Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617769  125 SNVTTQIGTHAYLPCRVKQLGNKSVSWirLRDGHILTvdravfiADQRFLaIKQPDKYWTLQIKYVQARDAGSYECQVST 204
Cdd:pfam07679   8 KDVEVQEGESARFTCTVTGTPDPEVSW--FKDGQPLR-------SSDRFK-VTYEGGTYTLTISNVQPDDSGKYTCVATN 77

                          90
                  ....*....|...
gi 442617769  205 EP-KVSARVQLQV 216
Cdd:pfam07679  78 SAgEAEASAELTV 90

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617769  222 EILGEPDRY-VKAGSNVVLRCIVRGalEPPTFIMWYHGaeqlaadsrrhrTQLDPNLPEASGEGQSTIGSLIIESAKKRD 300
Cdd:pfam13927   3 VITVSPSSVtVREGETVTLTCEATG--SPPPTITWYKN------------GEPISSGSTRSRSLSGSNSTLTISNVTRSD 68

                          90
                  ....*....|
gi 442617769  301 TGNYTCSPSN 310
Cdd:pfam13927  69 AGTYTCVASN 78

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617769 223 ILGEPDRY-VKAGSNVVLRCIVRGalEPPTFIMWYHGAEQLAADSRRHRTQldPNlpeasgegqstiGSLIIESAKKRDT 301
Cdd:cd20952    2 ILQGPQNQtVAVGGTVVLNCQATG--EPVPTISWLKDGVPLLGKDERITTL--EN------------GSLQIKGAEKSDT 65

                         90       100
                 ....*....|....*....|..
gi 442617769 302 GNYTC---SPSNSPSATVTLNI 320
Cdd:cd20952   66 GEYTCvalNLSGEATWSAVLDV 87

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 442617769 127 VTTQIGTHAYLPCRVKQL-GNKSVSWIRLRDGHILT--------VDRAVFIADQRFLAIKQPDKYWTLQIKYVQARDAGS 197
Cdd:cd00099    8 LSVQEGESVTLSCEVSSSfSSTYIYWYRQKPGQGPEfliylsssKGKTKGGVPGRFSGSRDGTSSFSLTISNLQPEDSGT 87

                 ....*.
gi 442617769 198 YECQVS 203
Cdd:cd00099   88 YYCAVS 93

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617769  222 EILGEPDRY-VKAGSNVVLRCIVRGalEPPTFIMWYHGaeqlaadsrrhrTQLDPNLPEASGEGQSTIGSLIIESAKKRD 300
Cdd:pfam13927   3 VITVSPSSVtVREGETVTLTCEATG--SPPPTITWYKN------------GEPISSGSTRSRSLSGSNSTLTISNVTRSD 68

                          90
                  ....*....|
gi 442617769  301 TGNYTCSPSN 310
Cdd:pfam13927  69 AGTYTCVASN 78

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617769  125 SNVTTQIGTHAYLPCRVKQLGNKSVSWirLRDGHILTvdravfiADQRFLaIKQPDKYWTLQIKYVQARDAGSYECQVST 204
Cdd:pfam07679   8 KDVEVQEGESARFTCTVTGTPDPEVSW--FKDGQPLR-------SSDRFK-VTYEGGTYTLTISNVQPDDSGKYTCVATN 77

                          90
                  ....*....|...
gi 442617769  205 EP-KVSARVQLQV 216
Cdd:pfam07679  78 SAgEAEASAELTV 90

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617769   125 SNVTTQIGTHAYLPCRVKQLGNKSVSWIRLRDGHILTVDRavfiadqrfLAIKQPDKYWTLQIKYVQARDAGSYECQVST 204
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGR---------FSVSRSGSTSTLTISNVTPEDSGTYTCAATN 72

                           90
                   ....*....|...
gi 442617769   205 E-PKVSARVQLQV 216
Cdd:smart00410  73 SsGSASSGTTLTV 85

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 442617769  230 YVKAGSNVVLRCIVRGALEPPTFImWYHGAEQLAADSRRHRTqldpnlpeasgEGQSTIGSLIIESAKKRDTGNYTCSPS 309
Cdd:pfam00047   7 TVLEGDSATLTCSASTGSPGPDVT-WSKEGGTLIESLKVKHD-----------NGRTTQSSLLISNVTKEDAGTYTCVVN 74

