Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 311033430  158 GSDVILLCSSEeGIPRPTYLWEKLDNTLKLPPT--ATQDQVQGTVTIRNISALSSGLYQCVASN 219
Cdd:pfam13927  16 GETVTLTCEAT-GSPPPTITWYKNGEPISSGSTrsRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Immunoglobulin (Ig)-like domain of protein zero (P0) and similar proteins; The members here are composed of the immunoglobulin (Ig) domain of protein zero (P0), a myelin membrane adhesion molecule. P0 accounts for over 50% of the total protein in peripheral nervous system (PNS) myelin. P0 is a single-pass transmembrane glycoprotein with a highly basic intracellular domain and an extracellular Ig domain. The extracellular domain of P0 (P0-ED) is similar to the Ig variable domain, carrying one acceptor sequence for N-linked glycosylation. P0 plays a role in membrane adhesion in the spiral wraps of the myelin sheath. The intracellular domain is thought to mediate membrane apposition of the cytoplasmic faces and may, through electrostatic interactions, interact directly with lipid headgroups. It is thought that homophilic interactions of the P0 extracellular domain mediate membrane juxtaposition in the extracellular space of PNS myelin. This group also contains the Ig domain of sodium channel subunit beta-2 (SCN2B), and of epithelial V-like antigen 1 (EVA). EVA, also known as myelin protein zero-like 2, is an adhesion molecule, which may play a role in structural organization of the thymus and early lymphocyte development. SCN2B subunits play a role in determining sodium channel density and function in neurons,and in control of electrical excitability in the brain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311033430  29 PGSIQVARGQPAVLPCTFTTSAALIN-LNVIWMVTPLsNANQPEQVILYQGGQMFDGAP-RFHGRVGFTGTMPATNVSIF 106
Cdd:cd05715    6 PRELNVLNGSDVRLTCTFTSCYTVGDaFSVTWTYQPE-GGNTTESMFHYSKGKPYILKVgRFKDRVSWAGNPSKKDASIV 84

                         90       100       110
                 ....*....|....*....|....*....|.
gi 311033430 107 INNTQLSDTGTYQCLVNNLPDIggrnIGVTG 137
Cdd:cd05715   85 ISNLQFSDNGTYTCDVKNPPDI----VGGHG 111

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 311033430 157 IGSDVILLCSSEeGIPRPTYLWEKLDNTLKLPPTATQDQVQGTVTI-RNISALSSGLYQCVASNAIGT 223
Cdd:cd04978   13 PGETGELICEAE-GNPQPTITWRLNGVPIEPAPEDMRRTVDGRTLIfSNLQPNDTAVYQCNASNVHGY 79

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 311033430   158 GSDVILLCSSEeGIPRPTYLWEKLDNTLKLPP---TATQDQVQGTVTIRNISALSSGLYQCVASNAIGTSTCLLDLQV 232
Cdd:smart00410   9 GESVTLSCEAS-GSPPPEVTWYKQGGKLLAESgrfSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTLTV 85

Immunoglobulin (Ig)-like domain of protein zero (P0) and similar proteins; The members here are composed of the immunoglobulin (Ig) domain of protein zero (P0), a myelin membrane adhesion molecule. P0 accounts for over 50% of the total protein in peripheral nervous system (PNS) myelin. P0 is a single-pass transmembrane glycoprotein with a highly basic intracellular domain and an extracellular Ig domain. The extracellular domain of P0 (P0-ED) is similar to the Ig variable domain, carrying one acceptor sequence for N-linked glycosylation. P0 plays a role in membrane adhesion in the spiral wraps of the myelin sheath. The intracellular domain is thought to mediate membrane apposition of the cytoplasmic faces and may, through electrostatic interactions, interact directly with lipid headgroups. It is thought that homophilic interactions of the P0 extracellular domain mediate membrane juxtaposition in the extracellular space of PNS myelin. This group also contains the Ig domain of sodium channel subunit beta-2 (SCN2B), and of epithelial V-like antigen 1 (EVA). EVA, also known as myelin protein zero-like 2, is an adhesion molecule, which may play a role in structural organization of the thymus and early lymphocyte development. SCN2B subunits play a role in determining sodium channel density and function in neurons,and in control of electrical excitability in the brain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311033430  29 PGSIQVARGQPAVLPCTFTTSAALIN-LNVIWMVTPLsNANQPEQVILYQGGQMFDGAP-RFHGRVGFTGTMPATNVSIF 106
Cdd:cd05715    6 PRELNVLNGSDVRLTCTFTSCYTVGDaFSVTWTYQPE-GGNTTESMFHYSKGKPYILKVgRFKDRVSWAGNPSKKDASIV 84

