPTTNRPveS 2286
Cdd:pfam13895    1 KPVLTPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDG-SAIS-----SSPNFFTLSVSAEDSGTYTCVARNGRGGKV--S 72


                   ....*..
gi 1799133945 2287 NPARVIV 2293
Cdd:pfam13895   73 NPVELTV 79

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

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 43.93 E-value: 7.93e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2209 QVDPPVQTVNEGEPSRIRCWVP-GHPNIQLQFVKRGRrPL----PAHARFSQGNLEIPRTLKSDEDEYICIATDPTTNRp 2283
Cdd:cd05724      1 RVEPSDTQVAVGEMAVLECSPPrGHPEPTVSWRKDGQ-PLnldnERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGER- 78

                           90
                   ....*....|
gi 1799133945 2284 vESNPARVIV 2293
Cdd:cd05724     79 -ESRAARLSV 87

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: 44.12 E-value: 8.41e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1799133945 3067 GDRAWFDCKVTGDPSAVISWTKEG----NDDLPPNAQVTGGRLLFTDLKEDNAGVYRCVAKTKAGPLQTRTVLNV 3137
Cdd:cd05867     14 GETARLDCQVEGIPTPNITWSINGapieGTDPDPRRHVSSGALILTDVQPSDTAVYQCEARNRHGNLLANAHVHV 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: 44.02 E-value: 9.52e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1060 PTVVDPPQtNLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPVCEPPR-CLQTSEGGYGTLTIHDAQPVDQGAYTCEAINV 1138
Cdd:cd05744      1 PHFLQAPG-DLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAhKMLVRENGRHSLIIEPVTKRDAGIYTCIARNR 79


                   ....
gi 1799133945 1139 KGRV 1142
Cdd:cd05744     80 AGEN 83

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: 43.32 E-value: 1.01e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1799133945 1080 LTCKAVAVPEPYINWRLNWGPVCEPPRcLQTSEGGYgtLTIHDAQPVDQGAYTCEAINVKG 1140
Cdd:cd05746      3 IPCSAQGDPEPTITWNKDGVQVTESGK-FHISPEGY--LAIRDVGVADQGRYECVARNTIG 60

Low-density lipoprotein receptor domain class A;

Pssm-ID: 395011 Cd Length: 37 Bit Score: 41.85 E-value: 1.16e-04

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 1799133945  562 SRCSSVQFECkRDGKCIDKALECNHKYDCEDGSDETEC 599
Cdd:pfam00057    1 STCSPNEFQC-GSGECIPRSWVCDGDPDCGDGSDEENC 37

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: 43.50 E-value: 1.19e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  840 PSEKEVRDGRDVSFECrarTSDNSVYPTVRWARVGGPLPSSAHDSGGR------LTINPVQLSDAGTYICVSDYNGNTVE 913
Cdd:cd05747     10 PRSLTVSEGESARFSC---DVDGEPAPTVTWMREGQIIVSSQRHQITSteykstFEISKVQMSDEGNYTVVVENSEGKQE 86


                   ....*.
gi 1799133945  914 ARATLS 919
Cdd:cd05747     87 AQFTLT 92

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

Pssm-ID: 409454 Cd Length: 89 Bit Score: 43.43 E-value: 1.25e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2589 VVEPRTWNGKPGERHQFRCITTGSPTPKITWTgPNGSPLphDVTPLEP------NILDFSNGRSELNGDYTCTASNPIGE 2662
Cdd:cd05868      3 ITAPTNLVLSPGEDGTLICRANGNPKPSISWL-TNGVPI--EIAPTDPsrkvdgDTIIFSKVQERSSAVYQCNASNEYGY 79


                   ....*....
gi 1799133945 2663 ASDHGNVNI 2671
Cdd:cd05868     80 LLANAFVNV 88

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: 43.46 E-value: 1.39e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2296 PIRPIIDPAEQTVPEGSPFKIRCYVPGHPSVQLTFRRVSG-QLNEDAD---------ENNGLLAVQRAELTDEGDYICTA 2365
Cdd:cd20954      1 PPRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKATGsTPGEYKDllydpnvriLPNGTLVFGHVQKENEGHYLCEA 80


                   .
gi 1799133945 2366 R 2366
Cdd:cd20954     81 K 81

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

Pssm-ID: 409473 Cd Length: 92 Bit Score: 43.22 E-value: 1.58e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1060 PTVVDPPQtNLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPVCEPPR--CLQTSEGGYGTLTIHDAQPVDQGAYTCEAIN 1137
Cdd:cd05892      1 PMFIQKPQ-NKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNTDriSLYQDNCGRICLLIQNANKKDAGWYTVSAVN 79


                   ....*
gi 1799133945 1138 VKGRV 1142
Cdd:cd05892     80 EAGVV 84

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 42.94 E-value: 1.58e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1799133945 2209 QVDPPVQTVNEGEPSRIRCWVPGHPNIQLQFVKRGRRPLPAHAR-----FSQGNLEIPRTLKSDEDEYICIAT 2276
Cdd:pfam13927    5 TVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRsrslsGSNSTLTISNVTRSDAGTYTCVAS 77

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 43.01 E-value: 1.67e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 3154 PVVYTVGQPAYLSCigKTETKPNQSVVWTKEEGDLPSGSRV----EQGV--LMLPSVHRDDEGSYTCEIVKEENPVFSTV 3227
Cdd:pfam07679    9 DVEVQEGESARFTC--TVTGTPDPEVSWFKDGQPLRSSDRFkvtyEGGTytLTISNVQPDDSGKYTCVATNSAGEAEASA 86


                   ....
gi 1799133945 3228 DLQI 3231
Cdd:pfam07679   87 ELTV 90

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

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 43.01 E-value: 1.69e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  835 QITVFPSEKEVRDGRDVSFECRARtsdNSVYPTVRWARVGGPLP-----SSAHDSGGRLTINPVQLSDAGTYICVSDYNG 909
Cdd:cd20976      3 SFSSVPKDLEAVEGQDFVAQCSAR---GKPVPRITWIRNAQPLQyaadrSTCEAGVGELHIQDVLPEDHGTYTCLAKNAA 79

                           90
                   ....*....|.
gi 1799133945  910 NTVEARATLSV 920
Cdd:cd20976     80 GQVSCSAWVTV 90

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: 1.75e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2118 IDPPNQ--TVNVNDPAQFRCWVPGQPRAQLKWSrKDGRPL----PNGILE--RDGFLRIDKSQLHDAGEYECTSTEPDGs 2189
Cdd:cd05738      2 IDMGPQlkVVEKARTATMLCAASGNPDPEISWF-KDFLPVdtatSNGRIKqlRSGALQIENSEESDQGKYECVATNSAG- 79

                           90
                   ....*....|.
gi 1799133945 2190 TQLSPPARLNV 2200
Cdd:cd05738     80 TRYSAPANLYV 90

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 42.95 E-value: 1.89e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2402 ITPQTQTIPEGDPARIQCTV-PGNPSAAQHLSFERVDGKGLPFGSSDDRGV----LTIPSTQLQDAGEYVCLYSPENSPP 2476
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSAsTGSPGPDVTWSKEGGTLIESLKVKHDNGRTtqssLLISNVTKEDAGTYTCVVNNPGGSA 80


                   ...
gi 1799133945 2477 VKT 2479
Cdd:pfam00047   81 TLS 83

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

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 43.01 E-value: 1.91e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2303 PAEQTVPEGSPFKIRCYVPGHPSVQLTFRRVSGQLNEDADENN-----GLLAVQRAELTDEGDYICTARD 2367
Cdd:cd20976      8 PKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADRSTceagvGELHIQDVLPEDHGTYTCLAKN 77

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: 43.07 E-value: 1.94e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2585 PPTAVVEPRTWNGKPGERHQFRCITTGSPTPKITWTGPNGSPLP--HDVTpLEPNILDFSNG-------RSELNGDYTCT 2655
Cdd:cd20954      1 PPRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKATGSTPGeyKDLL-YDPNVRILPNGtlvfghvQKENEGHYLCE 79