                  ....
gi 442617769  310 NSPS 313
Cdd:pfam00047  75 NPGG 78

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 442617769 127 VTTQIGTHAYLPCRVKQL-GNKSVSWIRLRDGHILT--------VDRAVFIADQRFLAIKQPDKYWTLQIKYVQARDAGS 197
Cdd:cd00099    8 LSVQEGESVTLSCEVSSSfSSTYIYWYRQKPGQGPEfliylsssKGKTKGGVPGRFSGSRDGTSSFSLTISNLQPEDSGT 87

                 ....*.
gi 442617769 198 YECQVS 203
Cdd:cd00099   88 YYCAVS 93

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. 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. The fourth Ig-like domain of hemolin 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 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, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617769 231 VKAGSNVVLRCIVRGalEPPTFIMWYHGAEQLaaDSRRHRTQLdpnlpeasgegqsTIGSLIIESAKKRDTGNYTCSPSN 310
Cdd:cd20978   13 VKGGQDVTLPCQVTG--VPQPKITWLHNGKPL--QGPMERATV-------------EDGTLTIINVQPEDTGYYGCVATN 75

                 ....*..
gi 442617769 311 SPSATVT 317
Cdd:cd20978   76 EIGDIYT 82

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. 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 titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617769 229 RYVKAGSNVVLRCIVRGAlePPTFIMWYHGAEQLAadsrrhrtqldpNLPEASGEGQSTIGSLIIESAKKRDTGNYTCSP 308
Cdd:cd20972   11 QEVAEGSKVRLECRVTGN--PTPVVRWFCEGKELQ------------NSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLA 76

                 ...
gi 442617769 309 SNS 311
Cdd:cd20972   77 TNS 79

First (N-terminal) immunoglobulin (Ig)-like domain of nectin-like molecule-3; 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-3, Necl-3 (also known as cell adhesion molecule 2 (CADM2), SynCAM2, IGSF4D). 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-3 accumulates in central and peripheral nervous system tissue, and has been shown to selectively interact with oligodendrocytes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617769 124 TSNVTTQIGTHAYLPCRVKQLGNKSVSWIRLRDGHILTVDRAVfIADQRFLAIKQPDKYWTLQIKYVQARDAGSYECQVS 203
Cdd:cd07701    4 TQNVTVVEGGTANLTCRVDQNDNTSLQWSNPAQQTLYFDDKKA-LRDNRIELVRASWHELSISISDVSLSDEGQYTCSLF 82

                         90
                 ....*....|....
gi 442617769 204 TEPKVSARVQLQVV 217
Cdd:cd07701   83 TMPVKTSKAYLTVL 96

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617769 231 VKAGSNVVLRCIVRGAlePPTFIMWYHGAEQLAADSR------RHRTQldpnlpeasgegqstigSLIIESAKKRDTGNY 304
Cdd:cd05857   16 VPAANTVKFRCPAAGN--PTPTMRWLKNGKEFKQEHRiggykvRNQHW-----------------SLIMESVVPSDKGNY 76

                         90
                 ....*....|....*....
gi 442617769 305 TCSPSN---SPSATVTLNI 320
Cdd:cd05857   77 TCVVENeygSINHTYHLDV 95

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617769 230 YVKAGSNVVLRCIVRGalEPPTFIMWYHGAEQLAADSRrhrtqldpnlpeASGEGQSTIGSLIIESAKKRDTGNYTCSPS 309
Cdd:cd05748    3 VVRAGESLRLDIPIKG--RPTPTVTWSKDGQPLKETGR------------VQIETTASSTSLVIKNAKRSDSGKYTLTLK 68

                         90
                 ....*....|...
gi 442617769 310 N-SPSATVTLNII 321
Cdd:cd05748   69 NsAGEKSATINVK 81

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 442617769 126 NVTTQIGTHAYLPCRVKQLGNKS---VSWIRLRDGHILTVdrAVF------------IADQRFLAIKQPDKYWTLQIKYV 190
Cdd:cd05718    8 EVTGFLGGSVTLPCSLTSPGTTKitqVTWMKIGAGSSQNV--AVFhpqygpsvpnpyAERVEFLAARLGLRNATLRIRNL 85

