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 2462523682 148 PQVLVASTTVLELSEAFTLNCSHENgTKPSYTWLKDGKPLLNDSRMLLSPDQKVLTITRVLMEDDDLYSCMVENPISQGR 227
Cdd:cd05740     2 PFISSNNSNPVEDKDAVTLTCEPET-QNTSYLWWFNGQSLPVTPRLTLSNGNRTLTLLNVTREDAGAYQCEISNPVSANR 80

                  ....*....
gi 2462523682 228 SLPVKITVY 236
Cdd:cd05740    81 SDPVTLDVI 89

Immunoglobulin (Ig)-like domain of human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) domains 2, 4, and 6, and similar domains; The members here are composed of the second, fourth, and sixth immunoglobulin (Ig)-like domains in human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) protein subfamily. The CEA family is a group of anchored or secreted glycoproteins expressed by epithelial cells, leukocytes, endothelial cells, and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. This group represents the CEACAM subfamily. CEACAM1 has many important cellular functions; it is a cell adhesion molecule and a signaling molecule that regulates the growth of tumor cells, an angiogenic factor, and a receptor for bacterial and viral pathogens, including mouse hepatitis virus (MHV). In mice, four isoforms of CEACAM1 generated by alternative splicing have either two [D1, D4] or four [D1-D4] Ig-like domains on the cell surface.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462523682 148 PQVLVASTTVLELSEAFTLNCSHENgTKPSYTWLKDGKPLLNDSRMLLSPDQKVLTITRVLMEDDDLYSCMVENPISQGR 227
Cdd:cd05740     2 PFISSNNSNPVEDKDAVTLTCEPET-QNTSYLWWFNGQSLPVTPRLTLSNGNRTLTLLNVTREDAGAYQCEISNPVSANR 80

                  ....*....
gi 2462523682 228 SLPVKITVY 236
Cdd:cd05740    81 SDPVTLDVI 89

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462523682  154 STTVLElSEAFTLNCSHENGTKPSYTWLKDG-KPLLNDSRMLLSPD--QKVLTITRVLMEDDDLYSCMVENPISQGRSlP 230
Cdd:smart00410   3 SVTVKE-GESVTLSCEASGSPPPEVTWYKQGgKLLAESGRFSVSRSgsTSTLTISNVTPEDSGTYTCAATNSSGSASS-G 80

                   ....*
gi 2462523682  231 VKITV 235
Cdd:smart00410  81 TTLTV 85

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462523682   43 IHGTVGKSALLSVQYSSTSSdrPVVKWQLKRDKPVTvvqsigtevigtlrpdYRDRIRLFENG---SLLLSDLQLADEGT 119
Cdd:smart00410   4 VTVKEGESVTLSCEASGSPP--PEVTWYKQGGKLLA----------------ESGRFSVSRSGstsTLTISNVTPEDSGT 65

                           90       100
                   ....*....|....*....|..
gi 2462523682  120 YevEISITDDTFTGEKTINLTV 141
Cdd:smart00410  66 Y--TCAATNSSGSASSGTTLTV 85

IL-1 receptor-like protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462523682 103 ENGS----LLLSDLQLADEGTYEVEISitDDTFTGEKTINLTVDvpisrpqvlvASTTVLELSEAF--TLNCSHENGTKP 176
Cdd:PHA02826   92 EIGDrsenLWIGNVINIDEGIYICTIS--SGNICEESTIRLTFD----------SGTINYQFNSGKdsKLHCYGTDGISS 159

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2462523682 177 SY-----TWLKDGKPLLNDSRMLLSPDQKVLTITRVLMEDDDLYSC 217
Cdd:PHA02826  160 TFkdytlTWYKNGNIVLYTDRIQLRNNNSTLVIKSATHDDSGIYTC 205