                   ....*.
gi 1799133945 2656 ASNPIG 2661
Cdd:cd20954     80 AKNGIG 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: 42.87 E-value: 2.11e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  836 ITVFPSEKEVRDGRDVSFECRArtsDNSVYPTVRWARVGGPLPSSAHD----SGGRLTINPVQLSDAGTYICVSDYNGNT 911
Cdd:cd20952      2 ILQGPQNQTVAVGGTVVLNCQA---TGEPVPTISWLKDGVPLLGKDERittlENGSLQIKGAEKSDTGEYTCVALNLSGE 78


                   ....*....
gi 1799133945  912 VEARATLSV 920
Cdd:cd20952     79 ATWSAVLDV 87

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

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 42.87 E-value: 2.29e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2688 VTVGEPLQVKCEAFGapgDPEPEVEWLHDPGPERGDLPDDFKPVTISEQFIrhpNVGLGNAGVYTCKGSSAHATATKNIY 2767
Cdd:cd20952     11 VAVGGTVVLNCQATG---EPVPTISWLKDGVPLLGKDERITTLENGSLQIK---GAEKSDTGEYTCVALNLSGEATWSAV 84


                   ...
gi 1799133945 2768 IEV 2770
Cdd:cd20952     85 LDV 87

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: 42.59 E-value: 2.39e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2120 PPNQTVNVNDPAQFRCWVPGQPRAQLKWsRKDGRPLP--NGILERDGFLRIDKSQLHDAGEYECTSTEPDGSTQLSppAR 2197
Cdd:cd05728      6 ISDTEADIGSSLRWECKASGNPRPAYRW-LKNGQPLAseNRIEVEAGDLRITKLSLSDSGMYQCVAENKHGTIYAS--AE 82


                   ...
gi 1799133945 2198 LNV 2200
Cdd:cd05728     83 LAV 85

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: 42.54 E-value: 2.41e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1799133945 2300 IIDPAEQTVPEGSPFKIRCYVPGH-PSVQLTFRRVSGQLNEDADENNGLLAVQRAELTDEGDYICT 2364
Cdd:cd05754      5 VEEPRSQEVRPGADVSFICRAKSKsPAYTLVWTRVNGTLPSRAMDFNGILTIRNVQLSDAGTYVCT 70

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: 42.45 E-value: 2.51e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1799133945 1072 VPRGTTFSLTCKAVAVPEPYINWRLNWGPVCEPPRCLQTSEGgygTLTIHDAQPVDQGAYTCEAINVKG 1140
Cdd:cd04969     14 AAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILPDG---SLKIKNVTKSDEGKYTCFAVNFFG 79

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: 43.02 E-value: 2.57e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 3067 GDRAWFDCKVTGDPSAVISWTKEGNDDL-------PPNAQVT---GGRLLFTDLKEDNAGVYRCVAKTKAGPLQTRTVLN 3136
Cdd:cd05726     14 GRTVTFQCETKGNPQPAIFWQKEGSQNLlfpyqppQPSSRFSvspTGDLTITNVQRSDVGYYICQALNVAGSILAKAQLE 93


                   .
gi 1799133945 3137 V 3137
Cdd:cd05726     94 V 94

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: 42.92 E-value: 2.69e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 3059 VSSESPQ---IGDRAWFDCKVTGDPSAVISWTKEGNDD----LPPNaQVTG-------GRLLFTDLKEDNAGVYRCVAKT 3124
Cdd:cd05765      4 VNSPTHQtvkVGETASFHCDVTGRPQPEITWEKQVPGKenliMRPN-HVRGnvvvtniGQLVIYNAQPQDAGLYTCTARN 82

                           90
                   ....*....|...
gi 1799133945 3125 KAGPLQTRTVLNV 3137
Cdd:cd05765     83 SGGLLRANFPLSV 95

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: 42.17 E-value: 3.05e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2116 PQIDP-PNQTVNVNDPAQFRCWVPGQPRAQLKWSrKDGRPLPNGILER---DGFLRIDK-SQLHDAGEYECTSTEPDGST 2190
Cdd:cd20958      2 PFIRPmGNLTAVAGQTLRLHCPVAGYPISSITWE-KDGRRLPLNHRQRvfpNGTLVIENvQRSSDEGEYTCTARNQQGQS 80

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: 42.54 E-value: 3.27e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2119 DPPNQTVNVNDPAQFRCWVPGQPRAQLKWSRK-DGRP---------LPNGILERDGFLRIDKSQLHDAGEYECTSTEPDG 2188
Cdd:cd05765      6 SPTHQTVKVGETASFHCDVTGRPQPEITWEKQvPGKEnlimrpnhvRGNVVVTNIGQLVIYNAQPQDAGLYTCTARNSGG 85


                   ....*..
gi 1799133945 2189 STQLSPP 2195
Cdd:cd05765     86 LLRANFP 92

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

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 42.00 E-value: 3.47e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2117 QIDPPNQTVNVNDPAQFRCWVP-GQPRAQLKWsRKDGRPL-----PNGILErDGFLRIDKSQLHDAGEYECTSTEPDGsT 2190
Cdd:cd05724      1 RVEPSDTQVAVGEMAVLECSPPrGHPEPTVSW-RKDGQPLnldneRVRIVD-DGNLLIAEARKSDEGTYKCVATNMVG-E 77

                           90
                   ....*....|
gi 1799133945 2191 QLSPPARLNV 2200
Cdd:cd05724     78 RESRAARLSV 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: 41.55 E-value: 3.54e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1799133945 2131 AQFRCWVPGQPRAQLKWsRKDGRPLPNGILER------DGFLRIDKSQLHDAGEYECTSTEPDGSTQ 2191
Cdd:cd00096      1 VTLTCSASGNPPPTITW-YKNGKPLPPSSRDSrrselgNGTLTISNVTLEDSGTYTCVASNSAGGSA 66

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

Pssm-ID: 409454 Cd Length: 89 Bit Score: 42.28 E-value: 3.64e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2496 VATPPLLSVAPGSPARFNCVAHSDTPARIRW---GFREENGPLPEHVNQDGDDIVISEAGDRNVGEYVCSATNDFGTGVA 2572
Cdd:cd05868      3 ITAPTNLVLSPGEDGTLICRANGNPKPSISWltnGVPIEIAPTDPSRKVDGDTIIFSKVQERSSAVYQCNASNEYGYLLA 82


                   .
gi 1799133945 2573 D 2573
Cdd:cd05868     83 N 83

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: 42.13 E-value: 3.77e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1799133945 2020 KVDPIRQTVDRDQPARFKCWVPGNSNVQLRWsRPGGAPLPSGVQEQ---QGILHIPRASDQEVGQYVCTATDPSD 2091
Cdd:cd20957      5 TIDPPVQTVDFGRTAVFNCSVTGNPIHTVLW-MKDGKPLGHSSRVQilsEDVLVIPSVKREDKGMYQCFVRNDGD 78

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 42.18 E-value: 3.86e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2301 IDPAEQTVPEGSPFKIRC-YVPGHPSVQLTFRRVSGQLNE-------DADENNGLLAVQRAELTDEGDYICTARDPDTGA 2372
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCsASTGSPGPDVTWSKEGGTLIEslkvkhdNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGSA 80


                   ....*
gi 1799133945 2373 PIDST 2377
Cdd:pfam00047   81 TLSTS 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 41.78 E-value: 4.06e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1799133945 3154 PVVYTVGQPAYLSCIGKTETKPnqSVVWTKEEGDLPSGSRVE------QGVLMLPSVHRDDEGSYTCE 3215
Cdd:pfam13927   10 SVTVREGETVTLTCEATGSPPP--TITWYKNGEPISSGSTRSrslsgsNSTLTISNVTRSDAGTYTCV 75

