Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 4335933    153 GHLIYLLCKCDqGLSHPTYRWYKVDENTLTPVT--EYFNPDTGILYIGNLTTFETGHYRCIASN 214
Cdd:pfam13927  16 GETVTLTCEAT-GSPPPTITWYKNGEPISSGSTrsRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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 4335933   22 VVVTVPeKTVNVKTGGNATLLCTYTSSQPLGNFF-IQWSFYSAKESQLHTIYYYSEGQSY--SYGEFKDRITAATSPG-- 96
Cdd:cd05715   1 MEVYTP-RELNVLNGSDVRLTCTFTSCYTVGDAFsVTWTYQPEGGNTTESMFHYSKGKPYilKVGRFKDRVSWAGNPSkk 79

                        90       100       110
                ....*....|....*....|....*....|
gi 4335933   97 NASITISNMQPSDTGSYTCEVFSPQDDAGQ 126
Cdd:cd05715  80 DASIVISNLQFSDNGTYTCDVKNPPDIVGG 109

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 4335933    153 GHLIYLLCKCDqGLSHPTYRWYKVDENTLTPVT--EYFNPDTGILYIGNLTTFETGHYRCIASN 214
Cdd:pfam13927  16 GETVTLTCEAT-GSPPPTITWYKNGEPISSGSTrsRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 4335933     158 LLCKCDqGLSHPTYRWYKVDENTLTP---VTEYFNPDTGILYIGNLTTFETGHYRCIASNIMGNSTCELDLT 226
Cdd:smart00410  14 LSCEAS-GSPPPEVTWYKQGGKLLAEsgrFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTLT 84

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 4335933   22 VVVTVPeKTVNVKTGGNATLLCTYTSSQPLGNFF-IQWSFYSAKESQLHTIYYYSEGQSY--SYGEFKDRITAATSPG-- 96
Cdd:cd05715   1 MEVYTP-RELNVLNGSDVRLTCTFTSCYTVGDAFsVTWTYQPEGGNTTESMFHYSKGKPYilKVGRFKDRVSWAGNPSkk 79

                        90       100       110
                ....*....|....*....|....*....|
gi 4335933   97 NASITISNMQPSDTGSYTCEVFSPQDDAGQ 126
Cdd:cd05715  80 DASIVISNLQFSDNGTYTCDVKNPPDIVGG 109

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4335933   24 VTVPEKTVNVKTGGNATLLCTYTSSQPLGNffIQWsFYSAKESQLHTIYYYSEGQSYSYGEFKDRITAATSPGN-ASITI 102
Cdd:cd00099   1 VTQSPRSLSVQEGESVTLSCEVSSSFSSTY--IYW-YRQKPGQGPEFLIYLSSSKGKTKGGVPGRFSGSRDGTSsFSLTI 77

                        90
                ....*....|....*..
gi 4335933  103 SNMQPSDTGSYTCEVFS 119
Cdd:cd00099  78 SNLQPEDSGTYYCAVSE 94

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 4335933   24 VTVPEKTVNVKTGGNATLLCTYTSSQPLGNffIQWsFYSAKESQLhTIYYYSEGQsysygeFKdRITAATSPG-----NA 98
Cdd:cd16097   2 VIQPEKSVSVAAGESATLHCTVTSLIPVGP--IQW-FRGAGPGRE-LIYNQKEGH------FP-RVTTVSDLTkrnnmDF 70

                        90       100
                ....*....|....*....|....*..
gi 4335933   99 SITISNMQPSDTGSYTCEVF---SPQD 122
Cdd:cd16097  71 SIRISNITPADAGTYYCVKFrkgSPDD 97

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 4335933   22 VVVTVPEKTVNVKTGGNATLLCTYTSSQP-LGNFFIQWSFYSAKESQlHTIYYYSEGQSYS--YGEFKDRItAATSP--- 95
Cdd:cd20960   1 LLITSAQTEIKKVAGENVTLPCHHQLGLEdQGTLDIEWLLLPSDKVE-KVVITYSGDRVYNhyYPALKGRV-AFTSNdls 78

                        90       100
                ....*....|....*....|..
gi 4335933   96 GNASITISNMQPSDTGSYTCEV 117
Cdd:cd20960  79 GDASLNISNLKLSDTGTYQCKV 100

