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 144953878  34 QVIQPEKSVSVAAGESATLRCAMTSLIPVGPIMWFRGAGAGRELIYNQKEGHFPRVTTVSELTKRNNLDFSISISNITPA 113
Cdd:cd16097    1 QVIQPEKSVSVAAGESATLHCTVTSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRISNITPA 80

                         90       100       110
                 ....*....|....*....|....*....|.
gi 144953878 114 DAGTYYCVKFRKGSPDDVEFKSGAGTELSVR 144
Cdd:cd16097   81 DAGTYYCVKFRKGSPDDVEFKSGAGTELSVR 111

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 144953878  34 QVIQPEKSVSVAAGESATLRCAMTSLIPVGPIMWFRGAGAGRELIYNQKEGHFPRVTTVSELTKRNNLDFSISISNITPA 113
Cdd:cd16097    1 QVIQPEKSVSVAAGESATLHCTVTSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRISNITPA 80

                         90       100       110
                 ....*....|....*....|....*....|.
gi 144953878 114 DAGTYYCVKFRKGSPDDVEFKSGAGTELSVR 144
Cdd:cd16097   81 DAGTYYCVKFRKGSPDDVEFKSGAGTELSVR 111

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 144953878    40 KSVSVAAGESATLRCAmTSLIPVGPIMWFRGAGagRELIYNQKeghfprvTTVSeltkRNNLDFSISISNITPADAGTYY 119
Cdd:smart00410   2 PSVTVKEGESVTLSCE-ASGSPPPEVTWYKQGG--KLLAESGR-------FSVS----RSGSTSTLTISNVTPEDSGTYT 67

                           90       100
                   ....*....|....*....|....
gi 144953878   120 CVkfrkGSPDDVEFKSgaGTELSV 143
Cdd:smart00410  68 CA----ATNSSGSASS--GTTLTV 85

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 144953878  34 QVIQPEKSVSVAAGESATLRCAMTSLIPVGPIMWFRGAGAGRELIYNQKEGHFPRVTTVSELTKRNNLDFSISISNITPA 113
Cdd:cd16097    1 QVIQPEKSVSVAAGESATLHCTVTSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRISNITPA 80

                         90       100       110
                 ....*....|....*....|....*....|.
gi 144953878 114 DAGTYYCVKFRKGSPDDVEFKSGAGTELSVR 144
Cdd:cd16097   81 DAGTYYCVKFRKGSPDDVEFKSGAGTELSVR 111

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 144953878   37 QPEKSVSVAAGESATLRCAMTSLI--PVGPIMWFRG-AGAGRE---LIYNQKEGHFPRVTTVSELTKRNNLDFSISISNI 110
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTYSSSMseASTSVYWYRQpPGKGPTfliAYYSNGSEEGVKKGRFSGRGDPSNGDGSLTIQNL 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 144953878  111 TPADAGTYYCVKFrkgspDDVEFKSGAGTELSVR 144
Cdd:pfam07686  81 TLSDSGTYTCAVI-----PSGEGVFGKGTRLTVL 109

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 144953878  33 LQVIQPEKSVSVAAGESATLRCAMTSLIPVGPIMWfrgagagreliYNQKEGHFPRVTTVSELTKRNNL----------- 101
Cdd:cd04980    1 IVMTQSPASLSVSPGERVTISCKASQSISSNYLAW-----------YQQKPGQAPKLLIYYASTLHSGVpsrfsgsgsgt 69

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 144953878 102 DFSISISNITPADAGTYYCVKFRKgSPddveFKSGAGTELSV 143
Cdd:cd04980   70 DFTLTISSVEPEDAAVYYCQQGYT-FP----YTFGGGTKLEI 106

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 144953878   37 QPEKSVSVAAGESATLRCAMTSLIPVGPIMWFRgagAGRELIYNQKEGHFPRVTTVSELTkrnnldfsisISNITPADAG 116
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSASTGSPGPDVTWSK---EGGTLIESLKVKHDNGRTTQSSLL----------ISNVTKEDAG 67

                          90
                  ....*....|....*....
gi 144953878  117 TYYCVKFRKGSPDDVEFKS 135
Cdd:pfam00047  68 TYTCVVNNPGGSATLSTSL 86

