NCBI Conserved Domain Search

Laminin B domain;

Pssm-ID: 214597 Cd Length: 127 Bit Score: 177.07 E-value: 4.67e-51

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537     785 RGQTLYWKLPEKFLGDKVTSYGGTLEYTFKFSGN--GNSDQSADVILRGNDIALQYKHREPFYADRENKVQIKIIETSWQ 862
Cdd:smart00281    1 DNEPVYWVAPEQFLGDKVTSYGGKLRYTLSFDGRrgGTHVSAPDVILEGNGLRISHPAEGPPLPDELTTVEVRFREENWQ 80

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*..
gi 71998537     863 RVDGQQATREHLLMTLADLDTLLIKSTYNDDCTDSQLLSANLEFAEP 909
Cdd:smart00281   81 YYGGRPVTREDLMMVLANLTAILIRATYSQQMAGSRLSDVSLEVAVP 127

Laminin B domain;

Pssm-ID: 214597 Cd Length: 127 Bit Score: 168.59 E-value: 4.09e-48

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537     493 DGVAKYWRLPQRFLGDKVTAYGGKMEFEIEFSGS--GHHSSEPMVVLKGNQNILVHRvrnQEHVLRSDSPVRITVETYET 570
Cdd:smart00281    1 DNEPVYWVAPEQFLGDKVTSYGGKLRYTLSFDGRrgGTHVSAPDVILEGNGLRISHP---AEGPPLPDELTTVEVRFREE 77

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|
gi 71998537     571 NYEQLNGAAATREDLLMVLADLDAFLIRATHVAHQTSTSLGDVSWEIAVD 620
Cdd:smart00281   78 NWQYYGGRPVTREDLMMVLANLTAILIRATYSQQMAGSRLSDVSLEVAVP 127

Laminin B (Domain IV);

Pssm-ID: 459652 Cd Length: 136 Bit Score: 157.43 E-value: 4.39e-44

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537    790 YWKLPEKFLGDKVTSYGGTLEYTFKFS---GNGNSDQSADVILRGNDIALQYKHREPFYADR--ENKVQIKIIETSWQRV 864
Cdd:pfam00052    1 YWSAPEQFLGNKLTSYGGYLTYTVRYEplpGGGSLNSEPDVILEGNGLRLSYSSPDQPPPDPgqEQTYSVRLHEENWRDS 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 71998537    865 DGQQATREHLLMTLADLDTLLIKSTYNDDCTDSQLLSANLEFAEPYGQGLTAAEVE 920
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: 152.64 E-value: 3.83e-43

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 71998537  286 GTTFSLTCKAVAVPEPYINWRLNWGPVCEPPRCLQTSEGGYGTLTIHDAQPVDQGAYTCEAINVKGRVLATPDCIVRV 363
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: 6.73e-42

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 3182 AARFDGDAFIELSSDEFPHLTSEkdeiVAFKFKTEQQNGVLLWQGQRPTvqqmEDYISVGIVNGHLHFSYELGGGAAHLI 3261
Cdd:cd00110    1 GVSFSGSSYVRLPTLPAPRTRLS----ISFSFRTTSPNGLLLYAGSQNG----GDFLALELEDGRLVLRYDLGSGSLVLS 72

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 71998537 3262 SEERVDDGKEHSVRFERKGREGQMRIDNYREVDGRSTGILAMLNVDGNIFVGGVPDISKATGGLFSNNFVGCIADVELN 3340
Cdd:cd00110   73 SKTPLNDGQWHSVSVERNGRSVTLSVDGERVVESGSPGGSALLNLDGPLYLGGLPEDLKSPGLPVSPGFVGCIRDLKVN 151

Laminin B (Domain IV);

Pssm-ID: 459652 Cd Length: 136 Bit Score: 145.11 E-value: 9.42e-40

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537    498 YWRLPQRFLGDKVTAYGGKMEFEIEFSGSGHHS---SEPMVVLKGNQNILVHRVRNQEHvLRSDSPVRITVETYETNYEQ 574
Cdd:pfam00052    1 YWSAPEQFLGNKLTSYGGYLTYTVRYEPLPGGGslnSEPDVILEGNGLRLSYSSPDQPP-PDPGQEQTYSVRLHEENWRD 79

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 71998537    575 LNGAAATREDLLMVLADLDAFLIRATHVAHQTSTSLGDVSWEIAVDRYTPDgLALEVE 632
Cdd:pfam00052   80 SDGAPVSREDFMMVLANLTAILIRATYSTGSGQVSLSNVSLDSAVPGGSGP-PASWVE 136

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: 143.08 E-value: 1.06e-39

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   45 VQITVF-PSEKEVRDGRDVSFECRARTSdnSVYPTVRWARVGGPLPSSAHDSGGRLTINPVQLSDAGTYICVSDYNGNTV 123
Cdd:cd05754    1 IQVTVEePRSQEVRPGADVSFICRAKSK--SPAYTLVWTRVNGTLPSRAMDFNGILTIRNVQLSDAGTYVCTGSNMLDTD 78


                 ....*..
gi 71998537  124 EARATLS 130
Cdd:cd05754   79 EATATLY 85

Laminin G domain;

Pssm-ID: 214598 [Multi-domain] Cd Length: 132 Bit Score: 144.02 E-value: 1.77e-39

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537    3209 VAFKFKTEQQNGVLLWQGQRPTVqqmeDYISVGIVNGHLHFSYELGGGAAHLISE-ERVDDGKEHSVRFERKGREGQMRI 3287
Cdd:smart00282    2 ISFSFRTTSPNGLLLYAGSKGGG----DYLALELRDGRLVLRYDLGSGPARLTSDpTPLNDGQWHRVAVERNGRSVTLSV 77

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 71998537    3288 DNYREVDGRSTGILAMLNVDGNIFVGGVPDISKATGGLFSNNFVGCIADVELNGV 3342
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: 4.48e-33

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   3213 FKTEQQNGVLLWQGQRPTvqqmeDYISVGIVNGHLHFSYELGGGAAHLIS-EERVDDGKEHSVRFERKGREGQMRIDNYR 3291
Cdd:pfam02210    1 FRTRQPNGLLLYAGGGGS-----DFLALELVNGRLVLRYDLGSGPESLLSsGKNLNDGQWHSVRVERNGNTLTLSVDGQT 75

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 71998537   3292 EVDGRSTGILAMLNVDGNIFVGGVPDISKATGGLFSNNFVGCIADVELNGV 3342
Cdd:pfam02210   76 VVSSLPPGESLLLNLNGPLYLGGLPPLLLLPALPVRAGFVGCIRDVRVNGE 126

Laminin G domain;

Pssm-ID: 395008 [Multi-domain] Cd Length: 131 Bit Score: 118.57 E-value: 1.39e-30

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   3213 FKTEQQNGVLLWQGQRPTvqqmEDYISVGIVNGHLHFSYELGGGAAHLISEERVDDGKEHSVRFERKGREGQMRIDNYRE 3292
Cdd:pfam00054    1 FRTTEPSGLLLYNGTQTE----RDFLALELRDGRLEVSYDLGSGAAVVRSGDKLNDGKWHSVELERNGRSGTLSVDGEAR 76

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 71998537   3293 VDGRS-TGILAMLNVDGNIFVGGVPDISKATGGL-FSNNFVGCIADVELNGVKLD 3345
Cdd:pfam00054   77 PTGESpLGATTDLDVDGPLYVGGLPSLGVKKRRLaISPSFDGCIRDVIVNGKPLD 131

Laminin G domain;

Pssm-ID: 214598 [Multi-domain] Cd Length: 132 Bit Score: 82.00 E-value: 1.10e-17

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537    2813 SIKMKLRPQadSDEHILMYFASDygsNTKQYTSLSLIANQVVLTVRRPDKEVQ-KIRSETLEAGELIDVAVRQAGNALVM 2891
Cdd:smart00282    1 SISFSFRTT--SPNGLLLYAGSK---GGGDYLALELRDGRLVLRYDLGSGPARlTSDPTPLNDGQWHRVAVERNGRSVTL 75

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....*..
gi 71998537    2892 TVDG----NQVSTIETDTLKPGTEIFIGGLPPGLNSPDDVVEQSFQGCVYEILINSQ 2944
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: 2.58e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 2793 PLGFTSdTSFLAVKRPV---KFESIKMKLRPqaDSDEHILMYFASDygsNTKQYTSLSLIANQVVLTVRRPDKEVqKIRS 2869
Cdd:cd00110    1 GVSFSG-SSYVRLPTLPaprTRLSISFSFRT--TSPNGLLLYAGSQ---NGGDFLALELEDGRLVLRYDLGSGSL-VLSS 73

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 71998537 2870 ET-LEAGELIDVAVRQAGNALVMTVDGNQV----STIETDTLKPGTEIFIGGLPPGLNSPDDVVEQSFQGCVYEILIN 2942
Cdd:cd00110   74 KTpLNDGQWHSVSVERNGRSVTLSVDGERVvesgSPGGSALLNLDGPLYLGGLPEDLKSPGLPVSPGFVGCIRDLKVN 151

Laminin G domain;

Pssm-ID: 214598 [Multi-domain] Cd Length: 132 Bit Score: 75.84 E-value: 1.44e-15

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537    2557 DIEITLNTANPKGIIFETKRINSGDllatpydtiHHEAKITDyGTVLYEFDIGNGRQIVE-TTNPINPNEWNVIKIKNDK 2635
Cdd:smart00282    1 SISFSFRTTSPNGLLLYAGSKGGGD---------YLALELRD-GRLVLRYDLGSGPARLTsDPTPLNDGQWHRVAVERNG 70

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 71998537    2636 NQVTIQLNDESATIRQHTNPLPSLSTgvNRPVFIGG-----RHEPTNEANDFRGIISQVVLSGH 2694
Cdd:smart00282   71 RSVTLSVDGGNRVSGESPGGLTILNL--DGPLYLGGlpedlKLPPLPVTPGFRGCIRNLKVNGK 132

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 65.28 E-value: 1.66e-12

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 71998537    271 PTVVDPPqTNLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPVCEPPRCLQTSEGGYGTLTIHDAQPVDQGAYTCEAIN 348
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: 3.00e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 2543 IELPPLSDEEiVNLDIEITLNTANPKGIIFETKRINSGDLLAtpydtihheAKITDyGTVLYEFDIGNGRQIVETTNPIN 2622
Cdd:cd00110   10 VRLPTLPAPR-TRLSISFSFRTTSPNGLLLYAGSQNGGDFLA---------LELED-GRLVLRYDLGSGSLVLSSKTPLN 78

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 71998537 2623 PNEWNVIKIKNDKNQVTIQLNDESATirQHTNPLPSLSTGVNRPVFIGG-----RHEPTNEANDFRGIISQVVL 2691
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: 3.05e-12

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 71998537     280 NLQVPRGTTFSLTCKAVAVPEPYINWRLNWG-PVCEPPRCLQTSEGGYGTLTIHDAQPVDQGAYTCEAINVKG 351
Cdd:smart00410    3 SVTVKEGESVTLSCEASGSPPPEVTWYKQGGkLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSG 75

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

Pssm-ID: 395007 Cd Length: 49 Bit Score: 63.53 E-value: 3.50e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 71998537    955 CECNGHAS---QCDKEYGYCLdCQHNTEGDQCERCKPGFVGDaRRGTPNDC 1002
Cdd:pfam00053    1 CDCNPHGSlsdTCDPETGQCL-CKPGVTGRHCDRCKPGYYGL-PSDPPQGC 49

Low-density lipoprotein receptor domain class A;

Pssm-ID: 395011 Cd Length: 37 Bit Score: 62.65 E-value: 4.23e-12

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 71998537    231 SDCKPTEFQCHDRRqCVPSSFHCDGTNDCHDGSDEVGC 268
Cdd:pfam00057    1 STCSPNEFQCGSGE-CIPRSWVCDGDPDCGDGSDEENC 37

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: 6.33e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   2828 ILMYFasdyGSNTKQYTSLSLIANQVVLTVRRPDKEVQKIRSET-LEAGELIDVAVRQAGNALVMTVDGNQVSTI----E 2902
Cdd:pfam02210    9 LLLYA----GGGGSDFLALELVNGRLVLRYDLGSGPESLLSSGKnLNDGQWHSVRVERNGNTLTLSVDGQTVVSSlppgE 84

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 71998537   2903 TDTLKPGTEIFIGGLPPGLNSPDDVVEQSFQGCVYEILINSQ 2944
Cdd:pfam02210   85 SLLLNLNGPLYLGGLPPLLLLPALPVRAGFVGCIRDVRVNGE 126

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: 62.37 E-value: 7.39e-12

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 71998537  955 CECNGHAS---QCDKEYGYCLdCQHNTEGDQCERCKPGFVGDARRgtPNDCQ 1003
Cdd:cd00055    2 CDCNGHGSlsgQCDPGTGQCE-CKPNTTGRRCDRCAPGYYGLPSQ--GGGCQ 50

Low-density lipoprotein receptor domain class A;

Pssm-ID: 395011 Cd Length: 37 Bit Score: 61.88 E-value: 8.80e-12

                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 71998537    148 QCMADEKACGNNECVKNDYVCDGEPDCRDRSDEANC 183
Cdd:pfam00057    2 TCSPNEFQCGSGECIPRSWVCDGDPDCGDGSDEENC 37

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: 60.30 E-value: 2.58e-11

                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 71998537  233 CKPTEFQCHDRRqCVPSSFHCDGTNDCHDGSDEVGC 268
Cdd:cd00112    1 CPPNEFRCANGR-CIPSSWVCDGEDDCGDGSDEENC 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: 58.80 E-value: 8.76e-11

                            10        20        30
                    ....*....|....*....|....*....|...
gi 71998537     233 CKPTEFQCHDRRqCVPSSFHCDGTNDCHDGSDE 265
Cdd:smart00192    2 CPPGEFQCDNGR-CIPSSWVCDGVDDCGDGSDE 33

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 60.27 E-value: 9.17e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 71998537     46 QITVFPSEKEVRDGRDVSFECRARTSDNsvyPTVRWARVGGPLPSSAH------DSGGRLTINPVQLSDAGTYICV 115
Cdd:pfam13927    3 VITVSPSSVTVREGETVTLTCEATGSPP---PTITWYKNGEPISSGSTrsrslsGSNSTLTISNVTRSDAGTYTCV 75

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 60.35 E-value: 1.25e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537    271 PTVVDPPQtNLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPVCEPPRCLQTSEGGYGTLTIHDAQPVDQGAYTCEAINVK 350
Cdd:pfam07679    1 PKFTQKPK-DVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSA 79


                   ....*.
gi 71998537    351 GRVLAT 356
Cdd:pfam07679   80 GEAEAS 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: 58.52 E-value: 1.80e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 71998537   1011 CHCNNHSPRG--CDSF-GRCLlCEHNTEGTHCERCKKGYYGDAtKGSPYDC 1058
Cdd:pfam00053    1 CDCNPHGSLSdtCDPEtGQCL-CKPGVTGRHCDRCKPGYYGLP-SDPPQGC 49

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 59.58 E-value: 2.46e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537     46 QITVFPSEKEVRDGRDVSFECRAR-TSDnsvyPTVRWARVGGPLPSSAH------DSGGRLTINPVQLSDAGTYICVSDY 118
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTgTPD----PEVSWFKDGQPLRSSDRfkvtyeGGTYTLTISNVQPDDSGKYTCVATN 77

                           90
                   ....*....|...
gi 71998537    119 NGNTVEARATLSV 131
Cdd:pfam07679   78 SAGEAEASAELTV 90

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

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 58.11 E-value: 3.96e-10

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 71998537  289 FSLTCKAVAVPEPYINWRLNWGPVCEPPRCLQTSEGGYGTLTIHDAQPVDQGAYTCEAINVKGR 352
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: 7.57e-10

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537      51 PSEKEVRDGRDVSFECRARTSDNsvyPTVRWARVGGPLPS-------SAHDSGGRLTINPVQLSDAGTYICVSDYNGNTV 123
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPP---PEVTWYKQGGKLLAesgrfsvSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSA 77