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 41.61 E-value: 4.29e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2494 RPVATPPLLSVAPGSPARFNCVAHSDTPARIRWgfREENGPLPehvnqDGDDIVISEAGDRNVGEYVCSATNDFGTGVAD 2573
Cdd:pfam13895    1 KPVLTPSPTVVTEGEPVTLTCSAPGNPPPSYTW--YKDGSAIS-----SSPNFFTLSVSAEDSGTYTCVARNGRGGKVSN 73


                   ....*.
gi 1799133945 2574 PVRLEV 2579
Cdd:pfam13895   74 PVELTV 79

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: 41.89 E-value: 4.34e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 3074 CKVTGDPSAVISWTKEG------NDDlpPNAQVTGGRLLFTDLKEDNAGVYRCVAKTKAGPLQTRTVLNV 3137
Cdd:cd05868     21 CRANGNPKPSISWLTNGvpieiaPTD--PSRKVDGDTIIFSKVQERSSAVYQCNASNEYGYLLANAFVNV 88

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

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 42.15 E-value: 4.45e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  835 QITVFPSEKEVRDGRDVSFECRArtsDNSVYPTVRWARVGGPLPSSAHDSGGRLTINPV-------------QLSDAGTY 901
Cdd:cd07693      2 RIVEHPSDLIVSKGDPATLNCKA---EGRPTPTIQWLKNGQPLETDKDDPRSHRIVLPSgslfflrvvhgrkGRSDEGVY 78

                           90       100
                   ....*....|....*....|
gi 1799133945  902 ICVS-DYNGNTVEARATLSV 920
Cdd:cd07693     79 VCVAhNSLGEAVSRNASLEV 98

Low-density lipoprotein receptor domain class A;

Pssm-ID: 395011 Cd Length: 37 Bit Score: 40.31 E-value: 4.81e-04

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 1799133945  977 RTCEPNEFKCNNNKCVQKMWLCDGDDDCGDNSDELNC 1013
Cdd:pfam00057    1 STCSPNEFQCGSGECIPRSWVCDGDPDCGDGSDEENC 37

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: 41.78 E-value: 4.82e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1799133945 2216 TVNEGEPSRIRCWVPGHPNIQLQFVKRGRRpLPAHAR---FSQGNLEI-PRTLKSDEDEYICIATDP 2278
Cdd:cd20958     11 TAVAGQTLRLHCPVAGYPISSITWEKDGRR-LPLNHRqrvFPNGTLVIeNVQRSSDEGEYTCTARNQ 76

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: 41.78 E-value: 5.48e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1799133945 2297 IRPIidpAEQTVPEGSPFKIRCYVPGHPSVQLTFRRVSGQLNEDADE---NNGLL---AVQRAEltDEGDYICTARDPD 2369
Cdd:cd20958      4 IRPM---GNLTAVAGQTLRLHCPVAGYPISSITWEKDGRRLPLNHRQrvfPNGTLvieNVQRSS--DEGEYTCTARNQQ 77

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: 41.71 E-value: 5.73e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1061 TVVDPPQTNLQVprGTTFSLTCKAVAVPEPYINWRLNWGPVCEPPRCLQTSEGGygTLTIHDAQPVDQGAYTCEAINVKG 1140
Cdd:cd20952      2 ILQGPQNQTVAV--GGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLENG--SLQIKGAEKSDTGEYTCVALNLSG 77


                   ....*
gi 1799133945 1141 RVLAT 1145
Cdd:cd20952     78 EATWS 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: 41.71 E-value: 5.96e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 3061 SESPQIGDRAWFDCKVT-GDPSAVISWTKEGN---DDLPPNAQVTGGR---LLFTDLKEDNAGVYRCVAKTKAGPLQTRT 3133
Cdd:cd20959     11 EGAAQVGMRAQLHCGVPgGDLPLNIRWTLDGQpisDDLGITVSRLGRRssiLSIDSLEASHAGNYTCHARNSAGSASYTA 90


                   ....
gi 1799133945 3134 VLNV 3137
Cdd:cd20959     91 PLTV 94

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: 41.77 E-value: 6.06e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1799133945 1073 PRGTTFSLTCKAVAVPEPYINWRLNWGPVcEPPRCLQTSEGGYgTLTIHDAQPVDQGAYTCEAINVKGRVLAT 1145
Cdd:cd05856     17 PVGSSVRLKCVASGNPRPDITWLKDNKPL-TPPEIGENKKKKW-TLSLKNLKPEDSGKYTCHVSNRAGEINAT 87

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: 6.18e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1799133945 2399 HPVITPQTQTIPEGDPARIQCTVPGNPSAA--------QHLSFERVDGKGLPFGSSDDRGVLTIPSTQLQDAGEYVC 2467
Cdd:cd05726      1 QFVVKPRDQVVALGRTVTFQCETKGNPQPAifwqkegsQNLLFPYQPPQPSSRFSVSPTGDLTITNVQRSDVGYYIC 77

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 41.23 E-value: 6.22e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1799133945 3066 IGDRAWFDCKVTGDPSAVISWTKEGNddlppnAQVTGGRLLFTDLKEDNAGVYRCVAKTKAGPLQTRTV 3134
Cdd:pfam13895   13 EGEPVTLTCSAPGNPPPSYTWYKDGS------AISSSPNFFTLSVSAEDSGTYTCVARNGRGGKVSNPV 75

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

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 41.64 E-value: 6.57e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1926 PQPVIDPPHLVVNEGEPAAFRCWVPGIPDCQITWHREQ-----LGGPLPHGVYQTGN--ALKIPQSQLHHAGRYICSAAN 1998
Cdd:cd20951      1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGvpidpSSIPGKYKIESEYGvhVLHIRRVTVEDSAVYSAVAKN 80

                           90
                   ....*....|....*
gi 1799133945 1999 QYGTGQSpPAVLEVK 2013
Cdd:cd20951     81 IHGEASS-SASVVVE 94

Second immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains; The members here are composed of the second immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs). Interactions between IgG and FcgammaR are important to the initiation of cellular and humoral response. IgG binding to FcgammaR leads to a cascade of signals and ultimately to functions such as antibody-dependent-cellular-cytotoxicity (ADCC), endocytosis, phagocytosis, release of inflammatory mediators, etc. FcgammaR has two Ig-like domains. This group also contains FcepsilonRI which binds IgE with high affinity.

Pssm-ID: 409411 Cd Length: 83 Bit Score: 41.14 E-value: 6.79e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1799133945 1933 PHLVVNEGEPAAFRCWvpgipdcqiTWHREQLggplpHGV--YQTGNALK---------IPQSQLHHAGRYICSA 1996
Cdd:cd05753      7 PSAVVFEGEPLTLRCH---------GWKDKKV-----HKVtyYKDGKALKfsyensnfsIPQATLSDSGSYHCSG 67

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: 41.39 E-value: 7.35e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1799133945 1075 GTTFSLTCKAVAVPEPYINWRLNWGPVCEPPRCLQ----TSEG---GYgtLTIHDAQPVDQGAYTCEAINVKGRV 1142
Cdd:cd20956     16 GPSVSLKCVASGNPLPQITWTLDGFPIPESPRFRVgdyvTSDGdvvSY--VNISSVRVEDGGEYTCTATNDVGSV 88

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

Pssm-ID: 409388 Cd Length: 84 Bit Score: 41.03 E-value: 7.56e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1799133945 3072 FDCKVTGDPSAVISWTKEGNDDLPPN--AQVTGGRLLFTDLKEDNAGVYRCVAKTKAGPLQT 3131
Cdd:cd05723     17 FECEVTGKPTPTVKWVKNGDVVIPSDyfKIVKEHNLQVLGLVKSDEGFYQCIAENDVGNAQA 78

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 40.84 E-value: 7.95e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2400 PVITPQTQTIPEGDPARIQCTVPGNPSAAQHLSfervdGKGLPFGSSDDrgvLTIPSTQLQDAGEYVCLYSPENSPPVkT 2479
Cdd:pfam13895    2 PVLTPSPTVVTEGEPVTLTCSAPGNPPPSYTWY-----KDGSAISSSPN---FFTLSVSAEDSGTYTCVARNGRGGKV-S 72


