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 24646195 197 QTIISQAGTHAYLPCNVKQLVKK-PISWLRMRDGHILT--------VDQTTFIADQRFQSVFSPNpERWSLQIKYVQLKD 267
Cdd:cd00099   6 RSLSVQEGESVTLSCEVSSSFSStYIYWYRQKPGQGPEfliylsssKGKTKGGVPGRFSGSRDGT-SSFSLTISNLQPED 84

                ....*....
gi 24646195 268 EGTYECQVS 276
Cdd:cd00099  85 SGTYYCAVS 93

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 24646195 197 QTIISQAGTHAYLPCNVKQLVKK-PISWLRMRDGHILT--------VDQTTFIADQRFQSVFSPNpERWSLQIKYVQLKD 267
Cdd:cd00099   6 RSLSVQEGESVTLSCEVSSSFSStYIYWYRQKPGQGPEfliylsssKGKTKGGVPGRFSGSRDGT-SSFSLTISNLQPED 84

                ....*....
gi 24646195 268 EGTYECQVS 276
Cdd:cd00099  85 SGTYYCAVS 93

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646195    207 AYLPCNVKQ--LVKKPISWLRMRDGHILTV------DQTTFIADQ---RFQSVFSPNPERWSLQIKYVQLKDEGTYECQV 275
Cdd:smart00406   2 VTLSCKFSGstFSSYYVSWVRQPPGKGLEWlgyigsNGSSYYQESykgRFTISKDTSKNDVSLTISNLRVEDTGTYYCAV 81

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24646195 221 ISWLRmrDGHILTVDqttfiaDQRFQSVfspnpERWSLQIKYVQLKDEGTYECqVSTEPKASAIVH 286
Cdd:cd20952  31 ISWLK--DGVPLLGK------DERITTL-----ENGSLQIKGAEKSDTGEYTC-VALNLSGEATWS 82

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 24646195 197 QTIISQAGTHAYLPCNVKQLVKKPISWLRmRDGHILTVDQTTFIADQRFQSV-FSPNpeRWSLQIKYVQLKDEGTYECQV 275
Cdd:cd05717   4 QDVTVVEGETLTLKCQVSLRDDSSLQWLN-PNGQTIYFNDKRALRDSRYQLLnHSAS--ELSISVSNVTLSDEGVYTCLH 80

                ....
gi 24646195 276 STEP 279
Cdd:cd05717  81 YTDP 84

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24646195   202 QAGTHAYLPCNVKQLVKKPISWLRmrDGHILTvdqttfiADQRFQsvFSPNPERWSLQIKYVQLKDEGTYECQVSTEP-K 280
Cdd:pfam07679  13 QEGESARFTCTVTGTPDPEVSWFK--DGQPLR-------SSDRFK--VTYEGGTYTLTISNVQPDDSGKYTCVATNSAgE 81

                  ....*..
gi 24646195   281 ASAIVHL 287
Cdd:pfam07679  82 AEASAEL 88