                    ....*...
gi 71998537     124 EARATLSV 131
Cdd:smart00410   78 SSGTTLTV 85

Laminin-type epidermal growth factor-like domai;

Pssm-ID: 214543 Cd Length: 46 Bit Score: 56.55 E-value: 7.60e-10

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|.
gi 71998537     955 CECN--GHAS-QCDKEYGYCLdCQHNTEGDQCERCKPGFVGDarrgTPNDC 1002
Cdd:smart00180    1 CDCDpgGSASgTCDPDTGQCE-CKPNVTGRRCDRCAPGYYGD----GPPGC 46

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: 56.59 E-value: 9.81e-10

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 71998537 1010 PCHCNNHSPRG--CDSF-GRCLlCEHNTEGTHCERCKKGYYGDATKG 1053
Cdd:cd00055    1 PCDCNGHGSLSgqCDPGtGQCE-CKPNTTGRRCDRCAPGYYGLPSQG 46

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: 57.40 E-value: 1.17e-09

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 71998537 2367 GDRAWFDCKVTGDPSAVISWTKEGN--DDLPPNAQVTGGRLLFTDLKEDNAGVYRCVAKTKAGPLQTRTVLNV 2437
Cdd:cd20978   16 GQDVTLPCQVTGVPQPKITWLHNGKplQGPMERATVEDGTLTIINVQPEDTGYYGCVATNEIGDIYTETLLHV 88

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 57.13 E-value: 1.39e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537    1232 PPHLVVNEGEPAAFRCWVPGIPDCQITWHREQLGGPLPHGVYQ-----TGNALKIPQSQLHHAGRYICSAANQYGTGQSp 1306
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSvsrsgSTSTLTISNVTPEDSGTYTCAATNSSGSASS- 79


                    ....*.
gi 71998537    1307 PAVLEV 1312
Cdd:smart00410   80 GTTLTV 85

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: 1.43e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1898 KPGERHQFRCITTGSPTPKITWTgPNGSPLPHD--------VTPLEP-----NIldfSNGRSELNGDYTCTASNPIGEAS 1964
Cdd:cd20956   14 QPGPSVSLKCVASGNPLPQITWT-LDGFPIPESprfrvgdyVTSDGDvvsyvNI---SSVRVEDGGEYTCTATNDVGSVS 89


                 ....*..
gi 71998537 1965 DHGNVNI 1971
Cdd:cd20956   90 HSARINV 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: 57.02 E-value: 1.51e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537  271 PTVVDPPQTNLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPVCEPPRCLQTSEggyGTLTIHDAQPVDQGAYTCEAINVK 350
Cdd:cd20978    1 PKFIQKPEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVED---GTLTIINVQPEDTGYYGCVATNEI 77


                 ...
gi 71998537  351 GRV 353
Cdd:cd20978   78 GDI 80

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: 3.37e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537    1420 PPNQTVNVNDPAQFRCWVPGQPRAQLKWSRKDGRPL---PNGILERDGF---LRIDKSQLHDAGEYECTSTepDGSTQLS 1493
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLaesGRFSVSRSGStstLTISNVTPEDSGTYTCAAT--NSSGSAS 78


                    ....*..
gi 71998537    1494 PPARLNV 1500
Cdd:smart00410   79 SGTTLTV 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: 56.00 E-value: 3.52e-09

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 71998537 1418 IDPPNQTVNVNDPAQFRCWVPGQPRAQLKWsRKDGRPLPNG----ILERDgFLRIDKSQLHDAGEYEC 1481
Cdd:cd20957    6 IDPPVQTVDFGRTAVFNCSVTGNPIHTVLW-MKDGKPLGHSsrvqILSED-VLVIPSVKREDKGMYQC 71

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: 3.73e-09

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 71998537  149 CMADEKACGNNECVKNDYVCDGEPDCRDRSDEANC 183
Cdd:cd00112    1 CPPNEFRCANGRCIPSSWVCDGEDDCGDGSDEENC 35

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: 5.23e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537    1512 PPVQTVNEGEPSRIRCWVPGHPNIQLQFVKRGRRPLPAHARFS------QGNLEIPRTLKSDEDEYICIATDpttNRPVE 1585
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSvsrsgsTSTLTISNVTPEDSGTYTCAATN---SSGSA 77


                    ....*...
gi 71998537    1586 SNPARVIV 1593
Cdd:smart00410   78 SSGTTLTV 85

Laminin-type epidermal growth factor-like domai;

Pssm-ID: 214543 Cd Length: 46 Bit Score: 53.85 E-value: 7.15e-09

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*...
gi 71998537     383 SCDTRGAVTPYPN-NYGTCECKSQVTGPNCDQCKPGAFHlseKSPEGC 429
Cdd:smart00180    2 DCDPGGSASGTCDpDTGQCECKPNVTGRRCDRCAPGYYG---DGPPGC 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: 55.20 E-value: 7.22e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537    2360 SSESPQIGDRAWFDCKVTGDPSAVISWTKEGNDDL--PPNAQVTG----GRLLFTDLKEDNAGVYRCVAKTKAGPLQTRT 2433
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLaeSGRFSVSRsgstSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                    ....
gi 71998537    2434 VLNV 2437
Cdd:smart00410   82 TLTV 85

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

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 54.71 E-value: 9.14e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1420 PPNQTVNVNDPAQFRCWVPGQPRAQLKWSRKDGRpLPNG---ILErDGFLRIDKSQLHDAGEYECTSTEPDGSTQLSppA 1496
Cdd:cd05725    4 PQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGE-LPKGryeILD-DHSLKIRKVTAGDMGSYTCVAENMVGKIEAS--A 79


                 ....
gi 71998537 1497 RLNV 1500
Cdd:cd05725   80 TLTV 83

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 54.57 E-value: 1.21e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 71998537   2365 QIGDRAWFDCKVTGDPSAVISWTKeGNDDLPPNA----QVTGGR--LLFTDLKEDNAGVYRCVAKTKAGPLQTRTVLNV 2437
Cdd:pfam07679   13 QEGESARFTCTVTGTPDPEVSWFK-DGQPLRSSDrfkvTYEGGTytLTISNVQPDDSGKYTCVATNSAGEAEASAELTV 90

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

Pssm-ID: 395007 Cd Length: 49 Bit Score: 53.13 E-value: 1.44e-08

                           10        20        30
                   ....*....|....*....|....*....|....*
gi 71998537    684 PAQGQCQCKASVIGPNCDRCAPNSFGLAPTNPQGC 718
Cdd:pfam00053   15 PETGQCLCKPGVTGRHCDRCKPGYYGLPSDPPQGC 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: 53.71 E-value: 2.84e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   47 ITVFPSEKEVRDGRDVSFECRARtsDNSVyPTVRWARVGGPLPSSA--HDSGGRLTINPVQLSDAGTYICVSD--YNGNT 122
Cdd:cd04968    4 KVRFPADTYALKGQTVTLECFAL--GNPV-PQIKWRKVDGSPSSQWeiTTSEPVLEIPNVQFEDEGTYECEAEnsRGKDT 80


                 ....*.
gi 71998537  123 VEARAT 128
Cdd:cd04968   81 VQGRII 86

Laminin-type epidermal growth factor-like domai;

Pssm-ID: 214543 Cd Length: 46 Bit Score: 52.31 E-value: 2.87e-08

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*.
gi 71998537    1011 CHCN--NHSPRGCDSF-GRCLlCEHNTEGTHCERCKKGYYGDATKG 1053
Cdd:smart00180    1 CDCDpgGSASGTCDPDtGQCE-CKPNVTGRRCDRCAPGYYGDGPPG 45

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: 53.17 E-value: 3.07e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   51 PSEKEVRDGRDVSFECRARtsdNSVYPTVRWARVGGPLPSSA----HDSGgrLTINPVQLSDAGTYICVSDYNGNTVEAR 126
Cdd:cd05725    4 PQNQVVLVDDSAEFQCEVG---GDPVPTVRWRKEDGELPKGRyeilDDHS--LKIRKVTAGDMGSYTCVAENMVGKIEAS 78


                 ....*
gi 71998537  127 ATLSV 131
Cdd:cd05725   79 ATLTV 83

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 52.95 E-value: 3.55e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 71998537   1700 PVIT--PQTQTIPEGDPARIQCTVPGNPSAA---QHLSFERVDGKGLPFGSSDDRGVLTIPSTQLQDAGEYVCLYS 1770
Cdd:pfam13927    2 PVITvsPSSVTVREGETVTLTCEATGSPPPTitwYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVAS 77

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: 3.77e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   51 PSEKEVRDGRDVSFECRARTSDNsvyPTVRWARVGGPLPSSA--HDSGGRLTINPVQLSDAGTYICVSDYNGNTVEARAT 128
Cdd:cd05728    6 ISDTEADIGSSLRWECKASGNPR---PAYRWLKNGQPLASENriEVEAGDLRITKLSLSDSGMYQCVAENKHGTIYASAE 82


                 ...
gi 71998537  129 LSV 131
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: 3.85e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   1418 IDPPNQTVNVNDPAQFRCWV-PGQPRAQLKWSRKDGRpLPNGILERDGFLRIDKSQLH-------DAGEYECTSTEPDGS 1489
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSAsTGSPGPDVTWSKEGGT-LIESLKVKHDNGRTTQSSLLisnvtkeDAGTYTCVVNNPGGS 79


                   ....
gi 71998537   1490 TQLS 1493
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: 3.95e-08

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537    1704 PQTQTIPEGDPARIQCTVPGNPSAaqHLSFERVDGKGLPFGS------SDDRGVLTIPSTQLQDAGEYVClySPENSPPV 1777
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPP--EVTWYKQGGKLLAESGrfsvsrSGSTSTLTISNVTPEDSGTYTC--AATNSSGS 76


                    ....*....
gi 71998537    1778 KTNPSTLNV 1786
Cdd:smart00410   77 ASSGTTLTV 85

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: 53.22 E-value: 4.19e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 2354 QVLLEVSSESPQIGDRAWFDCKVTGDPSAVISWTKEGN--DDLPPNAQ--VTGGRLLFTDLKEDNAGVYRCVAKTKAGPL 2429
Cdd:cd04978    1 YWIIEPPSLVLSPGETGELICEAEGNPQPTITWRLNGVpiEPAPEDMRrtVDGRTLIFSNLQPNDTAVYQCNASNVHGYL 80


                 ....*...
gi 71998537 2430 QTRTVLNV 2437
Cdd:cd04978   81 LANAFLHV 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: 52.84 E-value: 4.71e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537  273 VVDPPQtNLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPVCE-PPRCLQTSEGgyGTLTIHDAQPVDQGAYTCEAINVKG 351
Cdd:cd04978    2 WIIEPP-SLVLSPGETGELICEAEGNPQPTITWRLNGVPIEPaPEDMRRTVDG--RTLIFSNLQPNDTAVYQCNASNVHG 78


                 ....
gi 71998537  352 RVLA 355
Cdd:cd04978   79 YLLA 82

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 52.57 E-value: 5.63e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 71998537   1885 PPTAVVEPRTWNGKPGERHQFRCITTGSPTPKITWTgPNGSPLPHDVTPLEPN-----ILDFSNGRSELNGDYTCTASN 1958
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: 52.64 E-value: 5.98e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537  270 QPTVVDPPqTNLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPVcEPPRCLQTSEGGYGTLTIHDAQPVDQGAYTCEAINV 349
Cdd:cd20976    1 APSFSSVP-KDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPL-QYAADRSTCEAGVGELHIQDVLPEDHGTYTCLAKNA 78

                         90
                 ....*....|....
gi 71998537  350 KGRVlatpDCIVRV 363
Cdd:cd20976   79 AGQV----SCSAWV 88

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 52.64 E-value: 6.09e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   1886 PTAVVEPRTWNGKPGERHQFRCITTGSPTPKITWTgPNGSPLP----HDVTPlEPNI--LDFSNGRSELNGDYTCTASNP 1959
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWF-KDGQPLRssdrFKVTY-EGGTytLTISNVQPDDSGKYTCVATNS 78

                           90
                   ....*....|..
gi 71998537   1960 IGEASDHGNVNI 1971
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: 8.15e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   1598 RPIIDPAEQTVPEGSPFKIRCYVPGHPSVQLTFRRVSGQLNEDADennglLAVQRAELTDEGDYICTARDPDTGapIDST 1677
Cdd:pfam13895    1 KPVLTPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAISSSPN-----FFTLSVSAEDSGTYTCVARNGRGG--KVSN 73


                   ....*.
gi 71998537   1678 PATVHV 1683
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: 9.26e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 71998537   2354 QVLLEVSSESPQIGDRAWFDCKVTGDPSAVISWTKEG-----NDDLPPNAQVTGGRLLFTDLKEDNAGVYRCVAK 2423
Cdd:pfam13927    3 VITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGepissGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVAS 77

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: 1.00e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 71998537 2372 FDCKVTGDPSAVISWTKEGNDDLPPNA-----QVTGGRLLFTDLKEDNAGVYRCVAKTKAGPLQTRTV 2434
Cdd:cd00096    3 LTCSASGNPPPTITWYKNGKPLPPSSRdsrrsELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 51.63 E-value: 1.13e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   1227 QPVIDPPHLVVNEGEPAAFRCWVPGIPDCQITWHREqlGGPLPhgvyQTGNALkIPQSQLHHAGRYICSAANQYGTGQSP 1306
Cdd:pfam13895    1 KPVLTPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKD--GSAIS----SSPNFF-TLSVSAEDSGTYTCVARNGRGGKVSN 73


                   ....*.
gi 71998537   1307 PAVLEV 1312
Cdd:pfam13895   74 PVELTV 79

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

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 52.13 E-value: 1.16e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1228 PVIDPPH----LVVNEGEPAAFRCWVPGIPDCQITWHREqlgGPLP------HGVYQTGNALKIPQSQLHHAGRYICSAA 1297
Cdd:cd20970    1 PVISTPQpsftVTAREGENATFMCRAEGSPEPEISWTRN---GNLIiefntrYIVRENGTTLTIRNIRRSDMGIYLCIAS 77

                         90
                 ....*....|....*
gi 71998537 1298 NQYGTGQSPPAVLEV 1312
Cdd:cd20970   78 NGVPGSVEKRITLQV 92

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: 49.94 E-value: 1.19e-07

                            10        20        30
                    ....*....|....*....|....*....|...
gi 71998537     148 QCMADEKACGNNECVKNDYVCDGEPDCRDRSDE 180
Cdd:smart00192    1 TCPPGEFQCDNGRCIPSSWVCDGVDDCGDGSDE 33

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 51.41 E-value: 1.19e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   1225 PPQPVIDPPHLVVNEGEPAAFRCWVPGIPDCQITWHREqlGGPLPHG------VYQTGNALKIPQSQLHHAGRYICSAAN 1298
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKN--GEPISSGstrsrsLSGSNSTLTISNVTRSDAGTYTCVASN 78

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 51.35 E-value: 1.50e-07

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 71998537    1892 PRTWNGKPGERHQFRCITTGSPTPKITWTGPNGSPLPHD----VTPLEPN-ILDFSNGRSELNGDYTCTASNPIGEAS 1964
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESgrfsVSRSGSTsTLTISNVTPEDSGTYTCAATNSSGSAS 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: 51.43 E-value: 1.71e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537  277 PQTNLQVPrGTTFSLTCKAVAVPEPYINWRLNWGPV----CEPPRCLQTseggyGTLTIHDAQPVDQGAYTCEAINVKGR 352
Cdd:cd05867    6 PQSHLYGP-GETARLDCQVEGIPTPNITWSINGAPIegtdPDPRRHVSS-----GALILTDVQPSDTAVYQCEARNRHGN 79