                   ....*..
gi 1799133945 2480 NPSTLNV 2486
Cdd:pfam13895   73 NPVELTV 79

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: 41.22 E-value: 8.31e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2118 IDPP--NQTVNVNDPAQFRCWVPGQPRAQLKWSRkDGRPL----PNGILErDGFLRIDKSQLHDAGEYECTSTEPDGSTQ 2191
Cdd:cd20978      4 IQKPekNVVVKGGQDVTLPCQVTGVPQPKITWLH-NGKPLqgpmERATVE-DGTLTIINVQPEDTGYYGCVATNEIGDIY 81


                   ...
gi 1799133945 2192 LSP 2194
Cdd:cd20978     82 TET 84

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 41.09 E-value: 8.36e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1799133945 2400 PVIT--PQTQTIPEGDPARIQCTVPGNPSaaqhLSFE-RVDGKGLPFGS------SDDRGVLTIPSTQLQDAGEYVC 2467
Cdd:pfam07679    1 PKFTqkPKDVEVQEGESARFTCTVTGTPD----PEVSwFKDGQPLRSSDrfkvtyEGGTYTLTISNVQPDDSGKYTC 73

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: 41.22 E-value: 8.38e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1799133945 2597 GKPGERHQFRCITTGSPTPKITWTGPNGSPLPHD----VTPLEPNILDFSNGRSELNGDYTCTASNPIGEASDHGNVNI 2671
Cdd:cd20969     14 VDEGHTVQFVCRADGDPPPAILWLSPRKHLVSAKsngrLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLHV 92

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: 41.00 E-value: 8.61e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 3145 VTFTVADSLPVVYTVGQPAYLSCIGKTETkPNQSVVWTKEEGDLPSGSRVEQGVLMLPSVHRDDEGSYTC 3214
Cdd:cd05754      1 IQVTVEEPRSQEVRPGADVSFICRAKSKS-PAYTLVWTRVNGTLPSRAMDFNGILTIRNVQLSDAGTYVC 69

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

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 41.48 E-value: 8.87e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1799133945 1072 VPRGTTFSLTCKAVAVPEPYINWRLNWGPVCEPPRCLQTSEGGY-----GTLTIHDAQPVDQGAYTCEAINVKGRVLA 1144
Cdd:cd05726     11 VALGRTVTFQCETKGNPQPAIFWQKEGSQNLLFPYQPPQPSSRFsvsptGDLTITNVQRSDVGYYICQALNVAGSILA 88

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: 40.94 E-value: 9.07e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2302 DPAEQTVPEGSPFKIRCYVPGHPSVQLTFRR----VSGQLNEDADENNGLLAVQRAELTDEGDYICTARDPdtgapidST 2377
Cdd:cd20952      5 GPQNQTVAVGGTVVLNCQATGEPVPTISWLKdgvpLLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNL-------SG 77


                   ....*..
gi 1799133945 2378 PATVHVT 2384
Cdd:cd20952     78 EATWSAV 84

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

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 40.92 E-value: 9.17e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2673 PSLTVKTnppgPKLIVTVGEPLQVKCEAFGapgDPEPEVEWLHdpgpergdlPDDfKPVTISEQFIRHPN-------VGL 2745
Cdd:cd05764      1 PLITRHT----HELRVLEGQRATLRCKARG---DPEPAIHWIS---------PEG-KLISNSSRTLVYDNgtldiliTTV 63

                           90       100
                   ....*....|....*....|....*
gi 1799133945 2746 GNAGVYTCKGSSAHATATKNIYIEV 2770
Cdd:cd05764     64 KDTGAFTCIASNPAGEATARVELHI 88

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: 41.22 E-value: 9.33e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  845 VRDGRDVSFECRARTSDNsvyPTVRW-ARVGGPLPSSAHDS-----GGRLTINPVQLSDAGTYICVSDYNGNTVEARATL 918
Cdd:cd20969     14 VDEGHTVQFVCRADGDPP---PAILWlSPRKHLVSAKSNGRltvfpDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHL 90


                   ..
gi 1799133945  919 SV 920
Cdd:cd20969     91 HV 92

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: 9.62e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1060 PTVVDPPQTnLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPVCEPPRCLQTSEGGYGTLTIHDAQPVDQGAYTCEAINVK 1139
Cdd:cd20972      2 PQFIQKLRS-QEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNSV 80

                           90
                   ....*....|.
gi 1799133945 1140 GRVLATPDCIV 1150
Cdd:cd20972     81 GSDTTSAEIFV 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: 41.38 E-value: 1.00e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1926 PQPVIDPPHLVVNEGEPAAFRCWVPGIPDCQITWHREqlGGPLP---------HGVYQTGNA--LKIPQSQL--HHAGRY 1992
Cdd:cd07693      1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKN--GQPLEtdkddprshRIVLPSGSLffLRVVHGRKgrSDEGVY 78

                           90       100
                   ....*....|....*....|
gi 1799133945 1993 ICSAANQYGTGQSPPAVLEV 2012
Cdd:cd07693     79 VCVAHNSLGEAVSRNASLEV 98

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

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 40.86 E-value: 1.06e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1799133945 1936 VVNEGEPAAFRCWVPGIPDCQITWHReqLGGPLPHGVYQTGN---ALKIPQSQLHHAGRYICSAANQYGTGQ 2004
Cdd:cd05731      6 MVLRGGVLLLECIAEGLPTPDIRWIK--LGGELPKGRTKFENfnkTLKIENVSEADSGEYQCTASNTMGSAR 75

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

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 40.46 E-value: 1.15e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1799133945 3067 GDRAWFDCKVTGDPSAVISWTKEGNdDLPPN-AQVTGGR-LLFTDLKEDNAGVYRCVAKTKAGPLQTRTVLNV 3137
Cdd:cd05725     12 DDSAEFQCEVGGDPVPTVRWRKEDG-ELPKGrYEILDDHsLKIRKVTAGDMGSYTCVAENMVGKIEASATLTV 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: 40.46 E-value: 1.20e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1799133945 3155 VVYTVGQPAYLSCigKTETKPNQSVVWTKEEGDLPSGsRVEQ---GVLMLPSVHRDDEGSYTCE 3215
Cdd:cd05725      7 QVVLVDDSAEFQC--EVGGDPVPTVRWRKEDGELPKG-RYEIlddHSLKIRKVTAGDMGSYTCV 67

Second immunoglobulin (Ig)-like domain of Axl/Tyro3 family receptor tyrosine kinases (RTKs); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in the Axl/Tyro3 family of receptor tyrosine kinases (RTKs). This family includes Axl (also known as Ark, Ufo, and Tyro7), Tyro3 (also known as Sky, Rse, Brt, Dtk, and Tif), and Mer (also known as Nyk, c-Eyk, and Tyro12). Axl/Tyro3 family receptors have an extracellular portion with two Ig-like domains followed by two fibronectin-types III (FNIII) domains, a membrane-spanning single helix, and a cytoplasmic tyrosine kinase domain. Axl, Tyro3, and Mer are widely expressed in adult tissues, though they show higher expression in the brain, lymphatic and vascular systems, and testis. Axl, Tyro3, and Mer bind the vitamin K dependent protein Gas6 with high affinity, and in doing so activate their tyrosine kinase activity. Axl/Gas6 signaling may play a part in cell adhesion processes, prevention of apoptosis, and cell proliferation.

