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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1866093293 183 PKIVQGDFLRTTAGMTVELTCESHAGKPPAELTWL-DGEgnvVSDGIEYTTQLLGDGKRANAALKWTLTPRREHDGKTFT 261
Cdd:cd05759     2 PVIEGGPVISLQAGVPYNLTCRARGAKPAAEIIWFrDGE---QLEGAVYSKELLKDGKRETTVSTLLITPSDLDTGRTFT 78

                          90       100
                  ....*....|....*....|
gi 1866093293 262 CRSENPALTQPLHARISLEV 281
Cdd:cd05759    79 CRARNEAIPNGKETSITLDV 98

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1866093293 285 PEITLKVSADKIMELDNVKFTCEAVANPaDVNIKWYRNDEVIPGDH---------STTYVISRVTRDyNKDTISCEVSNA 355
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTP-DPEVSWFKDGQPLRSSDrfkvtyeggTYTLTISNVQPD-DSGKYTCVATNS 78

                          90
                  ....*....|..
gi 1866093293 356 VGTTKSTHTLNV 367
Cdd:pfam07679  79 AGEAEASAELTV 90

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1866093293 183 PKIVQGDFLRTTAGMTVELTCESHAGKPPAELTWL-DGEgnvVSDGIEYTTQLLGDGKRANAALKWTLTPRREHDGKTFT 261
Cdd:cd05759     2 PVIEGGPVISLQAGVPYNLTCRARGAKPAAEIIWFrDGE---QLEGAVYSKELLKDGKRETTVSTLLITPSDLDTGRTFT 78

                          90       100
                  ....*....|....*....|
gi 1866093293 262 CRSENPALTQPLHARISLEV 281
Cdd:cd05759    79 CRARNEAIPNGKETSITLDV 98

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1866093293 371 PVFRSTIENVAADIGSEVSLSCDVEGNPQPETMWTFEGSDavLSTESR-----------LVIPQLTIDRAGKYTCRATVa 439
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQP--LRSSDRfkvtyeggtytLTISNVQPDDSGKYTCVATN- 77

                          90
                  ....*....|...
gi 1866093293 440 GFAEISTDVLVFI 452
Cdd:pfam07679  78 SAGEAEASAELTV 90

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1866093293 455 PPRVRSPP-VQYGVEGEVVKLECIISSVPPPTrILWSRNSQhVDIDNNDGYEIVtepmaDGVKNNLIIHNADEDDFGQYN 533
Cdd:pfam13927   1 KPVITVSPsSVTVREGETVTLTCEATGSPPPT-ITWYKNGE-PISSGSTRSRSL-----SGSNSTLTISNVTRSDAGTYT 73

                  ....*
gi 1866093293 534 CTVWN 538
Cdd:pfam13927  74 CVASN 78

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1866093293 371 PVFRSTIE-NVAADIGSEVSLSCDVEGNPQPETMWTFEG------SDAVLSTESRLVIPQLTIDRAGKYTCRAT-VAGfa 442
Cdd:cd20978     1 PKFIQKPEkNVVVKGGQDVTLPCQVTGVPQPKITWLHNGkplqgpMERATVEDGTLTIINVQPEDTGYYGCVATnEIG-- 78

                  ....*...
gi 1866093293 443 EISTDVLV 450
Cdd:cd20978    79 DIYTETLL 86

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1866093293   83 PADRTAIVGKAAVLPCRVL-NKVGTLQWTRDAFglgsdRELKGFPRYTmiGSDDEGDFSLQISRVTLEDDALFQCQVGAA 161
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASgSPPPEVTWYKQGG-----KLLAESGRFS--VSRSGSTSTLTISNVTPEDSGTYTCAATNS 73

                           90
                   ....*....|....*..
gi 1866093293  162 DGVKgirsrNAAFTVYV 178
Cdd:smart00410  74 SGSA-----SSGTTLTV 85