Immunoglobulin (Ig)-like domain of human cartilage link protein (LP), and similar domains; The members here are composed of the immunoglobulin (Ig)-like domain similar to that found in human cartilage link protein (LP; also called hyaluronan and proteoglycan link protein). In cartilage, chondroitin-keratan sulfate proteoglycan (CSPG), aggrecan, forms cartilage link protein stabilized aggregates with hyaluronan (HA). These aggregates contribute to the tissue's load bearing properties. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. 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 4335933   36 GGNATLLCTYTSSQPLGNFF---IQWSFYSAKESQLHTIYYYSEGQSYSYGEFKDRIT-AATSPGNASITISNMQPSDTG 111
Cdd:cd05877  12 GGNVTLPCRYHYEPELSAPRkirVKWTKLEVDYAKEEDVLVAIGTRHKSYGSYQGRVFlRRADDLDASLVITDLRLEDYG 91

                ....*.
gi 4335933  112 SYTCEV 117
Cdd:cd05877  92 RYRCEV 97

Immunoglobulin Variable (IgV) domain of B7-H4; The members here are composed of the immunoglobulin variable (IgV) domain of B7-H4 (also known as B7-S1, B7x, or Vtcn1). B7-H4 is one of the B7 family of immune-regulatory ligands that act as negative regulators of T cell function; it contains one IgV domain and one IgC domain. The B7-family consists of structurally related cell-surface protein ligands, which bind to receptors on lymphocytes that regulate immune responses. The binding of B7-H4 to unidentified receptors results in the inhibition of TCR-mediated T cell proliferation, cell-cycle progression and IL-2 production. As a co-inhibitory molecule, B7-H4 is widely expressed in tumor tissues and its expression is significantly associated with poor prognosis in human cancers such as glioma, pancreatic cancer, oral squamous cell carcinoma, renal cell carcinoma, and lung cancer.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4335933   30 TVNVKT-----GGNATLLCTYTSSQPLGNFFIQWSfysaKESQLHTIYYYSEGQ---SYSYGEFKDRITAATSP---GNA 98
Cdd:cd20984   1 TVTAKHlagniGEDGILSCTFTPDIKLSDIVIQWL----KEGDSGLVHEFKEGKdelSRQSPMFRGRTSLFADQvhvGNA 76

                        90
                ....*....|....*....
gi 4335933   99 SITISNMQPSDTGSYTCEV 117
Cdd:cd20984  77 SLRLKNVQLTDAGTYLCII 95

First immunoglobulin (Ig) variable (V) domain of rat MRC OX-2 antigen, and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of rat MRC OX-2 antigen (also known as CD200) and similar proteins. MRC OX-2 is a membrane glycoprotein expressed in a variety of lymphoid and non-lymphoid cells in rats. It has a similar broad distribution pattern in humans. MRC OX-2 may regulate myeloid cell activity. The protein has an extracellular portion containing two Ig-like domains, a transmembrane portion, and a cytoplasmic portion.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4335933   24 VTVPEKTVNVKTGGNATLLCTYTSSQPLgnffIQWSFYSAKESQLHTIYYYSEGQSYSY-GEFKDRITAATS-PGNASIT 101
Cdd:cd05846   1 VVVHTGDTRAVLGGNATLSCNLTLPEEV----LQVTWQKIKASSPENIVTYSKKYGVKIqPSYVRRISFTSSgLNSTSIT 76

                        90
                ....*....|....*
gi 4335933  102 ISNMQPSDTGSYTCE 116
Cdd:cd05846  77 IWNVTLEDEGCYKCL 91

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) alpha chain and similar proteins; The members here are composed of the immunoglobulin (Ig) variable domain of the alpha chain of alpha/beta T-cell antigen receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are composed of alpha and beta, or gamma and delta polypeptide chains with variable (V) and constant (C) regions. This group represents the variable domain of the alpha chain of TCRs and also includes the variable domain of delta chains of TCRs. Alpha/beta TCRs recognize antigen as peptide fragments presented by major histocompatibility complex (MHC) molecules. The variable domain of TCRs is responsible for antigen recognition, and is located at the N-terminus of the receptor. Gamma/delta TCRs recognize intact protein antigens directly without antigen processing and recognize MHC independently of the bound peptide. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4335933   24 VTVPEKTVNVKTGGNATLLCTYTSSqplGNFFIQW-SFYSAKESQLhTIYYYSEGQSYSYGEFkdRITAATSPGNASITI 102
Cdd:cd04983   1 VTQSPQSLSVQEGENVTLNCNYSTS---TFYYLFWyRQYPGQGPQF-LIYISSDSGNKKKGRF--SATLDKSRKSSSLHI 74

