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 66730411  38 TVTTFTSAGNIGEDGTLSCTFEPDIKLNGIVIQWLKEGIKGLVHEFKEGKDDLSQQHEMFRGRTAVFADQVVVGNASLRL 117
Cdd:cd20984   1 TVTAKHLAGNIGEDGILSCTFTPDIKLSDIVIQWLKEGDSGLVHEFKEGKDELSRQSPMFRGRTSLFADQVHVGNASLRL 80

                        90       100       110
                ....*....|....*....|....*....|
gi 66730411 118 KNVQLTDAGTYTCYIHTSKGKGNANLEYKT 147
Cdd:cd20984  81 KNVQLTDAGTYLCIISNSKGTGNANMEYKT 110

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 66730411  38 TVTTFTSAGNIGEDGTLSCTFEPDIKLNGIVIQWLKEGIKGLVHEFKEGKDDLSQQHEMFRGRTAVFADQVVVGNASLRL 117
Cdd:cd20984   1 TVTAKHLAGNIGEDGILSCTFTPDIKLSDIVIQWLKEGDSGLVHEFKEGKDELSRQSPMFRGRTSLFADQVHVGNASLRL 80

                        90       100       110
                ....*....|....*....|....*....|
gi 66730411 118 KNVQLTDAGTYTCYIHTSKGKGNANLEYKT 147
Cdd:cd20984  81 KNVQLTDAGTYLCIISNSKGTGNANMEYKT 110

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66730411     46 GNIGEDGTLSCTFEPDIKlngIVIQWLKEGIKGLvhefkegkddlsqqheMFRGRTAVFADQvvvGNASLRLKNVQLTDA 125
Cdd:smart00410   6 VKEGESVTLSCEASGSPP---PEVTWYKQGGKLL----------------AESGRFSVSRSG---STSTLTISNVTPEDS 63

                           90       100
                   ....*....|....*....|.
gi 66730411    126 GTYTCYIHTSKG--KGNANLE 144
Cdd:smart00410  64 GTYTCAATNSSGsaSSGTTLT 84

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 66730411  38 TVTTFTSAGNIGEDGTLSCTFEPDIKLNGIVIQWLKEGIKGLVHEFKEGKDDLSQQHEMFRGRTAVFADQVVVGNASLRL 117
Cdd:cd20984   1 TVTAKHLAGNIGEDGILSCTFTPDIKLSDIVIQWLKEGDSGLVHEFKEGKDELSRQSPMFRGRTSLFADQVHVGNASLRL 80

                        90       100       110
                ....*....|....*....|....*....|
gi 66730411 118 KNVQLTDAGTYTCYIHTSKGKGNANLEYKT 147
Cdd:cd20984  81 KNVQLTDAGTYLCIISNSKGTGNANMEYKT 110

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 66730411  48 IGEDGTLSCTF--EPDIKLNGIVIQWLKEGIKGLVHEFKEGKDDLSQQHEMFRGRTAVFADQVVVGNASLRLKNVQLTDA 125
Cdd:cd20934  11 VGTDATLRCSFspEPGFSLAQLSVFWQLTDTKQLVHSFTESQDQGRDQGSAYANRTALFPDLLAQGNASLRLQRVRVADE 90

                ....*..
gi 66730411 126 GTYTCYI 132
Cdd:cd20934  91 GSYTCFV 97

Immunoglobulin Variable (IgV) domain of Programmed death ligand 1 (PD-L1); The members here are composed of the immunoglobulin variable (IgV) domain of Programmed death ligand 1 (PD-L1; also known as Cluster of Differentiation 274 (CD274)). PD-L1 is a cell-surface ligand that competes with PD-L2 for binding to the immunosuppressive receptor programmed death-1 (PD-1). PD-1 is a member of the B7 family that plays an important role in negatively regulating immune responses upon interaction with its two ligands, PD-L1 or PD-L2. Like PD-L2, PD-L1 interacts with PD-1 and suppresses T cell proliferation and cytokine production. The PD-1 receptor is expressed on the surface of activated T cells, while PD-L1 is expressed on cancer cells. When PD-1 and PD-L1 bind together, they form a molecular shield protecting tumor cells from being destroyed by the immune system. Thus, inhibiting the binding of PD-L1 to PD-1 with an antibody leads to killing of tumor cells by T cells. PD-1 inhibitors (such as Pembrolizumab, Nivolumab, and Cemiplimab) and PD-L1 inhibitors (such as Atezolizumab, Avelumab, and Durvalumab ) are an emerging class of immunotherapy that stimulate lymphocytes against tumor cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66730411  37 ITVTTFTSAGNIGEDGTLSCTF--EPDIKLNGIVIQWLKEGIKglVHEFKEGKDDLSQQHEMFRGRTAVFADQVVVGNAS 114
Cdd:cd20947   1 VTVPKDLYVVEYGSNMTIECKFpvEKQLDLAALIVYWEMEDKN--IIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAA 78

                        90
                ....*....|....*...
gi 66730411 115 LRLKNVQLTDAGTYTCYI 132
Cdd:cd20947  79 LQITDVKLQDAGVYRCMI 96

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 66730411    49 GEDGTLSCTFEPDIKLNGIVIQWLK----EGIKGLVHEFKEGkddlsQQHEMFRGRTAVFADqVVVGNASLRLKNVQLTD 124
Cdd:pfam07686  11 GGSVTLPCTYSSSMSEASTSVYWYRqppgKGPTFLIAYYSNG-----SEEGVKKGRFSGRGD-PSNGDGSLTIQNLTLSD 84

                          90
                  ....*....|.
gi 66730411   125 AGTYTCYIHTS 135
Cdd:pfam07686  85 SGTYTCAVIPS 95