Immunoglobulin (Ig)-like variable (V) domain of the Signal-Regulatory Protein (SIRP); The members here are composed of the immunoglobulin (Ig)-like domain of the Signal-Regulatory Protein (SIRP). The SIRPs belong to the "paired receptors" class of membrane proteins that comprise several genes coding for proteins with similar extracellular regions, but very different transmembrane/cytoplasmic regions with different (activating or inhibitory) signaling potentials. They are commonly on NK cells, but are also on many myeloid cells. Their extracellular region contains three immunoglobulin superfamily domains, a single V-set, and two C1-set IgSF domains. Their cytoplasmic tails that contain either ITIMs or transmembrane regions have positively charged residues that allow an association with adaptor proteins, such as DAP12/KARAP, containing ITAMs. There are 3 distinct SIRP members: alpha, beta, and gamma. SIRP alpha (also known as CD172a or SRC homology 2 domain-containing protein tyrosine phosphatase substrate 1/Shps-1) is a membrane receptor that interacts with a ligand CD47 expressed on many cells and gives an inhibitory signal through immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic region that interact with phosphatases SHP-1 and SHP-2. SIRP beta has a short cytoplasmic region and associates with a transmembrane adapter protein DAP12 containing immunoreceptor tyrosine-based activation motifs to give an activating signal. SIRP gamma contains a very short cytoplasmic region lacking obvious signaling motifs, but also binds CD47 with much less affinity. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1866093293  81 IEPADRTAI-VGKAAVLPCRV--LNKVGTLQWTRdafGLGSDREL----KG--FPRYTMIgSD----DEGDFSLQISRVT 147
Cdd:cd16097     3 IQPEKSVSVaAGESATLHCTVtsLIPVGPIQWFR---GAGPGRELiynqKEghFPRVTTV-SDltkrNNMDFSIRISNIT 78

                  ....*....
gi 1866093293 148 LEDDALFQC 156
Cdd:cd16097    79 PADAGTYYC 87

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1866093293 285 PEITLKVSADKIMELDNVKFTCEAVANPaDVNIKWYRNDEVI-----PGDHS-------TTYVISRVTRDyNKDTISCEV 352
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKP-DPEVKWYKNGVPIdpssiPGKYKieseygvHVLHIRRVTVE-DSAVYSAVA 78

                          90
                  ....*....|....*
gi 1866093293 353 SNAVGTTKSTHTLNV 367
Cdd:cd20951    79 KNIHGEASSSASVVV 93

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1866093293 454 GPPRVRSPPVQYGVEGEVVKLECIISSVPPPTRILWSRNSQHVDIDNNDGYEIVTEPMADGVKNNLIIHNADEDDFG-QY 532
Cdd:cd05758     1 GPPIITAEATQPAILGEKARLECLVFSSPPPDRIVWSWDEGFLESGSSGRFSVETFPTEPGVISVLHISGTQRSDFQtSF 80

                          90
                  ....*....|....*...
gi 1866093293 533 NCTVWNTFGQDSMIILLK 550
Cdd:cd05758    81 NCSAWNRFGEGTAIVSLG 98

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1866093293  461 PPVQYGVEGEVVKLECIISSVPPPTrILWSRNSQHVdIDNNDGYEIVTepmaDGVKNNLIIHNADEDDFGQYNCTVWNTF 540
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPE-VTWYKQGGKL-LAESGRFSVSR----SGSTSTLTISNVTPEDSGTYTCAATNSS 74

                           90
                   ....*....|
gi 1866093293  541 GQDSMIILLK 550
Cdd:smart00410  75 GSASSGTTLT 84

CD80-like C2-set immunoglobulin domain; These domains belong to the immunoglobulin superfamily.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1866093293 183 PKIVQGDFLRTTAGMTVELTCESHAGKPPAELTWLDGEGNVVsdGIEYTTQLLGDGKRANAALKWTLTPRREHDGKTFTC 262
Cdd:pfam08205   1 PTIEPPASLLEGEGPEVVATCSSAGGKPAPRITWYLDGKPLE--AAETSSEQDPESGLVTVTSELKLVPSRSDHGQSLTC 78

                          90
                  ....*....|
gi 1866093293 263 RSENPALTQP 272
Cdd:pfam08205  79 QVSYGALRGS 88

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1866093293 455 PPRVRSPP-VQYGVEGEVVKLECIISSVPPPTrILWSRNSQhVDIDNNDGYEIVtepmaDGVKNNLIIHNADEDDFGQYN 533
Cdd:pfam13927   1 KPVITVSPsSVTVREGETVTLTCEATGSPPPT-ITWYKNGE-PISSGSTRSRSL-----SGSNSTLTISNVTRSDAGTYT 73

