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 61966777  28 GQEVLYLAEGDNVRLGCPYVLDPEDYGPngLDIEWMqvnSDPAHHRENVFLSYQDKRINHGSLPHLQQRVRFAASDPSQy 107
Cdd:cd20960   6 AQTEIKKVAGENVTLPCHHQLGLEDQGT--LDIEWL---LLPSDKVEKVVITYSGDRVYNHYYPALKGRVAFTSNDLSG- 79

                        90       100
                ....*....|....*....|...
gi 61966777 108 DASINLMNLQVSDTATYECRVKK 130
Cdd:cd20960  80 DASLNISNLKLSDTGTYQCKVKK 102

Immunoglobulin Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins; The members here are composed of the Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins. CAR, which is encoded by human CXADR gene, is a cell adhesion molecule of the Immunoglobulin (Ig) superfamily. The CAR acts as a type I membrane receptor for group B1-B6 coxsackie viruses and subgroup C adenoviruses. For instance, adenovirus interacts with the coxsackievirus and adenovirus receptor to enter epithelial airway cells. The CAR is also shown to be involved in physiological processes such as neuronal and heart development, epithelial tight junction integrity, and tumor suppression. The CAR is a component of the epithelial apical junction complex that may function as a homophilic cell adhesion molecule and is essential for tight junction integrity. The CAR is also involved in transepithelial migration of leukocytes through adhesive interactions with JAML a transmembrane protein of the plasma membrane of leukocytes. The interaction between both receptors also mediates the activation of gamma-delta T-cells, a subpopulation of T-cells residing in epithelia and involved in tissue homeostasis and repair. The CAR is composed of one V-set and one C2-set Ig module, a single transmembrane helix, and an intracellular domain. This group belongs to the V-set of IgSF domains, having A, B, E and D strands in one beta-sheet and A', G, F, C, C' and C" in the other

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61966777  28 GQEVLYLAEGDNVRLGCPYVLDPEDYGPngLDIEWMqvnSDPAHHRENVFLSYQDKRINHGSLPHLQQRVRFAASDPSQy 107
Cdd:cd20960   6 AQTEIKKVAGENVTLPCHHQLGLEDQGT--LDIEWL---LLPSDKVEKVVITYSGDRVYNHYYPALKGRVAFTSNDLSG- 79

                        90       100
                ....*....|....*....|...
gi 61966777 108 DASINLMNLQVSDTATYECRVKK 130
Cdd:cd20960  80 DASLNISNLKLSDTGTYQCKVKK 102

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61966777   160 GNDVVLKCYASGGSQPlSYKWakisghhypyragsytsqhsYHSELSYQESFHSSINQGLNNGDLVLKDISRADDGLYQC 239
Cdd:pfam13927  16 GETVTLTCEATGSPPP-TITW--------------------YKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTC 74

                  ....
gi 61966777   240 TVAN 243
Cdd:pfam13927  75 VASN 78

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61966777 160 GNDVVLKCYASGGSQPlSYKWAKISGHHYPYRAGSytsqhsyhselsyqESFhssinqglnNGDLVLKDISRADDGLYQC 239
Cdd:cd05731  10 GGVLLLECIAEGLPTP-DIRWIKLGGELPKGRTKF--------------ENF---------NKTLKIENVSEADSGEYQC 65

                        90
                ....*....|....*..
gi 61966777 240 TVANNVGYSVCVVEVKV 256
Cdd:cd05731  66 TASNTMGSARHTISVTV 82

Immunoglobulin Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins; The members here are composed of the Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins. CAR, which is encoded by human CXADR gene, is a cell adhesion molecule of the Immunoglobulin (Ig) superfamily. The CAR acts as a type I membrane receptor for group B1-B6 coxsackie viruses and subgroup C adenoviruses. For instance, adenovirus interacts with the coxsackievirus and adenovirus receptor to enter epithelial airway cells. The CAR is also shown to be involved in physiological processes such as neuronal and heart development, epithelial tight junction integrity, and tumor suppression. The CAR is a component of the epithelial apical junction complex that may function as a homophilic cell adhesion molecule and is essential for tight junction integrity. The CAR is also involved in transepithelial migration of leukocytes through adhesive interactions with JAML a transmembrane protein of the plasma membrane of leukocytes. The interaction between both receptors also mediates the activation of gamma-delta T-cells, a subpopulation of T-cells residing in epithelia and involved in tissue homeostasis and repair. The CAR is composed of one V-set and one C2-set Ig module, a single transmembrane helix, and an intracellular domain. This group belongs to the V-set of IgSF domains, having A, B, E and D strands in one beta-sheet and A', G, F, C, C' and C" in the other