                         90       100       110
                 ....*....|....*....|....*....|.
gi 311033430 107 INNTQLSDTGTYQCLVNNLPDIggrnIGVTG 137
Cdd:cd05715   85 ISNLQFSDNGTYTCDVKNPPDI----VGGHG 111

Immunoglobulin (Ig)-like domain of epithelial V-like antigen (EVA) 1; The members here are composed of the immunoglobulin (Ig) domain of epithelial V-like antigen 1 (EVA 1). EVA is also known as myelin protein zero-like 2. EVA is an adhesion molecule and may play a role in the structural organization of the thymus and early lymphocyte development.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311033430  28 SPGSIQVARGQPAVLPCTFTTSAALIN-LNVIWMVTPLSNAnqPEQVILYQGGQMF---DGapRFHGRVGFTGTMPATNV 103
Cdd:cd05880    5 TSKEVEAVNGTDVRLKCTFSSSAPIGDtLVITWNFRPLDGG--REESVFYYHKRPYpppDG--RFKGRVVWDGNIMRRDA 80

                         90       100
                 ....*....|....*....|....*..
gi 311033430 104 SIFINNTQLSDTGTYQCLVNNLPDIGG 130
Cdd:cd05880   81 SILIWQLQPTDNGTYTCQVKNPPDVHG 107

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 311033430  158 GSDVILLCSSEeGIPRPTYLWEKLDNTLKLPPT--ATQDQVQGTVTIRNISALSSGLYQCVASN 219
Cdd:pfam13927  16 GETVTLTCEAT-GSPPPTITWYKNGEPISSGSTrsRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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 311033430 156 DIGSDVILLCSSEeGIPRPTYLWekLDNTLKLPptaTQDQVQ---GTVTIRNISALSSGLYQCVASNAIGT 223
Cdd:cd05728   12 DIGSSLRWECKAS-GNPRPAYRW--LKNGQPLA---SENRIEveaGDLRITKLSLSDSGMYQCVAENKHGT 76

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 311033430 152 QGSQD----IGSDVILLCSSEeGIPRPTYLWEKLDNTLKLPPTATQDQVQGTVTIRNISALSSGLYQCVASNAIGTST 225
Cdd:cd20952    4 QGPQNqtvaVGGTVVLNCQAT-GEPVPTISWLKDGVPLLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEAT 80

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 311033430  24 EVSESPgsIQVARGQPAVLPCTFTTSAA--LINLNVIWMvtpLSNANQPEQVILYQGGQMFDGAPRFHGRVG-FTGTMPA 100
Cdd:cd20934    1 RVPEDP--VVALVGTDATLRCSFSPEPGfsLAQLSVFWQ---LTDTKQLVHSFTESQDQGRDQGSAYANRTAlFPDLLAQ 75

                         90       100
                 ....*....|....*....|...
gi 311033430 101 TNVSIFINNTQLSDTGTYQCLVN 123
Cdd:cd20934   76 GNASLRLQRVRVADEGSYTCFVS 98