                        90       100
                ....*....|....*....|....*..
gi 4335933  103 SNMQPSDTGSYTCEVfspqDDAGQSQK 129
Cdd:cd04983  75 SAAQLSDSAVYFCAL----SESGGTGK 97

First (N-terminal) immunoglobulin (Ig)-like domain of nectin-like molecule-1 (Necl-1); member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of nectin-like molecule-1, Necl-1 (also known as celll adhesion molecule 3 (CADM3), SynCAM2, or IGSF4). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 - Necl-5). They all have an extracellular region containing three Ig-like domains, a transmembrane region, and a cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 has Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4335933   31 VNVKTGGNATLLCTYTSSQplgNFFIQWSfysakESQLHTIYYyseGQSYSYGEfkDRITAATS-PGNASITISNMQPSD 109
Cdd:cd05882   7 ETVAVGGTVTLKCGVKEHD---NSSLQWS-----NTAQQTLYF---GEKRALRD--NRIQLVKStPTELIISISNVQLSD 73

                        90
                ....*....|
gi 4335933  110 TGSYTCEVFS 119
Cdd:cd05882  74 EGEYTCSIFT 83

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4335933     26 VPEKTVNVKTGGNATLLCTYTSSQPLGNFFiqWSFYSakeSQLHTIYYYSEGQSYSygefkdritaatspGNASITISNM 105
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSASTGSPGPDVT--WSKEG---GTLIESLKVKHDNGRT--------------TQSSLLISNV 61

                          90
                  ....*....|....*
gi 4335933    106 QPSDTGSYTCEVFSP 120
Cdd:pfam00047  62 TKEDAGTYTCVVNNP 76

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 4335933  152 KGHLIYLLCKCDqGLSHPTYRWYKVDENTLT--PVTEYFNPdtgILYIGNLTTFETGHYRCIASNIMGNST 220
Cdd:cd05731   9 RGGVLLLECIAE-GLPTPDIRWIKLGGELPKgrTKFENFNK---TLKIENVSEADSGEYQCTASNTMGSAR 75

Immunoglobulin (Ig) lambda light chain variable (V) domain; The members here are composed of the immunoglobulin (Ig) light chain, lambda type, variable (V) domain. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. There are two types of light chains: kappa and lambda, each composed of a constant domain (CL) and a variable domain (VL). There are five types of heavy chains (alpha, gamma, delta, epsilon, and mu), which determines the type of immunoglobulin formed: IgA, IgG, IgD, IgE, and IgM, respectively. In higher vertebrates, there are two types of light chain, designated kappa and lambda, which seem to be functionally identical, and can associate with any of the heavy chains. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4335933   23 VVTVPEkTVNVKTGGNATLLCTYtSSQPLGNFFIQWsfYSAKESQL-HTIYYYSEGQSYSygeFKDRITAATSPGNASIT 101
Cdd:cd04984   1 VLTQPS-SLSVSPGETVTITCTG-SSGNISGNYVNW--YQQKPGSApRYLIYEDKHRPSG---IPDRFSGSKSGNTASLT 73

                        90
                ....*....|....*.
gi 4335933  102 ISNMQPSDTGSYTCEV 117
Cdd:cd04984  74 ISGAQTEDEADYYCQV 89

Immunoglobulin Variable (IgV) domain in HERV-H LTR-associating 2 (HHLA2); The members here are composed of the immunoglobulin variable (IgV) region in HERV-H LTR-associating 2 (HHLA2; also known as B7-H7/B7 homolog 7). HHLA2 is a member of the B7 family of immune regulatory proteins. Mature human HHLA2 consists of an extracellular domain (ECD) with three immunoglobulin-like domains, a transmembrane segment, and a cytoplasmic domain. HHLA2 is widely expressed in human cancers including non-small cell lung carcinoma (NSCLS), triple negative breast cancer (TNBC), and melanoma, but has limited expression on normal tissues. Interestingly, unlike other members of B7 family, HHLA2 is not expressed in mice or rats. HHLA2 functions as a T cell coinhibitory molecules as it inhibits the proliferation of activated CD4(+) and CD8(+) T cells and their cytokine production. Furthermore, HHLA2 is constitutively expressed on the surface of human monocytes and is induced on B cells after stimulation, however it is not inducible on T cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4335933   41 LLCTYTssqPLGNFFIQWsfYSAKESQLHTIYYYS----EGQSYSYGE----FKDRItaatSPGNASITISNMQPSDTGS 112
Cdd:cd16091  17 LPCSFT---PGSEVVIHW--YKQDSDIKVHSYYYGkdqlESQDQRYRNrtslFKDQI----SNGNASLLLRRVQLQDEGR 87