                 ...
gi 71998537  353 VLA 355
Cdd:cd05867   80 LLA 82

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 51.03 E-value: 1.89e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 71998537   1416 PQI--DPPNQTVNVNDPAQFRCWVPGQPRAQLKWsRKDGRPLPNGILERDGF------LRIDKSQLHDAGEYECT 1482
Cdd:pfam13927    2 PVItvSPSSVTVREGETVTLTCEATGSPPPTITW-YKNGEPISSGSTRSRSLsgsnstLTISNVTRSDAGTYTCV 75

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

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 50.65 E-value: 3.02e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537  277 PQTNLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPVCEPPRC-LQTSEGGYGTLTIHDAQPVDQGAYTCEAINVKGRvlA 355
Cdd:cd20973    3 TLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFqIDQDEDGLCSLIISDVCGDDSGKYTCKAVNSLGE--A 80


                 ....*...
gi 71998537  356 TPDCIVRV 363
Cdd:cd20973   81 TCSAELTV 88

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 50.58 E-value: 3.29e-07

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537    2180 PRVRVVSQGDNIVLKCSVQGAENGE------HFKWALLRGGSLVRQLGTEPTLEITKADPSnDFGVYRCNVEDNNGLVIG 2253
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEvtwykqGGKLLAESGRFSVSRSGSTSTLTISNVTPE-DSGTYTCAATNSSGSASS 79


                    ..
gi 71998537    2254 SA 2255
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: 3.46e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1225 PPQPVIDPPHLVVNEGEPAAFRCWVPGIPDCQITWHREqlGGPLPHG---VYQTGNALKIPQSQLHHAGRYICSAANQYG 1301
Cdd:cd20957    1 PLSATIDPPVQTVDFGRTAVFNCSVTGNPIHTVLWMKD--GKPLGHSsrvQILSEDVLVIPSVKREDKGMYQCFVRNDGD 78


                 ....
gi 71998537 1302 TGQS 1305
Cdd:cd20957   79 SAQA 82

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

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 50.47 E-value: 3.78e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1883 QEPPTAVVEprtwngKPGERHQFRCITTGSPTPKITWTGpNGSPL--PHDVTPLEPNILDFSNGRSELNGDYTCTASNPI 1960
Cdd:cd20978    5 QKPEKNVVV------KGGQDVTLPCQVTGVPQPKITWLH-NGKPLqgPMERATVEDGTLTIINVQPEDTGYYGCVATNEI 77


                 ..
gi 71998537 1961 GE 1962
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: 50.25 E-value: 3.97e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1701 VITPQTQTIPEGDPARIQCTVPGNpSAAQHLSFERVDGKgLPFGSSDDRGVLTIPSTQLQDAGEYVCLYS 1770
Cdd:cd05754    5 VEEPRSQEVRPGADVSFICRAKSK-SPAYTLVWTRVNGT-LPSRAMDFNGILTIRNVQLSDAGTYVCTGS 72

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 50.33 E-value: 4.50e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   1416 PQID--PPNQTVNVNDPAQFRCWVPGQPRAQLKWsRKDGRPLPNG----ILERDG--FLRIDKSQLHDAGEYECTSTEPD 1487
Cdd:pfam07679    1 PKFTqkPKDVEVQEGESARFTCTVTGTPDPEVSW-FKDGQPLRSSdrfkVTYEGGtyTLTISNVQPDDSGKYTCVATNSA 79

                           90
                   ....*....|...
gi 71998537   1488 GSTQLSppARLNV 1500
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: 4.86e-07

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537    1603 PAEQTVPEGSPFKIRCYVPGHPSVQLTFRRVSGQL-------NEDADENNGLLAVQRAELTDEGDYICTARDpdtGAPID 1675
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLlaesgrfSVSRSGSTSTLTISNVTPEDSGTYTCAATN---SSGSA 77


                    ....*...
gi 71998537    1676 STPATVHV 1683
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: 4.91e-07

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537    1984 PKLIVTVGEPLQVKCEAfgaPGDPEPEVEWLHDpGPERGDLPDDFKPVTISEQF-IRHPNVGLGNAGVYTCKGSSAHATA 2062
Cdd:smart00410    2 PSVTVKEGESVTLSCEA---SGSPPPEVTWYKQ-GGKLLAESGRFSVSRSGSTStLTISNVTPEDSGTYTCAATNSSGSA 77


                    ....*...
gi 71998537    2063 TKNIYIEV 2070
Cdd:smart00410   78 SSGTTLTV 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: 49.25 E-value: 5.30e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   62 VSFECRARTSDNsvyPTVRWARVGGPLPSSAHDS------GGRLTINPVQLSDAGTYICV 115
Cdd:cd00096    1 VTLTCSASGNPP---PTITWYKNGKPLPPSSRDSrrselgNGTLTISNVTLEDSGTYTCV 57

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: 48.50 E-value: 5.54e-07

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 71998537  383 SCDTRGAVTPYPNNY-GTCECKSQVTGPNCDQCKPGAFHLSEKsPEGC 429
Cdd:cd00055    3 DCNGHGSLSGQCDPGtGQCECKPNTTGRRCDRCAPGYYGLPSQ-GGGC 49

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: 5.81e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 71998537 1506 IQPQVDPPVQTVNEGEPSRIRCWVPGHPNIQLQFVKRGrRPLPAHAR---FSQGNLEIPRTLKSDEDEYICIATDP 1578
Cdd:cd20957    2 LSATIDPPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDG-KPLGHSSRvqiLSEDVLVIPSVKREDKGMYQCFVRND 76

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: 6.58e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1419 DPPNQTVNVNDPAQFRCWVPGQPRAQLKWsRKDGRPLPnGILER-----DGFLRIDKSQLHDAGEYECTSTEPDGSTQLS 1493
Cdd:cd20952    5 GPQNQTVAVGGTVVLNCQATGEPVPTISW-LKDGVPLL-GKDERittleNGSLQIKGAEKSDTGEYTCVALNLSGEATWS 82

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: 1.34e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537    1323 PIRQTVDRDQPARFKCWVPGNSNVQLRWSRPGGAPLPSG------VQEQQGILHIPRASDQEVGQYVCTATDPSDNTplq 1396
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESgrfsvsRSGSTSTLTISNVTPEDSGTYTCAATNSSGSA--- 77


                    ....*...
gi 71998537    1397 SEPVQLNI 1404
Cdd:smart00410   78 SSGTTLTV 85

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: 1.44e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 71998537 2367 GDRAWFDCKVTGDPSAVISWtKEGNDDLPPNA-----QVTGGR--LLFTDLKEDNAGVYRCVAKTKAGPLQTRTVLNV 2437
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: 1.52e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 71998537 1900 GERHQFRCITTGSPTPKITWTGPNGsPLPHDVTPLEP--NILDFSNGRSELNGDYTCTASNPIGEAS 1964
Cdd:cd05731   10 GGVLLLECIAEGLPTPDIRWIKLGG-ELPKGRTKFENfnKTLKIENVSEADSGEYQCTASNTMGSAR 75

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 48.16 E-value: 1.72e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   1415 APQIDPPNQTVNVNDPAQFRCWVPGQPRAQLKWsRKDGRPLPNGileRDGFlrIDKSQLHDAGEYECTSTEPDGSTQlSP 1494
Cdd:pfam13895    1 KPVLTPSPTVVTEGEPVTLTCSAPGNPPPSYTW-YKDGSAISSS---PNFF--TLSVSAEDSGTYTCVARNGRGGKV-SN 73


                   ....*.
gi 71998537   1495 PARLNV 1500
Cdd:pfam13895   74 PVELTV 79

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

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 48.77 E-value: 1.77e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 71998537 2367 GDRAWFDCKVTGDPSAVISWTKEGNDDLPPNAQ------VTGGRLLFTDLKEDNAGVYRCVAKTKAGPLQTRTVLNV 2437
Cdd:cd05763   14 GSTARLECAATGHPTPQIAWQKDGGTDFPAARErrmhvmPEDDVFFIVDVKIEDTGVYSCTAQNSAGSISANATLTV 90

Laminin G domain;

Pssm-ID: 395008 [Multi-domain] Cd Length: 131 Bit Score: 49.62 E-value: 2.04e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   2564 TANPKGIIFETKRINSGDLLAtpydtihheAKITDyGTVLYEFDIGNGRQIVETTNPINPNEWNVIKIKNDKNQVTIQLN 2643
Cdd:pfam00054    3 TTEPSGLLLYNGTQTERDFLA---------LELRD-GRLEVSYDLGSGAAVVRSGDKLNDGKWHSVELERNGRSGTLSVD 72

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 71998537   2644 DESATIRqhTNPLPSLSTG-VNRPVFIGG--------RHEPTNEAndFRGIISQVVLSGHNVG 2697
Cdd:pfam00054   73 GEARPTG--ESPLGATTDLdVDGPLYVGGlpslgvkkRRLAISPS--FDGCIRDVIVNGKPLD 131

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: 48.31 E-value: 2.19e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 71998537  286 GTTFSLTCKAVAVPEPYINWRLNWGPvcEPPRCLQTSEGGygTLTIHDAQPVDQGAYTCEAINVKGR 352
Cdd:cd04968   16 GQTVTLECFALGNPVPQIKWRKVDGS--PSSQWEITTSEP--VLEIPNVQFEDEGTYECEAENSRGK 78

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: 46.96 E-value: 2.23e-06

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 71998537  684 PAQGQCQCKASVIGPNCDRCAPNSFGLaPTNPQGC 718
Cdd:cd00055   16 PGTGQCECKPNTTGRRCDRCAPGYYGL-PSQGGGC 49

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 47.56 E-value: 2.79e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 71998537   1314 KPVIppKVDPIRQTVDRDQPARFKCWVPGNSNVQLRWSRPGGAPLPS-----GVQEQQGILHIPRASDQEVGQYVCTAT 1387
Cdd:pfam13927    1 KPVI--TVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGstrsrSLSGSNSTLTISNVTRSDAGTYTCVAS 77

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: 48.03 E-value: 2.87e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   48 TVFPSEKEvrDGRdVSFECRARTSDnsvYPTVRWARVGGPLP-SSAHDS--GGRLTI-NPVQLSDAGTYICVSDYNGNTV 123
Cdd:cd05849   11 TIYPEEST--EGK-VSVNCRARANP---FPIYKWRKNNLDIDlTNDRYSmvGGNLVInNPDKYKDAGRYVCIVSNIYGKV 84


                 ....*...
gi 71998537  124 EAR-ATLS 130
Cdd:cd05849   85 RSReATLS 92

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

Pssm-ID: 395007 Cd Length: 49 Bit Score: 46.58 E-value: 3.10e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 71998537    384 CDTRGAVTPYPN-NYGTCECKSQVTGPNCDQCKPGAFHLSEKSPEGC 429
Cdd:pfam00053    3 CNPHGSLSDTCDpETGQCLCKPGVTGRHCDRCKPGYYGLPSDPPQGC 49

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 47.56 E-value: 3.26e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   1973 PSLTVKTNPPgpklIVTVGEPLQVKCEAFGapgDPEPEVEWLHDpGPERGDLPDDFKPVTISEQFIRHPNVGLGNAGVYT 2052
Cdd:pfam13927    2 PVITVSPSSV----TVREGETVTLTCEATG---SPPPTITWYKN-GEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYT 73


                   ....
gi 71998537   2053 CKGS 2056
Cdd:pfam13927   74 CVAS 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: 3.27e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 71998537 2374 CKVTGDPSAVISWTKEGNDDLPPNAQVT---GGRLLFTDLKEDNAGVYRCVAKTKAGPLQTRTVLNV 2437
Cdd:cd20952   21 CQATGEPVPTISWLKDGVPLLGKDERITtleNGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 87

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: 47.55 E-value: 3.99e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1130 LRVRIMEPKRQIALPGDRVHWIC----QVTGYTtekihVEWTKVGEmSLPPNAKAYDGYLVLKGVEAENAGQYRCTATti 1205
Cdd:cd05754    1 IQVTVEEPRSQEVRPGADVSFICraksKSPAYT-----LVWTRVNG-TLPSRAMDFNGILTIRNVQLSDAGTYVCTGS-- 72

                         90
                 ....*....|...
gi 71998537 1206 TQYATDDALLTIS 1218
Cdd:cd05754   73 NMLDTDEATATLY 85

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 47.25 E-value: 4.47e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   1137 PKRQIALPGDRVHWICQVTGytTEKIHVEWTKVGEMsLPPN------AKAYDGYLVLKGVEAENAGQYRCTATTITQYAT 1210
Cdd:pfam07679    7 PKDVEVQEGESARFTCTVTG--TPDPEVSWFKDGQP-LRSSdrfkvtYEGGTYTLTISNVQPDDSGKYTCVATNSAGEAE 83


                   ....*..
gi 71998537   1211 DDALLTI 1217
Cdd:pfam07679   84 ASAELTV 90

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

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 47.64 E-value: 4.71e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1886 PTAVVEPRTWNGKPGERHQFRCITTGSPTPKITWTgPNGSplphDVTPLEPNILDF---------SNGRSELNGDYTCTA 1956
Cdd:cd05736    1 PVIRVYPEFQAKEPGVEASLRCHAEGIPLPRVQWL-KNGM----DINPKLSKQLTLiangselhiSNVRYEDTGAYTCIA 75


                 ....*....
gi 71998537 1957 SNPIGEASD 1965
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: 4.75e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537  276 PPQTNLQVP-----RGTTFSLTCKAVAVPEPYINWRlnwgPVCEP-PRCLQTSEGGyGTLTIHDAQPVDQGAYTCEAINV 349
Cdd:cd05851    1 PADINVKFKdtyalKGQNVTLECFALGNPVPVIRWR----KILEPmPATAEISMSG-AVLKIFNIQPEDEGTYECEAENI 75


                 ...
gi 71998537  350 KGR 352
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: 4.99e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 71998537 2366 IGDRAWFDCKVTGDPSAVISWTKEGnDDLPPNA--QVTGGRLLFTDLKEDNAGVYRCVAKTKAGPLQTRTVLNV 2437
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: 5.13e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537    1799 PPLLSVAPGSPARFNCVAHSDTPARIRWgFREENGPLPE----HVNQDGDD--IVISEAGDRNVGEYVCSATNDFGTGVA 1872
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTW-YKQGGKLLAEsgrfSVSRSGSTstLTISNVTPEDSGTYTCAATNSSGSASS 79


                    ....*..
gi 71998537    1873 dPVRLEV 1879
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: 5.41e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 71998537 1904 QFRCITTGSPTPKITWTGpNGSPLPHDVTPLEPNI-----LDFSNGRSELNGDYTCTASNPIGEAS 1964
Cdd:cd00096    2 TLTCSASGNPPPTITWYK-NGKPLPPSSRDSRRSElgngtLTISNVTLEDSGTYTCVASNSAGGSA 66

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: 47.31 E-value: 5.53e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1229 VID-PPHL-VVNEGEPAAFRCWVPGIPDCQITWHREQLGGPLPHG---VYQT-GNALKIPQSQLHHAGRYICSAANQYGT 1302
Cdd:cd05738    1 IIDmGPQLkVVEKARTATMLCAASGNPDPEISWFKDFLPVDTATSngrIKQLrSGALQIENSEESDQGKYECVATNSAGT 80

                         90
                 ....*....|.
gi 71998537 1303 GQSPPAVLEVK 1313
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: 46.78 E-value: 5.67e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 71998537 1419 DPPNQTVNVNDPAQFRCWVPGQ-PRAQLKWSRKDGrPLPNGILERDGFLRIDKSQLHDAGEYECTST 1484
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: 47.24 E-value: 6.19e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   48 TVFPSEKevrDGRDVSFECRARTSDnsvYPTVRWARVGGPLPSSAHDS----GGRLTI-NPVQLSDAGTYICVSDYNGNT 122
Cdd:cd04967   11 TIFPEDS---DEKKVALNCRARANP---VPSYRWLMNGTEIDLESDYRyslvDGTLVIsNPSKAKDAGHYQCLATNTVGS 84