                  ....*
gi 1866093293 534 CTVWN 538
Cdd:pfam13927  74 CVASN 78

Second immunoglobulin (Ig) domain of poliovirus receptor (PVR, also known as CD155 and Necl-5), and similar domains; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig) domain of poliovirus receptor (PVR, also known as CD155 and nectin-like protein 5 (Necl-5)) and similar proteins. Poliovirus (PV) binds to its cellular receptor (PVR/CD155) to initiate infection. CD155 is a membrane-anchored, single-span glycoprotein; its extracellular region has three Ig-like domains. There are four different isotypes of CD155 (referred to as alpha, beta, gamma, and delta), these result from alternate splicing of the CD155 mRNA, and have identical extracellular domains. CD155-beta and CD155-gamma are secreted, while CD155-alpha and CD155-delta are membrane-bound and function as PV receptors. The virus recognition site is contained in the amino-terminal domain, D1. Having the virus attachment site on the receptor distal from the plasma membrane may be important for successful initiation of infection of cells by the virus. CD155 binds in the poliovirus "canyon" and has a footprint similar to that of the intercellular adhesion molecule-1 receptor on human rhinoviruses. This group also includes the second Ig-like domain of nectin-1, also known as poliovirus receptor related protein(PVRL)1 or CD111.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1866093293 180 PEPPKIVQGDFLRTTaGMTVELTCESHAGKPPAELTWldgEGNVvsDGIEYTTQLLGDGKRANAALKWTLTPRREHDGKT 259
Cdd:cd05719     1 PTNSLEGGPALLIGG-EPTLVATCISANGKPPASVTW---ETDL--KGEASTTQVRGSNGTVTVTSRYRLVPSREADGQP 74

                          90       100
                  ....*....|....*....|..
gi 1866093293 260 FTCRSENPALTQPLHARISLEV 281
Cdd:cd05719    75 LTCVVEHPSLEKDQRISVTLNV 96

Second immunoglobulin (Ig) domain of nectin-3 and nectin-4 (poliovirus receptor related protein 4), and similar domains; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig) domain of nectin-3 (also known as poliovirus receptor related protein 3 or cluster of differentiation (CD) 113) and nectin-4 (poliovirus receptor related protein 4). Nectin-3 and nectin-4 belong to the nectin family comprised of four transmembrane glycoproteins (nectin-1 through -4). Nectins are synaptic cell adhesion molecules (CAMs) which facilitate adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. Nectin-2 and nectin-3 localize at Sertoli-spermatid junctions where they form heterophilic trans-interactions between the cells that are essential for the formation and maintenance of the junctions and for spermatid development. Nectin-3 has also been shown to form a heterophilic trans-interaction with nectin-1 in ciliary epithelia, establishing the apex-apex adhesion between the pigment and non-pigment cell layers. Nectin-4 has recently been identified in several types of breast carcinoma and can be used as a histological and serological marker for breast cancer.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1866093293 175 TVYVPPEPPKIVQGdflrttAGMTVELTCESHAGKPPAELTWldgEGNVvsDGIEyTTQLLGDGKRANAALKWTLTPRRE 254
Cdd:cd07704     2 LVSLNPGPALLIDG------GNETLAASCTAETGKPAASVTW---ETDL--GGME-SSRTFEHNRTATVTSEYHLVPTRF 69

                          90
                  ....*....|....*..
gi 1866093293 255 HDGKTFTCRSENPALTQ 271
Cdd:cd07704    70 ANGRPLTCVVSHPALQQ 86

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1866093293 371 PVFRSTIE-NVAADIGSEVSLSCDVEGNPQPETMWTFEG------SDAVLSTESRLVIPQLTIDRAGKYTCRAT-VAGfa 442
Cdd:cd20978     1 PKFIQKPEkNVVVKGGQDVTLPCQVTGVPQPKITWLHNGkplqgpMERATVEDGTLTIINVQPEDTGYYGCVATnEIG-- 78