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third 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, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 311033430 158 GSDVILLCSSEeGIPRPTYLWEKLDNtlKLPPTATQ-DQVQGTVTIRNISALSSGLYQCVASNAIGTST 225
Cdd:cd05731   10 GGVLLLECIAE-GLPTPDIRWIKLGG--ELPKGRTKfENFNKTLKIENVSEADSGEYQCTASNTMGSAR 75

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 311033430  157 IGSDVILLCSSEEGIPRPTYLWEKLDNTLKLPPTATQDQV---QGTVTIRNISALSSGLYQCVASNAIG 222
Cdd:pfam00047  10 EGDSATLTCSASTGSPGPDVTWSKEGGTLIESLKVKHDNGrttQSSLLISNVTKEDAGTYTCVVNNPGG 78

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E and, D strands in one sheet and A', G, F, C, C', and C" strands in the other.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311033430  25 VSESPGSIQVARGQPAVLPCTFTTSaaLINLNVIWMVTPLsnaNQPEQVILYQGGQMFDGAPRFHGRvgFTGTMPATNVS 104
Cdd:cd00099    1 VTQSPRSLSVQEGESVTLSCEVSSS--FSSTYIYWYRQKP---GQGPEFLIYLSSSKGKTKGGVPGR--FSGSRDGTSSF 73

                         90
                 ....*....|....*..
gi 311033430 105 IF-INNTQLSDTGTYQC 120
Cdd:cd00099   74 SLtISNLQPEDSGTYYC 90

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 311033430 147 PHCQIQGSQDIGSDVILLCSSEEGIPRPTYLWEKLDNTLKLPPTATQ---------DQVQGTVTIRNISALSSGLYQCVA 217
Cdd:cd20950    1 PTVNIPSSATIGNRAVLTCSEPDGSPPSEYTWFKDGVVMPTNPKSTRafsnssyslDPTTGELVFDPLSASDTGEYSCEA 80

                 ....*.
gi 311033430 218 SNAIGT 223
Cdd:cd20950   81 RNGYGT 86

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 311033430 157 IGSDVILLCSSEEGIPRPTYLWEKLDNTLKL--PPTATQDqvQGTVTIRNISALSSGLYQCVASNAIGT 223
Cdd:cd05724   11 VGEMAVLECSPPRGHPEPTVSWRKDGQPLNLdnERVRIVD--DGNLLIAEARKSDEGTYKCVATNMVGE 77

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 311033430 161 VILLCSSEeGIPRPTYLWEKLDNTLKLPPTATQDQVQGTVTIRNIS-ALSSGLYQCVASNAIGT 223
Cdd:cd04967   22 VALNCRAR-ANPVPSYRWLMNGTEIDLESDYRYSLVDGTLVISNPSkAKDAGHYQCLATNTVGS 84

Immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG); The members here are composed of the immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG). MOG, a minor component of the myelin sheath, is an important CNS-specific autoantigen, linked to the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). It is a transmembrane protein having an extracellular Ig domain. MOG is expressed in the CNS on the outermost lamellae of the myelin sheath, and on the surface of oligodendrocytes, and may participate in the completion, compaction, and/or maintenance of myelin. This group also includes butyrophilin (BTN). BTN is the most abundant protein in bovine milk-fat globule membrane (MFGM).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311033430  31 SIQVARGQPAVLPCTFTTSAALINLNVIWMVTPLSNAnqpeqVILYQGGQMFDG--APRFHGRVGFT-GTMPATNVSIFI 107
Cdd:cd05713    9 PILALVGEDAELPCHLSPKMSAEHMEVRWFRSQFSPV-----VHLYRDGQDQEEeqMPEYRGRTELLkDAIAEGSVALRI 83

                         90
                 ....*....|....*.
gi 311033430 108 NNTQLSDTGTYQCLVN 123
Cdd:cd05713   84 HNVRPSDEGQYTCFFR 99

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third 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 311033430 158 GSDVILLCSSEeGIPRPTYLWEKLDNtlKLPPTATQDQVQGTVTIRNISALSSGLYQCVASNAIGTST 225
Cdd:cd04968   16 GQTVTLECFAL-GNPVPQIKWRKVDG--SPSSQWEITTSEPVLEIPNVQFEDEGTYECEAENSRGKDT 80