Pssm-ID: 409407 Cd Length: 82 Bit Score: 40.53 E-value: 1.25e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1799133945 1070 LQVPRGTTFSLTCKAVAVPEPY-INWRLNWGPVCEPPrclqtsEGGYGTLTIHDAQpvDQGAYTCEAINVKG 1140
Cdd:cd05749      9 LAVTANTPFNLTCQAVGPPEPVeILWWQGGSPLGGPP------APSPSVLNVPGLN--ETTKFSCEAHNAKG 72

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: 40.45 E-value: 1.34e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2679 TNPPGPKLIVTVGEPLQVKCEAfgaPGDPEPEVEWLHDPGPERGDLPDdfkpVTISEQFIRHPNVGLGNAGVYTCKGSSA 2758
Cdd:cd20978      4 IQKPEKNVVVKGGQDVTLPCQV---TGVPQPKITWLHNGKPLQGPMER----ATVEDGTLTIINVQPEDTGYYGCVATNE 76

                           90
                   ....*....|..
gi 1799133945 2759 HATATKNIYIEV 2770
Cdd:cd20978     77 IGDIYTETLLHV 88

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: 40.94 E-value: 1.34e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2585 PPTAVVEPRTWNGKPGERHQFRCITTGSPTPKITWTGPNGSPLP--HDVTPLEPNILDFSNGR-------SELNGDYTCT 2655
Cdd:cd05734      1 PPRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWKHSKGSGVPqfQHIVPLNGRIQLLSNGSllikhvlEEDSGYYLCK 80


                   ....*.
gi 1799133945 2656 ASNPIG 2661
Cdd:cd05734     81 VSNDVG 86

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

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 40.01 E-value: 1.35e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1799133945 3163 AYLSCigKTETKPNQSVVWTKEEGDLPSGSRVE------QGVLMLPSVHRDDEGSYTCEIvkeENPVFSTV 3227
Cdd:cd00096      1 VTLTC--SASGNPPPTITWYKNGKPLPPSSRDSrrselgNGTLTISNVTLEDSGTYTCVA---SNSAGGSA 66

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: 40.28 E-value: 1.43e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1066 PQTNLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPvcepprcLQTSEGGYG----TLTIHDAQPVDQGAYTCEAINVKGR 1141
Cdd:cd05876      1 SSSSLVALRGQSLVLECIAEGLPTPTVKWLRPSGP-------LPPDRVKYQnhnkTLQLLNVGESDDGEYVCLAENSLGS 73


                   .
gi 1799133945 1142 V 1142
Cdd:cd05876     74 A 74

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: 40.39 E-value: 1.56e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  837 TVFPSEKEVRDGRDVSFECRARTSDNsvyPTVRWARVGGPLPSSAHDsGGR-------LTINPVQLSDAGTYICVSdYNG 909
Cdd:cd20949      3 TENAYVTTVKEGQSATILCEVKGEPQ---PNVTWHFNGQPISASVAD-MSKyriladgLLINKVTQDDTGEYTCRA-YQV 77


                   ...
gi 1799133945  910 NTV 912
Cdd:cd20949     78 NSI 80

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: 40.61 E-value: 1.60e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2493 PRPVATPPLLSVAPGSPARFNCVAHSDTPARIRWgFReeNGplpEHVNQDGDD-----------------IVISEAGDRN 2555
Cdd:cd07693      1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQW-LK--NG---QPLETDKDDprshrivlpsgslfflrVVHGRKGRSD 74

                           90       100
                   ....*....|....*....|....
gi 1799133945 2556 VGEYVCSATNDFGTGVADPVRLEV 2579
Cdd:cd07693     75 EGVYVCVAHNSLGEAVSRNASLEV 98

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: 40.70 E-value: 1.62e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 3053 IQVLLEVSSESPQIGDRAWFDCKVTGDPSAvISWTKEGNDDLPPNAQ----VTGG----RLLFTDLKEDNAGVYRCVAKT 3124
Cdd:cd04977      1 LQVKIIPSYAEISVGESKFFLCKVSGDAKN-INWVSPNGEKVLTKHGnlkvVNHGsvlsSLTIYNANINDAGIYKCVATN 79

                           90
                   ....*....|
gi 1799133945 3125 KAGPLQTRTV 3134
Cdd:cd04977     80 GKGTESEATV 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: 39.92 E-value: 1.65e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1799133945 1939 EGEPAAFRCWVPGIPDCQITWHREqlGGPLP----HGVYQTGnALKIPQSQLHHAGRYICSAANQYGT 2002
Cdd:cd05745      1 EGQTVDFLCEAQGYPQPVIAWTKG--GSQLSvdrrHLVLSSG-TLRISRVALHDQGQYECQAVNIVGS 65

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

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 40.09 E-value: 1.73e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  841 SEKEVRDGRDVSFECRArtsDNSVYPTVRWARVGGPLPS---SAHDSGGRLTINPVQLSDAGTYICVSDyngNTV-EARA 916
Cdd:cd05731      3 SSTMVLRGGVLLLECIA---EGLPTPDIRWIKLGGELPKgrtKFENFNKTLKIENVSEADSGEYQCTAS---NTMgSARH 76


                   ....*
gi 1799133945  917 TLSVV 921
Cdd:cd05731     77 TISVT 81

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 40.18 E-value: 1.74e-03

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1799133945   193 SSVEDNKIAWSKDsvllgvGSMTLAEDGRVTVYKKGDKHHLHIINATDADDGTYKMIVQGINVEADFEVRIT 264
Cdd:smart00410   19 SGSPPPEVTWYKQ------GGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTLT 84

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: 40.31 E-value: 1.83e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2606 RCITTGSPTPKITWTgPNGSPLPHDVTPLEPNI----LDFSNGRSELNGDYTCTASNPIGEASDHGNVNI 2671
Cdd:cd20976     22 QCSARGKPVPRITWI-RNAQPLQYAADRSTCEAgvgeLHIQDVLPEDHGTYTCLAKNAAGQVSCSAWVTV 90

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: 40.29 E-value: 1.97e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1799133945  851 VSFECRARTSDNSVYptvRWaRVGGPLPSSAHDS-----GGRLTI-NPVQLSDAGTYICVSDYNGNTVEAR 915
Cdd:cd05850     23 VTLACRARASPPATY---RW-KMNGTELKMEPDSryrlvAGNLVIsNPVKAKDAGSYQCLASNRRGTVVSR 89

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: 39.47 E-value: 2.20e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1799133945 3074 CKVTGDPSAVISWTKEGnddlppnAQVT---------GGRLLFTDLKEDNAGVYRCVAKTKAGPLQTRTVL 3135
Cdd:cd05746      5 CSAQGDPEPTITWNKDG-------VQVTesgkfhispEGYLAIRDVGVADQGRYECVARNTIGYASVSMVL 68

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: 40.28 E-value: 2.28e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1799133945 2604 QFRCITTGSPTPKITWTGPNGSPLPHDVTPLEPN-----ILDFSNGRSELNGDYTCTASNPIGE 2662
Cdd:cd05729     23 RLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVeekgwSLIIERAIPRDKGKYTCIVENEYGS 86

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: 39.92 E-value: 2.44e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1932 PPHLVVNEGEPAAFRCWVPGIPDCQITWHREQ--LGGPLPHGVYQTGNaLKIPQSQLHHAGRYICSAANQYGTGQSPPAV 2009
Cdd:cd20968      6 PTNVTIIEGLKAVLPCTTMGNPKPSVSWIKGDdlIKENNRIAVLESGS-LRIHNVQKEDAGQYRCVAKNSLGIAYSKPVT 84


                   ....
gi 1799133945 2010 LEVK 2013
Cdd:cd20968     85 IEVE 88

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: 39.23 E-value: 2.48e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1799133945 2314 FKIRCYVPGHPSVQLTFRRVSGQLNEDA------DENNGLLAVQRAELTDEGDYICTARDPDTG 2371
Cdd:cd00096      1 VTLTCSASGNPPPTITWYKNGKPLPPSSrdsrrsELGNGTLTISNVTLEDSGTYTCVASNSAGG 64

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

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 39.75 E-value: 2.55e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1799133945  848 GRDVSFECRARTSDNsvyPTVRWARVGGPLPSSAHDS---GGRLTINPVQLSDAGTYICVSDYNGNTVEARATLSV 920
Cdd:cd04969     17 GGDVIIECKPKASPK---PTISWSKGTELLTNSSRICilpDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