First immunoglobulin variable (IgV) domain of poliovirus receptor (PVR, also known as CD155 and necl-5), and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of poliovirus receptor (PVR, also known as CD155 and nectin-like protein 5 (necl-5)). Poliovirus (PV) binds to its cellular receptor (PVR/CD155) to initiate infection. CD155 is a membrane-anchored, single-span glycoprotein; its extracellular region has three Ig-like domains. There are four different isotypes of CD155 (referred to as alpha, beta, gamma, and delta), that result from alternate splicing of the CD155 mRNA, and have identical extracellular domains. CD155-beta and CD155-gamma are secreted; CD155-alpha and CD155-delta are membrane-bound and function as PV receptors. The virus recognition site is contained in the amino-terminal domain, D1. Having the virus attachment site on the receptor distal from the plasma membrane may be important for successful initiation of infection of cells by the virus. CD155 binds in the poliovirus "canyon" with a footprint similar to that of the intercellular adhesion molecule-1 receptor on human rhinoviruses. This group also includes the first Ig-like domain of nectin-1 (also known as poliovirus receptor related protein(PVRL)1; CD111), nectin-3 (also known as PVRL 3), nectin-4 (also known as PVRL4; LNIR receptor)and DNAX accessory molecule 1 (DNAM-1; CD226).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 144953878  34 QVIQPEKSVSVAAGESATLRCAMTSLIP--VGPIMWFRGAGAGRELI--YNQKEG-HFP-----RVTTVSELTKRNNLdf 103
Cdd:cd05718    1 QRVQVPTEVTGFLGGSVTLPCSLTSPGTtkITQVTWMKIGAGSSQNVavFHPQYGpSVPnpyaeRVEFLAARLGLRNA-- 78

                         90       100
                 ....*....|....*....|....*.
gi 144953878 104 SISISNITPADAGTYYC--VKFRKGS 127
Cdd:cd05718   79 TLRIRNLRVEDEGNYICefATFPQGN 104

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 144953878  40 KSVSVAAGESATLRCAMTSLIPVGP---IMW-FRGAGAGRE--LIYNQKEGHFP-------RVTTVSELTKRnnlDFSIS 106
Cdd:cd05880    7 KEVEAVNGTDVRLKCTFSSSAPIGDtlvITWnFRPLDGGREesVFYYHKRPYPPpdgrfkgRVVWDGNIMRR---DASIL 83

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 144953878 107 ISNITPADAGTYYC-VKfrkgSPDDVEFKSGagtELSVR 144
Cdd:cd05880   84 IWQLQPTDNGTYTCqVK----NPPDVHGPIG---EIRLR 115

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 144953878  40 KSVSVAAGESATLRCAMTSLIPVG---PIMW-FRGAGAGREL---------IYNQKEGHFP-RVTTVSELTKRnnlDFSI 105
Cdd:cd05715    7 RELNVLNGSDVRLTCTFTSCYTVGdafSVTWtYQPEGGNTTEsmfhyskgkPYILKVGRFKdRVSWAGNPSKK---DASI 83

                         90       100       110
                 ....*....|....*....|....*....|..
gi 144953878 106 SISNITPADAGTYYC-VKfrkgSPDDVEFKSG 136
Cdd:cd05715   84 VISNLQFSDNGTYTCdVK----NPPDIVGGHG 111

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) gamma chain; The members here are composed of the immunoglobulin (Ig) variable (V) domain of the gamma 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 antigens as peptide fragments presented by major histocompatibility complex (MHC) molecules. Gamma/delta TCRs recognize intact protein antigens directly without antigen processing and recognize 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 the standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 144953878  37 QPEKSVSVAAGESATLRCAMTSL-IPVGPIMWFRG-AGAGRE-LIY------NQKEGHFPRVTTVSELTKRNNLdFSISI 107
Cdd:cd04982    3 QPQLSITREESKSVTISCKVSGIdFSTTYIHWYRQkPGQALErLLYvsstsaVRKDSGKTKNKFEARKDVGKST-STLTI 81

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 144953878 108 SNITPADAGTYYCVKFRKGSPDDVE-FksGAGTELSV 143
Cdd:cd04982   82 TNLEKEDSATYYCAYWESGSGYYIKvF--GSGTKLIV 116

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 144953878  35 VIQPEkSVSVAAGESATLRCAMTSL-IPVGPIMWfrgagagreliYNQKEGHFPRvtTVSELTKR-------------NN 100
Cdd:cd04984    2 LTQPS-SLSVSPGETVTITCTGSSGnISGNYVNW-----------YQQKPGSAPR--YLIYEDKHrpsgipdrfsgskSG 67

