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 1214357793  26 ESPGSIQVARGQPAVLPCTFTTSAALINLNVIWMVTPLSnaNQPEQVILYQGGQmfDGAPRFHGRVGFTGTMPATNVSIF 105
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTYSSSMSEASTSVYWYRQPPG--KGPTFLIAYYSNG--SEEGVKKGRFSGRGDPSNGDGSLT 76

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1214357793 106 INNTQLSDTGTYQCLVNnlPDIGGRNIGVTGLTVL 140
Cdd:pfam07686  77 IQNLTLSDSGTYTCAVI--PSGEGVFGKGTRLTVL 109

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 1214357793  26 ESPGSIQVARGQPAVLPCTFTTSAALINLNVIWMVTPLSnaNQPEQVILYQGGQmfDGAPRFHGRVGFTGTMPATNVSIF 105
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTYSSSMSEASTSVYWYRQPPG--KGPTFLIAYYSNG--SEEGVKKGRFSGRGDPSNGDGSLT 76

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1214357793 106 INNTQLSDTGTYQCLVNnlPDIGGRNIGVTGLTVL 140
Cdd:pfam07686  77 IQNLTLSDSGTYTCAVI--PSGEGVFGKGTRLTVL 109

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1214357793 157 GSDVILLCSSEeGIPRPTYLWEKlDNTLKLP---PTATQDQVQGTVTIRNISALSSGLYQCVASN 218
Cdd:pfam13927  16 GETVTLTCEAT-GSPPPTITWYK-NGEPISSgstRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1214357793   28 PGSIQVARGQPAVLPCTFTTSAaliNLNVIWMvtplsnaNQPEQVILYQGGqmfdgaprfhgrvgFTGTMPATNVSIFIN 107
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSP---PPEVTWY-------KQGGKLLAESGR--------------FSVSRSGSTSTLTIS 56

                           90
                   ....*....|....*.
gi 1214357793  108 NTQLSDTGTYQCLVNN 123
Cdd:smart00410  57 NVTPEDSGTYTCAATN 72

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 1214357793  26 ESPGSIQVARGQPAVLPCTFTTSAALINLNVIWMVTPLSnaNQPEQVILYQGGQmfDGAPRFHGRVGFTGTMPATNVSIF 105
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTYSSSMSEASTSVYWYRQPPG--KGPTFLIAYYSNG--SEEGVKKGRFSGRGDPSNGDGSLT 76

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1214357793 106 INNTQLSDTGTYQCLVNnlPDIGGRNIGVTGLTVL 140
Cdd:pfam07686  77 IQNLTLSDSGTYTCAVI--PSGEGVFGKGTRLTVL 109

Immunoglobulin Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins; The members here are composed of the Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins. CAR, which is encoded by human CXADR gene, is a cell adhesion molecule of the Immunoglobulin (Ig) superfamily. The CAR acts as a type I membrane receptor for group B1-B6 coxsackie viruses and subgroup C adenoviruses. For instance, adenovirus interacts with the coxsackievirus and adenovirus receptor to enter epithelial airway cells. The CAR is also shown to be involved in physiological processes such as neuronal and heart development, epithelial tight junction integrity, and tumor suppression. The CAR is a component of the epithelial apical junction complex that may function as a homophilic cell adhesion molecule and is essential for tight junction integrity. The CAR is also involved in transepithelial migration of leukocytes through adhesive interactions with JAML a transmembrane protein of the plasma membrane of leukocytes. The interaction between both receptors also mediates the activation of gamma-delta T-cells, a subpopulation of T-cells residing in epithelia and involved in tissue homeostasis and repair. The CAR is composed of one V-set and one C2-set Ig module, a single transmembrane helix, and an intracellular domain. This group belongs to the V-set of IgSF domains, having A, B, E and D strands in one beta-sheet and A', G, F, C, C' and C" in the other

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1214357793  30 SIQVARGQPAVLPCTFTTSAALIN-LNVIWMVTPLSNANQpeQVILYQGGQMFDG-APRFHGRVGFTGTMPATNVSIFIN 107
Cdd:cd20960     9 EIKKVAGENVTLPCHHQLGLEDQGtLDIEWLLLPSDKVEK--VVITYSGDRVYNHyYPALKGRVAFTSNDLSGDASLNIS 86