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: 2.81e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1799133945 1930 IDPPHLVVNEGEPAAFRCWV-PGIPDCQITWHREQLGGPLPHGV-----YQTGNALKIPQSQLHHAGRYICSAAN 1998
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSAsTGSPGPDVTWSKEGGTLIESLKVkhdngRTTQSSLLISNVTKEDAGTYTCVVNN 75

Calcium-binding EGF-like domain;

Pssm-ID: 214542 [Multi-domain] Cd Length: 39 Bit Score: 38.00 E-value: 2.96e-03

                            10        20        30
                    ....*....|....*....|....*....|....*....
gi 1799133945  3411 DACASTNLCLNGANCRNANNhhGFSCECAEEFH-GEYCQ 3448
Cdd:smart00179    3 DECASGNPCQNGGTCVNTVG--SYRCECPPGYTdGRNCE 39

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: 2.96e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1930 IDPPHLVVNEGEPAAFRCWVP-GIPDCQITWHREqlGGPL----PHGVYQTGNALKIPQSQLHHAGRYICSAANQYGTGQ 2004
Cdd:cd05724      2 VEPSDTQVAVGEMAVLECSPPrGHPEPTVSWRKD--GQPLnldnERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGERE 79


                   ....*...
gi 1799133945 2005 SPPAVLEV 2012
Cdd:cd05724     80 SRAARLSV 87

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: 3.01e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1799133945 2210 VDPPVQTVNEGEPSRIRCWV-PGHPNIQLQFVK------RGRRPLPAHARFSQGNLEIPRTLKSDEDEYICIATDP 2278
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSAsTGSPGPDVTWSKeggtliESLKVKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNP 76

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 39.55 E-value: 3.04e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2203 PQAIQPqvdPPVQTVNEGEPSRIRCWVPGHPNIQLQFVKRGrRPLPAHARFSQGN------LEIPRTLKSDEDEYICIAT 2276
Cdd:pfam07679    1 PKFTQK---PKDVEVQEGESARFTCTVTGTPDPEVSWFKDG-QPLRSSDRFKVTYeggtytLTISNVQPDDSGKYTCVAT 76


                   ..
gi 1799133945 2277 DP 2278
Cdd:pfam07679   77 NS 78

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

Pssm-ID: 409442 Cd Length: 92 Bit Score: 39.84 E-value: 3.04e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1799133945 2604 QFRCITTGSPTPKITWTgPNGSPLphdvTPLEPN-------ILDFSNGRSELNGDYTCTASNPIGE 2662
Cdd:cd05856     23 RLKCVASGNPRPDITWL-KDNKPL----TPPEIGenkkkkwTLSLKNLKPEDSGKYTCHVSNRAGE 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: 39.15 E-value: 3.09e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1799133945 1075 GTTFSLTCKAVAVPEPYINWRLNWGPVCEPPRCLQTSEGgygTLTIHDAQPVDQGAYTCEAINVKGRV 1142
Cdd:cd05745      2 GQTVDFLCEAQGYPQPVIAWTKGGSQLSVDRRHLVLSSG---TLRISRVALHDQGQYECQAVNIVGSQ 66

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: 39.71 E-value: 3.10e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1799133945 1066 PQTnlqVPRGTTFSLTCKAVAVPEPYINWRLNWGPV---CEPPRCLQTSEGGYGTLTIHDAQPVDQGAYTCEAINVKG 1140
Cdd:cd20951      9 SHT---VWEKSDAKLRVEVQGKPDPEVKWYKNGVPIdpsSIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKNIHG 83

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: 39.84 E-value: 3.28e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1060 PTVVDPPqTNLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPV------CEPPRCLQTSEGGYGTLTIHDAQP-VDQGAYT 1132
Cdd:cd07693      1 PRIVEHP-SDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLetdkddPRSHRIVLPSGSLFFLRVVHGRKGrSDEGVYV 79


                   ....*...
gi 1799133945 1133 CEAINVKG 1140
Cdd:cd07693     80 CVAHNSLG 87

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

Pssm-ID: 409582 Cd Length: 91 Bit Score: 39.70 E-value: 3.46e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1799133945 1069 NLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPV-CEPPRCLQTSEGGYGTLTIHDAQPVDQGAYTCEAINVKGR 1141
Cdd:cd20990      9 DLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIrPDSAHKMLVRENGVHSLIIEPVTSRDAGIYTCIATNRAGQ 82

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: 39.08 E-value: 3.59e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1799133945 1062 VVDPPQTNlQVPRGTTFSLTCKAVA-VPEPYINWRLNWGPVcePPRCLQTSeggyGTLTIHDAQPVDQGAYTCEAIN 1137
Cdd:cd05754      4 TVEEPRSQ-EVRPGADVSFICRAKSkSPAYTLVWTRVNGTL--PSRAMDFN----GILTIRNVQLSDAGTYVCTGSN 73

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: 39.60 E-value: 3.72e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1925 PPQPVIDPPHLVVNEGEPAAFRCWVPGIPDCQITWHREQlgGPLP---------HGVYQTGN-ALKIPQSQLHHAGRYIC 1994
Cdd:cd20954      1 PPRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKAT--GSTPgeykdllydPNVRILPNgTLVFGHVQKENEGHYLC 78

                           90
                   ....*....|.
gi 1799133945 1995 SAANQYGTGQS 2005
Cdd:cd20954     79 EAKNGIGSGLS 89

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: 39.84 E-value: 3.77e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  836 ITVFPSEKEVRDGRDVSFECRArTSDNSVYPTVRWARVGGPL----------PSSAHDSGGRLTINPVQLSDAGTYICVS 905
Cdd:cd04970      5 ITLAPSNADITVGENATLQCHA-SHDPTLDLTFTWSFNGVPIdlekieghyrRRYGKDSNGDLEIVNAQLKHAGRYTCTA 83

                           90
                   ....*....|....*
gi 1799133945  906 DYNGNTVEARATLSV 920
Cdd:cd04970     84 QTVVDSDSASATLVV 98

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

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 39.55 E-value: 3.87e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1799133945 1940 GEPAAFRCWVPGIPDCQITWHR--EQLGGPLPHGVYQTGNALKIPQSQLHHA--GRYICSAANQYG 2001
Cdd:cd05736     15 GVEASLRCHAEGIPLPRVQWLKngMDINPKLSKQLTLIANGSELHISNVRYEdtGAYTCIAKNEGG 80

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

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 38.93 E-value: 3.98e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1066 PQTNLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPVcePPRclQTSEGGYG-TLTIHDAQPVDQGAYTCEAINVKGRVLA 1144
Cdd:cd05731      1 SESSTMVLRGGVLLLECIAEGLPTPDIRWIKLGGEL--PKG--RTKFENFNkTLKIENVSEADSGEYQCTASNTMGSARH 76


                   ....*..
gi 1799133945 1145 TPDCIVR 1151
Cdd:cd05731     77 TISVTVE 83

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

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 39.37 E-value: 4.16e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1799133945 3170 KTETKPNQSVVWTKEEGDLPSGSRV---EQGVLMLPSVHRDDEGSYTC 3214
Cdd:cd04969     25 KPKASPKPTISWSKGTELLTNSSRIcilPDGSLKIKNVTKSDEGKYTC 72

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: 39.40 E-value: 4.28e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1799133945 2600 GERHQFRCITTGSPTP-KITWTgPNGSPLPHD----VTPLEP--NILDFSNGRSELNGDYTCTASNPIGEAS 2664
Cdd:cd20959     17 GMRAQLHCGVPGGDLPlNIRWT-LDGQPISDDlgitVSRLGRrsSILSIDSLEASHAGNYTCHARNSAGSAS 87

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: 39.41 E-value: 4.28e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2579 VTEDQEPPTAVVEPrtwngkpGERHQFRCITTGSPTPKITWTgPNGSPLPHDVTPLEPN----ILDFSNGRSELNGDYTC 2654
Cdd:cd20970      3 ISTPQPSFTVTARE-------GENATFMCRAEGSPEPEISWT-RNGNLIIEFNTRYIVRengtTLTIRNIRRSDMGIYLC 74

                           90
                   ....*....|..
gi 1799133945 2655 TASNPIGEASDH 2666
Cdd:cd20970     75 IASNGVPGSVEK 86

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 38.70 E-value: 4.35e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2873 PKVEIEPPRVrVVSQGDNIVLKCSVQGaENGEHFKWalLRGGSLV--------RQLGTEPTLEITKADPSnDFGVYRCNV 2944
Cdd:pfam13927    2 PVITVSPSSV-TVREGETVTLTCEATG-SPPPTITW--YKNGEPIssgstrsrSLSGSNSTLTISNVTRS-DAGTYTCVA 76


                   .
gi 1799133945 2945 E 2945
Cdd:pfam13927   77 S 77

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 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" strands in the other.