                 ....*....
gi 71998537  123 VEAR-ATLS 130
Cdd:cd04967   85 VLSReATLQ 93

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: 6.29e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537    2454 PVVYTVGQPAYLSCigKTETKPNQSVVWTKEEGDLPSGS-RVE------QGVLMLPSVHRDDEGSYTCEIVKEENPVFST 2526
Cdd:smart00410    3 SVTVKEGESVTLSC--EASGSPPPEVTWYKQGGKLLAESgRFSvsrsgsTSTLTISNVTPEDSGTYTCAATNSSGSASSG 80


                    ....*
gi 71998537    2527 VDLQI 2531
Cdd:smart00410   81 TTLTV 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: 46.73 E-value: 7.22e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537    1137 PKRQIALPGDRVHWICQVTGYTTekIHVEWTKVGEMSLPPNAKA------YDGYLVLKGVEAENAGQYRCTATTITQYAT 1210
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPP--PEVTWYKQGGKLLAESGRFsvsrsgSTSTLTISNVTPEDSGTYTCAATNSSGSAS 78


                    ....*..
gi 71998537    1211 DDALLTI 1217
Cdd:smart00410   79 SGTTLTV 85

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: 7.84e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 71998537 1422 NQTVNVNDPAQFRCWVPGQPRAQLKWSRKDGrPLPNGILERDGF---LRIDKSQLHDAGEYECTSTEPDGSTQ 1491
Cdd:cd05731    4 STMVLRGGVLLLECIAEGLPTPDIRWIKLGG-ELPKGRTKFENFnktLKIENVSEADSGEYQCTASNTMGSAR 75

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

Pssm-ID: 409561 Cd Length: 92 Bit Score: 46.61 E-value: 7.91e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1503 PQAIQPQVDPPVqTVNEGEPSRIRCWVPGHPNIQLQFVKRGRRPLPA-----HARFSQGNLEIPRTLKSDEDEYICIATD 1577
Cdd:cd20969    1 RAAIRDRKAQQV-FVDEGHTVQFVCRADGDPPPAILWLSPRKHLVSAksngrLTVFPDGTLEVRYAQVQDNGTYLCIAAN 79

                         90
                 ....*....|....*.
gi 71998537 1578 PTTNrpvESNPARVIV 1593
Cdd:cd20969   80 AGGN---DSMPAHLHV 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: 46.40 E-value: 8.38e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 71998537 2270 QIVKFDDKSDASFTC-PIYSVPGSKVDWTYENGDLPSKAVPNGNKIEIKEFDDASAGTYVCKVSFDGNVVEGFVT 2343
Cdd:cd05754    9 RSQEVRPGADVSFICrAKSKSPAYTLVWTRVNGTLPSRAMDFNGILTIRNVQLSDAGTYVCTGSNMLDTDEATAT 83

Laminin-type epidermal growth factor-like domai;

Pssm-ID: 214543 Cd Length: 46 Bit Score: 44.99 E-value: 8.63e-06

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*...
gi 71998537     673 QCGP-GAVAPT-APAQGQCQCKASVIGPNCDRCAPNSFGlapTNPQGC 718
Cdd:smart00180    2 DCDPgGSASGTcDPDTGQCECKPNVTGRRCDRCAPGYYG---DGPPGC 46

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: 44.55 E-value: 1.01e-05

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 71998537 2711 DACASTNLCLNGANCRNANNhhGFSCECAEEFHGEYCQ 2748
Cdd:cd00054    3 DECASGNPCQNGGTCVNTVG--SYRCSCPPGYTGRNCE 38

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: 46.06 E-value: 1.01e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 71998537 1907 CITTGSPTPKITWTGPNGSPLPHDVTPLEPN-ILDFSNGRSELNGDYTCTASNPIGEASDHGNVNI 1971
Cdd:cd05876   17 CIAEGLPTPTVKWLRPSGPLPPDRVKYQNHNkTLQLLNVGESDDGEYVCLAENSLGSARHAYYVTV 82

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 46.48 E-value: 1.02e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   1228 PVID--PPHLVVNEGEPAAFRCWVPGIPDCQITWHREqlGGPLPHG-----VYQTGNA-LKIPQSQLHHAGRYICSAANQ 1299
Cdd:pfam07679    1 PKFTqkPKDVEVQEGESARFTCTVTGTPDPEVSWFKD--GQPLRSSdrfkvTYEGGTYtLTISNVQPDDSGKYTCVATNS 78


                   ...
gi 71998537   1300 YGT 1302
Cdd:pfam07679   79 AGE 81

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

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 46.35 E-value: 1.03e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   51 PSEKEVRDGRDVSFECRARTSDNsvyPTVRWARVGGPLPSSAH-----DSGGRLTINPVQLSDAGTYICV-SDYNGNTVE 124
Cdd:cd20970    9 SFTVTAREGENATFMCRAEGSPE---PEISWTRNGNLIIEFNTryivrENGTTLTIRNIRRSDMGIYLCIaSNGVPGSVE 85


                 ....*..
gi 71998537  125 ARATLSV 131
Cdd:cd20970   86 KRITLQV 92

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: 1.07e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 2454 PVVYTV--GQPAYLSCIgkTETKPNQSVVWTKEEGDLPSGSRVE---QGVLMLPSVHRDDEGSYTCEIVKEENPVFSTVD 2528
Cdd:cd20957    8 PPVQTVdfGRTAVFNCS--VTGNPIHTVLWMKDGKPLGHSSRVQilsEDVLVIPSVKREDKGMYQCFVRNDGDSAQATAE 85


                 ...
gi 71998537 2529 LQI 2531
Cdd:cd20957   86 LKL 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: 46.35 E-value: 1.09e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537  273 VVDPPQ--TNLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPVCEPPRCLQTSEGGyGTLTIHDAQPVDQGAYTCEAIN-V 349
Cdd:cd20970    2 VISTPQpsFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVRENG-TTLTIRNIRRSDMGIYLCIASNgV 80


                 ....
gi 71998537  350 KGRV 353
Cdd:cd20970   81 PGSV 84

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: 1.76e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 71998537   2366 IGDRAWFDCKV-TGDPSAVISWTKEGN------DDLPPNAQVTGGRLLFTDLKEDNAGVYRCVAKTKAGPLQTRTVL 2435
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: 1.80e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537     51 PSEKEVRDGRDVSFECRARTSdnSVYPTVRWARVGGPLPSSAHDSGGR-------LTINPVQLSDAGTYICVSDYNGNTV 123
Cdd:pfam00047    3 PPTVTVLEGDSATLTCSASTG--SPGPDVTWSKEGGTLIESLKVKHDNgrttqssLLISNVTKEDAGTYTCVVNNPGGSA 80


                   ....*.
gi 71998537    124 EARATL 129
Cdd:pfam00047   81 TLSTSL 86

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: 1.91e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1884 EPPTAVVEPrtwngkpGERHQFRCITTGSPTPKITWTgPNGSPL----PHDVTPLEPNILDFSNGRSELNGDYTCTASNP 1959
Cdd:cd04978    5 EPPSLVLSP-------GETGELICEAEGNPQPTITWR-LNGVPIepapEDMRRTVDGRTLIFSNLQPNDTAVYQCNASNV 76

                         90
                 ....*....|..
gi 71998537 1960 IGEASDHGNVNI 1971
Cdd:cd04978   77 HGYLLANAFLHV 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: 45.08 E-value: 2.17e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 71998537 1232 PPHLVVNEGEPAAFRCWVPGIPDCQITWHREqlGGPLPHGVYQT--GNALKIPQSQLHHAGRYICSAANQYGT 1302
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: 45.18 E-value: 2.33e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 71998537 1906 RCITTGSPTPKITWTgPNGSPLP---HDVTPLEPNILDFSNGRSELNGDYTCTASNPIGEASDH 1966
Cdd:cd20952   20 NCQATGEPVPTISWL-KDGVPLLgkdERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEATWS 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: 45.22 E-value: 2.38e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 71998537 1885 PPTAVVEPRTWNGKPGERHQFRCITTGSPTPKITWTgPNGSPLPHD--VTPLEPNILDFSNGRSELNGDYTCTASNP 1959
Cdd:cd20957    1 PLSATIDPPVQTVDFGRTAVFNCSVTGNPIHTVLWM-KDGKPLGHSsrVQILSEDVLVIPSVKREDKGMYQCFVRND 76

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: 2.41e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   51 PSEKEVRDGRDVSFECraRTSDNSvYPTVRWARVGGPL-PSSAH----DSGGR--LTINPVQLSDAGTYICVSDYNGNTV 123
Cdd:cd05744    7 PGDLEVQEGRLCRFDC--KVSGLP-TPDLFWQLNGKPVrPDSAHkmlvRENGRhsLIIEPVTKRDAGIYTCIARNRAGEN 83


                 ....*...
gi 71998537  124 EARATLSV 131
Cdd:cd05744   84 SFNAELVV 91

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: 2.47e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1423 QTVNvndpaqFRCWVPGQPRAQLKWSrKDGRPLP---NGILERDGFLRIDKSQLHDAGEYECTSTEPDGSTQLSppARLN 1499
Cdd:cd05745    3 QTVD------FLCEAQGYPQPVIAWT-KGGSQLSvdrRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTV--AQLT 73


                 .
gi 71998537 1500 V 1500
Cdd:cd05745   74 V 74

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 44.48 E-value: 3.07e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 71998537   1792 PPRPVATPPLLSVAPGSPARFNCVAHSDTPARIRW----GFREENGPLPEHVNQDGDDIVISEAGDRNVGEYVCSATN 1865
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: 44.93 E-value: 3.23e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 71998537 2367 GDRAWFDCKVTGDPSAVISWTKeGNDDLPPNAQVT---GGRLLFTDLKEDNAGVYRCVAKTKAGPLQTRTV 2434
Cdd:cd20968   14 GLKAVLPCTTMGNPKPSVSWIK-GDDLIKENNRIAvleSGSLRIHNVQKEDAGQYRCVAKNSLGIAYSKPV 83

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: 45.33 E-value: 3.37e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   46 QITVFPSEKEVRDGRDVSFECRARTSDNsvyPTVRWARVGG--------PLPSSAHDS---GGRLTINPVQLSDAGTYIC 114
Cdd:cd05726    1 QFVVKPRDQVVALGRTVTFQCETKGNPQ---PAIFWQKEGSqnllfpyqPPQPSSRFSvspTGDLTITNVQRSDVGYYIC 77

                         90
                 ....*....|....*..
gi 71998537  115 VSDYNGNTVEARATLSV 131
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: 44.75 E-value: 3.37e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1977 VKTNPPgpKLIVTVGEPLQVKCEAfgaPGDPEPEVEW------LHDPGPERGDLPDdfkpvtisEQFIRHPNVGLGNAGV 2050
Cdd:cd04978    2 WIIEPP--SLVLSPGETGELICEA---EGNPQPTITWrlngvpIEPAPEDMRRTVD--------GRTLIFSNLQPNDTAV 68

                         90       100
                 ....*....|....*....|.
gi 71998537 2051 YTCKGSSAHATATKNIYIEVV 2071
Cdd:cd04978   69 YQCNASNVHGYLLANAFLHVL 89

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 44.48 E-value: 3.45e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 71998537   1136 EPKRQIALPGDRVHWICQVTGYTTEKIHveWTKVGEMSLPPNA-----KAYDGYLVLKGVEAENAGQYRCTAT 1203
Cdd:pfam13927    7 SPSSVTVREGETVTLTCEATGSPPPTIT--WYKNGEPISSGSTrsrslSGSNSTLTISNVTRSDAGTYTCVAS 77

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: 44.88 E-value: 4.22e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1881 EDQEPPT-AVVEPRTWNGKPGERHQFRCITTGSPTpKITWTgPNGSPL-PHDVTPLEPNILDFSNGRSELNGDYTCTASN 1958
Cdd:cd04973    4 PPEAPPTyQISEVESYSAHPGDLLQLRCRLRDDVQ-SINWT-KDGVQLgENNRTRITGEEVQIKDAVPRDSGLYACVTSS 81

                         90
                 ....*....|...
gi 71998537 1959 PIGEASDHGNVNI 1971
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: 44.31 E-value: 4.95e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   51 PSEKEVRDGRDVSFECRARtsdNSVYPTVRWARVGGPL---PSSAHDSGGRLTINPVQLSDAGTYICVSDYNGNTVEARA 127
Cdd:cd20978    8 EKNVVVKGGQDVTLPCQVT---GVPQPKITWLHNGKPLqgpMERATVEDGTLTIINVQPEDTGYYGCVATNEIGDIYTET 84


                 ....
gi 71998537  128 TLSV 131
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: 5.01e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 71998537   1600 IIDPAEQTVPEGSPFKIRCYVPGHPSVQLTFRRVSGQLNE------DADENNGLLAVQRAELTDEGDYICTAR 1666
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: 5.34e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 71998537 2366 IGDRAWFDCKV-TGDPSAVISWTKEG---NDDLPPNAQVTGGRLLFTDLKEDNAGVYRCVAKTKAG 2427
Cdd:cd05724   11 VGEMAVLECSPpRGHPEPTVSWRKDGqplNLDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVG 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: 44.06 E-value: 5.52e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 71998537 1702 ITPQTQTIPEGDPARIQCTVPGNPsaAQHLSFeRVDGKGLPFGSS---DDRGVLTIPSTQLQDAGEYVC 1767
Cdd:cd20957    6 IDPPVQTVDFGRTAVFNCSVTGNP--IHTVLW-MKDGKPLGHSSRvqiLSEDVLVIPSVKREDKGMYQC 71

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: 5.74e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 71998537   59 GRDVSFECRARtsDNSVyPTVRWARVGGPLPSSAH--DSGGRLTINPVQLSDAGTYIC 114
Cdd:cd05851   16 GQNVTLECFAL--GNPV-PVIRWRKILEPMPATAEisMSGAVLKIFNIQPEDEGTYEC 70

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: 6.21e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1792 PPRPVATPPLLSVAPGSPARFNCVAHSDTPARIRWgFRE----ENGP-LPEHVNQDGDDIVISEAGDRNVGEYVCSATND 1866
Cdd:cd20972    1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRW-FCEgkelQNSPdIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNS 79


                 ...
gi 71998537 1867 FGT 1869
Cdd:cd20972   80 VGS 82

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

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 43.98 E-value: 6.48e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1229 VIDPPHLVVNEGEPAAFRCWVPGIPDCQITWhreQLGG----PLPHGVYQTGN--ALKIPQSQLHHAGRYICSAANQYGT 1302
Cdd:cd04978    3 IIEPPSLVLSPGETGELICEAEGNPQPTITW---RLNGvpiePAPEDMRRTVDgrTLIFSNLQPNDTAVYQCNASNVHGY 79

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

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 44.00 E-value: 6.97e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 71998537 1900 GERHQFRCITTGSPTPKITWTGPNGSPLPHDV-TPLEPN-ILDFSNGRSELNGDYTCTASNPIGEAS 1964
Cdd:cd05764   15 GQRATLRCKARGDPEPAIHWISPEGKLISNSSrTLVYDNgTLDILITTVKDTGAFTCIASNPAGEAT 81

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: 7.04e-05

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 71998537 1435 CWVPGQPRAQLKWSRKDGRPLPNGILER-DGFLRIDKSQLHDAGEYEC 1481
Cdd:cd04968   23 CFALGNPVPQIKWRKVDGSPSSQWEITTsEPVLEIPNVQFEDEGTYEC 70

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: 7.42e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537  271 PTVVDPPQtNLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPVCEPPR-CLQTSEGGYGTLTIHDAQPVDQGAYTCEAINV 349
Cdd:cd05744    1 PHFLQAPG-DLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAhKMLVRENGRHSLIIEPVTKRDAGIYTCIARNR 79


                 ....
gi 71998537  350 KGRV 353
Cdd:cd05744   80 AGEN 83

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 43.54 E-value: 7.54e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   1507 QPQVDPPVQTVNEGEPSRIRCWVPGHPNIQLQFVKRGrRPLPaharfSQGNLEIPRTLKSDEDEYICIATDPTTNRPveS 1586
Cdd:pfam13895    1 KPVLTPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDG-SAIS-----SSPNFFTLSVSAEDSGTYTCVARNGRGGKV--S 72