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) alpha chain and similar proteins; The members here are composed of the immunoglobulin (Ig) variable domain of the alpha chain of alpha/beta T-cell antigen receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are composed of alpha and beta, or gamma and delta polypeptide chains with variable (V) and constant (C) regions. This group represents the variable domain of the alpha chain of TCRs and also includes the variable domain of delta chains of TCRs. Alpha/beta TCRs recognize antigen as peptide fragments presented by major histocompatibility complex (MHC) molecules. The variable domain of TCRs is responsible for antigen recognition, and is located at the N-terminus of the receptor. Gamma/delta TCRs recognize intact protein antigens directly without antigen processing and recognize MHC independently of the bound peptide. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311033430  25 VSESPGSIQVARGQPAVLPCTFTTSAaliNLNVIWMVtplSNANQPEQVILYQGgqmFDGAPRFHGRVGFTGTMPATNVS 104
Cdd:cd04983    1 VTQSPQSLSVQEGENVTLNCNYSTST---FYYLFWYR---QYPGQGPQFLIYIS---SDSGNKKKGRFSATLDKSRKSSS 71

                         90
                 ....*....|....*.
gi 311033430 105 IFINNTQLSDTGTYQC 120
Cdd:cd04983   72 LHISAAQLSDSAVYFC 87

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 311033430  41 VLPCTFTTSAALInlnVIWMVtplSNANQPEQVILYQGGQMFDGAPRFHGRVG-FTGTMPATNVSIFINNTQLSDTGTYQ 119
Cdd:cd16091   16 ILPCSFTPGSEVV---IHWYK---QDSDIKVHSYYYGKDQLESQDQRYRNRTSlFKDQISNGNASLLLRRVQLQDEGRYK 89

                 ....*
gi 311033430 120 CLVNN 124
Cdd:cd16091   90 CYTST 94

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 311033430 150 QIQGSQDIGSDVILLCSSEeGIPRPTYLWekLDNTLKL---PPTATQDQvqGTVTIRNISALSSGLYQCVASNAIGT 223
Cdd:cd20978    8 EKNVVVKGGQDVTLPCQVT-GVPQPKITW--LHNGKPLqgpMERATVED--GTLTIINVQPEDTGYYGCVATNEIGD 79

Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in Perlecan. Perlecan is a large multi-domain heparin sulfate proteoglycan, important in tissue development and organogenesis. Perlecan can be represented as 5 major portions; its fourth major portion (domain IV) is a tandem repeat of immunoglobulin-like domains (Ig2-Ig15) which can vary in size due to alternative splicing. Perlecan binds many cellular and extracellular ligands. Its domain IV region has many binding sites. Some of these have been mapped at the level of individual Ig-like domains, including a site restricted to the Ig5 domain for heparin/sulfatide, a site restricted to the Ig3 domain for nidogen-1 and nidogen-2, a site restricted to Ig4-5 for fibronectin, and sites restricted to Ig2 and to Ig13-15 for fibulin-2. 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 311033430 158 GSDVILLCSSEEGIPRPTYLWEKLDNTLklpPTATQDqVQGTVTIRNISALSSGLYQCVASNAIGT 223
Cdd:cd05754   16 GADVSFICRAKSKSPAYTLVWTRVNGTL---PSRAMD-FNGILTIRNVQLSDAGTYVCTGSNMLDT 77

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311033430 147 PHCQIQ-GSQD--IGSDVILLCSSEeGIPRPTYLWEK---LDNTLKLPPTATQDQVQ----GTVTIRNISALSSGLYQCV 216
Cdd:cd05734    2 PRFVVQpNDQDgiYGKAVVLNCSAD-GYPPPTIVWKHskgSGVPQFQHIVPLNGRIQllsnGSLLIKHVLEEDSGYYLCK 80

