Immunoglobulin domain; This family contains immunoglobulin-like domains.

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gi 1917203277  36 PQVTVQPASTVQKPGGTVILGCVVE-PPRMNVTWRLNGKEL-NGSDDALGVLITHGTLVITALNNHTVGRYQCVAR 109
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATgSPPPTITWYKNGEPIsSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVAS 77

Immunoglobulin domain; This family contains immunoglobulin-like domains.

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gi 1917203277  36 PQVTVQPASTVQKPGGTVILGCVVE-PPRMNVTWRLNGKEL-NGSDDALGVLITHGTLVITALNNHTVGRYQCVAR 109
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATgSPPPTITWYKNGEPIsSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVAS 77

Immunoglobulin domain; This family contains immunoglobulin-like domains.

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gi 1917203277  36 PQVTVQPASTVQKPGGTVILGCVVE-PPRMNVTWRLNGKEL-NGSDDALGVLITHGTLVITALNNHTVGRYQCVAR 109
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATgSPPPTITWYKNGEPIsSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVAS 77

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

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1917203277  40 VQPASTVQKPGGTVILGCvvEPPR----MNVTWRLNGKELNgsDDALGVLITH-GTLVITALNNHTVGRYQCVARMPAGA 114
Cdd:cd05724     2 VEPSDTQVAVGEMAVLEC--SPPRghpePTVSWRKDGQPLN--LDNERVRIVDdGNLLIAEARKSDEGTYKCVATNMVGE 77

                  ....*....
gi 1917203277 115 VASVPATVT 123
Cdd:cd05724    78 RESRAARLS 86

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1917203277  37 QVTVQPASTVQKPGGTVILGCVVEP-PRMNVTWRLNGKELNGSDDALgvLITHGTLVITALNNHTVGRYQCVARMPA 112
Cdd:cd20957     3 SATIDPPVQTVDFGRTAVFNCSVTGnPIHTVLWMKDGKPLGHSSRVQ--ILSEDVLVIPSVKREDKGMYQCFVRNDG 77

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

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gi 1917203277  37 QVTVQPASTVQKPGGTVILGCVVE-PPRMNVTWRLNGKELNGSDDALGVLITHGTLVITALNNHTVGRYQCVARMPAG 113
Cdd:cd04978     1 YWIIEPPSLVLSPGETGELICEAEgNPQPTITWRLNGVPIEPAPEDMRRTVDGRTLIFSNLQPNDTAVYQCNASNVHG 78

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.

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gi 1917203277  53 VILGCVVE-PPRMNVTWRLNGKELNGSDDALGVLITH-GTLVITALNNHTVGRYQCVARMPAGAVASVPA 120
Cdd:cd00096     1 VTLTCSASgNPPPTITWYKNGKPLPPSSRDSRRSELGnGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

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

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gi 1917203277  38 VTVQPASTVQKPGGTVILGCVVE-PPRMNVTWRLNGKELNGSDDALGVLiTHGTLVITALNNHTVGRYQCVARMPAGAvA 116
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQATgEPVPTISWLKDGVPLLGKDERITTL-ENGSLQIKGAEKSDTGEYTCVALNLSGE-A 79

                  ....*..
gi 1917203277 117 SVPATVT 123
Cdd:cd20952    80 TWSAVLD 86

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

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gi 1917203277  39 TVQPASTVQKPGGTVILGCVVE---PPRmnVTWRLNGKELNGSDDALGVLITHGTLVITAL-----NNHTVGRYQCVARM 110
Cdd:cd05722     5 LSEPSDIVAMRGGPVVLNCSAEsdpPPK--IEWKKDGVLLNLVSDERRQQLPNGSLLITSVvhskhNKPDEGFYQCVAQN 82

                          90
                  ....*....|....
gi 1917203277 111 -PAGAVASVPATVT 123
Cdd:cd05722    83 eSLGSIVSRTARVT 96

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

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gi 1917203277  62 PRMNVTWRLNGKELNGSDDalgVLITHGTLVITALNNHTVGRYQCVARMPAGAV-ASVPATV 122
Cdd:cd05728    27 PRPAYRWLKNGQPLASENR---IEVEAGDLRITKLSLSDSGMYQCVAENKHGTIyASAELAV 85