                   ....*..
gi 71998537   1587 NPARVIV 1593
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: 43.54 E-value: 8.13e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1509 QVDPPVQTVNEGEPSRIRCWVP-GHPNIQLQFVKRGRrPL----PAHARFSQGNLEIPRTLKSDEDEYICIATDPTTNRp 1583
Cdd:cd05724    1 RVEPSDTQVAVGEMAVLECSPPrGHPEPTVSWRKDGQ-PLnldnERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGER- 78

                         90
                 ....*....|
gi 71998537 1584 vESNPARVIV 1593
Cdd:cd05724   79 -ESRAARLSV 87

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: 8.24e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 71998537  291 LTCKAVAVPEPYINWRLNWGPVCEPPRcLQTSEGGYgtLTIHDAQPVDQGAYTCEAINVKG 351
Cdd:cd05746    3 IPCSAQGDPEPTITWNKDGVQVTESGK-FHISPEGY--LAIRDVGVADQGRYECVARNTIG 60

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: 43.73 E-value: 9.50e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 71998537 2367 GDRAWFDCKVTGDPSAVISWTKEG----NDDLPPNAQVTGGRLLFTDLKEDNAGVYRCVAKTKAGPLQTRTVLNV 2437
Cdd:cd05867   14 GETARLDCQVEGIPTPNITWSINGapieGTDPDPRRHVSSGALILTDVQPSDTAVYQCEARNRHGNLLANAHVHV 88

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: 9.87e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   51 PSEKEVRDGRDVSFECrarTSDNSVYPTVRWARVGGPLPSSAHDSGGR------LTINPVQLSDAGTYICVSDYNGNTVE 124
Cdd:cd05747   10 PRSLTVSEGESARFSC---DVDGEPAPTVTWMREGQIIVSSQRHQITSteykstFEISKVQMSDEGNYTVVVENSEGKQE 86


                 ....*.
gi 71998537  125 ARATLS 130
Cdd:cd05747   87 AQFTLT 92

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: 1.25e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537  271 PTVVDPPQtNLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPVCEPPR--CLQTSEGGYGTLTIHDAQPVDQGAYTCEAIN 348
Cdd:cd05892    1 PMFIQKPQ-NKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNTDriSLYQDNCGRICLLIQNANKKDAGWYTVSAVN 79


                 ....*
gi 71998537  349 VKGRV 353
Cdd:cd05892   80 EAGVV 84

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 43.01 E-value: 1.32e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   2454 PVVYTVGQPAYLSCigKTETKPNQSVVWTKEEGDLPSGSRV----EQGV--LMLPSVHRDDEGSYTCEIVKEENPVFSTV 2527
Cdd:pfam07679    9 DVEVQEGESARFTC--TVTGTPDPEVSWFKDGQPLRSSDRFkvtyEGGTytLTISNVQPDDSGKYTCVATNSAGEAEASA 86


                   ....
gi 71998537   2528 DLQI 2531
Cdd:pfam07679   87 ELTV 90

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

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 43.46 E-value: 1.40e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1596 PIRPIIDPAEQTVPEGSPFKIRCYVPGHPSVQLTFRRVSG-QLNEDAD---------ENNGLLAVQRAELTDEGDYICTA 1665
Cdd:cd20954    1 PPRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKATGsTPGEYKDllydpnvriLPNGTLVFGHVQKENEGHYLCEA 80


                 .
gi 71998537 1666 R 1666
Cdd:cd20954   81 K 81

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

Pssm-ID: 409454 Cd Length: 89 Bit Score: 43.05 E-value: 1.47e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1889 VVEPRTWNGKPGERHQFRCITTGSPTPKITWTgPNGSPLphDVTPLEP------NILDFSNGRSELNGDYTCTASNPIGE 1962
Cdd:cd05868    3 ITAPTNLVLSPGEDGTLICRANGNPKPSISWL-TNGVPI--EIAPTDPsrkvdgDTIIFSKVQERSSAVYQCNASNEYGY 79


                 ....*....
gi 71998537 1963 ASDHGNVNI 1971
Cdd:cd05868   80 LLANAFVNV 88

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 42.55 E-value: 1.50e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 71998537   1509 QVDPPVQTVNEGEPSRIRCWVPGHPNIQLQFVKRGRRPLPAHAR-----FSQGNLEIPRTLKSDEDEYICIAT 1576
Cdd:pfam13927    5 TVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRsrslsGSNSTLTISNVTRSDAGTYTCVAS 77

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

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 43.01 E-value: 1.51e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   46 QITVFPSEKEVRDGRDVSFECRARtsdNSVYPTVRWARVGGPLP-----SSAHDSGGRLTINPVQLSDAGTYICVSDYNG 120
Cdd:cd20976    3 SFSSVPKDLEAVEGQDFVAQCSAR---GKPVPRITWIRNAQPLQyaadrSTCEAGVGELHIQDVLPEDHGTYTCLAKNAA 79

                         90
                 ....*....|.
gi 71998537  121 NTVEARATLSV 131
Cdd:cd20976   80 GQVSCSAWVTV 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: 1.56e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   1702 ITPQTQTIPEGDPARIQCTV-PGNPSAAQHLSFERVDGKGLPFGSSDDRGV----LTIPSTQLQDAGEYVCLYSPENSPP 1776
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSAsTGSPGPDVTWSKEGGTLIESLKVKHDNGRTtqssLLISNVTKEDAGTYTCVVNNPGGSA 80


                   ...
gi 71998537   1777 VKT 1779
Cdd:pfam00047   81 TLS 83

Low-density lipoprotein receptor domain class A;

Pssm-ID: 395011 Cd Length: 37 Bit Score: 41.08 E-value: 1.64e-04

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 71998537    188 RTCEPNEFKCNNNKCVQKMWLCDGDDDCGDNSDELNC 224
Cdd:pfam00057    1 STCSPNEFQCGSGECIPRSWVCDGDPDCGDGSDEENC 37

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: 1.66e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1603 PAEQTVPEGSPFKIRCYVPGHPSVQLTFRRVSGQLNEDADENN-----GLLAVQRAELTDEGDYICTARD 1667
Cdd:cd20976    8 PKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADRSTceagvGELHIQDVLPEDHGTYTCLAKN 77

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

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 42.69 E-value: 1.86e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1418 IDPPNQ--TVNVNDPAQFRCWVPGQPRAQLKWSrKDGRPL----PNGILE--RDGFLRIDKSQLHDAGEYECTSTEPDGs 1489
Cdd:cd05738    2 IDMGPQlkVVEKARTATMLCAASGNPDPEISWF-KDFLPVdtatSNGRIKqlRSGALQIENSEESDQGKYECVATNSAG- 79

                         90
                 ....*....|.
gi 71998537 1490 TQLSPPARLNV 1500
Cdd:cd05738   80 TRYSAPANLYV 90

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

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 43.07 E-value: 1.96e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1885 PPTAVVEPRTWNGKPGERHQFRCITTGSPTPKITWTGPNGSPLP--HDVTpLEPNILDFSNG-------RSELNGDYTCT 1955
Cdd:cd20954    1 PPRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKATGSTPGeyKDLL-YDPNVRILPNGtlvfghvQKENEGHYLCE 79


                 ....*.
gi 71998537 1956 ASNPIG 1961
Cdd:cd20954   80 AKNGIG 85

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

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 42.59 E-value: 1.97e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1420 PPNQTVNVNDPAQFRCWVPGQPRAQLKWsRKDGRPLP--NGILERDGFLRIDKSQLHDAGEYECTSTEPDGSTQLSppAR 1497
Cdd:cd05728    6 ISDTEADIGSSLRWECKASGNPRPAYRW-LKNGQPLAseNRIEVEAGDLRITKLSLSDSGMYQCVAENKHGTIYAS--AE 82


                 ...
gi 71998537 1498 LNV 1500
Cdd:cd05728   83 LAV 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: 42.48 E-value: 2.10e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   47 ITVFPSEKEVRDGRDVSFECRArtsDNSVYPTVRWARVGGPLPSSAHD----SGGRLTINPVQLSDAGTYICVSDYNGNT 122
Cdd:cd20952    2 ILQGPQNQTVAVGGTVVLNCQA---TGEPVPTISWLKDGVPLLGKDERittlENGSLQIKGAEKSDTGEYTCVALNLSGE 78


                 ....*....
gi 71998537  123 VEARATLSV 131
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: 42.48 E-value: 2.25e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1988 VTVGEPLQVKCEAFGapgDPEPEVEWLHDPGPERGDLPDDFKPVTISEQFIrhpNVGLGNAGVYTCKGSSAHATATKNIY 2067
Cdd:cd20952   11 VAVGGTVVLNCQATG---EPVPTISWLKDGVPLLGKDERITTLENGSLQIK---GAEKSDTGEYTCVALNLSGEATWSAV 84


                 ...
gi 71998537 2068 IEV 2070
Cdd:cd20952   85 LDV 87

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

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 42.45 E-value: 2.36e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 71998537  283 VPRGTTFSLTCKAVAVPEPYINWRLNWGPVCEPPRCLQTSEGgygTLTIHDAQPVDQGAYTCEAINVKG 351
Cdd:cd04969   14 AAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILPDG---SLKIKNVTKSDEGKYTCFAVNFFG 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: 42.16 E-value: 2.47e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 71998537 1600 IIDPAEQTVPEGSPFKIRCYVPGH-PSVQLTFRRVSGQLNEDADENNGLLAVQRAELTDEGDYICT 1664
Cdd:cd05754    5 VEEPRSQEVRPGADVSFICRAKSKsPAYTLVWTRVNGTLPSRAMDFNGILTIRNVQLSDAGTYVCT 70

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: 2.82e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 71998537 1431 AQFRCWVPGQPRAQLKWsRKDGRPLPNGILER------DGFLRIDKSQLHDAGEYECTSTEPDGSTQ 1491
Cdd:cd00096    1 VTLTCSASGNPPPTITW-YKNGKPLPPSSRDSrrselgNGTLTISNVTLEDSGTYTCVASNSAGGSA 66

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: 42.64 E-value: 3.08e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 2367 GDRAWFDCKVTGDPSAVISWTKEGNDDL-------PPNAQVT---GGRLLFTDLKEDNAGVYRCVAKTKAGPLQTRTVLN 2436
Cdd:cd05726   14 GRTVTFQCETKGNPQPAIFWQKEGSQNLlfpyqppQPSSRFSvspTGDLTITNVQRSDVGYYICQALNVAGSILAKAQLE 93


                 .
gi 71998537 2437 V 2437
Cdd:cd05726   94 V 94

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: 3.12e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1416 PQIDP-PNQTVNVNDPAQFRCWVPGQPRAQLKWSrKDGRPLPNGILER---DGFLRIDK-SQLHDAGEYECTSTEPDGST 1490
Cdd:cd20958    2 PFIRPmGNLTAVAGQTLRLHCPVAGYPISSITWE-KDGRRLPLNHRQRvfpNGTLVIENvQRSSDEGEYTCTARNQQGQS 80

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: 3.14e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 71998537 1320 KVDPIRQTVDRDQPARFKCWVPGNSNVQLRWsRPGGAPLPSGVQEQ---QGILHIPRASDQEVGQYVCTATDPSD 1391
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: 3.19e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   1601 IDPAEQTVPEGSPFKIRC-YVPGHPSVQLTFRRVSGQLNE-------DADENNGLLAVQRAELTDEGDYICTARDPDTGA 1672
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCsASTGSPGPDVTWSKEGGTLIEslkvkhdNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGSA 80


                   ....*
gi 71998537   1673 PIDST 1677
Cdd:pfam00047   81 TLSTS 85

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 42.15 E-value: 3.35e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 2359 VSSESPQ---IGDRAWFDCKVTGDPSAVISWTKEGNDD----LPPNaQVTG-------GRLLFTDLKEDNAGVYRCVAKT 2424
Cdd:cd05765    4 VNSPTHQtvkVGETASFHCDVTGRPQPEITWEKQVPGKenliMRPN-HVRGnvvvtniGQLVIYNAQPQDAGLYTCTARN 82

                         90
                 ....*....|...
gi 71998537 2425 KAGPLQTRTVLNV 2437
Cdd:cd05765   83 SGGLLRANFPLSV 95

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 42.15 E-value: 3.73e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1419 DPPNQTVNVNDPAQFRCWVPGQPRAQLKWSRK-DGRP---------LPNGILERDGFLRIDKSQLHDAGEYECTSTEPDG 1488
Cdd:cd05765    6 SPTHQTVKVGETASFHCDVTGRPQPEITWEKQvPGKEnlimrpnhvRGNVVVTNIGQLVIYNAQPQDAGLYTCTARNSGG 85


                 ....*..
gi 71998537 1489 STQLSPP 1495
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: 41.62 E-value: 3.93e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1417 QIDPPNQTVNVNDPAQFRCWVP-GQPRAQLKWsRKDGRPL-----PNGILErDGFLRIDKSQLHDAGEYECTSTEPDGsT 1490
Cdd:cd05724    1 RVEPSDTQVAVGEMAVLECSPPrGHPEPTVSW-RKDGQPLnldneRVRIVD-DGNLLIAEARKSDEGTYKCVATNMVG-E 77

                         90
                 ....*....|
gi 71998537 1491 QLSPPARLNV 1500
Cdd:cd05724   78 RESRAARLSV 87

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 41.40 E-value: 3.96e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 71998537   2454 PVVYTVGQPAYLSCIGKTETKPnqSVVWTKEEGDLPSGSRVE------QGVLMLPSVHRDDEGSYTCE 2515
Cdd:pfam13927   10 SVTVREGETVTLTCEATGSPPP--TITWYKNGEPISSGSTRSrslsgsNSTLTISNVTRSDAGTYTCV 75

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: 4.19e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1796 VATPPLLSVAPGSPARFNCVAHSDTPARIRW---GFREENGPLPEHVNQDGDDIVISEAGDRNVGEYVCSATNDFGTGVA 1872
Cdd:cd05868    3 ITAPTNLVLSPGEDGTLICRANGNPKPSISWltnGVPIEIAPTDPSRKVDGDTIIFSKVQERSSAVYQCNASNEYGYLLA 82


                 .
gi 71998537 1873 D 1873
Cdd:cd05868   83 N 83

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 41.61 E-value: 4.27e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   1794 RPVATPPLLSVAPGSPARFNCVAHSDTPARIRWgfREENGPLPehvnqDGDDIVISEAGDRNVGEYVCSATNDFGTGVAD 1873
Cdd:pfam13895    1 KPVLTPSPTVVTEGEPVTLTCSAPGNPPPSYTW--YKDGSAIS-----SSPNFFTLSVSAEDSGTYTCVARNGRGGKVSN 73


                   ....*.
gi 71998537   1874 PVRLEV 1879
Cdd:pfam13895   74 PVELTV 79

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: 4.39e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   46 QITVFPSEKEVRDGRDVSFECRArtsDNSVYPTVRWARVGGPLPSSAHDSGGRLTINPV-------------QLSDAGTY 112
Cdd:cd07693    2 RIVEHPSDLIVSKGDPATLNCKA---EGRPTPTIQWLKNGQPLETDKDDPRSHRIVLPSgslfflrvvhgrkGRSDEGVY 78

                         90       100
                 ....*....|....*....|
gi 71998537  113 ICVS-DYNGNTVEARATLSV 131
Cdd:cd07693   79 VCVAhNSLGEAVSRNASLEV 98

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: 4.83e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1226 PQPVIDPPHLVVNEGEPAAFRCWVPGIPDCQITWHREQ-----LGGPLPHGVYQTGN--ALKIPQSQLHHAGRYICSAAN 1298
Cdd:cd20951    1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGvpidpSSIPGKYKIESEYGvhVLHIRRVTVEDSAVYSAVAKN 80