                 ....*..
gi 311033430 217 ASNAIGT 223
Cdd:cd05734   81 VSNDVGA 87

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311033430   24 EVSESPGSIQVARGQPAVLPCTFTtsaalinlnviwmvtplsnANQPEQVILYQGGQMFDGAPRFHGRVGFTgtmpatNV 103
Cdd:pfam13927   3 VITVSPSSVTVREGETVTLTCEAT-------------------GSPPPTITWYKNGEPISSGSTRSRSLSGS------NS 57

                          90       100
                  ....*....|....*....|.
gi 311033430  104 SIFINNTQLSDTGTYQCLVNN 124
Cdd:pfam13927  58 TLTISNVTRSDAGTYTCVASN 78

First immunoglobulin (Ig) variable (V) domain of rat MRC OX-2 antigen, and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of rat MRC OX-2 antigen (also known as CD200) and similar proteins. MRC OX-2 is a membrane glycoprotein expressed in a variety of lymphoid and non-lymphoid cells in rats. It has a similar broad distribution pattern in humans. MRC OX-2 may regulate myeloid cell activity. The protein has an extracellular portion containing two Ig-like domains, a transmembrane portion, and a cytoplasmic portion.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311033430  37 GQPAVLPCTFTTSAALinLNVIWMVTplsNANQPEQVILYQGGQMFDGAPRFHGRVGFTGTMPaTNVSIFINNTQLSDTG 116
Cdd:cd05846   13 GGNATLSCNLTLPEEV--LQVTWQKI---KASSPENIVTYSKKYGVKIQPSYVRRISFTSSGL-NSTSITIWNVTLEDEG 86

                         90       100
                 ....*....|....*....|....
gi 311033430 117 TYQCLVNNLPDigGRNIGVTGLTV 140
Cdd:cd05846   87 CYKCLFNTFPD--GIKSGTACLTV 108

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. 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 telokin Ig domain 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 311033430 169 EGIPRPTYLWEKLDNTLKLPPTATQDQVQG---TVTIRNISALSSGLYQCVASNAIGTSTCLLDLQV 232
Cdd:cd20973   22 EGYPDPEVKWMKDDNPIVESRRFQIDQDEDglcSLIISDVCGDDSGKYTCKAVNSLGEATCSAELTV 88

First immunoglobulin variable (IgV) domain of DNAX accessory molecule 1, and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of DNAX accessory molecule 1 (DNAM-1, also known as CD226). DNAM-1 is a transmembrane protein having two Ig-like domains. It is an adhesion molecule which plays a part in tumor-directed cytotoxicity and adhesion in natural killer (NK) cells and T lymphocytes. It has been shown to regulate the NK cell killing of several tumor types, including myeloma cells and ovarian carcinoma cells. DNAM-1 interacts specifically with poliovirus receptor (PVR; CD155) and nectin -2 (CD211), other members of the Ig superfamily. DNAM-1 is expressed in most peripheral T cells, NK cells, monocytes and a subset of B lymphocytes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311033430  41 VLPCTFTTSAALINlnVIWMVTPlsnaNQPEQVILY--QGGQMFDgaPRFHGRVGF-TGTMPATNVSIFINNTQLSDTGT 117
Cdd:cd05889   18 SLECVYPSTGILTQ--VEWTKIG----GQKDNIAVYhpTHGMHIR--KPYAGRVYFlNSTMASNNMSLSFRNASEDDVGY 89

                         90
                 ....*....|
gi 311033430 118 YQCLVNNLPD 127
Cdd:cd05889   90 YSCSLYTYPQ 99

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 311033430 159 SDVILLCSSEeGIPRPTYLWEK-LDNTLKLPPTATQD---QVQGTVTIRNISALSSGLYQCVASNAIG 222
Cdd:cd20953   19 SSIALLCPAQ-GYPAPSFRWYKfIEGTTRKQAVVLNDrvkQVSGTLIIKDAVVEDSGKYLCVVNNSVG 85