                          90       100
                  ....*....|....*....|....*...
gi 1214357793 108 NTQLSDTGTYQCLVNNLPDIGGRNIGVT 135
Cdd:cd20960    87 NLKLSDTGTYQCKVKKAPGYAWSKITLI 114

Immunoglobulin Variable (IgV) domain of B7-H4; The members here are composed of the immunoglobulin variable (IgV) domain of B7-H4 (also known as B7-S1, B7x, or Vtcn1). B7-H4 is one of the B7 family of immune-regulatory ligands that act as negative regulators of T cell function; it contains one IgV domain and one IgC domain. The B7-family consists of structurally related cell-surface protein ligands, which bind to receptors on lymphocytes that regulate immune responses. The binding of B7-H4 to unidentified receptors results in the inhibition of TCR-mediated T cell proliferation, cell-cycle progression and IL-2 production. As a co-inhibitory molecule, B7-H4 is widely expressed in tumor tissues and its expression is significantly associated with poor prognosis in human cancers such as glioma, pancreatic cancer, oral squamous cell carcinoma, renal cell carcinoma, and lung cancer.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1214357793  35 RGQPAVLPCTFTTSAALINLNVIWMVTPLSNANQPEQvilYQGGQMFDGAPRFHGRVG-FTGTMPATNVSIFINNTQLSD 113
Cdd:cd20984    11 IGEDGILSCTFTPDIKLSDIVIQWLKEGDSGLVHEFK---EGKDELSRQSPMFRGRTSlFADQVHVGNASLRLKNVQLTD 87

                          90       100
                  ....*....|....*....|..
gi 1214357793 114 TGTYQCLVNNLPDIGGRNIGVT 135
Cdd:cd20984    88 AGTYLCIISNSKGTGNANMEYK 109

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 1214357793 156 IGSDVILLCSSEeGIPRPTYLWEKLDNTLKLPPTATQDQVQGTVTI-RNISALSSGLYQCVASNAIGT 222
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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1214357793   28 PGSIQVARGQPAVLPCTFTTSAaliNLNVIWMvtplsnaNQPEQVILYQGGqmfdgaprfhgrvgFTGTMPATNVSIFIN 107
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSP---PPEVTWY-------KQGGKLLAESGR--------------FSVSRSGSTSTLTIS 56

                           90
                   ....*....|....*.
gi 1214357793  108 NTQLSDTGTYQCLVNN 123
Cdd:smart00410  57 NVTPEDSGTYTCAATN 72

First immunoglobulin (Ig) domain of nectin-4, and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of nectin-4 (also known as poliovirus receptor related protein 4 or LNIR receptor). Nectin-4 belongs to the nectin family, which is comprised of four transmembrane glycoproteins (nectins-1 through -4). Nectins are synaptic cell adhesion molecules (CAMs) which participate in adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. For example nectin-4 trans-interacts with nectin-1. Nectin-4 has also been shown to interact with the actin filament-binding protein, afadin. Unlike the other nectins, which are widely expressed in adult tissues, nectin-4 is mainly expressed during embryogenesis, and is not detected in normal adult tissue or in serum. Nectin-4 is re-expressed in breast carcinoma, and patients having metastatic breast cancer have a circulating form of nectin-4 formed from the ectodomain

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1214357793  30 SIQVARGQPAVLPCTFTTSAALINLNVIWMvtpLSNANQPEQVIL---YQGGQMFDGAprFHGRVGFTGTMPATNVSIFI 106
Cdd:cd05888     2 VVTVVLGQDAKLPCFYRGDSGEQVGQVAWA---RVDAGEGAQEIAllhSKYGLHVFPA--YEGRVEQPPPPRPADGSVLL 76

                          90
                  ....*....|....*....
gi 1214357793 107 NNTQLSDTGTYQCLVNNLP 125
Cdd:cd05888    77 RNAVQADEGEYECRVSTFP 95

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 1214357793  25 SESPGSIQVARGQPAVLPCTFTTSAALINLN---VIWmvTPLSNANQPEQVILYQGGQMFDGAPRFHGRVGFTGTMPaTN 101
Cdd:cd05877     1 ETVQAKVFSHRGGNVTLPCRYHYEPELSAPRkirVKW--TKLEVDYAKEEDVLVAIGTRHKSYGSYQGRVFLRRADD-LD 77