                         90
                 ....*....|....*
gi 71998537 1299 QYGTGQSpPAVLEVK 1313
Cdd:cd20951   81 IHGEASS-SASVVVE 94

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: 41.51 E-value: 4.86e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 2374 CKVTGDPSAVISWTKEG------NDDlpPNAQVTGGRLLFTDLKEDNAGVYRCVAKTKAGPLQTRTVLNV 2437
Cdd:cd05868   21 CRANGNPKPSISWLTNGvpieiaPTD--PSRKVDGDTIIFSKVQERSSAVYQCNASNEYGYLLANAFVNV 88

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

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 41.40 E-value: 5.04e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 71998537 1516 TVNEGEPSRIRCWVPGHPNIQLQFVKRGRRpLPAHAR---FSQGNLEI-PRTLKSDEDEYICIATDP 1578
Cdd:cd20958   11 TAVAGQTLRLHCPVAGYPISSITWEKDGRR-LPLNHRqrvFPNGTLVIeNVQRSSDEGEYTCTARNQ 76

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 41.23 E-value: 5.57e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 71998537   2366 IGDRAWFDCKVTGDPSAVISWTKEGNddlppnAQVTGGRLLFTDLKEDNAGVYRCVAKTKAGPLQTRTV 2434
Cdd:pfam13895   13 EGEPVTLTCSAPGNPPPSYTWYKDGS------AISSSPNFFTLSVSAEDSGTYTCVARNGRGGKVSNPV 75

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: 5.62e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 71998537 1233 PHLVVNEGEPAAFRCWvpgipdcqiTWHREQLggplpHGV--YQTGNALK---------IPQSQLHHAGRYICSA 1296
Cdd:cd05753    7 PSAVVFEGEPLTLRCH---------GWKDKKV-----HKVtyYKDGKALKfsyensnfsIPQATLSDSGSYHCSG 67

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: 5.70e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 2361 SESPQIGDRAWFDCKVT-GDPSAVISWTKEGN---DDLPPNAQVTGGR---LLFTDLKEDNAGVYRCVAKTKAGPLQTRT 2433
Cdd:cd20959   11 EGAAQVGMRAQLHCGVPgGDLPLNIRWTLDGQpisDDLGITVSRLGRRssiLSIDSLEASHAGNYTCHARNSAGSASYTA 90


                 ....
gi 71998537 2434 VLNV 2437
Cdd:cd20959   91 PLTV 94

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: 41.33 E-value: 5.82e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537  272 TVVDPPQTNLQVprGTTFSLTCKAVAVPEPYINWRLNWGPVCEPPRCLQTSEGGygTLTIHDAQPVDQGAYTCEAINVKG 351
Cdd:cd20952    2 ILQGPQNQTVAV--GGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLENG--SLQIKGAEKSDTGEYTCVALNLSG 77


                 ....*
gi 71998537  352 RVLAT 356
Cdd:cd20952   78 EATWS 82

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

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 41.40 E-value: 5.84e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 71998537 1597 IRPIidpAEQTVPEGSPFKIRCYVPGHPSVQLTFRRVSGQLNEDADE---NNGLL---AVQRAEltDEGDYICTARDPD 1669
Cdd:cd20958    4 IRPM---GNLTAVAGQTLRLHCPVAGYPISSITWEKDGRRLPLNHRQrvfPNGTLvieNVQRSS--DEGEYTCTARNQQ 77

Sixth immunoglobulin (Ig) domain of contactin-2; The members here are composed of the sixth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module by contacts between IG domains 1 and 4, and domains 2 and 3. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-2 is also expressed in retinal amacrine cells (AC) in the developing chick retina, corresponding to the period of formation and maturation of AC processes.

Pssm-ID: 409440 Cd Length: 102 Bit Score: 41.57 E-value: 6.00e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   46 QITVFPSEKEVRDGRDVSFECRArTSDNSVYPTVRWARVGGPLP----------SSAHDSGGRLTINPVQLSDAGTYICV 115
Cdd:cd05854    4 KITLAPSSADINQGENLTLQCHA-SHDPTMDLTFTWSLDDFPIDldkpnghyrrMEVKETIGDLVIVNAQLSHAGTYTCT 82

                         90       100
                 ....*....|....*....|.
gi 71998537  116 SDYNGNTVEARATLSVvsYGP 136
Cdd:cd05854   83 AQTVVDSASASATLVV--RGP 101

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: 41.38 E-value: 6.09e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 71998537  284 PRGTTFSLTCKAVAVPEPYINWRLNWGPVCepPRCLQTSEGGYGTLTIHDAQPVDQGAYTCEAINVKGRVLAT 356
Cdd:cd05856   17 PVGSSVRLKCVASGNPRPDITWLKDNKPLT--PPEIGENKKKKWTLSLKNLKPEDSGKYTCHVSNRAGEINAT 87

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: 6.13e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 71998537 2372 FDCKVTGDPSAVISWTKEGNDDLPPN--AQVTGGRLLFTDLKEDNAGVYRCVAKTKAGPLQT 2431
Cdd:cd05723   17 FECEVTGKPTPTVKWVKNGDVVIPSDyfKIVKEHNLQVLGLVKSDEGFYQCIAENDVGNAQA 78

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 41.09 E-value: 6.71e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 71998537   1700 PVIT--PQTQTIPEGDPARIQCTVPGNPSaaqhLSFE-RVDGKGLPFGS------SDDRGVLTIPSTQLQDAGEYVC 1767
Cdd:pfam07679    1 PKFTqkPKDVEVQEGESARFTCTVTGTPD----PEVSwFKDGQPLRSSDrfkvtyEGGTYTLTISNVQPDDSGKYTC 73

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

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 41.39 E-value: 7.31e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 71998537  286 GTTFSLTCKAVAVPEPYINWRLNWGPVCEPPRCLQ----TSEG---GYgtLTIHDAQPVDQGAYTCEAINVKGRV 353
Cdd:cd20956   16 GPSVSLKCVASGNPLPQITWTLDGFPIPESPRFRVgdyvTSDGdvvSY--VNISSVRVEDGGEYTCTATNDVGSV 88

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: 7.54e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 71998537 1699 HPVITPQTQTIPEGDPARIQCTVPGNPSAA--------QHLSFERVDGKGLPFGSSDDRGVLTIPSTQLQDAGEYVC 1767
Cdd:cd05726    1 QFVVKPRDQVVALGRTVTFQCETKGNPQPAifwqkegsQNLLFPYQPPQPSSRFSVSPTGDLTITNVQRSDVGYYIC 77

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 40.84 E-value: 7.62e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   1700 PVITPQTQTIPEGDPARIQCTVPGNPSAAQHLSfervdGKGLPFGSSDDrgvLTIPSTQLQDAGEYVCLYSPENSPPVkT 1779
Cdd:pfam13895    2 PVLTPSPTVVTEGEPVTLTCSAPGNPPPSYTWY-----KDGSAISSSPN---FFTLSVSAEDSGTYTCVARNGRGGKV-S 72


                   ....*..
gi 71998537   1780 NPSTLNV 1786
Cdd:pfam13895   73 NPVELTV 79

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: 8.11e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537  271 PTVVDPPQTnLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPVCEPPRCLQTSEGGYGTLTIHDAQPVDQGAYTCEAINVK 350
Cdd:cd20972    2 PQFIQKLRS-QEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNSV 80

                         90
                 ....*....|.
gi 71998537  351 GRVLATPDCIV 361
Cdd:cd20972   81 GSDTTSAEIFV 91

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: 8.34e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 71998537 1897 GKPGERHQFRCITTGSPTPKITWTGPNGSPLPHD----VTPLEPNILDFSNGRSELNGDYTCTASNPIGEASDHGNVNI 1971
Cdd:cd20969   14 VDEGHTVQFVCRADGDPPPAILWLSPRKHLVSAKsngrLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLHV 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: 40.47 E-value: 8.94e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 71998537 1236 VVNEGEPAAFRCWVPGIPDCQITWHReqLGGPLPHGVYQTGN---ALKIPQSQLHHAGRYICSAANQYGTGQ 1304
Cdd:cd05731    6 MVLRGGVLLLECIAEGLPTPDIRWIK--LGGELPKGRTKFENfnkTLKIENVSEADSGEYQCTASNTMGSAR 75

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: 40.62 E-value: 9.00e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 2445 VTFTVADSLPVVYTVGQPAYLSCIGKTETkPNQSVVWTKEEGDLPSGSRVEQGVLMLPSVHRDDEGSYTC 2514
Cdd:cd05754    1 IQVTVEEPRSQEVRPGADVSFICRAKSKS-PAYTLVWTRVNGTLPSRAMDFNGILTIRNVQLSDAGTYVC 69

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: 9.30e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1973 PSLTVKTnppgPKLIVTVGEPLQVKCEAFGapgDPEPEVEWLHdpgpergdlPDDfKPVTISEQFIRHPN-------VGL 2045
Cdd:cd05764    1 PLITRHT----HELRVLEGQRATLRCKARG---DPEPAIHWIS---------PEG-KLISNSSRTLVYDNgtldiliTTV 63

                         90       100
                 ....*....|....*....|....*
gi 71998537 2046 GNAGVYTCKGSSAHATATKNIYIEV 2070
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: 40.84 E-value: 9.38e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   56 VRDGRDVSFECRARTSDNsvyPTVRW-ARVGGPLPSSAHDS-----GGRLTINPVQLSDAGTYICVSDYNGNTVEARATL 129
Cdd:cd20969   14 VDEGHTVQFVCRADGDPP---PAILWlSPRKHLVSAKSNGRltvfpDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHL 90


                 ..
gi 71998537  130 SV 131
Cdd:cd20969   91 HV 92

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

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 40.56 E-value: 9.58e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1602 DPAEQTVPEGSPFKIRCYVPGHPSVQLTFRR----VSGQLNEDADENNGLLAVQRAELTDEGDYICTARDPdtgapidST 1677
Cdd:cd20952    5 GPQNQTVAVGGTVVLNCQATGEPVPTISWLKdgvpLLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNL-------SG 77


                 ....*..
gi 71998537 1678 PATVHVT 1684
Cdd:cd20952   78 EATWSAV 84

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: 41.00 E-value: 9.65e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1226 PQPVIDPPHLVVNEGEPAAFRCWVPGIPDCQITWHREqlGGPLP---------HGVYQTGNA--LKIPQSQL--HHAGRY 1292
Cdd:cd07693    1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKN--GQPLEtdkddprshRIVLPSGSLffLRVVHGRKgrSDEGVY 78

                         90       100
                 ....*....|....*....|
gi 71998537 1293 ICSAANQYGTGQSPPAVLEV 1312
Cdd:cd07693   79 VCVAHNSLGEAVSRNASLEV 98

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: 41.09 E-value: 9.72e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 71998537  283 VPRGTTFSLTCKAVAVPEPYINWRLNWGPVCEPPRCLQTSEGGY-----GTLTIHDAQPVDQGAYTCEAINVKGRVLA 355
Cdd:cd05726   11 VALGRTVTFQCETKGNPQPAIFWQKEGSQNLLFPYQPPQPSSRFsvsptGDLTITNVQRSDVGYYICQALNVAGSILA 88

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

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 40.84 E-value: 9.76e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1418 IDPP--NQTVNVNDPAQFRCWVPGQPRAQLKWSRkDGRPL----PNGILErDGFLRIDKSQLHDAGEYECTSTEPDGSTQ 1491
Cdd:cd20978    4 IQKPekNVVVKGGQDVTLPCQVTGVPQPKITWLH-NGKPLqgpmERATVE-DGTLTIINVQPEDTGYYGCVATNEIGDIY 81


                 ...
gi 71998537 1492 LSP 1494
Cdd:cd20978   82 TET 84

Calcium-binding EGF-like domain;

Pssm-ID: 214542 [Multi-domain] Cd Length: 39 Bit Score: 39.15 E-value: 1.00e-03

                            10        20        30
                    ....*....|....*....|....*....|....*....
gi 71998537    2711 DACASTNLCLNGANCRNANNhhGFSCECAEEFH-GEYCQ 2748
Cdd:smart00179    3 DECASGNPCQNGGTCVNTVG--SYRCECPPGYTdGRNCE 39

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: 1.03e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 71998537 2463 AYLSCigKTETKPNQSVVWTKEEGDLPSGSRVE------QGVLMLPSVHRDDEGSYTCEIvkeENPVFSTV 2527
Cdd:cd00096    1 VTLTC--SASGNPPPTITWYKNGKPLPPSSRDSrrselgNGTLTISNVTLEDSGTYTCVA---SNSAGGSA 66

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: 1.04e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 71998537 2367 GDRAWFDCKVTGDPSAVISWTKEGNdDLPPN-AQVTGGR-LLFTDLKEDNAGVYRCVAKTKAGPLQTRTVLNV 2437
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: 1.06e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 71998537 2455 VVYTVGQPAYLSCigKTETKPNQSVVWTKEEGDLPSGsRVEQ---GVLMLPSVHRDDEGSYTCE 2515
Cdd:cd05725    7 QVVLVDDSAEFQC--EVGGDPVPTVRWRKEDGELPKG-RYEIlddHSLKIRKVTAGDMGSYTCV 67

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: 40.63 E-value: 1.17e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 71998537 1132 VRIMEPKRQIAlpGDRVHWICQVTGYTTEKIHveWTKVGEmSLPPN--AKAY-DGYLVLKGVE-AENAGQYRCTAT 1203
Cdd:cd20958    4 IRPMGNLTAVA--GQTLRLHCPVAGYPISSIT--WEKDGR-RLPLNhrQRVFpNGTLVIENVQrSSDEGEYTCTAR 74

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: 40.55 E-value: 1.22e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1885 PPTAVVEPRTWNGKPGERHQFRCITTGSPTPKITWTGPNGSPLP--HDVTPLEPNILDFSNGR-------SELNGDYTCT 1955
Cdd:cd05734    1 PPRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWKHSKGSGVPqfQHIVPLNGRIQLLSNGSllikhvlEEDSGYYLCK 80


                 ....*.
gi 71998537 1956 ASNPIG 1961
Cdd:cd05734   81 VSNDVG 86

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: 1.28e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 2353 IQVLLEVSSESPQIGDRAWFDCKVTGDPSAvISWTKEGNDDLPPNAQ----VTGG----RLLFTDLKEDNAGVYRCVAKT 2424
Cdd:cd04977    1 LQVKIIPSYAEISVGESKFFLCKVSGDAKN-INWVSPNGEKVLTKHGnlkvVNHGsvlsSLTIYNANINDAGIYKCVATN 79

                         90
                 ....*....|
gi 71998537 2425 KAGPLQTRTV 2434
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: 1.36e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 71998537 1239 EGEPAAFRCWVPGIPDCQITWHREqlGGPLP----HGVYQTGnALKIPQSQLHHAGRYICSAANQYGT 1302
Cdd:cd05745    1 EGQTVDFLCEAQGYPQPVIAWTKG--GSQLSvdrrHLVLSSG-TLRISRVALHDQGQYECQAVNIVGS 65

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: 1.37e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537  277 PQTNLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPvcepprcLQTSEGGYG----TLTIHDAQPVDQGAYTCEAINVKGR 352
Cdd:cd05876    1 SSSSLVALRGQSLVLECIAEGLPTPTVKWLRPSGP-------LPPDRVKYQnhnkTLQLLNVGESDDGEYVCLAENSLGS 73


                 .
gi 71998537  353 V 353
Cdd:cd05876   74 A 74

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: 40.14 E-value: 1.37e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 71998537  281 LQVPRGTTFSLTCKAVAVPEPY-INWRLNWGPVCEPPrclqtsEGGYGTLTIHDAQpvDQGAYTCEAINVKG 351
Cdd:cd05749    9 LAVTANTPFNLTCQAVGPPEPVeILWWQGGSPLGGPP------APSPSVLNVPGLN--ETTKFSCEAHNAKG 72

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: 1.38e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   48 TVFPSEKEVRDGRDVSFECRARTSDNsvyPTVRWARVGGPLPSSAHDsGGR-------LTINPVQLSDAGTYICVSdYNG 120
Cdd:cd20949    3 TENAYVTTVKEGQSATILCEVKGEPQ---PNVTWHFNGQPISASVAD-MSKyriladgLLINKVTQDDTGEYTCRA-YQV 77


