Immunoglobulin variable (IgV)-like domain in complement receptor of the immunoglobulin superfamily (CRIg); The members here are composed of the immunoglobulin variable (IgV) region of the complement receptor of the immunoglobulin superfamily (CRIg). The N-terminal domain of CRIg (also known as Z39Ig and V-set and Ig domain-containing 4 (VSIG4) belongs to the IgV family of immunoglobulin-like domains while the C-terminal domain of CRIg belongs to the IgC family of immunoglobulin-like domains. Like all members of this family, the CRIg domain contains two beta-sheets: one composed of strands A', G, F, C, C' and C", and the other of strands B, E and D. The complement system is an important part of the innate immune system and is required for removal of pathogens from the bloodstream. After exposure to pathogens, the third component of the complement system, C3, is cleaved to C3b which, after recruitment of factor B, initiates formation of the alternative pathway convertases. CRIg, a complement receptor expressed on macrophages, binds to C3b and iC3b mediating phagocytosis of the particles. It is also a potent inhibitor of the alternative pathway convertases and a negative regulator of T cell activation. 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, such as, T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as, 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6005958   21 PILEVPESVTGPWKGDVNLPCTYDPLQGYTQVLVKWLVQRGSDPVTIFLRDSSGDHIQQAKYQGRLHVSHKVPGDVSLQL 100
Cdd:cd16089   1 PILEGPESITGPWKGSVNLPCTYVPEEGYTQVLVKWLVQRDSDPVTIFLRDSSGDHIQQAKYRGRLEVSKDTPGDVSLQL 80

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 6005958  101 STLEMDDRSHYTCEVTWQTPDGNQVVRDKITELRVQK 137
Cdd:cd16089  81 DTLEMDDRGHYTCQVTWQTPDGNLIVREKTTELRVQK 117

Immunoglobulin variable (IgV)-like domain in complement receptor of the immunoglobulin superfamily (CRIg); The members here are composed of the immunoglobulin variable (IgV) region of the complement receptor of the immunoglobulin superfamily (CRIg). The N-terminal domain of CRIg (also known as Z39Ig and V-set and Ig domain-containing 4 (VSIG4) belongs to the IgV family of immunoglobulin-like domains while the C-terminal domain of CRIg belongs to the IgC family of immunoglobulin-like domains. Like all members of this family, the CRIg domain contains two beta-sheets: one composed of strands A', G, F, C, C' and C", and the other of strands B, E and D. The complement system is an important part of the innate immune system and is required for removal of pathogens from the bloodstream. After exposure to pathogens, the third component of the complement system, C3, is cleaved to C3b which, after recruitment of factor B, initiates formation of the alternative pathway convertases. CRIg, a complement receptor expressed on macrophages, binds to C3b and iC3b mediating phagocytosis of the particles. It is also a potent inhibitor of the alternative pathway convertases and a negative regulator of T cell activation. 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, such as, T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as, 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6005958   21 PILEVPESVTGPWKGDVNLPCTYDPLQGYTQVLVKWLVQRGSDPVTIFLRDSSGDHIQQAKYQGRLHVSHKVPGDVSLQL 100
Cdd:cd16089   1 PILEGPESITGPWKGSVNLPCTYVPEEGYTQVLVKWLVQRDSDPVTIFLRDSSGDHIQQAKYRGRLEVSKDTPGDVSLQL 80

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 6005958  101 STLEMDDRSHYTCEVTWQTPDGNQVVRDKITELRVQK 137
Cdd:cd16089  81 DTLEMDDRGHYTCQVTWQTPDGNLIVREKTTELRVQK 117

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 6005958    142 KPTVTTGSGyGFTVPQGMRISLQCQARGSPPISYIWYKQQTNNQE-----PIKVATLSTLLFKPAVIADSGSYFCTAK 214
Cdd:pfam13927   1 KPVITVSPS-SVTVREGETVTLTCEATGSPPPTITWYKNGEPISSgstrsRSLSGSNSTLTISNVTRSDAGTYTCVAS 77

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 6005958     24 EVPESVTGPWKGDVNLPCTYDPLQGYTQVLVKWLVQRGSDPVTIFL---RDSSGDHIQQAKYQGRLHVShkvPGDVSLQL 100
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTYSSSMSEASTSVYWYRQPPGKGPTFLIayySNGSEEGVKKGRFSGRGDPS---NGDGSLTI 77

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 6005958    101 STLEMDDRSHYTCEVTwqtpDGNQVVRDKITELRV 135
Cdd:pfam07686  78 QNLTLSDSGTYTCAVI----PSGEGVFGKGTRLTV 108