Class II major histocompatibility complex (MHC) alpha chain immunoglobulin domain of histocompatibility antigen (HLA) DQ and related proteins; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class II alpha chain of histocompatibility antigen (HLA) DQ. MHC class II molecules are encoded by three different loci, HLA-DR, -DQ, and -DP, which are about 70% similar to each other. HLA-DQ (DQ) is a cell surface receptor protein found on antigen presenting cells. It is an alphabeta heterodimer of type MHC class II. The alpha and beta chains are encoded by two loci, HLA-DQA1 and HLA-DQB1, that are adjacent to each other on chromosome band 6p21.3. A person often produces two alpha-chain and two beta chain variants and thus 4 isoforms of DQ. Two autoimmune diseases in which HLA-DQ is involved are celiac disease and diabetes mellitus type 1. DQ is one of several antigens involved in rejection of organ transplants. DQ8 is a split antigen of the DQ3 broad antigen. MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes, and they are expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway, of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain had two globular domains (N- and C-terminal), and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

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gi 1917203277  34 EVPQVTVQPASTVQkPGGTVILGCVVE---PPRMNVTWRLNGK 73
Cdd:cd21008     1 EVPEVTVFPKSPVT-LGQPNTLICLVDnifPPVINITWLSNGH 42

Immunoglobulin (Ig)-like domain of semaphorin 4D (Sema4D) and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of semaphorin 4D (Sema4D) and similar proteins. Sema4D is a Class IV semaphorin. Semaphorins are classified based on structural features additional to the Sema domain. Sema4D has extracellular Sema and Ig domains, a transmembrane domain, and a short cytoplasmic domain. Sema4D plays a part in the development of GABAergic synapses. Sema4D in addition is an immune semaphorin. It is abundant on resting T cells; its expression is weak on resting B cells and antigen presenting cells (APCs), but is upregulated by various stimuli. The receptor used by Sema4D in the immune system is CD72. Sem4D enhances the activation of B cells and DCs through binding CD72, perhaps by reducing CD72s inhibitory signals. The receptor used by Sema4D in the non-lymphatic tissues is plexin-B1. Sem4D is anchored to the cell surface but its extracellular domain can be released from the cell surface by a metalloprotease-dependent process. Sem4D may mediate its effects in its membrane-bound form and/or its cleaved form.

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gi 1917203277  48 KPGGTVILGCVVEPPRMNVTWRLNGKELNGSDDAlgVLITHGTLVITALNNHTVGRYQCVA 108
Cdd:cd05873     9 KLGGNAELKCSPKSNLARVVWKFQGKVLKAESPK--YGLYGDGLLIFNASEADAGRYQCLS 67

Immunoglobulin (Ig)-like domain of the class IV semaphorin Sema4B; The members here are composed of the immunoglobulin (Ig)-like domain of Sema4B and similar proteins. Sema4B is a Class IV semaphorin. Semaphorins are classified based on structural features additional to the Sema domain. Sema4B has extracellular Sema and Ig domains, a transmembrane domain, and a short cytoplasmic domain. Sema4B has been shown to preferentially regulate the development of the postsynaptic specialization at the glutamatergic synapses. This cytoplasmic domain includes a PDZ-binding motif upon which the synaptic localization of Sem4B is dependent. Sema4B is a ligand of CLCP1. CLCP1 was identified in an expression profiling analysis, which compared a highly metastic lung cancer subline with its low metastic parental line. Sema4B was shown to promote CLCP1 endocytosis and their interaction is a potential target for therapeutic intervention of metastasis.

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gi 1917203277  49 PGGTVILGCvvePPRMNV---TWRLNGKELNGSDDALgVLITHGTLVITALNNHTvGRYQCVA 108
Cdd:cd05872    10 AGADVVLPC---QLRSNLaspVWLFNGTPLNAQFSYL-RLGTDGLLILVTSPEHS-GTYRCYS 67

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

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gi 1917203277  37 QVTVQPASTVQKPGGTVILGCV-VEPPRMNVTWrLNGKELNGSDDALGVLIThGTLVITALNNHTVGRYQCVARMPAGAV 115
Cdd:cd20968     1 KITRPPTNVTIIEGLKAVLPCTtMGNPKPSVSW-IKGDDLIKENNRIAVLES-GSLRIHNVQKEDAGQYRCVAKNSLGIA 78

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gi 1917203277 116 ASVPATV 122
Cdd:cd20968    79 YSKPVTI 85