                 ...
gi 71998537  121 NTV 123
Cdd:cd20949   78 NSI 80

First immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-2; 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-2 (OCAM/mamFas II, RNCAM). NCAM-2 is organized similarly to NCAM-1, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. 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: 409452 Cd Length: 93 Bit Score: 40.42 E-value: 1.44e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 2353 IQVLLEVSSESPQIGDRAWFDCKVTGDPSAvISWTKEGNDDLPPNAQVT------GGRLLFTDLKEDNAGVYRCVAKTKA 2426
Cdd:cd05866    1 LQVSISLSKVELSVGESKFFTCTAIGEPES-IDWYNPQGEKIVSSQRVVvqkegvRSRLTIYNANIEDAGIYRCQATDAK 79


                 ....*....
gi 71998537 2427 GPLQTRTVL 2435
Cdd:cd05866   80 GQTQEATVV 88

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: 1.44e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   52 SEKEVRDGRDVSFECRArtsDNSVYPTVRWARVGGPLPS---SAHDSGGRLTINPVQLSDAGTYICVSDyngNTV-EARA 127
Cdd:cd05731    3 SSTMVLRGGVLLLECIA---EGLPTPDIRWIKLGGELPKgrtKFENFNKTLKIENVSEADSGEYQCTAS---NTMgSARH 76


                 ....*
gi 71998537  128 TLSVV 132
Cdd:cd05731   77 TISVT 81

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: 40.07 E-value: 1.52e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1979 TNPPGPKLIVTVGEPLQVKCEAfgaPGDPEPEVEWLHDPGPERGDLPDdfkpVTISEQFIRHPNVGLGNAGVYTCKGSSA 2058
Cdd:cd20978    4 IQKPEKNVVVKGGQDVTLPCQV---TGVPQPKITWLHNGKPLQGPMER----ATVEDGTLTIINVQPEDTGYYGCVATNE 76

                         90
                 ....*....|..
gi 71998537 2059 HATATKNIYIEV 2070
Cdd:cd20978   77 IGDIYTETLLHV 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: 40.61 E-value: 1.54e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1793 PRPVATPPLLSVAPGSPARFNCVAHSDTPARIRWgFReeNGplpEHVNQDGDD-----------------IVISEAGDRN 1855
Cdd:cd07693    1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQW-LK--NG---QPLETDKDDprshrivlpsgslfflrVVHGRKGRSD 74

                         90       100
                 ....*....|....*....|....
gi 71998537 1856 VGEYVCSATNDFGTGVADPVRLEV 1879
Cdd:cd07693   75 EGVYVCVAHNSLGEAVSRNASLEV 98

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: 1.59e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1906 RCITTGSPTPKITWTgPNGSPLPHDVTPLEPNI----LDFSNGRSELNGDYTCTASNPIGEASDHGNVNI 1971
Cdd:cd20976   22 QCSARGKPVPRITWI-RNAQPLQYAADRSTCEAgvgeLHIQDVLPEDHGTYTCLAKNAAGQVSCSAWVTV 90

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

Pssm-ID: 143223 Cd Length: 69 Bit Score: 39.47 E-value: 1.82e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 71998537 2374 CKVTGDPSAVISWTKEGnddlppnAQVT---------GGRLLFTDLKEDNAGVYRCVAKTKAGPLQTRTVL 2435
Cdd:cd05746    5 CSAQGDPEPTITWNKDG-------VQVTesgkfhispEGYLAIRDVGVADQGRYECVARNTIGYASVSMVL 68

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: 1.91e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 71998537 1614 FKIRCYVPGHPSVQLTFRRVSGQLNEDA------DENNGLLAVQRAELTDEGDYICTARDPDTG 1671
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPSSrdsrrsELGNGTLTISNVTLEDSGTYTCVASNSAGG 64

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: 39.91 E-value: 2.16e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 71998537   62 VSFECRARTSDNSVYptvRWaRVGGPLPSSAHDS-----GGRLTI-NPVQLSDAGTYICVSDYNGNTVEAR 126
Cdd:cd05850   23 VTLACRARASPPATY---RW-KMNGTELKMEPDSryrlvAGNLVIsNPVKAKDAGSYQCLASNRRGTVVSR 89

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: 2.30e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 71998537   59 GRDVSFECRARTSDNsvyPTVRWARVGGPLPSSAHDS---GGRLTINPVQLSDAGTYICVSDYNGNTVEARATLSV 131
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: 2.32e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 71998537   1230 IDPPHLVVNEGEPAAFRCWV-PGIPDCQITWHREQLGGPLPHGV-----YQTGNALKIPQSQLHHAGRYICSAAN 1298
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSAsTGSPGPDVTWSKEGGTLIESLKVkhdngRTTQSSLLISNVTKEDAGTYTCVVNN 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: 39.71 E-value: 2.37e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 71998537  277 PQTnlqVPRGTTFSLTCKAVAVPEPYINWRLNWGPV---CEPPRCLQTSEGGYGTLTIHDAQPVDQGAYTCEAINVKG 351
Cdd:cd20951    9 SHT---VWEKSDAKLRVEVQGKPDPEVKWYKNGVPIdpsSIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKNIHG 83

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

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 39.53 E-value: 2.41e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1232 PPHLVVNEGEPAAFRCWVPGIPDCQITWHREQ--LGGPLPHGVYQTGNaLKIPQSQLHHAGRYICSAANQYGTGQSPPAV 1309
Cdd:cd20968    6 PTNVTIIEGLKAVLPCTTMGNPKPSVSWIKGDdlIKENNRIAVLESGS-LRIHNVQKEDAGQYRCVAKNSLGIAYSKPVT 84


                 ....
gi 71998537 1310 LEVK 1313
Cdd:cd20968   85 IEVE 88

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 39.55 E-value: 2.46e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   1503 PQAIQPqvdPPVQTVNEGEPSRIRCWVPGHPNIQLQFVKRGrRPLPAHARFSQGN------LEIPRTLKSDEDEYICIAT 1576
Cdd:pfam07679    1 PKFTQK---PKDVEVQEGESARFTCTVTGTPDPEVSWFKDG-QPLRSSDRFKVTYeggtytLTISNVQPDDSGKYTCVAT 76


                   ..
gi 71998537   1577 DP 1578
Cdd:pfam07679   77 NS 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: 39.49 E-value: 2.49e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 71998537   1510 VDPPVQTVNEGEPSRIRCWV-PGHPNIQLQFVK------RGRRPLPAHARFSQGNLEIPRTLKSDEDEYICIATDP 1578
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSAsTGSPGPDVTWSKeggtliESLKVKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNP 76

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: 2.55e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 71998537  286 GTTFSLTCKAVAVPEPYINWRLNWGPVCEPPRCLQTSEGgygTLTIHDAQPVDQGAYTCEAINVKGRV 353
Cdd:cd05745    2 GQTVDFLCEAQGYPQPVIAWTKGGSQLSVDRRHLVLSSG---TLRISRVALHDQGQYECQAVNIVGSQ 66

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

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 39.90 E-value: 2.62e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 71998537 1904 QFRCITTGSPTPKITWTGPNGSPLPHDVTPLEPN-----ILDFSNGRSELNGDYTCTASNPIGE 1962
Cdd:cd05729   23 RLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVeekgwSLIIERAIPRDKGKYTCIVENEYGS 86

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: 39.31 E-value: 2.94e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1230 IDPPHLVVNEGEPAAFRCWVP-GIPDCQITWHREqlGGPL----PHGVYQTGNALKIPQSQLHHAGRYICSAANQYGTGQ 1304
Cdd:cd05724    2 VEPSDTQVAVGEMAVLECSPPrGHPEPTVSWRKD--GQPLnldnERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGERE 79


                 ....*...
gi 71998537 1305 SPPAVLEV 1312
Cdd:cd05724   80 SRAARLSV 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: 39.31 E-value: 2.95e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 71998537  280 NLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPV-CEPPRCLQTSEGGYGTLTIHDAQPVDQGAYTCEAINVKGR 352
Cdd:cd20990    9 DLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIrPDSAHKMLVRENGVHSLIIEPVTSRDAGIYTCIATNRAGQ 82

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: 2.99e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   47 ITVFPSEKEVRDGRDVSFECRArTSDNSVYPTVRWARVGGPL----------PSSAHDSGGRLTINPVQLSDAGTYICVS 116
Cdd:cd04970    5 ITLAPSNADITVGENATLQCHA-SHDPTLDLTFTWSFNGVPIdlekieghyrRRYGKDSNGDLEIVNAQLKHAGRYTCTA 83

                         90
                 ....*....|....*
gi 71998537  117 DYNGNTVEARATLSV 131
Cdd:cd04970   84 QTVVDSDSASATLVV 98

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

Pssm-ID: 409442 Cd Length: 92 Bit Score: 39.46 E-value: 3.17e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 71998537 1904 QFRCITTGSPTPKITWTgPNGSPLphdvTPLEPN-------ILDFSNGRSELNGDYTCTASNPIGE 1962
Cdd:cd05856   23 RLKCVASGNPRPDITWL-KDNKPL----TPPEIGenkkkkwTLSLKNLKPEDSGKYTCHVSNRAGE 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: 39.55 E-value: 3.20e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 71998537 1240 GEPAAFRCWVPGIPDCQITWHR--EQLGGPLPHGVYQTGNALKIPQSQLHHA--GRYICSAANQYG 1301
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: 3.26e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537  277 PQTNLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPVcePPRclQTSEGGYG-TLTIHDAQPVDQGAYTCEAINVKGRVLA 355
Cdd:cd05731    1 SESSTMVLRGGVLLLECIAEGLPTPDIRWIKLGGEL--PKG--RTKFENFNkTLKIENVSEADSGEYQCTASNTMGSARH 76


                 ....*..
gi 71998537  356 TPDCIVR 362
Cdd:cd05731   77 TISVTVE 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: 39.46 E-value: 3.26e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537  271 PTVVDPPqTNLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPV------CEPPRCLQTSEGGYGTLTIHDAQP-VDQGAYT 343
Cdd:cd07693    1 PRIVEHP-SDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLetdkddPRSHRIVLPSGSLFFLRVVHGRKGrSDEGVYV 79


                 ....*...
gi 71998537  344 CEAINVKG 351
Cdd:cd07693   80 CVAHNSLG 87

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: 39.22 E-value: 3.52e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1225 PPQPVIDPPHLVVNEGEPAAFRCWVPGIPDCQITWHREQlgGPLP---------HGVYQTGN-ALKIPQSQLHHAGRYIC 1294
Cdd:cd20954    1 PPRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKAT--GSTPgeykdllydPNVRILPNgTLVFGHVQKENEGHYLC 78

                         90
                 ....*....|.
gi 71998537 1295 SAANQYGTGQS 1305
Cdd:cd20954   79 EAKNGIGSGLS 89

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: 3.77e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   47 ITVFPSEKEVRDGRDVSFECRARTSDNSVYptVRW------------ARVGGPLPSSAHDSGGR------------LTIN 102
Cdd:cd00099    1 VTQSPRSLSVQEGESVTLSCEVSSSFSSTY--IYWyrqkpgqgpeflIYLSSSKGKTKGGVPGRfsgsrdgtssfsLTIS 78

                         90       100
                 ....*....|....*....|..
gi 71998537  103 PVQLSDAGTYICVSDYNGNTVE 124
Cdd:cd00099   79 NLQPEDSGTYYCAVSESGGTDK 100

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

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 38.98 E-value: 3.86e-03

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 71998537 2470 KTETKPNQSVVWTKEEGDLPSGSRV---EQGVLMLPSVHRDDEGSYTC 2514
Cdd:cd04969   25 KPKASPKPTISWSKGTELLTNSSRIcilPDGSLKIKNVTKSDEGKYTC 72

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: 4.02e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1879 VTEDQEPPTAVVEPrtwngkpGERHQFRCITTGSPTPKITWTgPNGSPLPHDVTPLEPN----ILDFSNGRSELNGDYTC 1954
Cdd:cd20970    3 ISTPQPSFTVTARE-------GENATFMCRAEGSPEPEISWT-RNGNLIIEFNTRYIVRengtTLTIRNIRRSDMGIYLC 74

                         90
                 ....*....|..
gi 71998537 1955 TASNPIGEASDH 1966
Cdd:cd20970   75 IASNGVPGSVEK 86

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: 4.04e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537  271 PTVVDPPQTNLQVPrGTTFSLTCKAVAVPEPYINWRLNwGPVCEPPRCLQTSEGGYGT-LTIHDAQPVDQGAYTCEAINV 349
Cdd:cd05736    1 PVIRVYPEFQAKEP-GVEASLRCHAEGIPLPRVQWLKN-GMDINPKLSKQLTLIANGSeLHISNVRYEDTGAYTCIAKNE 78


                 ..
gi 71998537  350 KG 351
Cdd:cd05736   79 GG 80

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: 4.06e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 71998537  273 VVDPPQTNlQVPRGTTFSLTCKAVA-VPEPYINWRLNWGPVcePPRCLQTSeggyGTLTIHDAQPVDQGAYTCEAIN 348
Cdd:cd05754    4 TVEEPRSQ-EVRPGADVSFICRAKSkSPAYTLVWTRVNGTL--PSRAMDFN----GILTIRNVQLSDAGTYVCTGSN 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: 38.53 E-value: 4.29e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1899 PGERHQFRCITTGSPTPKITWTGPNGSpLPHD-VTPLEPNILDFSNGRSELNGDYTCTASNPIGEASDHGnvnigpSLTV 1977
Cdd:cd05725   11 VDDSAEFQCEVGGDPVPTVRWRKEDGE-LPKGrYEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIEASA------TLTV 83

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: 39.01 E-value: 4.30e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 71998537 1900 GERHQFRCITTGSPTP-KITWTgPNGSPLPHD----VTPLEP--NILDFSNGRSELNGDYTCTASNPIGEAS 1964
Cdd:cd20959   17 GMRAQLHCGVPGGDLPlNIRWT-LDGQPISDDlgitVSRLGRrsSILSIDSLEASHAGNYTCHARNSAGSAS 87

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

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 38.54 E-value: 4.50e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 71998537 1140 QIALPGDRVHWICQVTGYTTEkiHVEWTKVGEmSLPPNAKAYDGY---LVLKGVEAENAGQYRCTA 1202
Cdd:cd05731    5 TMVLRGGVLLLECIAEGLPTP--DIRWIKLGG-ELPKGRTKFENFnktLKIENVSEADSGEYQCTA 67

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: 38.46 E-value: 4.54e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 71998537 1715 ARIQCTVPGNPSAaqHLSFERvDGKGLPFGSSDDR------GVLTIPSTQLQDAGEYVC 1767
Cdd:cd00096    1 VTLTCSASGNPPP--TITWYK-NGKPLPPSSRDSRrselgnGTLTISNVTLEDSGTYTC 56

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 38.70 E-value: 4.56e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   2173 PKVEIEPPRVrVVSQGDNIVLKCSVQGaENGEHFKWalLRGGSLV--------RQLGTEPTLEITKADPSnDFGVYRCNV 2244
Cdd:pfam13927    2 PVITVSPSSV-TVREGETVTLTCEATG-SPPPTITW--YKNGEPIssgstrsrSLSGSNSTLTISNVTRS-DAGTYTCVA 76


                   .
gi 71998537   2245 E 2245
Cdd:pfam13927   77 S 77

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: 38.61 E-value: 4.63e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537  279 TNLQVPRGTTFSLTCKAVAVPEPYINWRLNWGPVCepPRCLQTSEGGYGTLTIHDAQPVDQGAYTCEAINVKGRVLATPD 358
Cdd:cd05764    8 HELRVLEGQRATLRCKARGDPEPAIHWISPEGKLI--SNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEATARVE 85


