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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35215304    143 TEGSDLTLQCEsASGTKPIVYYWQRirekeGEDEHLPPKSR--IDYNNPGRVL-LQNLTMASSGLYQCTAGNEAGKESCV 219
Cdd:smart00410   7 KEGESVTLSCE-ASGSPPPEVTWYK-----QGGKLLAESGRfsVSRSGSTSTLtISNVTPEDSGTYTCAATNSSGSASSG 80

                   ....*
gi 35215304    220 VRVTV 224
Cdd:smart00410  81 TTLTV 85

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 35215304    25 VAE-EKVTLPCHhQLGLPEKDTLDIEWLLTDNEGNQKVVITYSSRhvyNNLTEEQKGRVAFASNFLAGDASLQIEPLKPS 103
Cdd:pfam07686   8 VALgGSVTLPCT-YSSSMSEASTSVYWYRQPPGKGPTFLIAYYSN---GSEEGVKKGRFSGRGDPSNGDGSLTIQNLTLS 83

                          90       100
                  ....*....|....*....|....*.
gi 35215304   104 DEGRYTCKVKNSGRYVWSHVI-LKVL 128
Cdd:pfam07686  84 DSGTYTCAVIPSGEGVFGKGTrLTVL 109

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35215304   143 TEGSDLTLQCEsASGTKPIVYYWQRirekegEDEHLPPKSRIDY-NNPGRVLL--QNLTMASSGLYQCTAGNEAGKESCV 219
Cdd:pfam07679  13 QEGESARFTCT-VTGTPDPEVSWFK------DGQPLRSSDRFKVtYEGGTYTLtiSNVQPDDSGKYTCVATNSAGEAEAS 85

                  ....*
gi 35215304   220 VRVTV 224
Cdd:pfam07679  86 AELTV 90

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 35215304 148 LTLQCEsASGTKPIVYYWQrireKEGEDEHLPPKSRIDYNNPGRVL-LQNLTMASSGLYQCTAGNEAGKES 217
Cdd:cd00096   1 VTLTCS-ASGNPPPTITWY----KNGKPLPPSSRDSRRSELGNGTLtISNVTLEDSGTYTCVASNSAGGSA 66

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 35215304    25 VAE-EKVTLPCHhQLGLPEKDTLDIEWLLTDNEGNQKVVITYSSRhvyNNLTEEQKGRVAFASNFLAGDASLQIEPLKPS 103
Cdd:pfam07686   8 VALgGSVTLPCT-YSSSMSEASTSVYWYRQPPGKGPTFLIAYYSN---GSEEGVKKGRFSGRGDPSNGDGSLTIQNLTLS 83

                          90       100
                  ....*....|....*....|....*.
gi 35215304   104 DEGRYTCKVKNSGRYVWSHVI-LKVL 128
Cdd:pfam07686  84 DSGTYTCAVIPSGEGVFGKGTrLTVL 109

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 35215304  18 THTEIKRVAEEKVTLPCHHQLGLPEKDTLDIEWLLTDNEGNQKVVITYSSRHVYNNLTEEQKGRVAFASNFLAGDASLQI 97
Cdd:cd05880   5 TSKEVEAVNGTDVRLKCTFSSSAPIGDTLVITWNFRPLDGGREESVFYYHKRPYPPPDGRFKGRVVWDGNIMRRDASILI 84

                        90
                ....*....|....*..
gi 35215304  98 EPLKPSDEGRYTCKVKN 114
Cdd:cd05880  85 WQLQPTDNGTYTCQVKN 101

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 35215304  18 THTEIKRVAEEKVTLPCHHQLGLPEKDTLDIEWLLTDNEGNQKVVITYSSR-HVYNNLTEEQKGRVAFASNFLAGDASLQ 96
Cdd:cd05715   5 TPRELNVLNGSDVRLTCTFTSCYTVGDAFSVTWTYQPEGGNTTESMFHYSKgKPYILKVGRFKDRVSWAGNPSKKDASIV 84

                        90
                ....*....|....*...
gi 35215304  97 IEPLKPSDEGRYTCKVKN 114
Cdd:cd05715  85 ISNLQFSDNGTYTCDVKN 102

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35215304     28 EKVTLPCHhqlgLPEKDTLDIEWLLTDNEgnqkvVITYSSRhvynnlteeqkgrvaFASNFLAGDASLQIEPLKPSDEGR 107
Cdd:smart00410  10 ESVTLSCE----ASGSPPPEVTWYKQGGK-----LLAESGR---------------FSVSRSGSTSTLTISNVTPEDSGT 65