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61966777  28 GQEVLYLAEGDNVRLGCPYVLDPEDYGPngLDIEWMqvnSDPAHHRENVFLSYQDKRINHGSLPHLQQRVRFAASDPSQy 107
Cdd:cd20960   6 AQTEIKKVAGENVTLPCHHQLGLEDQGT--LDIEWL---LLPSDKVEKVVITYSGDRVYNHYYPALKGRVAFTSNDLSG- 79

                        90       100
                ....*....|....*....|...
gi 61966777 108 DASINLMNLQVSDTATYECRVKK 130
Cdd:cd20960  80 DASLNISNLKLSDTGTYQCKVKK 102

Immunoglobulin (Ig)-like domain of protein zero (P0) and similar proteins; The members here are composed of the immunoglobulin (Ig) domain of protein zero (P0), a myelin membrane adhesion molecule. P0 accounts for over 50% of the total protein in peripheral nervous system (PNS) myelin. P0 is a single-pass transmembrane glycoprotein with a highly basic intracellular domain and an extracellular Ig domain. The extracellular domain of P0 (P0-ED) is similar to the Ig variable domain, carrying one acceptor sequence for N-linked glycosylation. P0 plays a role in membrane adhesion in the spiral wraps of the myelin sheath. The intracellular domain is thought to mediate membrane apposition of the cytoplasmic faces and may, through electrostatic interactions, interact directly with lipid headgroups. It is thought that homophilic interactions of the P0 extracellular domain mediate membrane juxtaposition in the extracellular space of PNS myelin. This group also contains the Ig domain of sodium channel subunit beta-2 (SCN2B), and of epithelial V-like antigen 1 (EVA). EVA, also known as myelin protein zero-like 2, is an adhesion molecule, which may play a role in structural organization of the thymus and early lymphocyte development. SCN2B subunits play a role in determining sodium channel density and function in neurons,and in control of electrical excitability in the brain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61966777  30 EVLYLAEGDNVRLGCP----YVLdpedygPNGLDIEW--MQVNSDPahhRENVFLSYQDKRINhGSLPHLQQRVRFAAsD 103
Cdd:cd05715   7 RELNVLNGSDVRLTCTftscYTV------GDAFSVTWtyQPEGGNT---TESMFHYSKGKPYI-LKVGRFKDRVSWAG-N 75

                        90       100
                ....*....|....*....|....*.
gi 61966777 104 PSQYDASINLMNLQVSDTATYECRVK 129
Cdd:cd05715  76 PSKKDASIVISNLQFSDNGTYTCDVK 101

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61966777   160 GNDVVLKCYASGGSQPlSYKWakisghhypyragsytsqhsYHSELSYQESFHSSINQGLNNGDLVLKDISRADDGLYQC 239
Cdd:pfam13927  16 GETVTLTCEATGSPPP-TITW--------------------YKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTC 74

                  ....
gi 61966777   240 TVAN 243
Cdd:pfam13927  75 VASN 78

Immunoglobulin (Ig)-like domain of chondroitin sulfate proteoglycans (CSPGs), human cartilage link protein (LP), and similar domains; The members here are composed of the immunoglobulin (Ig)-like domain similar to that found in chondroitin sulfate proteoglycans (CSPGs) and human cartilage link protein (LP). Included in this group are the CSPGs aggrecan, versican, and neurocan. In CSPGs, this Ig-like domain is followed by hyaluronan (HA)-binding tandem repeats, and a C-terminal region with epidermal growth factor-like, lectin-like, and complement regulatory protein-like domains. Separating these N- and C-terminal regions is a nonhomologous glycosaminoglycan attachment region. In cartilage, aggrecan forms cartilage link protein stabilized aggregates with hyaluronan (HA). These aggregates contribute to the tissue's load bearing properties. Aggrecan and versican have a wide distribution in connective tissue and extracellular matrices. Neurocan is localized almost exclusively in nervous tissue. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. There is considerable evidence that HA-binding CSPGs are involved in developmental processes in the central nervous system. Members of the vertebrate HPLN (hyaluronan/HA and proteoglycan binding link) protein family are physically linked adjacent to CSPG genes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61966777  28 GQEVLYLAEGDNVRLGCPYVLDPEDYGpNGLD---IEWMQVNSDPAHHRENVFLSYQDKRINHGSlpHLQQRVRFAASDP 104
Cdd:cd05714   3 ESAKVFSHLGGNVTLPCKFYRDPTAFG-SGIHkirIKWTKLTSDSGYLKEVDVLVAMGNVVYHKK--TYGGRVSVPLKPG 79

                        90       100
                ....*....|....*....|....
gi 61966777 105 SQYDASINLMNLQVSDTATYECRV 128
Cdd:cd05714  80 SDSDASLVITDLTASDYGLYRCEV 103