                 ...
gi 71998537  359 CIV 361
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: 4.65e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 71998537 1607 TVPEGSPFKIRCYVPGHPSVQLTFRRVSGQLNEDAD-----ENNGLLAVQRAELTDEGDYICTA 1665
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: 4.76e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 71998537 2353 IQVLLEVSSESPQIGDRAWFDCKVTGDPSAVISWTKEGNdDLPPNAQV---TGGRLLFTDLKEDNAGVYRCVA 2422
Cdd:cd20957    2 LSATIDPPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGK-PLGHSSRVqilSEDVLVIPSVKREDKGMYQCFV 73

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 38.78 E-value: 4.97e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 71998537   1323 PIRQTVDRDQPARFKCWVPGNSNVQLRWSRpGGAPLPSG----VQEQQGI--LHIPRASDQEVGQYVCTATDPS 1390
Cdd:pfam07679    7 PKDVEVQEGESARFTCTVTGTPDPEVSWFK-DGQPLRSSdrfkVTYEGGTytLTISNVQPDDSGKYTCVATNSA 79

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 38.78 E-value: 5.54e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   1986 LIVTVGEPLQVKCEAFGapgDPEPEVEWLHDPGPERGDlpDDFKpVTISEQ--FIRHPNVGLGNAGVYTCKGSSAHATAT 2063
Cdd:pfam07679   10 VEVQEGESARFTCTVTG---TPDPEVSWFKDGQPLRSS--DRFK-VTYEGGtyTLTISNVQPDDSGKYTCVATNSAGEAE 83


                   ....*..
gi 71998537   2064 KNIYIEV 2070
Cdd:pfam07679   84 ASAELTV 90

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

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 38.64 E-value: 5.54e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 71998537 2367 GDRAWFDCKVTGDPSAVISWTKEGNDDLPPNAQ---VTGGRLL-FTDLKEDNAGVYRCVAKTKAGP 2428
Cdd:cd20970   17 GENATFMCRAEGSPEPEISWTRNGNLIIEFNTRyivRENGTTLtIRNIRRSDMGIYLCIASNGVPG 82

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: 38.68 E-value: 5.57e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 71998537 1240 GEPAAFRCWVPGIPDCQITWhREQLGGPLPHGVYQTGNA-LKIPQSQLHHAGRYICSAANQYG 1301
Cdd:cd04968   16 GQTVTLECFALGNPVPQIKW-RKVDGSPSSQWEITTSEPvLEIPNVQFEDEGTYECEAENSRG 77

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: 5.72e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1885 PPTAVVEPRTWNGKPGERHQFRCITTGSPTPKITWTGpNGSPLPHdvtplEPNILDFSNGR----------SELNGDYTC 1954
Cdd:cd20972    1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFC-EGKELQN-----SPDIQIHQEGDlhsliiaeafEEDTGRYSC 74

                         90
                 ....*....|
gi 71998537 1955 TASNPIGEAS 1964
Cdd:cd20972   75 LATNSVGSDT 84

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: 5.98e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 71998537 1245 FRCWVPGIPDCQITWHREqlGGPLPHGVY-----QTGNA-LKIPQSQLHHAGRYICSAANQYGTGQS 1305
Cdd:cd00096    3 LTCSASGNPPPTITWYKN--GKPLPPSSRdsrrsELGNGtLTISNVTLEDSGTYTCVASNSAGGSAS 67

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: 6.13e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   77 PTVRWARVGGPLPSSAHD----SGGRLTINPVQLSDAGTYICV-SDYNGNTVEARATLSV 131
Cdd:cd05724   28 PTVSWRKDGQPLNLDNERvrivDDGNLLIAEARKSDEGTYKCVaTNMVGERESRAARLSV 87

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

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 38.30 E-value: 6.14e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 71998537 1603 PAEQTVPEGSPFKIRCYVPGHPSVQLTFRRVSGQLNEDAD--ENNGLLAVQRAELTDEGDYICTA 1665
Cdd:cd04968    8 PADTYALKGQTVTLECFALGNPVPQIKWRKVDGSPSSQWEitTSEPVLEIPNVQFEDEGTYECEA 72

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: 6.43e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1421 PNQTVNVNDPAQFRCWVPGQPRAQLKWSRkDGRPLPNGILERDG-----------FLRIDKSQLHDAGEYECTSTEPDGS 1489
Cdd:cd20956    9 SEQTLQPGPSVSLKCVASGNPLPQITWTL-DGFPIPESPRFRVGdyvtsdgdvvsYVNISSVRVEDGGEYTCTATNDVGS 87

                         90
                 ....*....|.
gi 71998537 1490 TQLSppARLNV 1500
Cdd:cd20956   88 VSHS--ARINV 96

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: 38.15 E-value: 6.44e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 71998537  280 NLQVPRGTTFSLTCKA-VAVPEPYINWRLNWGPVCEPPRCLQTSEGGygTLTIHDAQPVDQGAYTCEAINVKG 351
Cdd:cd05724    6 DTQVAVGEMAVLECSPpRGHPEPTVSWRKDGQPLNLDNERVRIVDDG--NLLIAEARKSDEGTYKCVATNMVG 76

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: 38.31 E-value: 6.50e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 71998537 2271 IVKFDD-----KSDASFTCPIYSVPG-SKVDWTYENGDLPSKAVPNGNKIEIKEFDDASAGTYVCKVS 2332
Cdd:cd20930    5 ISGYDDnwylgRNEATLTCDVRSNPEpTGYDWSTTSGPFPTSAVAQGPQLLIHSVDRLVNTTFICTVT 72

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: 6.63e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 71998537 1796 VATPPLLSVAPGSPARFNCVAHSDTPA-RIRWGfrEENGPLPEHVNQDGDDIVISEAGDRNVGEYVCSATNDFGT 1869
Cdd:cd05754    5 VEEPRSQEVRPGADVSFICRAKSKSPAyTLVWT--RVNGTLPSRAMDFNGILTIRNVQLSDAGTYVCTGSNMLDT 77

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: 38.26 E-value: 6.80e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1795 PVATPPLLS----VAPGSPARFNCVAHSDTPARIRWgFReeNGPLPEHVNQ------DGDDIVISEAGDRNVGEYVCSAT 1864
Cdd:cd20970    1 PVISTPQPSftvtAREGENATFMCRAEGSPEPEISW-TR--NGNLIIEFNTryivreNGTTLTIRNIRRSDMGIYLCIAS 77

                         90
                 ....*....|....*
gi 71998537 1865 NDFGTGVADPVRLEV 1879
Cdd:cd20970   78 NGVPGSVEKRITLQV 92

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: 38.34 E-value: 7.16e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 2358 EVSSESPQIGDRAWFDCKVTgDPSAVISWTKEGNdDLPPN--AQVTGGRLLFTDLKEDNAGVYRCVAktkAGPLQTRTVL 2435
Cdd:cd04973   15 EVESYSAHPGDLLQLRCRLR-DDVQSINWTKDGV-QLGENnrTRITGEEVQIKDAVPRDSGLYACVT---SSPSGSDTTY 89

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

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 38.15 E-value: 7.20e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 71998537 1796 VATPPLLSVAPGSPARFNCVAHSDTPARIRWgfREENGPLPEHVNQDGDD--IVISEAGDRNVGEYVCSATNDFGTGVA 1872
Cdd:cd05725    1 VKRPQNQVVLVDDSAEFQCEVGGDPVPTVRW--RKEDGELPKGRYEILDDhsLKIRKVTAGDMGSYTCVAENMVGKIEA 77

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 38.39 E-value: 7.50e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   1791 TPPRPVAtppllsVAPGSPARFNCVAHSDTPARIRWGFREEngPLPE----HVNQDGDD--IVISEAGDRNVGEYVCSAT 1864
Cdd:pfam07679    5 QKPKDVE------VQEGESARFTCTVTGTPDPEVSWFKDGQ--PLRSsdrfKVTYEGGTytLTISNVQPDDSGKYTCVAT 76


                   ....*
gi 71998537   1865 NDFGT 1869
Cdd:pfam07679   77 NSAGE 81

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

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 38.30 E-value: 7.76e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 71998537 2367 GDRAWFDCKVTGDPSAVISWTKEGN----DDLPPNAQVT---GGRLLFTDL-----KEDNAGVYRCVAKTKAGPLQTR 2432
Cdd:cd07693   15 GDPATLNCKAEGRPTPTIQWLKNGQpletDKDDPRSHRIvlpSGSLFFLRVvhgrkGRSDEGVYVCVAHNSLGEAVSR 92

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

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 38.14 E-value: 7.92e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1229 VIDPP--HLVVNEGEPAAFRCWVPGIPDCQITW-HReqlGGPL--PHGVYQ-TGNALKIPQSQLHHAGRYICSAANQYGT 1302
Cdd:cd20978    3 FIQKPekNVVVKGGQDVTLPCQVTGVPQPKITWlHN---GKPLqgPMERATvEDGTLTIINVQPEDTGYYGCVATNEIGD 79


                 ....*..
gi 71998537 1303 GQSPPAV 1309
Cdd:cd20978   80 IYTETLL 86

Immunoglobulin (Ig)-like domain of class III semaphorin Sema3; The members here are composed of the immunoglobulin (Ig)-like domain of Sema3 and similar proteins. Semaphorins are classified based on structural features additional to the Sema domain. Sema3 is a Class III semaphorin that is secreted. It is a vertebrate class having a Sema domain, an Ig domain, a short basic domain. They have been shown to be axonal guidance cues and have a part in the regulation of the cardiovascular, immune, and respiratory systems. Sema3A, the prototype member of this class III subfamily, induces growth cone collapse and is an inhibitor of axonal sprouting. In perinatal rat cortex, it acts as a chemoattractant and functions to direct the orientated extension of apical dendrites. It may play a role, prior to the development of apical dendrites, in signaling the radial migration of newborn cortical neurons towards the upper layers. Sema3A selectively inhibits vascular endothelial growth factor receptor (VEGF)-induced angiogenesis and induces microvascular permeability. This group also includes Sema3B, -C, -D, -E, -G.

Pssm-ID: 409455 Cd Length: 92 Bit Score: 38.10 E-value: 8.15e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 2455 VVYTV-GQPAYLSCIGKTetkPNQSVVWTKE------EGDLPSGSRV---EQGvLMLPSVHRDDEGSYTC 2514
Cdd:cd05871    6 VVYGVeGNSTFLECLPKS---PQATVKWLFQrggdqrKEEVKSEERLivtDRG-LLLRSLQRSDAGVYTC 71

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: 38.38 E-value: 8.21e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1597 IRPIIDPAEQTVPEGSPFKIRCYVP-GHPSVQLTFRRVSGQLNEDAD---------ENNGLL---AVQRAELTDEGDYIC 1663
Cdd:cd20965    3 LDPQVKTKEKKPVEGKPFKLDCNVPpGYPKPTIEWKKQLVSDSSKADtildrritiSPNGDLyftNVTKEDVSTDYKYVC 82


                 ....*
gi 71998537 1664 TARDP 1668
Cdd:cd20965   83 VAKTP 87

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: 37.76 E-value: 8.42e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 71998537 1703 TPQTQTIPEGDPARIQCTVPGNPsaAQHLSFERVDGKgLPFGSS---DDRGvLTIPSTQLQDAGEYVCL 1768
Cdd:cd05725    3 RPQNQVVLVDDSAEFQCEVGGDP--VPTVRWRKEDGE-LPKGRYeilDDHS-LKIRKVTAGDMGSYTCV 67

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: 36.95 E-value: 8.53e-03

                         10        20
                 ....*....|....*....|
gi 71998537  921 QCICPPGYVGTSCEDCAPGY 940
Cdd:cd00055   20 QCECKPNTTGRRCDRCAPGY 39

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

Pssm-ID: 395007 Cd Length: 49 Bit Score: 36.95 E-value: 8.57e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 71998537   1061 CPCPGASD----CYLDNeGQvaCRiCPAGLQGRLCNECAPGYTRSNKPAGRVC 1109
Cdd:pfam00053    1 CDCNPHGSlsdtCDPET-GQ--CL-CKPGVTGRHCDRCKPGYYGLPSDPPQGC 49

Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in Perlecan. Perlecan is a large multi-domain heparin sulfate proteoglycan, important in tissue development and organogenesis. Perlecan can be represented as 5 major portions; its fourth major portion (domain IV) is a tandem repeat of immunoglobulin-like domains (Ig2-Ig15) which can vary in size due to alternative splicing. Perlecan binds many cellular and extracellular ligands. Its domain IV region has many binding sites. Some of these have been mapped at the level of individual Ig-like domains, including a site restricted to the Ig5 domain for heparin/sulfatide, a site restricted to the Ig3 domain for nidogen-1 and nidogen-2, a site restricted to Ig4-5 for fibronectin, and sites restricted to Ig2 and to Ig13-15 for fibulin-2. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409412 Cd Length: 85 Bit Score: 37.92 E-value: 8.72e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 71998537 1889 VVEPRTWNGKPGERHQFRCIT-TGSPTPKITWTGPNGsPLP---HDVTplepNILDFSNGRSELNGDYTCTASN 1958
Cdd:cd05754    5 VEEPRSQEVRPGADVSFICRAkSKSPAYTLVWTRVNG-TLPsraMDFN----GILTIRNVQLSDAGTYVCTGSN 73

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: 38.30 E-value: 8.79e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1226 PQPVIDPPHLVVNEGEPAAFRCWVPGIPDCQITWHREQLGGP----LPHGVYqtGNA-------LKIPQSQLHHAGRYIC 1294
Cdd:cd05765    1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEKQVPGKEnlimRPNHVR--GNVvvtnigqLVIYNAQPQDAGLYTC 78


                 ....*..
gi 71998537 1295 SAANQYG 1301
Cdd:cd05765   79 TARNSGG 85

Laminin-type epidermal growth factor-like domai;

Pssm-ID: 214543 Cd Length: 46 Bit Score: 36.52 E-value: 8.85e-03

                            10        20
                    ....*....|....*....|
gi 71998537     921 QCICPPGYVGTSCEDCAPGY 940
Cdd:smart00180   19 QCECKPNVTGRRCDRCAPGY 38

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 37.76 E-value: 8.93e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537    272 TVVDPPQTNlqVPRGTTFSLTCKAVAVPEPYINWRLNWGPVcepprclqtseGGYGTLTIHDAQPVDQGAYTCEAINVKG 351
Cdd:pfam13895    2 PVLTPSPTV--VTEGEPVTLTCSAPGNPPPSYTWYKDGSAI-----------SSSPNFFTLSVSAEDSGTYTCVARNGRG 68

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 38.01 E-value: 9.20e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537   2173 PKVEIEPPRVrVVSQGDNIVLKCSVQGAENGEhFKWalLRGGSLVRQ--------LGTEPTLEITKADPSnDFGVYRCNV 2244
Cdd:pfam07679    1 PKFTQKPKDV-EVQEGESARFTCTVTGTPDPE-VSW--FKDGQPLRSsdrfkvtyEGGTYTLTISNVQPD-DSGKYTCVA 75

                           90
                   ....*....|....*..
gi 71998537   2245 EdnNGLviGSAFTAVSV 2261
Cdd:pfam07679   76 T--NSA--GEAEASAEL 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: 37.87 E-value: 9.39e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 71998537 1416 PQIDPP----NQTVNVNDPAQFRCWVPGQPRAQLKWSRKDGRPL---PNGILERDG-FLRIDKSQLHDAGEYECTST 1484
Cdd:cd20970    1 PVISTPqpsfTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIefnTRYIVRENGtTLTIRNIRRSDMGIYLCIAS 77

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

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 37.93 E-value: 9.75e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998537 1900 GERHQFRCITTGSPTPKITWTgPNGSPLP----HDVtplepnildFSNG--------RSELNGDYTCTASNPIGEaSDHG 1967
Cdd:cd20958   15 GQTLRLHCPVAGYPISSITWE-KDGRRLPlnhrQRV---------FPNGtlvienvqRSSDEGEYTCTARNQQGQ-SASR 83


                 ....
gi 71998537 1968 NVNI 1971
Cdd:cd20958   84 SVFV 87