                           90       100
                   ....*....|....*....|
gi 35215304    108 YTCKVKNSGRYVWSHVILKV 127
Cdd:smart00410  66 YTCAATNSSGSASSGTTLTV 85

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 35215304  28 EKVTLPCHhqLgLPEKDTLDIE--WLLTDNEgnqKVVityssrHVYNN---LTEEQ----KGRVAFASNFLA-GDASLQI 97
Cdd:cd05713  16 EDAELPCH--L-SPKMSAEHMEvrWFRSQFS---PVV------HLYRDgqdQEEEQmpeyRGRTELLKDAIAeGSVALRI 83

                        90       100       110
                ....*....|....*....|....*....|
gi 35215304  98 EPLKPSDEGRYTCKVKNSGRYVWSHVILKV 127
Cdd:cd05713  84 HNVRPSDEGQYTCFFRSGSFYEEATLELKV 113

Immunoglobulin I-set domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 35215304    74 LTEEQKGRVAFasnfLAGDASLQIEPLKPSDEGRYTCKVKNSGRYVWSHVILKV 127
Cdd:pfam07679  41 LRSSDRFKVTY----EGGTYTLTISNVQPDDSGKYTCVATNSAGEAEASAELTV 90

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35215304  30 VTLPCHHQlGLPEkdtLDIEWLLtdnEGNQKVVITYSSRHVYNnlteeqkgrvafasnflaGDASLQIEPLKPSDEGRYT 109
Cdd:cd00096   1 VTLTCSAS-GNPP---PTITWYK---NGKPLPPSSRDSRRSEL------------------GNGTLTISNVTLEDSGTYT 55

                        90
                ....*....|....*
gi 35215304 110 CKVKNSGRYVWSHVI 124
Cdd:cd00096  56 CVASNSAGGSASASV 70

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 35215304  28 EKVTLPCHHQLGLPEKdtldIEWLLTDNegNQKVVITYSSRHVYNNLTEEQKGRVA-FASNFLAGDASLQIEPLKPSDEG 106
Cdd:cd16091  13 EDCILPCSFTPGSEVV----IHWYKQDS--DIKVHSYYYGKDQLESQDQRYRNRTSlFKDQISNGNASLLLRRVQLQDEG 86

                        90       100
                ....*....|....*....|.
gi 35215304 107 RYTCKVKNSGRYVWSHVILKV 127
Cdd:cd16091  87 RYKCYTSTIIGNQESFVNLKV 107

Immunoglobulin variable domain (IgV) in Cluster of Differentiation (CD) 80; The members here are composed of the immunoglobulin variable region (IgV) in the Cluster of Differentiation (CD) 80). 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 cluster of differentiation 152/CD152) on T cells. signaling through CD28 augments the T-cell response, whereas CTLA-4 signaling attenuates it. CD80 contains two Ig-like domains, an amino-terminal immunoglobulin variable (IgV)-like domain characteristic of adhesion molecules and a membrane proximal immunoglobulin constant (IgC)-like domain similar to the constant domains of antigen receptors. Members of the Ig family are components of immunoglobulin, T-cell receptors, CD1 cell surface glycoproteins, secretory glycoproteins A/C, and Major Histocompatibility Complex (MHC) class I/II molecules. In immunoglobulins, each chain is composed of one variable domain (IgV) and one or more IgC domains. These names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. The IgV domain is responsible for antigen binding, and the IgC domain is involved in oligomerization and molecular interactions.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35215304  28 EKVTLPCHHQLGLPEKDTLDIEWlltdnEGNQKVVITYSSRHVynNLTEEQKGRVAFAsnfLAGDASLQIEPLKPSDEGR 107
Cdd:cd16086  10 EKALLSCDYNVSVDELAQVRIYW-----QKDDKMVLTIISGDV--KVWPEYKNRTLFD---ITNNLSIVILALRLSDRGT 79

                        90
                ....*....|
gi 35215304 108 YTCKVKNSGR 117
Cdd:cd16086  80 YTCVVQKKER 89