                          90       100
                  ....*....|....*....|....*.
gi 1214357793 102 VSIFINNTQLSDTGTYQC-LVNNLPD 126
Cdd:cd05877    78 ASLVITDLRLEDYGRYRCeVIDGLED 103

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1214357793 157 GSDVILLCSSEeGIPRPTYLWEKLDNTLKLPP--TATQDqvqGTVTIRNISALSSGLYQCVASNAIGT--STCLLDL 229
Cdd:cd04969    17 GGDVIIECKPK-ASPKPTISWSKGTELLTNSSriCILPD---GSLKIKNVTKSDEGKYTCFAVNFFGKanSTGSLSV 89

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 1214357793  24 VSESPGSIQVARGQPAVLPCTFTTSaaLINLNVIWMVTPLsnaNQPEQVILYQGGQMFDGAPRFHGRvgFTGTMPATNVS 103
Cdd:cd00099     1 VTQSPRSLSVQEGESVTLSCEVSSS--FSSTYIYWYRQKP---GQGPEFLIYLSSSKGKTKGGVPGR--FSGSRDGTSSF 73

                          90
                  ....*....|....*..
gi 1214357793 104 IF-INNTQLSDTGTYQC 119
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 1214357793 146 PHCQIQGSQDIGSDVILLCSSEEGIPRPTYLWEKLDNTLKLPPTATQ---------DQVQGTVTIRNISALSSGLYQCVA 216
Cdd:cd20950     1 PTVNIPSSATIGNRAVLTCSEPDGSPPSEYTWFKDGVVMPTNPKSTRafsnssyslDPTTGELVFDPLSASDTGEYSCEA 80

                  ....*.
gi 1214357793 217 SNAIGT 222
Cdd:cd20950    81 RNGYGT 86

Immunoglobulin (Ig)-like domain of protein zero (P0); 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 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1214357793  36 GQPAVLPCTFTTSAALI-NLNVIWMVTPlSNANQPEQVILYQGGQMF-DGAPRFHGRVGFTGTMPATNVSIFINNTQLSD 113
Cdd:cd05879    14 GSDVTLSCSFWSSEWISdDISFTWHYQP-DGSRDAISIFHYGKGQPYiDNVGPFKERIEWVGNPSRKDGSIVIHNLDYTD 92

                          90       100
                  ....*....|....*....|..
gi 1214357793 114 TGTYQCLVNNLPDIGGRNIGVT 135
Cdd:cd05879    93 NGTFTCDVKNPPDIVGKSSQVT 114

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 1214357793 160 VILLCSSEeGIPRPTYLWEKLDNTLKLPPTATQDQVQGTVTIRNIS-ALSSGLYQCVASNAIGT 222
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 1214357793  30 SIQVARGQPAVLPCTFTTSAALINLNVIWMVTPLSNAnqpeqVILYQGGQMFDG--APRFHGRVGFT-GTMPATNVSIFI 106
Cdd:cd05713     9 PILALVGEDAELPCHLSPKMSAEHMEVRWFRSQFSPV-----VHLYRDGQDQEEeqMPEYRGRTELLkDAIAEGSVALRI 83

                          90
                  ....*....|....*.
gi 1214357793 107 NNTQLSDTGTYQCLVN 122
Cdd:cd05713    84 HNVRPSDEGQYTCFFR 99

First immunoglobulin (Ig) domain of contactin-2; 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-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. 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. 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-2 is also expressed in retinal amacrine cells in the developing chick retina, corresponding to the period of formation and maturation of AC processes. This group belongs to the I-set of IgSF domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1214357793 160 VILLCSSEEGiPRPTYLWEKLDNTLKLPPTATQDQVQGTVTIRN-ISALSSGLYQCVASNAIGT 222
Cdd:cd05850    23 VTLACRARAS-PPATYRWKMNGTELKMEPDSRYRLVAGNLVISNpVKAKDAGSYQCLASNRRGT 85

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1214357793 155 DIGSDVILLCSSEeGIPRPTYLWEKLDNTLKLPPTATQDQVQGT-VTIRNISALSSGLYQCVASN-AIGTSTCLLDLQV 231
Cdd:cd20970    15 REGENATFMCRAE-GSPEPEISWTRNGNLIIEFNTRYIVRENGTtLTIRNIRRSDMGIYLCIASNgVPGSVEKRITLQV 92

