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 767910569  22 PVISVHPPWTTFFKGERVTLTCNGFQFYATEKTTWYHRHYWGEKlTLTPGNTLE--VRESGLYRCQARGSPRSNPVRLLF 99
Cdd:cd05752    1 AVVSLDPPWTTVFQGEKVTLTCQGFYSPEQNSTQWYHNGTLISS-TSSSYRIVAatVNDSGEYRCQTQGSSLSDPVHLEV 79

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910569   294 PSGGQAVEGEMLVLVCSVaEGTGDTTFSWHREDMQESLGRK----TQRSLRAELELPAIRQSHAGGYYCTADNSYGPVQS 369
Cdd:smart00410   1 PPSVTVKEGESVTLSCEA-SGSPPPEVTWYKQGGKLLAESGrfsvSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASS 79

                   ....*..
gi 767910569   370 MVlNVTV 376
Cdd:smart00410  80 GT-TLTV 85

First immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains; The members here are composed of the first 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910569  22 PVISVHPPWTTFFKGERVTLTCNGFQFYATEKTTWYHRHYWGEKlTLTPGNTLE--VRESGLYRCQARGSPRSNPVRLLF 99
Cdd:cd05752    1 AVVSLDPPWTTVFQGEKVTLTCQGFYSPEQNSTQWYHNGTLISS-TSSSYRIVAatVNDSGEYRCQTQGSSLSDPVHLEV 79

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910569   294 PSGGQAVEGEMLVLVCSVaEGTGDTTFSWHREDMQESLGRK----TQRSLRAELELPAIRQSHAGGYYCTADNSYGPVQS 369
Cdd:smart00410   1 PPSVTVKEGESVTLSCEA-SGSPPPEVTWYKQGGKLLAESGrfsvSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASS 79

                   ....*..
gi 767910569   370 MVlNVTV 376
Cdd:smart00410  80 GT-TLTV 85

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 767910569 293 QPSGGQAVEGEMLVLVCSvAEGTGDTTFSWHRED--MQESLGRKTQRSLRAELELPAIRQSHAGGYYCTADNSYGP 366
Cdd:cd20970    8 PSFTVTAREGENATFMCR-AEGSPEPEISWTRNGnlIIEFNTRYIVRENGTTLTIRNIRRSDMGIYLCIASNGVPG 82

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910569   21 KPVISVHPPWTTFFKGERVTLTCNgFQFYATEKTTWYH--------RHYWGEklTLTPGNTLEVRE-----SGLYRCQAR 87
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCE-ATGSPPPTITWYKngepissgSTRSRS--LSGSNSTLTISNvtrsdAGTYTCVAS 77

First immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains; The members here are composed of the first 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910569  22 PVISVHPPWTTFFKGERVTLTCNGFQFYATEKTTWYHRHYWGEKlTLTPGNTLE--VRESGLYRCQARGSPRSNPVRLLF 99
Cdd:cd05752    1 AVVSLDPPWTTVFQGEKVTLTCQGFYSPEQNSTQWYHNGTLISS-TSSSYRIVAatVNDSGEYRCQTQGSSLSDPVHLEV 79

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910569   294 PSGGQAVEGEMLVLVCSVaEGTGDTTFSWHREDMQESLGRK----TQRSLRAELELPAIRQSHAGGYYCTADNSYGPVQS 369
Cdd:smart00410   1 PPSVTVKEGESVTLSCEA-SGSPPPEVTWYKQGGKLLAESGrfsvSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASS 79

                   ....*..
gi 767910569   370 MVlNVTV 376
Cdd:smart00410  80 GT-TLTV 85

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 767910569 293 QPSGGQAVEGEMLVLVCSvAEGTGDTTFSWHRED--MQESLGRKTQRSLRAELELPAIRQSHAGGYYCTADNSYGP 366
Cdd:cd20970    8 PSFTVTAREGENATFMCR-AEGSPEPEISWTRNGnlIIEFNTRYIVRENGTTLTIRNIRRSDMGIYLCIASNGVPG 82

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767910569  104 LILQAPYS-VFEGDTLVLRCHRRRKEKltaVKYTWNGNIlSISNKSWDLLIPQASSNNNGNYRCIgYGDENDVFRSN 179
Cdd:pfam13895   2 PVLTPSPTvVTEGEPVTLTCSAPGNPP---PSYTWYKDG-SAISSSPNFFTLSVSAEDSGTYTCV-ARNGRGGKVSN 73

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910569   21 KPVISVHPPWTTFFKGERVTLTCNgFQFYATEKTTWYH--------RHYWGEklTLTPGNTLEVRE-----SGLYRCQAR 87
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCE-ATGSPPPTITWYKngepissgSTRSRS--LSGSNSTLTISNvtrsdAGTYTCVAS 77

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910569  290 LETQPSGGQAVEGEMLVLVCSvAEGTGDTTFSWHREDmqeSLGRKTQRSLRaelelPAIRQSHAGGYYCTADNSYGPVQS 369
Cdd:pfam13895   2 PVLTPSPTVVTEGEPVTLTCS-APGNPPPSYTWYKDG---SAISSSPNFFT-----LSVSAEDSGTYTCVARNGRGGKVS 72

                  ....*..
gi 767910569  370 MVLNVTV 376
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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910569 293 QPSGGQAVEGEMLVLVCSVAEGTGDTTFSWHREDMQESLGRKTQRSLR-AELELPAIRQSHAGGYYCTADNSYGPVQSMV 371
Cdd:cd05724    3 EPSDTQVAVGEMAVLECSPPRGHPEPTVSWRKDGQPLNLDNERVRIVDdGNLLIAEARKSDEGTYKCVATNMVGERESRA 82

                 ....*
gi 767910569 372 LNVTV 376
Cdd:cd05724   83 ARLSV 87

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910569  291 ETQPSGGQAVEGEMLVLVCSVaEGTGDTTFSWHR--EDMQESL-GRKTQRSLRAELELPAIRQSHAGGYYCTADNSYGPV 367
Cdd:pfam07679   4 TQKPKDVEVQEGESARFTCTV-TGTPDPEVSWFKdgQPLRSSDrFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAGEA 82

                  ....*....
gi 767910569  368 QSmVLNVTV 376
Cdd:pfam07679  83 EA-SAELTV 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767910569 305 LVLVCSVaEGTGDTTFSWHREDMQESLGRKTQRSL---RAELELPAIRQSHAGGYYCTADNSYG 365
Cdd:cd00096    1 VTLTCSA-SGNPPPTITWYKNGKPLPPSSRDSRRSelgNGTLTISNVTLEDSGTYTCVASNSAG 63

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910569 299 AVEGEMLVLVCsVAEGTGDTTFSWHREDMQESLGRKTQRSLRAELELPAIRQSHAGGYYCTADNSYGPVQ 368
Cdd:cd05876    7 ALRGQSLVLEC-IAEGLPTPTVKWLRPSGPLPPDRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGSAR 75