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 296434251  21 PILEVPESVTGPWKGDVNLPCTYDPLQGYTQVLVKWLVQRGSDPVTIFLRDSSGDHIQQAKYQGRLHVSHKVPGDVSLQL 100
Cdd:cd16089    1 PILEGPESITGPWKGSVNLPCTYVPEEGYTQVLVKWLVQRDSDPVTIFLRDSSGDHIQQAKYRGRLEVSKDTPGDVSLQL 80

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 296434251 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 296434251  21 PILEVPESVTGPWKGDVNLPCTYDPLQGYTQVLVKWLVQRGSDPVTIFLRDSSGDHIQQAKYQGRLHVSHKVPGDVSLQL 100
Cdd:cd16089    1 PILEGPESITGPWKGSVNLPCTYVPEEGYTQVLVKWLVQRDSDPVTIFLRDSSGDHIQQAKYRGRLEVSKDTPGDVSLQL 80

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 296434251 101 STLEMDDRSHYTCEVTWQTPDGNQVVRDKITELRVQK 137
Cdd:cd16089   81 DTLEMDDRGHYTCQVTWQTPDGNLIVREKTTELRVQK 117

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 296434251  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 296434251   24 EVPESVTGPWKGDVNLPCTYDPLQGYTQVLVKWLVQR-GSDPVTIFLR--DSSGDHIQQAKYQGRLHVShkvPGDVSLQL 100
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTYSSSMSEASTSVYWYRQPpGKGPTFLIAYysNGSEEGVKKGRFSGRGDPS---NGDGSLTI 77

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 296434251  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 296434251  21 PILEVPESVTGPWKGDVNLPCTYDPLQGYTQVLVKWLVQRGSDPVTIFLRDSSGDHIQQAKYQGRLHVSHKVPGDVSLQL 100
Cdd:cd16089    1 PILEGPESITGPWKGSVNLPCTYVPEEGYTQVLVKWLVQRDSDPVTIFLRDSSGDHIQQAKYRGRLEVSKDTPGDVSLQL 80

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 296434251 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 296434251  25 VPESVTGPWKGDVNLPCTYDPLQGYTQVLVKWLVQRG--SDPVTIFlRDSSGDHIqQAKYQGRLHVSHKVPG--DVSLQL 100
Cdd:cd05718    5 VPTEVTGFLGGSVTLPCSLTSPGTTKITQVTWMKIGAgsSQNVAVF-HPQYGPSV-PNPYAERVEFLAARLGlrNATLRI 82

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 296434251 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 296434251  35 GDVNLPCTYD---PLQGYTQVLVKWLVQRGSD--PVTIFLrdSSGDHIQQ-AKYQGRLHVSHKVPGDVSLQLSTLEMDDR 108
Cdd:cd05877   13 GNVTLPCRYHyepELSAPRKIRVKWTKLEVDYakEEDVLV--AIGTRHKSyGSYQGRVFLRRADDLDASLVITDLRLEDY 90

                         90       100
                 ....*....|....*....|....*...
gi 296434251 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 296434251   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 296434251 143 PTVTTGSGYGF-TVPQGMRISLQCQARGSPPISYIWYK--QQTNNQEPI----KVATLS-TLLFKPAVIADSGSYFCTAK 214
Cdd:cd20953    2 PKIPGLSKSQPlTVSSASSIALLCPAQGYPAPSFRWYKfiEGTTRKQAVvlndRVKQVSgTLIIKDAVVEDSGKYLCVVN 81

                 ....*.
gi 296434251 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 296434251 143 PTVTTGSgygfTVPQGMRISLQCQAR-GSPPISYIWYKQQT-NNQEPIKVA-----------TLSTLLFKPAVIADSGSY 209
Cdd:cd20950    1 PTVNIPS----SATIGNRAVLTCSEPdGSPPSEYTWFKDGVvMPTNPKSTRafsnssysldpTTGELVFDPLSASDTGEY 76

                         90
                 ....*....|....*...
gi 296434251 210 FCTAKGQVGSEQHSDIVK 227
Cdd:cd20950   77 SCEARNGYGTPMRSNAVR 94

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. 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 Lingo-1 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 296434251 153 FTVPQGMRISLQCQARGSPPISYIWYKQ-----QTNNQEPIKVATLSTLLFKPAVIADSGSYFCTAKGQVGSEQ 221
Cdd:cd20969   12 VFVDEGHTVQFVCRADGDPPPAILWLSPrkhlvSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGNDS 85

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 296434251 154 TVPQGMRISLQCQARG-SPPISYIWYK--QQTNNQEPIKVATL-----STLLFKPAVIADSGSYFCTAKGQVG 218
Cdd:cd05750   10 TVQEGSKLVLKCEATSeNPSPRYRWFKdgKELNRKRPKNIKIRnkkknSELQINKAKLEDSGEYTCVVENILG 82

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 296434251 160 RISLQCQARGSPPISYIWYKQQTN-NQEPIKVATL---STLLFKPAVIADSGSYFCTAKGQVGS 219
Cdd:cd05848   21 KVILNCEARGNPVPTYRWLRNGTEiDTESDYRYSLidgNLIISNPSEVKDSGRYQCLATNSIGS 84