                        90
                ....*....|
gi 4335933  113 YTCEVFSPQD 122
Cdd:cd16091  88 YKCYTSTIIG 97

Immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG); The members here are composed of the immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG). MOG, a minor component of the myelin sheath, is an important CNS-specific autoantigen, linked to the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). It is a transmembrane protein having an extracellular Ig domain. MOG is expressed in the CNS on the outermost lamellae of the myelin sheath, and on the surface of oligodendrocytes, and may participate in the completion, compaction, and/or maintenance of myelin. This group also includes butyrophilin (BTN). BTN is the most abundant protein in bovine milk-fat globule membrane (MFGM).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4335933   24 VTVPEKTVNVKTGGNATLLCTYTSSQPLGNFFIQWsfYSAKESQLhtIYYYSEGQ---SYSYGEFKDR---ITAATSPGN 97
Cdd:cd05713   3 VIGPTEPILALVGEDAELPCHLSPKMSAEHMEVRW--FRSQFSPV--VHLYRDGQdqeEEQMPEYRGRtelLKDAIAEGS 78

                        90
                ....*....|....*...
gi 4335933   98 ASITISNMQPSDTGSYTC 115
Cdd:cd05713  79 VALRIHNVRPSDEGQYTC 96

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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4335933  152 KGHLIYLLCKcDQGLSHPTYRWYKVDEnTLTPVTEYFNPDTGILYIGNLTTFETGHYRCIASNIMG--NSTCELDL 225
Cdd:cd04969  16 KGGDVIIECK-PKASPKPTISWSKGTE-LLTNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGkaNSTGSLSV 89

Immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), aggrecan; The members here are composed of the immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), aggrecan. In CSPGs, the 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 HA. These aggregates contribute to the tissue's load bearing properties. Aggrecan has a wide distribution in connective tissue and extracellular matrices. 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 4335933   56 IQWSFYSaKESQLhTIYYYSEGQSYSYGEFKDRITAATSP---GNASITISNMQPSDTGSYTCEVFSPQDDagqSQKSVI 132
Cdd:cd05900  41 IKWSFIS-KEKES-VLLVATEGKVRVNTEYLDRVSLPNYPaipSDATLEITELRSNDSGTYRCEVMHGIED---NYDTVE 115

                ...
gi 4335933  133 VNV 135
Cdd:cd05900 116 VQV 118

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and similar proteins; member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and related proteins. The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members: VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1) and VEGFR-3 (Flt-4). VEGF-A interacts with both VEGFR-1 and VEGFR-2. VEGFR-1 binds strongest to VEGF; VEGF-2 binds more weakly. VEGFR-3 appears not to bind VEGF, but binds other members of the VEGF family (VEGF-C and -D). VEGFRs bind VEGFs with high affinity with the IG-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic, and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth. This group also contains alpha-type platelet-derived growth factor receptor precursor (PDGFR)-alpha (CD140a), and PDGFR-beta (CD140b). PDGFRs alpha and beta have an extracellular component with five Ig-like domains, a transmembrane segment, and a cytoplasmic portion that has protein tyrosine kinase activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4335933   21 GVVVTVPEKTVNVKTGGNATLLCTYTSSQPLGNFFiQWSFYSAKESQLHTIyyysegqsysygefKDRITAATSPGN--- 97
Cdd:cd05742   2 DLELSPNAEPTVLPQGETLVLNCTANVNLNEVVDF-QWTYPSEKEGKLALL--------------KPDIKVDWSEPGefv 66

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 4335933   98 ASITISNMQPSDTGSYTCEVFSpqddaGQSQKSVIVNVLV 137
Cdd:cd05742  67 STLTIPEATLKDSGTYTCAARS-----GVMKKEKQTSVSV 101