Immunoglobulin (Ig)-like domain of human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) domains 2, 4, and 6, and similar domains; The members here are composed of the second, fourth, and sixth immunoglobulin (Ig)-like domains in human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) protein subfamily. The CEA family is a group of anchored or secreted glycoproteins expressed by epithelial cells, leukocytes, endothelial cells, and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. This group represents the CEACAM subfamily. CEACAM1 has many important cellular functions; it is a cell adhesion molecule and a signaling molecule that regulates the growth of tumor cells, an angiogenic factor, and a receptor for bacterial and viral pathogens, including mouse hepatitis virus (MHV). In mice, four isoforms of CEACAM1 generated by alternative splicing have either two [D1, D4] or four [D1-D4] Ig-like domains on the cell surface.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462523682 148 PQVLVASTTVLELSEAFTLNCSHENgTKPSYTWLKDGKPLLNDSRMLLSPDQKVLTITRVLMEDDDLYSCMVENPISQGR 227
Cdd:cd05740     2 PFISSNNSNPVEDKDAVTLTCEPET-QNTSYLWWFNGQSLPVTPRLTLSNGNRTLTLLNVTREDAGAYQCEISNPVSANR 80

                  ....*....
gi 2462523682 228 SLPVKITVY 236
Cdd:cd05740    81 SDPVTLDVI 89

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462523682 147 RPQVLV-ASTTVLELSEAFTLNCSHENGTKPSYTWLKDGKPLLN--DSRMLLSPDQKVLTITRVLMEDDDLYSCMVEN 221
Cdd:pfam13927   1 KPVITVsPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSgsTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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 2462523682  41 RLIHGTVGKSALLSVQYSSTSSDR-PVVKW-QLKRDKPVTVVQSIGTEVIGTLRPDYRDRIR---LFENGSLLLSDLQLA 115
Cdd:pfam07686   4 REVTVALGGSVTLPCTYSSSMSEAsTSVYWyRQPPGKGPTFLIAYYSNGSEEGVKKGRFSGRgdpSNGDGSLTIQNLTLS 83

                          90       100
                  ....*....|....*....|....*.
gi 2462523682 116 DEGTYEVEIsITDDTFTGEKTINLTV 141
Cdd:pfam07686  84 DSGTYTCAV-IPSGEGVFGKGTRLTV 108

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462523682 165 TLNCSHENGTKPSYTWLKDGKPLLNDSRMLLSpDQKVLTITRVLMEDDDLYSCMVENPISQGRS 228
Cdd:cd20957    20 VFNCSVTGNPIHTVLWMKDGKPLGHSSRVQIL-SEDVLVIPSVKREDKGMYQCFVRNDGDSAQA 82

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462523682 152 VASTTVLELSEAFTLNCSHENGTKPSYTWLKDGKPLLNDSRMLLSPDQkvLTITRVLMEDDDLYSCMVEN 221
Cdd:cd05728     5 VISDTEADIGSSLRWECKASGNPRPAYRWLKNGQPLASENRIEVEAGD--LRITKLSLSDSGMYQCVAEN 72

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 2462523682 154 STTVLELSEAFTLNCSHENGT-KPSYTWLKDGKPL-LNDSRMLLSPDQKvLTITRVLMEDDDLYSCMVENPISQGRSLPV 231
Cdd:cd05724     5 SDTQVAVGEMAVLECSPPRGHpEPTVSWRKDGQPLnLDNERVRIVDDGN-LLIAEARKSDEGTYKCVATNMVGERESRAA 83

                  ....
gi 2462523682 232 KITV 235
Cdd:cd05724    84 RLSV 87

Immunoglobulin I-set domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2462523682 175 KPSYTWLKDGKPLLNDSRMLLSPDQKV--LTITRVLMEDDDLYSCMVENPISQ 225
Cdd:pfam07679  29 DPEVSWFKDGQPLRSSDRFKVTYEGGTytLTISNVQPDDSGKYTCVATNSAGE 81

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462523682   43 IHGTVGKSALLSVQYSSTSSdrPVVKWQLKRDKPVTvvqsigtevigtlrpdYRDRIRLFENG---SLLLSDLQLADEGT 119
Cdd:smart00410   4 VTVKEGESVTLSCEASGSPP--PEVTWYKQGGKLLA----------------ESGRFSVSRSGstsTLTISNVTPEDSGT 65

                           90       100
                   ....*....|....*....|..
gi 2462523682  120 YevEISITDDTFTGEKTINLTV 141
Cdd:smart00410  66 Y--TCAATNSSGSASSGTTLTV 85