Pssm-ID: 409355 [Multi-domain] Cd Length: 111 Bit Score: 39.62 E-value: 4.57e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  836 ITVFPSEKEVRDGRDVSFECRARTSDNSVYptVRW------------ARVGGPLPSSAHDSGGR------------LTIN 891
Cdd:cd00099      1 VTQSPRSLSVQEGESVTLSCEVSSSFSSTY--IYWyrqkpgqgpeflIYLSSSKGKTKGGVPGRfsgsrdgtssfsLTIS 78

                           90       100
                   ....*....|....*....|..
gi 1799133945  892 PVQLSDAGTYICVSDYNGNTVE 913
Cdd:cd00099     79 NLQPEDSGTYYCAVSESGGTDK 100

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: 38.92 E-value: 4.79e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2599 PGERHQFRCITTGSPTPKITWTGPNGSpLPHD-VTPLEPNILDFSNGRSELNGDYTCTASNPIGEASDHGnvnigpSLTV 2677
Cdd:cd05725     11 VDDSAEFQCEVGGDPVPTVRWRKEDGE-LPKGrYEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIEASA------TLTV 83

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: 39.17 E-value: 4.89e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1060 PTVVDPPQTNLQVPrGTTFSLTCKAVAVPEPYINWRLNwGPVCEPPRCLQTSEGGYGT-LTIHDAQPVDQGAYTCEAINV 1138
Cdd:cd05736      1 PVIRVYPEFQAKEP-GVEASLRCHAEGIPLPRVQWLKN-GMDINPKLSKQLTLIANGSeLHISNVRYEDTGAYTCIAKNE 78


                   ..
gi 1799133945 1139 KG 1140
Cdd:cd05736     79 GG 80

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: 5.07e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1068 TNLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPVCepPRCLQTSEGGYGTLTIHDAQPVDQGAYTCEAINVKGRVLATPD 1147
Cdd:cd05764      8 HELRVLEGQRATLRCKARGDPEPAIHWISPEGKLI--SNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEATARVE 85


                   ...
gi 1799133945 1148 CIV 1150
Cdd:cd05764     86 LHI 88

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: 39.03 E-value: 5.15e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1799133945 2307 TVPEGSPFKIRCYVPGHPSVQLTFRRVSGQLNEDAD-----ENNGLLAVQRAELTDEGDYICTA 2365
Cdd:cd20970     13 TAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTryivrENGTTLTIRNIRRSDMGIYLCIA 76

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: 38.67 E-value: 5.54e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1799133945 3053 IQVLLEVSSESPQIGDRAWFDCKVTGDPSAVISWTKEGNdDLPPNAQV---TGGRLLFTDLKEDNAGVYRCVA 3122
Cdd:cd20957      2 LSATIDPPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGK-PLGHSSRVqilSEDVLVIPSVKREDKGMYQCFV 73

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: 38.08 E-value: 5.77e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1799133945 2415 ARIQCTVPGNPSAaqHLSFERvDGKGLPFGSSDDR------GVLTIPSTQLQDAGEYVC 2467
Cdd:cd00096      1 VTLTCSASGNPPP--TITWYK-NGKPLPPSSRDSRrselgnGTLTISNVTLEDSGTYTC 56

Third immunoglobulin domain of Nectin-like Protein-5, and similar domains; The members here are composed of the third immunoglobulin domain of Nectin-like Protein-5 (also known as Cluster of Differentiation 155 (CD155)). Nectin-like Protein-5 mediates NK (Natural Killer) cell adhesion and triggers NK cell effector functions. CD155 binds two different NK cell receptors: CD96 and CD226. These interactions accumulate at the cell-cell contact site, leading to the formation of a mature immunological synapse between NK cell and target cell. This may trigger adhesion and secretion of lytic granules and IFN-gamma and activate cytotoxicity of activated NK cells. CD155 may also promote NK cell-target cell modular exchange, and PVR transfer to the NK cell. This transfer is more important in some tumor cells expressing a lot of PVR, and may trigger fratricide NK cell activation, providing tumors with a mechanism of immunoevasion. Moreover, CD155 plays a role in mediating tumor cell invasion and migration.

Pssm-ID: 409524 Cd Length: 86 Bit Score: 38.70 E-value: 5.81e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1799133945 2971 IVKFDD-----KSDASFTCPIYSVPG-SKVDWTYENGDLPSKAVPNGNKIEIKEFDDASAGTYVCKVS 3032
Cdd:cd20930      5 ISGYDDnwylgRNEATLTCDVRSNPEpTGYDWSTTSGPFPTSAVAQGPQLLIHSVDRLVNTTFICTVT 72

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: 38.54 E-value: 6.04e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945  866 PTVRWARVGGPLPSSAHD----SGGRLTINPVQLSDAGTYICV-SDYNGNTVEARATLSV 920
Cdd:cd05724     28 PTVSWRKDGQPLNLDNERvrivDDGNLLIAEARKSDEGTYKCVaTNMVGERESRAARLSV 87

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

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 38.64 E-value: 6.08e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1799133945 3067 GDRAWFDCKVTGDPSAVISWTKEGNDDLPPNAQ---VTGGRLL-FTDLKEDNAGVYRCVAKTKAGP 3128
Cdd:cd20970     17 GENATFMCRAEGSPEPEISWTRNGNLIIEFNTRyivRENGTTLtIRNIRRSDMGIYLCIASNGVPG 82

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 38.78 E-value: 6.13e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1799133945 2023 PIRQTVDRDQPARFKCWVPGNSNVQLRWSRpGGAPLPSG----VQEQQGI--LHIPRASDQEVGQYVCTATDPS 2090
Cdd:pfam07679    7 PKDVEVQEGESARFTCTVTGTPDPEVSWFK-DGQPLRSSdrfkVTYEGGTytLTISNVQPDDSGKYTCVATNSA 79

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: 38.69 E-value: 6.34e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1799133945 2496 VATPPLLSVAPGSPARFNCVAHSDTPA-RIRWGfrEENGPLPEHVNQDGDDIVISEAGDRNVGEYVCSATNDFGT 2569
Cdd:cd05754      5 VEEPRSQEVRPGADVSFICRAKSKSPAyTLVWT--RVNGTLPSRAMDFNGILTIRNVQLSDAGTYVCTGSNMLDT 77

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: 38.54 E-value: 6.47e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1799133945 1069 NLQVPRGTTFSLTCKA-VAVPEPYINWRLNWGPVCEPPRCLQTSEGGygTLTIHDAQPVDQGAYTCEAINVKG 1140
Cdd:cd05724      6 DTQVAVGEMAVLECSPpRGHPEPTVSWRKDGQPLNLDNERVRIVDDG--NLLIAEARKSDEGTYKCVATNMVG 76

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: 38.70 E-value: 6.53e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2121 PNQTVNVNDPAQFRCWVPGQPRAQLKWSRkDGRPLPNGILERDG-----------FLRIDKSQLHDAGEYECTSTEPDGS 2189
Cdd:cd20956      9 SEQTLQPGPSVSLKCVASGNPLPQITWTL-DGFPIPESPRFRVGdyvtsdgdvvsYVNISSVRVEDGGEYTCTATNDVGS 87