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) beta chain; The members here are composed of the immunoglobulin (Ig) variable domain of the beta chain of alpha/beta T-cell antigen receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are composed of alpha and beta, or gamma and delta, polypeptide chains with variable (V) and constant (C) regions. This group includes the variable domain of the alpha chain of alpha/beta TCRs. Alpha/beta TCRs recognize antigen as peptide fragments presented by major histocompatibility complex (MHC) molecules. The variable domain of TCRs is responsible for antigen recognition, and is located at the N-terminus of the receptor. Gamma/delta TCRs recognize intact protein antigens directly without antigen processing and recognize MHC independently of the bound peptide. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4335933   33 VKTGGNATLLCtytsSQPLGNFFIQWsfYSAKESQ-LHTIYYYSEGQSYSYGEFK-DRITAA-TSPGNASITISNMQPSD 109
Cdd:cd05899  10 KRRGQSVTLRC----SQKSGHDNMYW--YRQDPGKgLQLLFYSYGGGLNEEGDLPgDRFSASrPSLTRSSLTIKSAEPED 83

                        90
                ....*....|....*..
gi 4335933  110 TGSYTCEVFSPQDDAGQ 126
Cdd:cd05899  84 SAVYLCASSLGGGADEA 100

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) delta chain; The members here are composed of the immunoglobulin (Ig) variable (V) domain of the delta chain of gamma/delta T-cell receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are heterodimers consisting of alpha and beta chains or gamma and delta chains. Each chain contains a variable (V) and a constant (C) region. The majority of T cells contain alpha/beta TCRs, but a small subset contain gamma/delta TCRs. Alpha/beta TCRs recognize antigen as peptide fragments presented by major histocompatibility complex (MHC) molecules. Gamma/delta TCRs recognize intact protein antigens; they recognize protein antigens directly and without antigen processing, and MHC independently of the bound peptide. Gamma/delta T cells can also be stimulated by non-peptide antigens such as small phosphate- or amine-containing compounds. The variable domain of gamma/delta TCRs is responsible for antigen recognition and is located at the N-terminus of the receptor. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4335933   24 VTVPEKTVNVKTGGNATLLCTYTSSQplGNFFIQWSFYSAKESQLHTIYYYSEGQSYSYGEFKDRITAATSpgNASITIS 103
Cdd:cd07706   2 VTQAQPDVSVQVGEEVTLNCRYETSW--TNYYLFWYKQLPSGEMTFLIRQDSSEQNAKSGRYSVNFQKAQK--SISLTIS 77

                        90
                ....*....|....*....
gi 4335933  104 NMQPSDTGSYTCEVFSPQD 122
Cdd:cd07706  78 ALQLEDSAKYFCALSLPYD 96

Immunoglobulin (Ig) light chain, kappa type, variable (V) domain; The members here are composed of the immunoglobulin (Ig) light chain, kappa type, variable (V) domain. This group contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. There are two types of light chains: kappa and lambda, each composed of a constant domain (CL) and a variable domain (VL). There are five types of heavy chains (alpha, gamma, delta, epsilon, and mu), which determines the type of immunoglobulin formed: IgA, IgG, IgD, IgE, and IgM, respectively. In higher vertebrates, there are two types of light chain, designated kappa and lambda, which seem to be functionally identical, and can associate with any of the heavy chains.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4335933   22 VVVTVPEKTVNVKTGGNATLLCTytSSQPLGNFFIQWsfYSAKESQLHTIYYYseGQSYSYGEFKDRITAATSPGNASIT 101
Cdd:cd04980   1 IVMTQSPASLSVSPGERVTISCK--ASQSISSNYLAW--YQQKPGQAPKLLIY--YASTLHSGVPSRFSGSGSGTDFTLT 74

                        90
                ....*....|....*
gi 4335933  102 ISNMQPSDTGSYTCE 116
Cdd:cd04980  75 ISSVEPEDAAVYYCQ 89

N-terminal immunoglobulin (Ig)-like domain of T-cell surface antigen CD2, and similar domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain (or domain 1) of T-cell surface antigen Clusters of Differentiation (CD) 2 and similar proteins. CD2 is a T-cell specific surface glycoprotein and is critically important for mediating adhesion between T cells and antigen-presenting cells or between cytolytic T cells and target cells. CD2 is located on chromosome 1 at 1p13 in humans and on chromosome 3 in mice. CD2 contains an extracellular domain with two or Ig-like domains, a single transmembrane segment, and a cytoplasmic region rich in proline and basic residues.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4335933   28 EKTVNVKTGGNATLlctYTSSQPLGNFFIQWSFYSAKESQlhtiYYYSEGQSYsYGEFKDRITAATSPGnaSITISNMQP 107
Cdd:cd05775   2 SGEVYGALGGNVTL---TISSLQDDIDEIKWKKTKDKIVE----WENNIGPTY-FGSFKDRVLLDKESG--SLTIKNLTK 71