Immunoglobulin (Ig)-like domain of epithelial V-like antigen (EVA) 1; The members here are composed of the immunoglobulin (Ig) domain of epithelial V-like antigen 1 (EVA 1). EVA is also known as myelin protein zero-like 2. EVA is an adhesion molecule and may play a role in the structural organization of the thymus and early lymphocyte development.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61966777  31 VLYLAEGDNVRLGCP-YVLDPEdygPNGLDIEWMQVNSDPAHHrENVFlsYQDKRINHGSLPHLQQRVRFAAsDPSQYDA 109
Cdd:cd05880   8 EVEAVNGTDVRLKCTfSSSAPI---GDTLVITWNFRPLDGGRE-ESVF--YYHKRPYPPPDGRFKGRVVWDG-NIMRRDA 80

                        90       100
                ....*....|....*....|
gi 61966777 110 SINLMNLQVSDTATYECRVK 129
Cdd:cd05880  81 SILIWQLQPTDNGTYTCQVK 100

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61966777 160 GNDVVLKCYASGGSQPlSYKWAKISGhhypyragsyTSQHSYHsELSYQESFHSsinqgLNNGDLVLKDISRADDGLYQC 239
Cdd:cd20954  16 GQDVMLHCQADGFPTP-TVTWKKATG----------STPGEYK-DLLYDPNVRI-----LPNGTLVFGHVQKENEGHYLC 78

                        90
                ....*....|....*...
gi 61966777 240 TVANNVGYSVC-VVEVKV 256
Cdd:cd20954  79 EAKNGIGSGLSkVIFLKV 96

Immunoglobulin variable (IgV)-like domain in complement receptor of the immunoglobulin superfamily (CRIg); The members here are composed of the immunoglobulin variable (IgV) region of the complement receptor of the immunoglobulin superfamily (CRIg). The N-terminal domain of CRIg (also known as Z39Ig and V-set and Ig domain-containing 4 (VSIG4) belongs to the IgV family of immunoglobulin-like domains while the C-terminal domain of CRIg belongs to the IgC family of immunoglobulin-like domains. Like all members of this family, the CRIg domain contains two beta-sheets: one composed of strands A', G, F, C, C' and C", and the other of strands B, E and D. The complement system is an important part of the innate immune system and is required for removal of pathogens from the bloodstream. After exposure to pathogens, the third component of the complement system, C3, is cleaved to C3b which, after recruitment of factor B, initiates formation of the alternative pathway convertases. CRIg, a complement receptor expressed on macrophages, binds to C3b and iC3b mediating phagocytosis of the particles. It is also a potent inhibitor of the alternative pathway convertases and a negative regulator of T cell activation. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as, T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as, butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61966777  39 NVRLGCPYVldPEDyGPNGLDIEWM-QVNSDPAhhreNVFLsyqdkriNHGSLPHLQQ---RVRFAASDPSQYDASINLM 114
Cdd:cd16089  16 SVNLPCTYV--PEE-GYTQVLVKWLvQRDSDPV----TIFL-------RDSSGDHIQQakyRGRLEVSKDTPGDVSLQLD 81

                        90
                ....*....|....
gi 61966777 115 NLQVSDTATYECRV 128
Cdd:cd16089  82 TLEMDDRGHYTCQV 95

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61966777 159 YGNDVVLKCYASGGSQP-LSYKWAKISGHHypyragsytsQHsYHSELSyqesfhSSINQGLNNGDLVLKDISRADDGLY 237
Cdd:cd05734  15 YGKAVVLNCSADGYPPPtIVWKHSKGSGVP----------QF-QHIVPL------NGRIQLLSNGSLLIKHVLEEDSGYY 77

                        90
                ....*....|..
gi 61966777 238 QCTVANNVGYSV 249
Cdd:cd05734  78 LCKVSNDVGADI 89

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61966777   160 GNDVVLKCYASGGSQPlSYKWakisghhypYRAGSYTSQHSYHSeLSYQESFHSsinqglnngdLVLKDISRADDGLYQC 239
Cdd:pfam07679  15 GESARFTCTVTGTPDP-EVSW---------FKDGQPLRSSDRFK-VTYEGGTYT----------LTISNVQPDDSGKYTC 73

                          90
                  ....*....|....*..
gi 61966777   240 TVANNVGYSVCVVEVKV 256
Cdd:pfam07679  74 VATNSAGEAEASAELTV 90

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.

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 61966777 220 NNGDLVLKDISRA-DDGLYQCTVANNVGYSVCV-VEVKV 256
Cdd:cd20958  51 PNGTLVIENVQRSsDEGEYTCTARNQQGQSASRsVFVKV 89

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 61966777 209 ESFHSSINQ-GLNNGDLVLKDISRADDGLYQCTVANNVGYSVCVVEVKV 256
Cdd:cd20973  40 ESRRFQIDQdEDGLCSLIISDVCGDDSGKYTCKAVNSLGEATCSAELTV 88