Immunoglobulin (Ig)-like domain of chondroitin sulfate proteoglycans (CSPGs), human cartilage link protein (LP), and similar domains; The members here are composed of the immunoglobulin (Ig)-like domain similar to that found in chondroitin sulfate proteoglycans (CSPGs) and human cartilage link protein (LP). Included in this group are the CSPGs aggrecan, versican, and neurocan. In CSPGs, this Ig-like domain is followed by hyaluronan (HA)-binding tandem repeats, and a C-terminal region with epidermal growth factor-like, lectin-like, and complement regulatory protein-like domains. Separating these N- and C-terminal regions is a nonhomologous glycosaminoglycan attachment region. In cartilage, aggrecan forms cartilage link protein stabilized aggregates with hyaluronan (HA). These aggregates contribute to the tissue's load bearing properties. Aggrecan and versican have a wide distribution in connective tissue and extracellular matrices. Neurocan is localized almost exclusively in nervous tissue. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. There is considerable evidence that HA-binding CSPGs are involved in developmental processes in the central nervous system. 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 35215304  28 EKVTLPCHHQLgLPE-----KDTLDIEWL-LTDNEGNQKVVITYSSRHVYNNLTEEQKGRVAFASNFLA-GDASLQIEPL 100
Cdd:cd05714  13 GNVTLPCKFYR-DPTafgsgIHKIRIKWTkLTSDSGYLKEVDVLVAMGNVVYHKKTYGGRVSVPLKPGSdSDASLVITDL 91

                        90
                ....*....|..
gi 35215304 101 KPSDEGRYTCKV 112
Cdd:cd05714  92 TASDYGLYRCEV 103

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 35215304  30 VTLPCHHQlglPEKDTLDI--EWLLTDNEGNQKVVITYSS-RHVynnLTEEQKGRVAfASNFLAGDASLQIEPLKPSDEG 106
Cdd:cd16089  17 VNLPCTYV---PEEGYTQVlvKWLVQRDSDPVTIFLRDSSgDHI---QQAKYRGRLE-VSKDTPGDVSLQLDTLEMDDRG 89

                ....*.
gi 35215304 107 RYTCKV 112
Cdd:cd16089  90 HYTCQV 95

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35215304 134 PKCELegepTEGSDLTLQCeSASGTKPIVYYWQRI-REKEGEDEHLPPKSRIdynnpGRVLLQNLTMASSGLYQCTAGNE 212
Cdd:cd20976   9 KDLEA----VEGQDFVAQC-SARGKPVPRITWIRNaQPLQYAADRSTCEAGV-----GELHIQDVLPEDHGTYTCLAKNA 78

                        90
                ....*....|..
gi 35215304 213 AGKESCVVRVTV 224
Cdd:cd20976  79 AGQVSCSAWVTV 90

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 35215304 145 GSDLTLQCESASGTKPiVYYWQRirekegEDEHLPPKSRIDYNNpGRVLLQNLTMASSGLYQCTAGNEAG 214
Cdd:cd05728  14 GSSLRWECKASGNPRP-AYRWLK------NGQPLASENRIEVEA-GDLRITKLSLSDSGMYQCVAENKHG 75

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 35215304   144 EGSDLTLQCE------------------SASGTKPIVYYWQRIREKEGEDEHLPPKSRIDYNNpGRVLLQNLTMASSGLY 205
Cdd:pfam07686  10 LGGSVTLPCTysssmseastsvywyrqpPGKGPTFLIAYYSNGSEEGVKKGRFSGRGDPSNGD-GSLTIQNLTLSDSGTY 88

                          90       100
                  ....*....|....*....|
gi 35215304   206 QC-TAGNEAGKESCVVRVTV 224
Cdd:pfam07686  89 TCaVIPSGEGVFGKGTRLTV 108

Immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), versican; The members here are composed of the immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), versican. In CSPGs, the Ig-like domain is followed by hyaluronan (HA)-binding tandem repeats, and a C-terminal region with epidermal growth factor-like, lectin-like, and complement regulatory protein-like domains. Separating these N- and C-terminal regions is a nonhomologous glycosaminoglycan attachment region. In cartilage, the CSPG aggrecan (not included in this group) forms cartilage link protein stabilized aggregates with HA. These aggregates contribute to the tissue's load bearing properties. Like aggrecan, versican has a wide distribution in connective tissue and extracellular matrices. 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 35215304  16 LGTHTEIKRVAEEKVTLPCHHQL--GLP-----EKDTLDIEW--LLTDNEGN---QKVVITYSSRHVynNLTEEQKGRVA 83
Cdd:cd05901   1 VRKSSRVHGSLSGSVVLPCRFSTlpTLPpsyniTSEFLRIKWtkIQVDKNGKdhkETTVLVAQNGII--KIGQEYMGRVS 78