                        90       100
                ....*....|....*....|....*.
gi 4335933  108 SDTGSYTCEVFSPQDDAGQSQKSVIV 133
Cdd:cd05775  72 EDSGTYELEITSTNGKVLSSKFTLEV 97

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 4335933   36 GGNATLLCT-YTSSQPLGN----FFIQWSFYSAKESQLH--TIYYYSEGQSYSYGEFKDRITAATSP---GNASITISNM 105
Cdd:cd05714  12 GGNVTLPCKfYRDPTAFGSgihkIRIKWTKLTSDSGYLKevDVLVAMGNVVYHKKTYGGRVSVPLKPgsdSDASLVITDL 91

                        90
                ....*....|..
gi 4335933  106 QPSDTGSYTCEV 117
Cdd:cd05714  92 TASDYGLYRCEV 103

First immunoglobulin (Ig) domain of Cluster of Differentiation (CD) 4; member of the V-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig) domain of Cluster of Differentiation (CD) 4. CD4 and CD8 are the two primary co-receptor proteins found on the surface of T cells, and the presence of either CD4 or CD8 determines the function of the T cell. CD4 is found on helper T cells, where it is required for the binding of MHC (major histocompatibility complex) class II molecules, while CD8 is found on cytotoxic T cells, where it is required for the binding of MHC class I molecules. CD4 contains four immunoglobulin domains, with the first three included in this hierarchy. The fourth domain has a general Ig architecture, but has slight topological changes in the arrangement of beta strands relative to the other structures in this family and is not specifically included in the hierarchy.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4335933   28 EKTVNVKTGGNATLLCTYTSSQPLgnffiqwsFYSAKESQLHTI-----YYYSEGQSYSYGEFKDRITAATSpGNASITI 102
Cdd:cd07690   1 KKVVLGKKGDTAELPCTASQKKSI--------QFHWKNSNQIKIlgnqgSFLTKGPSKLNDRADSRRNLWDQ-GSFPLII 71

                        90
                ....*....|....*
gi 4335933  103 SNMQPSDTGSYTCEV 117
Cdd:cd07690  72 KNLKIEDSDTYICEV 86

First (N-terminal) immunoglobulin (Ig)-like domain of the nectin-like molecules; member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 (CADM3)), Necl-2 (CADM1), Necl-3 (CADM2), and similar proteins. At least five nectin-like molecules have been identified (Necl-1 to Necl-5). They all have an extracellular region containing three Ig-like domains, a transmembrane region, and a cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1, Necl-2, and Necl-3 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue, and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues and is a putative tumour suppressor gene which is downregulated in aggressive neuroblastoma. Necl-3 accumulates in central and peripheral nervous system tissue and has been shown to selectively interact with oligodendrocytes. This group also contains Class-I MHC-restricted T-cell-associated molecule (CRTAM), whose expression pattern is consistent with its expression in Class-I MHC-restricted T-cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4335933   29 KTVNVKTGGNATLLCTYTSSQplgNFFIQWSFYSAkesqlHTIYYysegqsysyGEFK----DRITAAT-SPGNASITIS 103
Cdd:cd05717   4 QDVTVVEGETLTLKCQVSLRD---DSSLQWLNPNG-----QTIYF---------NDKRalrdSRYQLLNhSASELSISVS 66

                        90
                ....*....|....*.
gi 4335933  104 NMQPSDTGSYTCEVFS 119
Cdd:cd05717  67 NVTLSDEGVYTCLHYT 82

Second 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 second immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. 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 4335933  151 EKGHLIYLLCKCdQGLSHPTYRWYKVDENTLTPVTEYFNPD----TGILYIGNLTTFETGHYRCIASNIMGNSTCELDLT 226
Cdd:cd20953  16 SSASSIALLCPA-QGYPAPSFRWYKFIEGTTRKQAVVLNDRvkqvSGTLIIKDAVVEDSGKYLCVVNNSVGGESVETVLT 94