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 1214357793  40 VLPCTFTTSAALInlnVIWMVtplSNANQPEQVILYQGGQMFDGAPRFHGRVG-FTGTMPATNVSIFINNTQLSDTGTYQ 118
Cdd:cd16091    16 ILPCSFTPGSEVV---IHWYK---QDSDIKVHSYYYGKDQLESQDQRYRNRTSlFKDQISNGNASLLLRRVQLQDEGRYK 89

                  ....*
gi 1214357793 119 CLVNN 123
Cdd:cd16091    90 CYTST 94

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1214357793 156 IGSDVILLCSSEeGIPRPTYLWEKldNTLKLPPTA----TQDQVQGTVTIRNISALSSGLYQCVASNAIGTSTCLLDLQV 231
Cdd:pfam07679  14 EGESARFTCTVT-GTPDPEVSWFK--DGQPLRSSDrfkvTYEGGTYTLTISNVQPDDSGKYTCVATNSAGEAEASAELTV 90

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. 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 this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus 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 1214357793 157 GSDVILLCSSEeGIPRPTYLWEKLDNTLKLPPTATQDQVQ-GTVTIRNISALSSGLYQCVASNAIGTSTCLLDLQV 231
Cdd:cd20976    16 GQDFVAQCSAR-GKPVPRITWIRNAQPLQYAADRSTCEAGvGELHIQDVLPEDHGTYTCLAKNAAGQVSCSAWVTV 90

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 1214357793 146 PHCQIQ-GSQD--IGSDVILLCSSEeGIPRPTYLWEK---LDNTLKLPPTATQDQVQ----GTVTIRNISALSSGLYQCV 215
Cdd:cd05734     2 PRFVVQpNDQDgiYGKAVVLNCSAD-GYPPPTIVWKHskgSGVPQFQHIVPLNGRIQllsnGSLLIKHVLEEDSGYYLCK 80

                  ....*..
gi 1214357793 216 ASNAIGT 222
Cdd:cd05734    81 VSNDVGA 87

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 1214357793  36 GQPAVLPCTFTTSAALINLNVIWMvtpLSNANQPEQVILYQGGQMFDGAPRFHGRVGFT-GTMPATNVSIFINNTQLSDT 114
Cdd:cd05718    14 GGSVTLPCSLTSPGTTKITQVTWM---KIGAGSSQNVAVFHPQYGPSVPNPYAERVEFLaARLGLRNATLRIRNLRVEDE 90

                          90       100
                  ....*....|....*....|....*
gi 1214357793 115 GTYQCLVNNLPdiGGRNIGVTGLTV 139
Cdd:cd05718    91 GNYICEFATFP--QGNRQGTTWLRV 113

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1214357793 155 DIGSDVILLCSSEeGIPRPTYLWekLDNTLKLPPTATQDQVQ----GTVTIRNISALSSGLYQCVASNAIGTSTCLLDLQ 230
Cdd:cd20969    15 DEGHTVQFVCRAD-GDPPPAILW--LSPRKHLVSAKSNGRLTvfpdGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLH 91

                  .
gi 1214357793 231 V 231
Cdd:cd20969    92 V 92

Fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule); The members here are composed of the fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1214357793 157 GSDVILLCSSEeGIPRPTYLWEKLDNTLKLPPTATQDQVQG-TVTIRNISALSSGLYQCVASNAIG 221
Cdd:cd05868    14 GEDGTLICRAN-GNPKPSISWLTNGVPIEIAPTDPSRKVDGdTIIFSKVQERSSAVYQCNASNEYG 78

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 1214357793 168 EGIPRPTYLWEKLDNTLKLPPTATQDQVQG---TVTIRNISALSSGLYQCVASNAIGTSTCLLDLQV 231
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 1214357793  40 VLPCTFTTSAALINlnVIWMVTPlsnaNQPEQVILY--QGGQMFDgaPRFHGRVGF-TGTMPATNVSIFINNTQLSDTGT 116
Cdd:cd05889    18 SLECVYPSTGILTQ--VEWTKIG----GQKDNIAVYhpTHGMHIR--KPYAGRVYFlNSTMASNNMSLSFRNASEDDVGY 89

                          90
                  ....*....|
gi 1214357793 117 YQCLVNNLPD 126
Cdd:cd05889    90 YSCSLYTYPQ 99