                        90       100       110
                ....*....|....*....|....*....|
gi 35215304  84 FASNFLA-GDASLQIEPLKPSDEGRYTCKV 112
Cdd:cd05901  79 VPSHPEDqGDASLTIVKLRASDAGVYRCEV 108

N-terminal immunoglobulin (Ig)-like domain of the signaling lymphocyte activation molecule (SLAM) family; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of the signaling lymphocyte activation molecule (SLAM) family and similar proteins. The SLAM family is a group of immune-cell specific receptors that can regulate both adaptive and innate immune responses. Members of this group include proteins such as CD84, SLAM (CD150), Ly-9 (CD229), NTB-A (ly-108, SLAM6), 19A (CRACC), and SLAMF9. The genes coding for the SLAM family are nested on chromosome 1, in humans at 1q23, and in mice at 1H2. The SLAM family is a subset of the CD2 family, which also includes CD2 and CD58 located on chromosome 1 at 1p13 in humans. In mice, CD2 is located on chromosome 3, and there is no CD58 homolog. The SLAM family proteins are organized as an extracellular domain with either two or four Ig-like domains, a single transmembrane segment, and a cytoplasmic region having Tyr-based motifs. The extracellular domain is organized as a membrane-distal Ig variable (IgV) domain that is responsible for ligand recognition and a membrane-proximal truncated Ig constant-2 (IgC2) domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35215304  20 TEIKRVAEEKVTLPchhqLGLPEKDTLD-IEWL-------LTDNEGNQKVVITYSSRhvynnlteeQKGRVafasNFLAG 91
Cdd:cd16842   1 KEVNGILGGSVTFP----LNISDGQEIEnITWSfktslavIAPGEGGAPEIIITDKS---------YKERL----NISQN 63

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 35215304  92 DASLQIEPLKPSDEGRYTCKV--KNSGRYVWSHVILKV 127
Cdd:cd16842  64 DYSLQISNLTMEDAGSYRARIntKNSRVTITKEFTLHI 101

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 35215304  30 VTLPCHH--QLGLPEKDtLDIEWLLTDNEgnQKVVITYSSRHVYNNLTEEQKGRVAFASNFLA-GDASLQIEPLKPSDEG 106
Cdd:cd20934  15 ATLRCSFspEPGFSLAQ-LSVFWQLTDTK--QLVHSFTESQDQGRDQGSAYANRTALFPDLLAqGNASLRLQRVRVADEG 91

                        90       100
                ....*....|....*....|...
gi 35215304 107 RYTC--KVKNSGRyvwSHVILKV 127
Cdd:cd20934  92 SYTCfvSVQDFGS---AAVSLQV 111

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 35215304  30 VTLPCHHQLGLPEKdTLDIEWLLTDN-EGNQKVVITYSSRHVynNLTEEQKGRVAFASNFLAGDASLQIEPLKPSDEGRY 108
Cdd:cd05888  11 AKLPCFYRGDSGEQ-VGQVAWARVDAgEGAQEIALLHSKYGL--HVFPAYEGRVEQPPPPRPADGSVLLRNAVQADEGEY 87

                ....
gi 35215304 109 TCKV 112
Cdd:cd05888  88 ECRV 91

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35215304 145 GSDLTLQCESASGTKPivyyWQRIREKEGEdehlPPKSRIDYNNPGRVL-LQNLTMASSGLYQCTAGNEAGKESCVVRVT 223
Cdd:cd05731  10 GGVLLLECIAEGLPTP----DIRWIKLGGE----LPKGRTKFENFNKTLkIENVSEADSGEYQCTASNTMGSARHTISVT 81

                ..
gi 35215304 224 VQ 225
Cdd:cd05731  82 VE 83

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
                ....*....|....*....|....*
gi 35215304  91 GDASLQIEPLKPSDEGRYTCKVKNS 115
Cdd:cd05724  50 DDGNLLIAEARKSDEGTYKCVATNM 74