Immunoglobulin variable (IgV)-like domain in complement receptor of the immunoglobulin superfamily (CRIg); The members here are composed of the immunoglobulin variable (IgV) region of the complement receptor of the immunoglobulin superfamily (CRIg). The N-terminal domain of CRIg (also known as Z39Ig and V-set and Ig domain-containing 4 (VSIG4) belongs to the IgV family of immunoglobulin-like domains while the C-terminal domain of CRIg belongs to the IgC family of immunoglobulin-like domains. Like all members of this family, the CRIg domain contains two beta-sheets: one composed of strands A', G, F, C, C' and C", and the other of strands B, E and D. The complement system is an important part of the innate immune system and is required for removal of pathogens from the bloodstream. After exposure to pathogens, the third component of the complement system, C3, is cleaved to C3b which, after recruitment of factor B, initiates formation of the alternative pathway convertases. CRIg, a complement receptor expressed on macrophages, binds to C3b and iC3b mediating phagocytosis of the particles. It is also a potent inhibitor of the alternative pathway convertases and a negative regulator of T cell activation. 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, such as, T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as, 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6005958   21 PILEVPESVTGPWKGDVNLPCTYDPLQGYTQVLVKWLVQRGSDPVTIFLRDSSGDHIQQAKYQGRLHVSHKVPGDVSLQL 100
Cdd:cd16089   1 PILEGPESITGPWKGSVNLPCTYVPEEGYTQVLVKWLVQRDSDPVTIFLRDSSGDHIQQAKYRGRLEVSKDTPGDVSLQL 80

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 6005958  101 STLEMDDRSHYTCEVTWQTPDGNQVVRDKITELRVQK 137
Cdd:cd16089  81 DTLEMDDRGHYTCQVTWQTPDGNLIVREKTTELRVQK 117

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 6005958   25 VPESVTGPWKGDVNLPCTYDPLQGYTQVLVKWLVQRG--SDPVTIFlRDSSGDHIqQAKYQGRLHVSHKVPG--DVSLQL 100
Cdd:cd05718   5 VPTEVTGFLGGSVTLPCSLTSPGTTKITQVTWMKIGAgsSQNVAVF-HPQYGPSV-PNPYAERVEFLAARLGlrNATLRI 82

                        90       100       110
                ....*....|....*....|....*....|....*
gi 6005958  101 STLEMDDRSHYTCEVTwQTPDGNqvvRDKITELRV 135
Cdd:cd05718  83 RNLRVEDEGNYICEFA-TFPQGN---RQGTTWLRV 113

Immunoglobulin (Ig)-like domain of human cartilage link protein (LP), and similar domains; The members here are composed of the immunoglobulin (Ig)-like domain similar to that found in human cartilage link protein (LP; also called hyaluronan and proteoglycan link protein). In cartilage, chondroitin-keratan sulfate proteoglycan (CSPG), aggrecan, forms cartilage link protein stabilized aggregates with hyaluronan (HA). These aggregates contribute to the tissue's load bearing properties. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. Members of the vertebrate HPLN (hyaluronan/HA and proteoglycan binding link) protein family are physically linked adjacent to CSPG genes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6005958   35 GDVNLPCTYD---PLQGYTQVLVKWLVQRGSD--PVTIFLrdSSGDHIQQ-AKYQGRLHVSHKVPGDVSLQLSTLEMDDR 108
Cdd:cd05877  13 GNVTLPCRYHyepELSAPRKIRVKWTKLEVDYakEEDVLV--AIGTRHKSyGSYQGRVFLRRADDLDASLVITDLRLEDY 90

                        90       100
                ....*....|....*....|....*...
gi 6005958  109 SHYTCEVTWQTPDGNQVVrdkitELRVQ 136
Cdd:cd05877  91 GRYRCEVIDGLEDESVVV-----ALRLR 113

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 6005958     154 TVPQGMRISLQCQARGSPPISYIWYKQqtnNQEPI---------KVATLSTLLFKPAVIADSGSYFCTAKGQVGSEQHS 223
Cdd:smart00410   5 TVKEGESVTLSCEASGSPPPEVTWYKQ---GGKLLaesgrfsvsRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSG 80

Second 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 second immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. 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 6005958  143 PTVTTGSGYGF-TVPQGMRISLQCQARGSPPISYIWYK--QQTNNQEPI----KVATLS-TLLFKPAVIADSGSYFCTAK 214
Cdd:cd20953   2 PKIPGLSKSQPlTVSSASSIALLCPAQGYPAPSFRWYKfiEGTTRKQAVvlndRVKQVSgTLIIKDAVVEDSGKYLCVVN 81