                  ....*...
gi 1866093293 443 EISTDVLV 450
Cdd:cd20978    79 DIYTETLL 86

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1866093293 383 DIGSEVSLSCDVEGNPQPETMWTFEGSdaVLSTESRLVIPQLTIDRAGKYTCRATVAGFAEISTDVLVFI 452
Cdd:pfam13895  12 TEGEPVTLTCSAPGNPPPSYTWYKDGS--AISSSPNFFTLSVSAEDSGTYTCVARNGRGGKVSNPVELTV 79

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1866093293 285 PEITLKVSADKIMELDNVKFTCEAVANPaDVNIKWYRNDEVIPGDH---------STTYVISRVTRDyNKDTISCEVSNA 355
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTP-DPEVSWFKDGQPLRSSDrfkvtyeggTYTLTISNVQPD-DSGKYTCVATNS 78

                          90
                  ....*....|..
gi 1866093293 356 VGTTKSTHTLNV 367
Cdd:pfam07679  79 AGEAEASAELTV 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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1866093293 472 VKLECIISSVPPPTrILWSRNSQHVDIDNNDGYEIVTepmadgVKNNLIIHNADEDDFGQYNCTVWNTFG 541
Cdd:cd00096     1 VTLTCSASGNPPPT-ITWYKNGKPLPPSSRDSRRSEL------GNGTLTISNVTLEDSGTYTCVASNSAG 63

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1866093293 456 PRVRSPPVQYGV-EGEVVKLECIISSVPPPtRILWSRNSQHVDIDNN------DGYEIVTepmadgvknnLIIHNADEDD 528
Cdd:cd05892     1 PMFIQKPQNKKVlEGDPVRLECQISAIPPP-QIFWKKNNEMLQYNTDrislyqDNCGRIC----------LLIQNANKKD 69

                          90
                  ....*....|...
gi 1866093293 529 FGQYNCTVWNTFG 541
Cdd:cd05892    70 AGWYTVSAVNEAG 82

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1866093293 378 ENVAADIGSEVSLSCDVEGNPQPETMWTFEGSDAVLSTE--------SRLVIPQLTIDRAGKYTCRAT 437
Cdd:cd20970    10 FTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTryivrengTTLTIRNIRRSDMGIYLCIAS 77

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1866093293 455 PPRVRSPPVQYGVEGEVVKLECIISSVPPPtRILWSRNSQHVDIDNNDGYeIVTEpmadGVKNNLIIHNADEDDFGQYNC 534
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTP-DLFWQLNGKPVRPDSAHKM-LVRE----NGRHSLIIEPVTKRDAGIYTC 74

                          90
                  ....*....|
gi 1866093293 535 TVWNTFGQDS 544
Cdd:cd05744    75 IARNRAGENS 84

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1866093293 374 RSTIENVAADIGSEVSLSCDVEGNPQPETMWTFEGSDAvlsTESR-------------LVIPQLTIDRAGKYTCRAT-VA 439
Cdd:cd20973     1 IQTLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPI---VESRrfqidqdedglcsLIISDVCGDDSGKYTCKAVnSL 77

                          90
                  ....*....|.
gi 1866093293 440 GFAEISTDVLV 450
Cdd:cd20973    78 GEATCSAELTV 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1866093293 451 FIKGPPRVRSppvqyGVEGEVVKLECIISSVPPPTrILWSRNSQHvdIDNNDGYEIVTepmadgvKNNLIIHNADEDDFG 530
Cdd:cd20978     3 FIQKPEKNVV-----VKGGQDVTLPCQVTGVPQPK-ITWLHNGKP--LQGPMERATVE-------DGTLTIINVQPEDTG 67

                          90
                  ....*....|.
gi 1866093293 531 QYNCTVWNTFG 541
Cdd:cd20978    68 YYGCVATNEIG 78

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1866093293 288 TLKVSADKIMELDNVKFTCEAVANPaDVNIKWYRNDEVIPGdhSTTYVISRVTRDyNKDTISCEVSNAVGTTKS-THTLN 366
Cdd:pfam13895   3 VLTPSPTVVTEGEPVTLTCSAPGNP-PPSYTWYKDGSAISS--SPNFFTLSVSAE-DSGTYTCVARNGRGGKVSnPVELT 78

                  .
gi 1866093293 367 V 367
Cdd:pfam13895  79 V 79

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1866093293 285 PEITLKVSADKIMELDNVKFTCEAVANPaDVNIKWYRNDEVI-----PGDHS-------TTYVISRVTRDyNKDTISCEV 352
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKP-DPEVKWYKNGVPIdpssiPGKYKieseygvHVLHIRRVTVE-DSAVYSAVA 78