Immunoglobulin Variable (IgV) domain at the N-terminus of CD33 and related Siglecs (sialic acid-binding Ig-like lectins); The members here are composed of the immunoglobulin (Ig) domain at the N-terminus of Cluster of Differentiation (CD) 33 and related Siglecs (sialic acid-binding Ig-like lectins). Siglec refers to a structurally related protein family that specifically recognizes sialic acid in oligosaccharide chains of glycoproteins and glycolipids. Siglecs are type I transmembrane proteins, organized as an extracellular module composed of Ig-like domains, an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains, followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG, the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311033430  27 ESPGSIQVARGQPAVLPCTFT------TSAALInlnVIW--------MVTPLSNANQPEQVilyqggqmfdgAPRFHGRV 92
Cdd:cd05712    4 QMPKSVTVQEGLCVLIPCSFSypadywVSNPVH---GYWyrggpypkYRPPVATNNRTREV-----------HESTQGRF 69

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 311033430  93 GFTGTMPATNVSIFINNTQLSDTGTYQCLVnnlpDIGGRNI 133
Cdd:cd05712   70 RLLGDPGKKNCSLSISDARPEDSGKYFFRV----ERGDSNK 106

Immunoglobulin-like Ig0 domain of basigin-1 (BSG1) and similar proteins; The members here are composed of the immunoglobulin (Ig) domain of the collagenase stimulatory factor, basigin-1 (BSG1; also known as Cluster of Differentiation 147 (CD147) and Extracellular Matrix Metalloproteinase Inducer (EMMPRIN)) and similar proteins. CD147 is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily. It is expressed in nearly all cells including platelets and fibroblasts and is involved in inflammatory diseases, and cancer progression. CD147 is highly expressed in several cancers and used as a prognostic marker. The two primary isoforms of CD147 that are related to cancer progression have been identified: CD147 Ig1-Ig2 (also called Basigin-2) that is ubiquitously expressed in most tissues and CD147 Ig0-Ig1-Ig2 (also called Basigin-1) that is retinal specific and implicated in retinoblastoma. Studies showed that CD147 Ig0 domain is a potent stimulator of interleukin-6 and suggest that the CD147 Ig0 dimer is the functional unit required for activity.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 311033430  68 NQPEQVIlyqgGQMFDGAPRFHGRVGFTGTMPATNvSIFINNTQLSDTGTYQCLVNNLPD 127
Cdd:cd20940   39 QEPNEIC----SQLWDGARLDRVHINATYHQHATS-TISIDNLTEEDTGTYECRASNDPD 93

Immunoglobulin (Ig) light chain, kappa type, variable (V) domain; The members here are composed of the immunoglobulin (Ig) light chain, kappa type, variable (V) domain. This group contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. There are two types of light chains: kappa and lambda, each composed of a constant domain (CL) and a variable domain (VL). There are five types of heavy chains (alpha, gamma, delta, epsilon, and mu), which determines the type of immunoglobulin formed: IgA, IgG, IgD, IgE, and IgM, respectively. In higher vertebrates, there are two types of light chain, designated kappa and lambda, which seem to be functionally identical, and can associate with any of the heavy chains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311033430  23 LEVSESPGSIQVARGQPAVLPCTFTTSAALINLNviWMvtpLSNANQPEQVILYQGGQMFDGAPrfhGRvgFTGTMPATN 102
Cdd:cd04980    1 IVMTQSPASLSVSPGERVTISCKASQSISSNYLA--WY---QQKPGQAPKLLIYYASTLHSGVP---SR--FSGSGSGTD 70

                         90
                 ....*....|....*....
gi 311033430 103 VSIFINNTQLSDTGTYQCL 121
Cdd:cd04980   71 FTLTISSVEPEDAAVYYCQ 89

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.