                ....*.
gi 6005958  215 GQVGSE 220
Cdd:cd20953  82 NSVGGE 87

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6005958  143 PTVTTGSgygfTVPQGMRISLQCQAR-GSPPISYIWYKQQT-NNQEPIKVA-----------TLSTLLFKPAVIADSGSY 209
Cdd:cd20950   1 PTVNIPS----SATIGNRAVLTCSEPdGSPPSEYTWFKDGVvMPTNPKSTRafsnssysldpTTGELVFDPLSASDTGEY 76

                        90
                ....*....|....*...
gi 6005958  210 FCTAKGQVGSEQHSDIVK 227
Cdd:cd20950  77 SCEARNGYGTPMRSNAVR 94

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 6005958    154 TVPQGMRISLQCQARGSPPISYIWYKqqtNNQEpikVATLSTLLFKPAVIADSGSYFCTAKGQVGSEQ 221
Cdd:pfam13895  10 VVTEGEPVTLTCSAPGNPPPSYTWYK---DGSA---ISSSPNFFTLSVSAEDSGTYTCVARNGRGGKV 71

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 6005958  154 TVPQGMRISLQCQARG-SPPISYIWYK--QQTNNQEPIKVATL-----STLLFKPAVIADSGSYFCTAKGQVG 218
Cdd:cd05750  10 TVQEGSKLVLKCEATSeNPSPRYRWFKdgKELNRKRPKNIKIRnkkknSELQINKAKLEDSGEYTCVVENILG 82

Immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6005958  143 PTVTTGSGYGFTVPQGMRISLQCQARGSPPISYIWYKQQTN---NQEPIKVATLST------LLFKPAVIADSGSYFCTA 213
Cdd:cd05874   1 PTITHQSPKDYIVDPRENIVIQCEAKGKPPPSFSWTRNGTHfdiDKDPKVTMKPNTgtlvinIMNGEKAEAYEGVYQCTA 80

                        90
                ....*....|...
gi 6005958  214 KGQVGSEQHSDIV 226
Cdd:cd05874  81 RNERGAAVSNNIV 93

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 6005958  155 VPQGMRISLQCQARGSPPISYIWYKqqtnNQEPIKVA----------TLSTLLFKPAVIADSGSYFCTAKGQVGSEQHS 223
Cdd:cd05857  16 VPAANTVKFRCPAAGNPTPTMRWLK----NGKEFKQEhriggykvrnQHWSLIMESVVPSDKGNYTCVVENEYGSINHT 90

Seventh 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 seventh 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 6005958  155 VPQGMRISLQCQARGSPPISYIW----------YKQQTNNQEpIKVATLSTLLFKPAVIADSGSYFCTAKGQVGS 219
Cdd:cd20954  13 VAAGQDVMLHCQADGFPTPTVTWkkatgstpgeYKDLLYDPN-VRILPNGTLVFGHVQKENEGHYLCEAKNGIGS 86

Immunoglobulin Variable (IgV) domain in HERV-H LTR-associating 2 (HHLA2); The members here are composed of the immunoglobulin variable (IgV) region in HERV-H LTR-associating 2 (HHLA2; also known as B7-H7/B7 homolog 7). HHLA2 is a member of the B7 family of immune regulatory proteins. Mature human HHLA2 consists of an extracellular domain (ECD) with three immunoglobulin-like domains, a transmembrane segment, and a cytoplasmic domain. HHLA2 is widely expressed in human cancers including non-small cell lung carcinoma (NSCLS), triple negative breast cancer (TNBC), and melanoma, but has limited expression on normal tissues. Interestingly, unlike other members of B7 family, HHLA2 is not expressed in mice or rats. HHLA2 functions as a T cell coinhibitory molecules as it inhibits the proliferation of activated CD4(+) and CD8(+) T cells and their cytokine production. Furthermore, HHLA2 is constitutively expressed on the surface of human monocytes and is induced on B cells after stimulation, however it is not inducible on T cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6005958   29 VTGPWKGDVNLPCTYDPLQgytQVLVKWLVQRGSDPVTIFLRDSsgDHI--QQAKYQGR--LHVSHKVPGDVSLQLSTLE 104
Cdd:cd16091   7 VVCLLSEDCILPCSFTPGS---EVVIHWYKQDSDIKVHSYYYGK--DQLesQDQRYRNRtsLFKDQISNGNASLLLRRVQ 81

                        90       100
                ....*....|....*....|
gi 6005958  105 MDDRSHYTCEVTwqTPDGNQ 124
Cdd:cd16091  82 LQDEGRYKCYTS--TIIGNQ 99

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6005958      36 DVNLPCTY--DPLQGYTqvlVKWLVQRGSDPVTIFLRDSSGDH-IQQAKYQGRLHVSHKV-PGDVSLQLSTLEMDDRSHY 111
Cdd:smart00406   1 SVTLSCKFsgSTFSSYY---VSWVRQPPGKGLEWLGYIGSNGSsYYQESYKGRFTISKDTsKNDVSLTISNLRVEDTGTY 77