                           90
                   ....*....|.
gi 1799133945 2190 TQLSppARLNV 2200
Cdd:cd20956     88 VSHS--ARINV 96

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: 6.60e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1929 VIDPP--HLVVNEGEPAAFRCWVPGIPDCQITW-HReqlGGPL--PHGVYQ-TGNALKIPQSQLHHAGRYICSAANQYGT 2002
Cdd:cd20978      3 FIQKPekNVVVKGGQDVTLPCQVTGVPQPKITWlHN---GKPLqgPMERATvEDGTLTIINVQPEDTGYYGCVATNEIGD 79


                   ....*..
gi 1799133945 2003 GQSPPAV 2009
Cdd:cd20978     80 IYTETLL 86

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 38.39 E-value: 6.83e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2686 LIVTVGEPLQVKCEAFGapgDPEPEVEWLHDPGPERGDlpDDFKpVTISEQ--FIRHPNVGLGNAGVYTCKGSSAHATAT 2763
Cdd:pfam07679   10 VEVQEGESARFTCTVTG---TPDPEVSWFKDGQPLRSS--DRFK-VTYEGGtyTLTISNVQPDDSGKYTCVATNSAGEAE 83


                   ....*..
gi 1799133945 2764 KNIYIEV 2770
Cdd:pfam07679   84 ASAELTV 90

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

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 38.72 E-value: 6.86e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2585 PPTAVVEPRTWNGKPGERHQFRCITTGSPTPKITWTGpNGSPLPHdvtplEPNILDFSNGR----------SELNGDYTC 2654
Cdd:cd20972      1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFC-EGKELQN-----SPDIQIHQEGDlhsliiaeafEEDTGRYSC 74

                           90
                   ....*....|
gi 1799133945 2655 TASNPIGEAS 2664
Cdd:cd20972     75 LATNSVGSDT 84

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

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 38.64 E-value: 7.18e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2495 PVATPPLLS----VAPGSPARFNCVAHSDTPARIRWgFReeNGPLPEHVNQ------DGDDIVISEAGDRNVGEYVCSAT 2564
Cdd:cd20970      1 PVISTPQPSftvtAREGENATFMCRAEGSPEPEISW-TR--NGNLIIEFNTryivreNGTTLTIRNIRRSDMGIYLCIAS 77

                           90
                   ....*....|....*
gi 1799133945 2565 NDFGTGVADPVRLEV 2579
Cdd:cd20970     78 NGVPGSVEKRITLQV 92

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: 38.68 E-value: 7.34e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1926 PQPVIDPPHLVVNEGEPAAFRCWVPGIPDCQITWHREQLGGP----LPHGVYqtGNA-------LKIPQSQLHHAGRYIC 1994
Cdd:cd05765      1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEKQVPGKEnlimRPNHVR--GNVvvtnigqLVIYNAQPQDAGLYTC 78


                   ....*..
gi 1799133945 1995 SAANQYG 2001
Cdd:cd05765     79 TARNSGG 85

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: 38.08 E-value: 7.60e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1799133945 1945 FRCWVPGIPDCQITWHREqlGGPLPHGVY-----QTGNA-LKIPQSQLHHAGRYICSAANQYGTGQS 2005
Cdd:cd00096      3 LTCSASGNPPPTITWYKN--GKPLPPSSRdsrrsELGNGtLTISNVTLEDSGTYTCVASNSAGGSAS 67

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: 38.69 E-value: 7.88e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1799133945 3067 GDRAWFDCKVTGDPSAVISWTKEGN----DDLPPNAQVT---GGRLLFTDL-----KEDNAGVYRCVAKTKAGPLQTR 3132
Cdd:cd07693     15 GDPATLNCKAEGRPTPTIQWLKNGQpletDKDDPRSHRIvlpSGSLFFLRVvhgrkGRSDEGVYVCVAHNSLGEAVSR 92

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

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 38.15 E-value: 7.90e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1799133945 2496 VATPPLLSVAPGSPARFNCVAHSDTPARIRWgfREENGPLPEHVNQDGDD--IVISEAGDRNVGEYVCSATNDFGTGVA 2572
Cdd:cd05725      1 VKRPQNQVVLVDDSAEFQCEVGGDPVPTVRW--RKEDGELPKGRYEILDDhsLKIRKVTAGDMGSYTCVAENMVGKIEA 77

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: 38.31 E-value: 8.10e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1799133945 2589 VVEPRTWNGKPGERHQFRCIT-TGSPTPKITWTGPNGsPLP---HDVTplepNILDFSNGRSELNGDYTCTASN 2658
Cdd:cd05754      5 VEEPRSQEVRPGADVSFICRAkSKSPAYTLVWTRVNG-TLPsraMDFN----GILTIRNVQLSDAGTYVCTGSN 73

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 37.76 E-value: 8.79e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 1061 TVVDPPQTNlqVPRGTTFSLTCKAVAVPEPYINWRLNWGPVcepprclqtseGGYGTLTIHDAQPVDQGAYTCEAINVKG 1140
Cdd:pfam13895    2 PVLTPSPTV--VTEGEPVTLTCSAPGNPPPSYTWYKDGSAI-----------SSSPNFFTLSVSAEDSGTYTCVARNGRG 68

Second 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 second 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. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of this group show that the second Ig domain lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM).

Pssm-ID: 409557 Cd Length: 101 Bit Score: 38.77 E-value: 8.93e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799133945 2297 IRPIIDPAEQTVPEGSPFKIRCYVP-GHPSVQLTFRRVSGQLNEDAD---------ENNGLL---AVQRAELTDEGDYIC 2363
Cdd:cd20965      3 LDPQVKTKEKKPVEGKPFKLDCNVPpGYPKPTIEWKKQLVSDSSKADtildrritiSPNGDLyftNVTKEDVSTDYKYVC 82


                   ....*
gi 1799133945 2364 TARDP 2368
Cdd:cd20965     83 VAKTP 87

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: 37.85 E-value: 9.21e-03

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gi 1799133945 3175 PNQSVVWTKEEGDLPSGSRVEQ------GVLMLPSVHRDDEGSYTCEIVKEENPVFSTVD 3228
Cdd:cd05743     14 PTPIINWRLNWGHVPDSARVSItseggyGTLTIRDVKESDQGAYTCEAINTRGMVFGIPD 73

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: 38.15 E-value: 9.24e-03

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gi 1799133945 2403 TPQTQTIPEGDPARIQCTVPGNPsaAQHLSFERVDGKgLPFGSS---DDRGvLTIPSTQLQDAGEYVCL 2468
Cdd:cd05725      3 RPQNQVVLVDDSAEFQCEVGGDP--VPTVRWRKEDGE-LPKGRYeilDDHS-LKIRKVTAGDMGSYTCV 67

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 38.01 E-value: 9.25e-03

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gi 1799133945 2491 TPPRPVAtppllsVAPGSPARFNCVAHSDTPARIRWGFREEngPLPE----HVNQDGDD--IVISEAGDRNVGEYVCSAT 2564
Cdd:pfam07679    5 QKPKDVE------VQEGESARFTCTVTGTPDPEVSWFKDGQ--PLRSsdrfKVTYEGGTytLTISNVQPDDSGKYTCVAT 76


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gi 1799133945 2565 NDFGT 2569
Cdd:pfam07679   77 NSAGE 81

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: 38.32 E-value: 9.33e-03

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gi 1799133945 2600 GERHQFRCITTGSPTPKITWTgPNGSPLP----HDVtplepnildFSNG--------RSELNGDYTCTASNPIGEaSDHG 2667
Cdd:cd20958     15 GQTLRLHCPVAGYPISSITWE-KDGRRLPlnhrQRV---------FPNGtlvienvqRSSDEGEYTCTARNQQGQ-SASR 83


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gi 1799133945 2668 NVNI 2671
Cdd:cd20958     84 SVFV 87