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first 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. This group belongs to the I-set of IgSF domains.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 296434251 160 RISLQCQARGSPPISYIWYKQQTN-NQEPIKVATL---STLLFKPAVIADSGSYFCTAKGQVGS 219
Cdd:cd04967   21 KVALNCRARANPVPSYRWLMNGTEiDLESDYRYSLvdgTLVISNPSKAKDAGHYQCLATNTVGS 84

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
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 296434251 164 QCQARGSPPISYIWYK--QQTNNQEPIKVATlSTLLFKPAVIADSGSYFCTAKGQVGS 219
Cdd:cd05728   20 ECKASGNPRPAYRWLKngQPLASENRIEVEA-GDLRITKLSLSDSGMYQCVAENKHGT 76

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 296434251 155 VPQGMRISLQCQARGSPPISYIW----------YKQQTNNQEpIKVATLSTLLFKPAVIADSGSYFCTAKGQVGS 219
Cdd:cd20954   13 VAAGQDVMLHCQADGFPTPTVTWkkatgstpgeYKDLLYDPN-VRILPNGTLVFGHVQKENEGHYLCEAKNGIGS 86

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296434251    36 DVNLPCTY--DPLQGYTqvlVKWLVQRGSDPVTIFLRDSSGDH-IQQAKYQGRLHVSHKV-PGDVSLQLSTLEMDDRSHY 111
Cdd:smart00406   1 SVTLSCKFsgSTFSSYY---VSWVRQPPGKGLEWLGYIGSNGSsYYQESYKGRFTISKDTsKNDVSLTISNLRVEDTGTY 77

                   ....
gi 296434251   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 296434251  24 EVPES-VTGPWKGDVNLPCTYDPLQGYT--QVLVKWLVQRGSDPVTIFLRDSSGDHIQQAKYQGRLHVSHK--VPGDVSL 98
Cdd:cd20934    1 RVPEDpVVALVGTDATLRCSFSPEPGFSlaQLSVFWQLTDTKQLVHSFTESQDQGRDQGSAYANRTALFPDllAQGNASL 80

                         90       100
                 ....*....|....*....|....*..
gi 296434251  99 QLSTLEMDDRSHYTCEVTWQTPDGNQV 125
Cdd:cd20934   81 RLQRVRVADEGSYTCFVSVQDFGSAAV 107

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 296434251 160 RISLQCQARGSPPISYIWYKQQTNNQEPIKV----------ATLSTLLFKPAVIADSGSYFCTAKGQVGSEQHS 223
Cdd:cd05869   19 QITLTCEASGDPIPSITWRTSTRNISSEEKTldghivvrshARVSSLTLKYIQYTDAGEYLCTASNTIGQDSQS 92

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.

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gi 296434251 168 RGSPPISYIWYKQQTNNQEPIKV-----ATLSTLLFKPAVIADSGSYFCTAKGQVGSEQHSDIVK 227
Cdd:cd05748   17 KGRPTPTVTWSKDGQPLKETGRVqiettASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSATINVK 81

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 296434251 143 PTVTTGSGYGFTVPQGMRISLQCQARGSPPISYIWykqqTNNQEPIKVATLSTLLFKPaviaDSGSYFCTAKG 215
Cdd:cd05733    1 PTITEQSPKDYIVDPRDNITIKCEAKGNPQPTFRW----TKDGKFFDPAKDPRVSMRR----RSGTLVIDNHN 65

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.

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gi 296434251  154 TVPQGMRISLQCQAR-GSPPISYIWYKQQTNNQEPIKVA------TLSTLLFKPAVIADSGSYFCTA 213
Cdd:pfam00047   7 TVLEGDSATLTCSAStGSPGPDVTWSKEGGTLIESLKVKhdngrtTQSSLLISNVTKEDAGTYTCVV 73

Immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

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gi 296434251 157 QGMRISLQCQARGSPPISYIWYKQQT--NNQEPIK--VAT-------LSTLLFKPAVIADSGSYFCTA 213
Cdd:cd05735   17 KGQKKEMSCTAHGEKPIIVRWEKEDTiiNPSEMSRylVTTkevgdevISTLQILPTVREDSGFFSCHA 84

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 296434251 154 TVPQGMRISLQCQARGSPPISYIWYKQqtNNQEPIKVATLST-----LLFKPAVIADSGSYFCTAKGQVGS 219
Cdd:cd20952   10 TVAVGGTVVLNCQATGEPVPTISWLKD--GVPLLGKDERITTlengsLQIKGAEKSDTGEYTCVALNLSGE 78

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (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. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). 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 296434251 154 TVPQGMRISLQCQARGSPPISYIWYKQQTNNQEP-------IKV---ATLSTLLFKPAVIADSGSYFCTAKGQVGSEQHS 223
Cdd:cd05732   12 TAVELEQITLTCEAEGDPIPEITWRRATRGISFEegdldgrIVVrghARVSSLTLKDVQLTDAGRYDCEASNRIGGDQQS 91