                   ....
gi 6005958     112 TCEV 115
Cdd:smart00406  78 YCAV 81

Immunoglobulin Variable (IgV) domain of B7-H3, a member of the B7 family of immune checkpoint molecules; The members here are composed of the immunoglobulin variable (IgV) domain of B7-H3 also known as CD276), a member of the B7 family of immune checkpoint molecules. B7-H3 is an important immune checkpoint member of the B7 family and shares homology with other B7 ligands such as programmed death ligand 1 (PD-L1). The B7 family molecules interact with CD28 on T-cells to provide co-stimulatory signals that regulate T-cell activation and T-helper cell differentiation. Although B7-H3 has been shown to have both co-stimulatory and co-inhibitory effects on T-cell responses, the most current studies describe B7-H3 as a T cell inhibitor that promotes tumor aggressiveness and proliferation. Moreover, B7-H3 is highly overexpressed on a wide range of human solid cancers and promotes tumor growth, metastasis, and drug resistance. Thus, B7-H3 expression in tumors often correlates with both negative prognosis and poor clinical outcome in cancer patients. B7-H3 protein contains a predicted signal peptide, V- and C-like Ig domains (IgV and IgC), a transmembrane region, and an intracellular tail.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6005958   24 EVPES-VTGPWKGDVNLPCTYDPLQGYT--QVLVKWLVQRGSDPVTIFLRDSSGDHIQQAKYQGRLHVSHK--VPGDVSL 98
Cdd:cd20934   1 RVPEDpVVALVGTDATLRCSFSPEPGFSlaQLSVFWQLTDTKQLVHSFTESQDQGRDQGSAYANRTALFPDllAQGNASL 80

                        90       100
                ....*....|....*....|....*..
gi 6005958   99 QLSTLEMDDRSHYTCEVTWQTPDGNQV 125
Cdd:cd20934  81 RLQRVRVADEGSYTCFVSVQDFGSAAV 107

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 6005958  168 RGSPPISYIWYKQQTNNQEPIKV-----ATLSTLLFKPAVIADSGSYFCTAKGQVGSEQHSDIVK 227
Cdd:cd05748  17 KGRPTPTVTWSKDGQPLKETGRVqiettASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSATINVK 81

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

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gi 6005958  160 RISLQCQARGSPPISYIWYKQQTNNQEPIKV----------ATLSTLLFKPAVIADSGSYFCTAKGQVGSEQHS 223
Cdd:cd05869  19 QITLTCEASGDPIPSITWRTSTRNISSEEKTldghivvrshARVSSLTLKYIQYTDAGEYLCTASNTIGQDSQS 92

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. 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 lacks a C" strand.

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gi 6005958  143 PTVTTGSGYGFTVPQGMRISLQCQARGSPPISYIWykqqTNNQEPIKVATLSTLLFKPaviaDSGSYFCTAKG 215
Cdd:cd05733   1 PTITEQSPKDYIVDPRDNITIKCEAKGNPQPTFRW----TKDGKFFDPAKDPRVSMRR----RSGTLVIDNHN 65

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6005958  158 GMRISLQCQARGSPPISYIWYK--QQTNNQEPIK---VATLSTLLFKPAVIADSGSYFCTAKGQVGSEQhsDIVKFVVKD 232
Cdd:cd05736  15 GVEASLRCHAEGIPLPRVQWLKngMDINPKLSKQltlIANGSELHISNVRYEDTGAYTCIAKNEGGVDE--DISSLFVED 92

                .
gi 6005958  233 S 233
Cdd:cd05736  93 S 93

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.

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gi 6005958   36 DVNLPCTYDPLQGYTQVLVKWLVQRGSDPVTIFLRDSSGDHIQQAKYQGR--LHVSHKVPGDVSLQLSTLEMDDRSHYTC 113
Cdd:cd20984  14 DGILSCTFTPDIKLSDIVIQWLKEGDSGLVHEFKEGKDELSRQSPMFRGRtsLFADQVHVGNASLRLKNVQLTDAGTYLC 93

                        90
                ....*....|
gi 6005958  114 EVTWQTPDGN 123
Cdd:cd20984  94 IISNSKGTGN 103

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

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gi 6005958  154 TVPQGMRISLQCQARGSPPISYIWYKQqtNNQEPIKVATLST-----LLFKPAVIADSGSYFCTAKGQVGS 219
Cdd:cd20952  10 TVAVGGTVVLNCQATGEPVPTISWLKD--GVPLLGKDERITTlengsLQIKGAEKSDTGEYTCVALNLSGE 78