Immunoglobulin Variable (IgV) domain of T cell Immunoglobulin Domain and Mucin Domain 3 (Tim-3), and similar domains; The members here are composed of the immunoglobulin variable (IgV) domain of T cell immunoglobulin domain and mucin domain 3 (Tim-3; also known as Hepatitis A virus cellular receptor 2 (HAVcr-2) and Cluster of Differentiation 366 (CD366)) and similar proteins. TIM-3 is a checkpoint inhibitor in immune responses to tumors, as well as involved in chronic viral infections. Thus, Tim-3 has emerged as one of most promising immune checkpoint targets for cancer immunotherapy. Tim-3 is highly expressed on Th1 lymphocytes and CD11b(+) macrophages and is upregulated on activated T and myeloid cells. TIM-3 regulates macrophage, activation and inhibits Th1 mediated immune responses to promote immunological tolerance. There are three TIM family members in humans (TIM-1, TIM-3, and TIM-4) and eight members in mice (TIM-1 to TIM-8). The IgV domain of human TIM-3 has been shown to bind ligands such as carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1), high mobility group protein B1 (HMGB1)and galectin-9 (GAL9). The binding of GAL9 to TIM-3 can negatively regulate Th1 immune response, enhance immune tolerance and inhibit anti#tumor immunity. Dysregulation of the TIM-3/GAL9 pathway is implicated in numerous chronic autoimmune diseases, such as multiple sclerosis and systemic lupus erythematosus.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1214357793  30 SIQVARGQPAVLPCTFTTSAALINLNVIWM--VTPLSnanQPEQVILYQGGqmFDGAPRFHGRVGFTGTMPATNVSIFIN 107
Cdd:cd20982     2 EYRAEVGHNAYLPCSYTTAAPGNLVPVCWGkgACPVS---YCGNVLLRTDE--RDVTYQKSSRYQLKGDFSKGDVSLTIE 76

                          90
                  ....*....|....
gi 1214357793 108 NTQLSDTGTYQCLV 121
Cdd:cd20982    77 NVTLADSGIYCCRI 90

Immunoglobulin variable domain (IgV) in Cluster of Differentiation (CD) 86; The members here are composed of the immunoglobulin variable region (IgV) in the Cluster of Differentiation (CD) 86). Glycoproteins B7-1 (also known as cluster of differentiation (CD) 80) and B7-2 (also known as CD86) are expressed on antigen-presenting cells and deliver the co-stimulatory signal through CD28 and CTLA-4 (also known as CD152) on T cells. signaling through CD28 augments the T-cell response, whereas CTLA-4 signaling attenuates it. The CTLA-4 and B7-2 monomers are both two-layer beta-sandwiches that display the chain topology characteristic of the immunoglobulin variable (V-type) domains present in antigen receptors. The front and back sheets of B7-2 are composed of AGFCC'C" and BED strands, respectively. Members of the IgV family 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1214357793  39 AVLPCTFTTSA--ALINLNVIWMvtplsnaNQPEQVI--LYQGGQMFDG-APRFHGRVGFTgtmpATNVSIFINNTQLSD 113
Cdd:cd16087    11 AYLPCQFKNPQniSLSELVVFWQ-------DQKKLVLyeLYLGKEKLDNvNSKYIGRTSFD----QENWTLQLHNVQIKD 79

                  ....*...
gi 1214357793 114 TGTYQCLV 121
Cdd:cd16087    80 QGTYQCFI 87

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 1214357793  22 LEVSESPGSIQVARGQPAVLPCTFTTSAALINLNviWMvtpLSNANQPEQVILYQGGQMFDGAPrfhGRvgFTGTMPATN 101
Cdd:cd04980     1 IVMTQSPASLSVSPGERVTISCKASQSISSNYLA--WY---QQKPGQAPKLLIYYASTLHSGVP---SR--FSGSGSGTD 70

                          90
                  ....*....|....*....
gi 1214357793 102 VSIFINNTQLSDTGTYQCL 120
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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1214357793 142 PPSAPHCQIQgsqdigSDVILLCSSEeGIPRPTYLWEKLDNTLKLPPTATQ-DQVQGTVTIRNISALSSGLYQCVASNAI 220
Cdd:cd05760     7 PASAAEIQPS------SRVTLRCHID-GHPRPTYQWFRDGTPLSDGQGNYSvSSKERTLTLRSAGPDDSGLYYCCAHNAF 79

                  ....*
gi 1214357793 221 GtSTC 225
Cdd:cd05760    80 G-SVC 83