                         90       100
                 ....*....|....*....|....*...
gi 442617769 191 QARDAGSYECQVSTEPKVSARVQLQVVV 218
Cdd:cd05718   86 RVEDEGNYICEFATFPQGNRQGTTWLRV 113

C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C); The members here are composed of the C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C). MyBP-C consists of repeated domains, Ig and fibronectin type 3, and various linkers. Three isoforms of MYBP-C exist: slow-skeletal (ssMyBP-C), fast-skeletal (fsMyBP-C), and cardiac (cMyBP-C). cMYBP-C has insertions between and inside domains and an additional cardiac-specific Ig domain at the N-terminus. For cMYBP_C an interaction has been demonstrated between this C5 domain and the Ig C8 domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617769 231 VKAGSNVVLRCIVRGalEPPTFIMWYHGAEQLAADSRRHRTqldpnlpeasgEGQSTIGSLIIESAKKRDTGNYTCS--- 307
Cdd:cd05894    7 VVAGNKLRLDVPISG--EPAPTVTWSRGDKAFTATEGRVRV-----------ESYKDLSSFVIEGAEREDEGVYTITvtn 73

                         90
                 ....*....|...
gi 442617769 308 PSNSPSATVTLNI 320
Cdd:cd05894   74 PVGEDHASLFVKV 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 442617769 123 ATSNVTTQIGTHAYLPCRVKQLGNKSVSWIRlRDGHILTVDRAVFIADQRFLAIKQPDKYWTLQIKYVQARDAGSYECQV 202
Cdd:cd05717    2 HTQDVTVVEGETLTLKCQVSLRDDSSLQWLN-PNGQTIYFNDKRALRDSRYQLLNHSASELSISVSNVTLSDEGVYTCLH 80

                         90
                 ....*....|....
gi 442617769 203 STEPKVSARVQLQV 216
Cdd:cd05717   81 YTDPVSTKKVTVTV 94

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617769 126 NVTTQIGTHAYLPCRVKQLGNKSVSWirLRDGHILTVDravfiaDQRFLAIKQPdkywTLQIKYVQARDAGSYEC-QVST 204
Cdd:cd20952    8 NQTVAVGGTVVLNCQATGEPVPTISW--LKDGVPLLGK------DERITTLENG----SLQIKGAEKSDTGEYTCvALNL 75

                         90
                 ....*....|..
gi 442617769 205 EPKVSARVQLQV 216
Cdd:cd20952   76 SGEATWSAVLDV 87

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617769 126 NVTTQIGTHAYLPCRVKQLGNKSVSWIRlrDGHILTVDR--AVFiadqrflaikqPDKywTLQIKYVQ-ARDAGSYECQV 202
Cdd:cd20958    9 NLTAVAGQTLRLHCPVAGYPISSITWEK--DGRRLPLNHrqRVF-----------PNG--TLVIENVQrSSDEGEYTCTA 73

                         90
                 ....*....|....*.
gi 442617769 203 STEPKVSARVQLQVVV 218
Cdd:cd20958   74 RNQQGQSASRSVFVKV 89

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617769 127 VTTQIGTHAYLPCRV--KQLGNKSVSWIRLRDG----HILTVDRAVFIADQ------RFLAIKQPDKY-WTLQIKYVQAR 193
Cdd:cd04982    8 ITREESKSVTISCKVsgIDFSTTYIHWYRQKPGqaleRLLYVSSTSAVRKDsgktknKFEARKDVGKStSTLTITNLEKE 87

                 ....*..
gi 442617769 194 DAGSYEC 200
Cdd:cd04982   88 DSATYYC 94

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617769 124 TSNVTTQIGTHAYLPCRVKQLGNKSVSWIRLRDgHILTVDRAVFIADQRFLAIKQPDKYWTLQIKYVQARDAGSYECQVS 203
Cdd:cd05882    4 TQDETVAVGGTVTLKCGVKEHDNSSLQWSNTAQ-QTLYFGEKRALRDNRIQLVKSTPTELIISISNVQLSDEGEYTCSIF 82

                         90
                 ....*....|...
gi 442617769 204 TEPKVSARVQLQV 216
Cdd:cd05882   83 TMPVRTAKATVTV 95