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 66730411  49 GEDGTLSCTFEPDIKL-NGIVIQWLKEGIKGLVHE--FKEGKDDLSQQHEMFRGRtAVFADQVVVGNASLRLKNVQLTDA 125
Cdd:cd05880  14 GTDVRLKCTFSSSAPIgDTLVITWNFRPLDGGREEsvFYYHKRPYPPPDGRFKGR-VVWDGNIMRRDASILIWQLQPTDN 92

                ....*..
gi 66730411 126 GTYTCYI 132
Cdd:cd05880  93 GTYTCQV 99

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66730411    43 TSAGNIGEDGTLSCTFEPDIKlnGIVIQWLKEGikglvhefkEGKDDLSQQHEMFRGRTavfadqvvvgNASLRLKNVQL 122
Cdd:pfam00047   5 TVTVLEGDSATLTCSASTGSP--GPDVTWSKEG---------GTLIESLKVKHDNGRTT----------QSSLLISNVTK 63

                          90
                  ....*....|....*....
gi 66730411   123 TDAGTYTCYIHTSKGKGNA 141
Cdd:pfam00047  64 EDAGTYTCVVNNPGGSATL 82

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 66730411  46 GNIGEDGTLSCTFEPDIKLNGIVIQWLKEGIKG----LVHEFKEGKDDLSQQHEMFRGRTAVFADQvvvgNASLRLKNVQ 121
Cdd:cd05718  11 GFLGGSVTLPCSLTSPGTTKITQVTWMKIGAGSsqnvAVFHPQYGPSVPNPYAERVEFLAARLGLR----NATLRIRNLR 86

                        90
                ....*....|...
gi 66730411 122 LTDAGTYTCYIHT 134
Cdd:cd05718  87 VEDEGNYICEFAT 99

Third 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 third 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 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, 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, and 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 Slit2 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
                ....*....|....*....|....*....|....*....|....*..
gi 66730411  95 EMFRGRTAVFADQvvvgnaSLRLKNVQLTDAGTYTCYIHTSKGKGNA 141
Cdd:cd05725  37 ELPKGRYEILDDH------SLKIRKVTAGDMGSYTCVAENMVGKIEA 77

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66730411    37 ITVTTFTSAGNIGEDGTLSCTFE----PDIklngiviQWlkegikglvheFKEGKDDLSQQHEMFRgrtavfadqVVVGN 112
Cdd:pfam13927   4 ITVSPSSVTVREGETVTLTCEATgsppPTI-------TW-----------YKNGEPISSGSTRSRS---------LSGSN 56

                          90
                  ....*....|....*...
gi 66730411   113 ASLRLKNVQLTDAGTYTC 130
Cdd:pfam13927  57 STLTISNVTRSDAGTYTC 74

Immunoglobulin Variable (IgV) domain of B7-H2 (B7 homolog 2); The members here are composed of the immunoglobulin variable (IgV) domain of B7-H2 (B7 homolog 2 also known as ICOSL (inducible T cell costimulator ligand) or CD275). B7-H2 is a ligand for the T-cell-specific cell surface receptor ICOS and acts as a costimulatory signal for T-cell proliferation and cytokine secretion. The interaction of ICOS with ICOSL (B7-H2) regulates T cell activation and expansion, is involved in T cell dependent B cell activation, and T-helper cell differentiation. It is a member of the B7 family of immune regulatory proteins and shares homology with other B7 ligands, such as B7-1, B7-2, B7-H1 (PD-L1), PD-L2, and B7-H3. The extracellular domains of B7 proteins contain two Ig-like domains and all members have short cytoplasmic domains. These ligands are typically expressed on antigen presenting cells (such as macrophages, B cells and dendritic cells) and have the ability to regulate T-cell proliferation and function. Tumor cells are also capable of expressing the B7 family members in order to evade immune surveillance.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66730411  48 IGEDGTLSCTFEPD--IKLNGIVIQWLKEGIKGLVHEFKEGKDDLSQQHEMFRGRTAVFADQVVVGNASLRLKNVQLTDA 125
Cdd:cd20935   7 VGSDVELSCICPEGsrFDLNDLYVYWQISESETVVTYHLPQNSSLENVDSHYRNRALLSLDSMKQGDFSLRLFNVTPQDE 86

                ....*..
gi 66730411 126 GTYTCYI 132
Cdd:cd20935  87 QKFHCLV 93

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66730411  37 ITVTTFTSAGNIGEDGTLSC--TFEPDIKL------NGIVIQWLKEGIKglvHEFKEGKDDlsqqhemfrgrtavfadqv 108
Cdd:cd04970   5 ITLAPSNADITVGENATLQChaSHDPTLDLtftwsfNGVPIDLEKIEGH---YRRRYGKDS------------------- 62

                        90       100
                ....*....|....*....|....*..
gi 66730411 109 vvgNASLRLKNVQLTDAGTYTCYIHTS 135
Cdd:cd04970  63 ---NGDLEIVNAQLKHAGRYTCTAQTV 86

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
                ....*....|....*....|....*..
gi 66730411 112 NASLRLKNVQLTDAGTYTCYIHTSKGK 138
Cdd:cd20952  52 NGSLQIKGAEKSDTGEYTCVALNLSGE 78

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 66730411  49 GEDGTLSCTF--EP-DIKLNGIVIQWLKEGikglVHEFKEgKDDL--SQQHEM----FRGRtaVFADQVVVGNASLRLKN 119
Cdd:cd05877  12 GGNVTLPCRYhyEPeLSAPRKIRVKWTKLE----VDYAKE-EDVLvaIGTRHKsygsYQGR--VFLRRADDLDASLVITD 84

                        90
                ....*....|.
gi 66730411 120 VQLTDAGTYTC 130
Cdd:cd05877  85 LRLEDYGRYRC 95