Second immunoglobulin (Ig)-like domain of protein tyrosine kinase (PTK) 7; The members here are composed of the second immunoglobulin (Ig)-like domain in protein tyrosine kinase (PTK) 7, also known as CCK4. PTK7 is a subfamily of the receptor protein tyrosine kinase family, and is referred to as an RPTK-like molecule. RPTKs transduce extracellular signals across the cell membrane and play important roles in regulating cell proliferation, migration, and differentiation. PTK7 is organized as an extracellular portion having seven Ig-like domains, a single transmembrane region, and a cytoplasmic tyrosine kinase-like domain. PTK7 is considered a pseudokinase as it has several unusual residues in some of the highly conserved tyrosine kinase (TK) motifs; it is predicted to lack TK activity. PTK7 may function as a cell-adhesion molecule. PTK7 mRNA is expressed at high levels in placenta, melanocytes, liver, lung, pancreas, and kidney. PTK7 is overexpressed in several cancers, including melanoma and colon cancer lines.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462523682 153 ASTTVLELSEAFTLNCSHENGTKPSYTWLKDGKPLLND-SRMLLSPDQKVLTITRVLMEDDDLYSCMVENPISQ 225
Cdd:cd05760     8 ASAAEIQPSSRVTLRCHIDGHPRPTYQWFRDGTPLSDGqGNYSVSSKERTLTLRSAGPDDSGLYYCCAHNAFGS 81

First immunoglobulin variable (IgV) domain of nectin-1, and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of nectin-1 (also known as poliovirus receptor related protein 1 (PVRL1) or cluster of differentiation (CD) 111). Nectin-1 belongs to the nectin family comprised of four transmembrane glycoproteins (nectins-1 through -4). Nectins are synaptic cell adhesion molecules (CAMs) which facilitate adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. In addition nectins heterophilically trans-interact with other CAMs such as nectin-like molecules (Necls), nectin-1 for example, has been shown to trans-interact with Necl-1. Nectins also interact with various other proteins, including the actin filament (F-actin)-binding protein, afadin. Mutation in the human nectin-1 gene is associated with cleft lip/palate ectodermal dysplasia syndrome (CLPED1). Nectin-1 is a major receptor for herpes simplex virus through interaction with the viral envelope glycoprotein D.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462523682  82 SIGTEVIgtlrPDYRDRIRL----FENGSLLLSDLQLADEGTYEVEISiTDDTFTGEKTINLTV 141
Cdd:cd05886    54 SMGVSVL----PPYRERVTFlnpsFTDGTIRLSRLELEDEGVYICEFA-TFPTGNRESQLNLTV 112

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; 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. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2462523682 166 LNCSHENGTKPSYTWLKDGKPLLNDSRMLLSPDQK---VLTITRVLMEDDDLYSCMVEN 221
Cdd:cd05729    24 LECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEkgwSLIIERAIPRDKGKYTCIVEN 82

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462523682 145 ISRPQVLVastTVLELSEAfTLNCSHENGTKPSYTWLKDGKPLLNDSRMLLSpDQKVLTITRVLMEDDDLYSCMVENPIS 224
Cdd:cd20968     2 ITRPPTNV---TIIEGLKA-VLPCTTMGNPKPSVSWIKGDDLIKENNRIAVL-ESGSLRIHNVQKEDAGQYRCVAKNSLG 76

                          90
                  ....*....|.
gi 2462523682 225 QGRSLPVKITV 235
Cdd:cd20968    77 IAYSKPVTIEV 87

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
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2462523682 166 LNCSHENGTKPSYTWLKDGKPLLNDSRM---LLSPDQKVLTITRVLMEDDDLYSCMVEN 221
Cdd:cd05857    24 FRCPAAGNPTPTMRWLKNGKEFKQEHRIggyKVRNQHWSLIMESVVPSDKGNYTCVVEN 82

large tegument protein UL36; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462523682  314 DKDSPETEENPAPEPRSATEPGPPGYSVSPAvpGRSPGLPIRSARRYPRSPARSPATGRTHsspprapsspgRSRSASRT 393
Cdd:PHA03247  2604 DRGDPRGPAPPSPLPPDTHAPDPPPPSPSPA--ANEPDPHPPPTVPPPERPRDDPAPGRVS-----------RPRRARRL 2670

                   ....*
gi 2462523682  394 LRTAG 398
Cdd:PHA03247  2671 GRAAQ 2675

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 2462523682  45 GTVGKSALLSVQYS-STSSDRPVVKWQLKRDKPVTVVQSIGTEVIGTLRPDYRDRIRLFE------NGSLLLSDLQLADE 117
Cdd:cd20984     9 GNIGEDGILSCTFTpDIKLSDIVIQWLKEGDSGLVHEFKEGKDELSRQSPMFRGRTSLFAdqvhvgNASLRLKNVQLTDA 88