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 144953878 101 LDFSISISNITPADAGTYYCvkfrkGSPDDVEFKSGAGTELSV 143
Cdd:cd04984   68 NTASLTISGAQTEDEADYYC-----QVWDSNSYVFGGGTKLTV 105

Immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1; The members here are composed of the immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. NRG-1 belongs to the neuregulin gene family which is comprised of four genes. This group represents NRG-1. NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, and heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. The NRG-1 protein binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. NRG-1 has multiple functions, for example, in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 144953878  40 KSVSVAAGESATLRCAMTSLIPVGPIMWFRGagaGRELIYNQKEGH--FPRVTTVSELtkrnnldfsiSISNITPADAGT 117
Cdd:cd05895    7 KSQEVAAGSKLVLRCETSSEYPSLRFKWFKN---GKEINRKNKPENikIQKKKKKSEL----------RINKASLADSGE 73

                 ...
gi 144953878 118 YYC 120
Cdd:cd05895   74 YMC 76

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 144953878  36 IQPeKSVSVAAGESATLRCAMTSLIPVGPIMWFRGagaGRELIYNQkeghfPRVTTVSeltkrnnlDFSISISNITPADA 115
Cdd:cd05724    2 VEP-SDTQVAVGEMAVLECSPPRGHPEPTVSWRKD---GQPLNLDN-----ERVRIVD--------DGNLLIAEARKSDE 64

                 ....*.
gi 144953878 116 GTYYCV 121
Cdd:cd05724   65 GTYKCV 70

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        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 144953878  35 VIQPEKSVSVAAGESATLRCamtsliPVG--PI---MWFRGagaGRELIYNQKEGHFPRVTTVseltkrnnldfsisISN 109
Cdd:cd20958    3 FIRPMGNLTAVAGQTLRLHC------PVAgyPIssiTWEKD---GRRLPLNHRQRVFPNGTLV--------------IEN 59

                         90
                 ....*....|...
gi 144953878 110 ITPA-DAGTYYCV 121
Cdd:cd20958   60 VQRSsDEGEYTCT 72

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 144953878  50 ATLRCAMTSlIPVGPIMWFRGagagRELIYNQKEGHFPRVTTVSELTkrnnldfsisISNITPADAGTYYCV 121
Cdd:cd00096    1 VTLTCSASG-NPPPTITWYKN----GKPLPPSSRDSRRSELGNGTLT----------ISNVTLEDSGTYTCV 57

First immunoglobulin (Ig) domain of nectin-4, and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of nectin-4 (also known as poliovirus receptor related protein 4 or LNIR receptor). Nectin-4 belongs to the nectin family, which is comprised of four transmembrane glycoproteins (nectins-1 through -4). Nectins are synaptic cell adhesion molecules (CAMs) which participate in adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. For example nectin-4 trans-interacts with nectin-1. Nectin-4 has also been shown to interact with the actin filament-binding protein, afadin. Unlike the other nectins, which are widely expressed in adult tissues, nectin-4 is mainly expressed during embryogenesis, and is not detected in normal adult tissue or in serum. Nectin-4 is re-expressed in breast carcinoma, and patients having metastatic breast cancer have a circulating form of nectin-4 formed from the ectodomain

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 144953878  40 KSVSVAAGESATLRC--AMTSLIPVGPIMWFR-GAGAGRE--LIYNQKEGH--FPRVT-TVSELTKRNNLDFSISISNIT 111
Cdd:cd05888    1 DVVTVVLGQDAKLPCfyRGDSGEQVGQVAWARvDAGEGAQeiALLHSKYGLhvFPAYEgRVEQPPPPRPADGSVLLRNAV 80

                 ....*....
gi 144953878 112 PADAGTYYC 120
Cdd:cd05888   81 QADEGEYEC 89

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

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gi 144953878  33 LQVIQPEKSVSVAAGESATLRCAMT-SLIPVGP--IMWFRGAGAGRE---------LIYNQ-KEGHFPRVTTVSELTKRn 99
Cdd:cd20960    1 LLITSAQTEIKKVAGENVTLPCHHQlGLEDQGTldIEWLLLPSDKVEkvvitysgdRVYNHyYPALKGRVAFTSNDLSG- 79

                         90       100
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gi 144953878 100 nlDFSISISNITPADAGTYYCvKFRKG 126
Cdd:cd20960   80 --DASLNISNLKLSDTGTYQC-KVKKA 103