                          90
                  ....*....|....*
gi 1866093293 353 SNAVGTTKSTHTLNV 367
Cdd:cd20951    79 KNIHGEASSSASVVV 93

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1866093293 468 EGEVVKLECIISSVPPPTrILWSRN------SQHVDIDNNDGYEIvtepmadgvknnLIIHNADEDDFGQYNCTVWNTFG 541
Cdd:cd05748     6 AGESLRLDIPIKGRPTPT-VTWSKDgqplkeTGRVQIETTASSTS------------LVIKNAKRSDSGKYTLTLKNSAG 72

                  ....*....
gi 1866093293 542 QDSMIILLK 550
Cdd:cd05748    73 EKSATINVK 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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1866093293 468 EGEVVKLECIISSVPPPTrILWSRNSQHVdIDNNDGYEIvtepMADGvkNNLIIHNADEDDFGQYNCTVWN 538
Cdd:cd20970    16 EGENATFMCRAEGSPEPE-ISWTRNGNLI-IEFNTRYIV----RENG--TTLTIRNIRRSDMGIYLCIASN 78

Fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains; member of the C2-set IgSF domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains. The CEA family is a group of anchored or secreted glycoproteins, expressed by epithelial cells, leukocytes, endothelial cells and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), also known as CD66e (Cluster of Differentiation 66e), is a cell surface glycoprotein that plays a role in cell adhesion, intracellular signaling and tumor progression. Diseases associated with CEACAM5 include lung cancer and rectum cancer. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1866093293 385 GSEVSLSCDVEGNPQPETMWTFegSDAVLSTESRLVIPQLTIDRAGKYTCRA 436
Cdd:cd20948    10 GENLNLSCHAASNPPAQYSWTI--NGTFQTSSQELFLPAITENNEGTYTCSA 59

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1866093293  78 EFAIEPADRTAIVGKAAVLPCRVL-NKVGTLQWTRDafglgsDRELKGFPRYTMigSDDEGDFSLQISRVTLEDDALFQC 156
Cdd:pfam07679   2 KFTQKPKDVEVQEGESARFTCTVTgTPDPEVSWFKD------GQPLRSSDRFKV--TYEGGTYTLTISNVQPDDSGKYTC 73

                  ..
gi 1866093293 157 QV 158
Cdd:pfam07679  74 VA 75

Second immunoglobulin (Ig) domain of Nectin-2 and Nectin-like protein 5, and similar domains; member of the C1-set of the Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig) domain of nectin-2 (also known as poliovirus receptor related protein 2 or Cluster of Differentiation 112 (CD112)), nectin-like protein 5 (CD155), and similar proteins. Nectins and Nectin-like molecules are a family of Ca(2+)-independent immunoglobulin-like transmembrane glycoproteins belonging to the class of adhesion receptors, consisting of nine members (nectins 1 through 4 and nectin-like proteins 1 through 5). Nectins are synaptic cell adhesion molecules (CAMs) which facilitate adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. Nectin-2 and nectin-3 localize at Sertoli-spermatid junctions where they form heterophilic trans-interactions between the cells that are essential for the formation and maintenance of the junctions and for spermatid development. CD155 is the fifth member in the nectin-like molecule family, and functions as the receptor of poliovirus; therefore, CD155 is also referred to as Necl-5, or PVR. In contrast to all other family members, CD155 lacks self-adhesion capacity, yet it shares with nectins the feature to interact with other nectins. For instance, CD155 heterophilically trans-interacts with nectin-3, thereby contributing significantly to the establishment of adherens junctions between epithelial cells. This group belongs to the Constant 1 (C1)-set of IgSF domains, which has one beta-sheet that is formed by strands A-B-E-D and the other strands by G-F-C-C'.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1866093293 202 TCESHAGKPPAELTW---LDGEGNvvsdgieyTTQLLG-DGKRANAALKWTLTPRREHDGKTFTCRSENPALTQP 272
Cdd:cd07703    21 RCVSANGRPPARISWsstLNGNAN--------TTQVPGpDSGTVTVTSEYSLVPTPEANGKEVTCKVEHETLEEP 87