                          90
                  ....*....|...
gi 2462523682 118 GTYEVEISITDDT 130
Cdd:cd20984    89 GTYLCIISNSKGT 101

Immunoglobulin (Ig)-like domain in the polymeric Ig receptor (pIgR) and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain in the polymeric Ig receptor (pIgR) and similar proteins. pIgR delivers dimeric IgA and pentameric IgM to mucosal secretions. Polymeric immunoglobulin (pIgs) are the first defense against pathogens and toxins. IgA and IgM can form polymers via an 18-residue extension at their C-termini referred to as the tailpiece. pIgR transports pIgs across mucosal epithelia into mucosal secretions. Human pIgR is a glycosylated type I transmembrane protein, comprised of a 620-residue extracellular region, a 23-residue transmembrane region, and a 103-residue cytoplasmic tail. The extracellular region contains five domains that share sequence similarity with Ig variable (v) regions. This group also contains the Ig-like extracellular domains of other receptors such as NK cell receptor Nkp44 and myeloid receptors, among others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462523682 154 STTVLELSEAFTLNCSH-------------ENGTKPSYTWLKDGKPllNDSRMLLSPDQK----VLTITRVLMEDDDLYS 216
Cdd:cd05716     5 EVVTGVEGGSVTIQCPYppkyassrkywckWGSEGCQTLVSSEGVV--PGGRISLTDDPDngvfTVTLNQLRKEDAGWYW 82

                          90
                  ....*....|....*...
gi 2462523682 217 CMVENPISQGRSLPVKIT 234
Cdd:cd05716    83 CGVGDDGDRGLTVQVKLV 100

Fourth 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 fourth 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
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2462523682 176 PSYTWLKDGKPLLNDSRMLL----SPDQKV---LTITRVLMEDDDLYSCMVENPISQ 225
Cdd:cd20956    31 PQITWTLDGFPIPESPRFRVgdyvTSDGDVvsyVNISSVRVEDGGEYTCTATNDVGS 87

IL-1 receptor-like protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462523682 103 ENGS----LLLSDLQLADEGTYEVEISitDDTFTGEKTINLTVDvpisrpqvlvASTTVLELSEAF--TLNCSHENGTKP 176
Cdd:PHA02826   92 EIGDrsenLWIGNVINIDEGIYICTIS--SGNICEESTIRLTFD----------SGTINYQFNSGKdsKLHCYGTDGISS 159

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2462523682 177 SY-----TWLKDGKPLLNDSRMLLSPDQKVLTITRVLMEDDDLYSC 217
Cdd:PHA02826  160 TFkdytlTWYKNGNIVLYTDRIQLRNNNSTLVIKSATHDDSGIYTC 205

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462523682 148 PQVLVASTTVLELSEAFTLNCSHENGTKP--SYTWLKDGKPL---LNDSRMLLSPDQKVLTITRV--LMEDDDLYSCMVE 220
Cdd:cd21008     3 PEVTVFPKSPVTLGQPNTLICLVDNIFPPviNITWLSNGHSVtegVSETSFLSKSDHSFLKISYLtfLPSADDIYDCKVE 82

                  .
gi 2462523682 221 N 221
Cdd:cd21008    83 H 83

Second Ig-like domain of Junctional adhesion molecule-1 (JAM1); a member of the I-set of IgSF domains; The members here are composed of the second Ig-like domain of Junctional adhesion molecule-1 (JAM1). JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The IgSF is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. 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 second Ig-like domain of JAM1 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, the A strand of the I-set is discontinuous but lacks 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 2462523682 165 TLNCSHENGTKPS-YTWLKDGKPL---------LNDSRMLLSPDQKVLTITRVLMEDDDLYSCMVEN 221
Cdd:cd20950    16 VLTCSEPDGSPPSeYTWFKDGVVMptnpkstraFSNSSYSLDPTTGELVFDPLSASDTGEYSCEARN 82

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462523682 168 CSHENGTKPSYTWLKDGKPLLNDSRMLLSPDQKvLTITRVLMEDDDLYSCMVENPISQGRS 228
Cdd:cd04969    24 CKPKASPKPTISWSKGTELLTNSSRICILPDGS-LKIKNVTKSDEGKYTCFAVNFFGKANS 83