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 442796434  20 LSITTPEQRIEKAKGETAYLPCKFTLSPEDQGPLDIEWLISPSDNqiVDQVIILYSGDKIYDNYYPDLKGRVHFTSNDvK 99
Cdd:cd20960    1 LLITSAQTEIKKVAGENVTLPCHHQLGLEDQGTLDIEWLLLPSDK--VEKVVITYSGDRVYNHYYPALKGRVAFTSND-L 77

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 442796434 100 SGDASINVTNLQLSDIGTYQCKVKKAPGVANKKFLLT 136
Cdd:cd20960   78 SGDASLNISNLKLSDTGTYQCKVKKAPGYAWSKITLI 114

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 442796434  20 LSITTPEQRIEKAKGETAYLPCKFTLSPEDQGPLDIEWLISPSDNqiVDQVIILYSGDKIYDNYYPDLKGRVHFTSNDvK 99
Cdd:cd20960    1 LLITSAQTEIKKVAGENVTLPCHHQLGLEDQGTLDIEWLLLPSDK--VEKVVITYSGDRVYNHYYPALKGRVAFTSND-L 77

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 442796434 100 SGDASINVTNLQLSDIGTYQCKVKKAPGVANKKFLLT 136
Cdd:cd20960   78 SGDASLNISNLKLSDTGTYQCKVKKAPGYAWSKITLI 114

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442796434    36 TAYLPCKFTLSpeDQGPLDIEWLISPSDNQivdqVIILYSGDKIYDNYYPD-LKGRVHFTSNDVKSgDASINVTNLQLSD 114
Cdd:smart00406   1 SVTLSCKFSGS--TFSSYYVSWVRQPPGKG----LEWLGYIGSNGSSYYQEsYKGRFTISKDTSKN-DVSLTISNLRVED 73

                   ....*...
gi 442796434   115 IGTYQCKV 122
Cdd:smart00406  74 TGTYYCAV 81

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 442796434  20 LSITTPEQRIEKAKGETAYLPCKFTLSPEDQGPLDIEWLISPSDNqiVDQVIILYSGDKIYDNYYPDLKGRVHFTSNDvK 99
Cdd:cd20960    1 LLITSAQTEIKKVAGENVTLPCHHQLGLEDQGTLDIEWLLLPSDK--VEKVVITYSGDRVYNHYYPALKGRVAFTSND-L 77

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 442796434 100 SGDASINVTNLQLSDIGTYQCKVKKAPGVANKKFLLT 136
Cdd:cd20960   78 SGDASLNISNLKLSDTGTYQCKVKKAPGYAWSKITLI 114

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 442796434  20 LSITTPEQrIEKAKGETAYLPCKFTLSPEDQGPLDIEWLISPSDNQiVDQVIILYSGDKIYDNYYPDLKGRVHFTSNDVK 99
Cdd:cd05715    1 MEVYTPRE-LNVLNGSDVRLTCTFTSCYTVGDAFSVTWTYQPEGGN-TTESMFHYSKGKPYILKVGRFKDRVSWAGNPSK 78

                         90       100
                 ....*....|....*....|....*..
gi 442796434 100 SgDASINVTNLQLSDIGTYQCKVKKAP 126
Cdd:cd05715   79 K-DASIVISNLQFSDNGTYTCDVKNPP 104

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 442796434  34 GETAYLPCKFTLSPEDQGpLDIEWLiSPSDNQIVDQviiLYSGDKIYDNYYPDLKGRVHFTSNDVKSGDASINVTNLQLS 113
Cdd:cd20984   12 GEDGILSCTFTPDIKLSD-IVIQWL-KEGDSGLVHE---FKEGKDELSRQSPMFRGRTSLFADQVHVGNASLRLKNVQLT 86

                         90       100
                 ....*....|....*....|....
gi 442796434 114 DIGTYQCKVKKAPGVANKKFLLTV 137
Cdd:cd20984   87 DAGTYLCIISNSKGTGNANMEYKT 110

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 442796434  21 SITTPEQRIEKAKGETAYLPCKftLSPE-DQGPLDIEWLISPSDNqivdqVIILY-SGDKIYDNYYPDLKGRVHFTSNDV 98
Cdd:cd05713    2 SVIGPTEPILALVGEDAELPCH--LSPKmSAEHMEVRWFRSQFSP-----VVHLYrDGQDQEEEQMPEYRGRTELLKDAI 74

                         90       100
                 ....*....|....*....|..
gi 442796434  99 KSGDASINVTNLQLSDIGTYQC 120
Cdd:cd05713   75 AEGSVALRIHNVRPSDEGQYTC 96

N-terminal immunoglobulin (Ig)-like domain of T-cell surface antigen CD2, and similar domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain (or domain 1) of T-cell surface antigen Clusters of Differentiation (CD) 2 and similar proteins. CD2 is a T-cell specific surface glycoprotein and is critically important for mediating adhesion between T cells and antigen-presenting cells or between cytolytic T cells and target cells. CD2 is located on chromosome 1 at 1p13 in humans and on chromosome 3 in mice. CD2 contains an extracellular domain with two or Ig-like domains, a single transmembrane segment, and a cytoplasmic region rich in proline and basic residues.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442796434  58 LISPSDNQIVDQVIILYSGDKI--YDN-----YYPDLKGRVHFtsnDVKSGDASInvTNLQLSDIGTYQCKVKKAPG-VA 129
Cdd:cd05775   15 LTISSLQDDIDEIKWKKTKDKIveWENnigptYFGSFKDRVLL---DKESGSLTI--KNLTKEDSGTYELEITSTNGkVL 89

                 ....*....
gi 442796434 130 NKKFLLTVL 138
Cdd:cd05775   90 SSKFTLEVL 98

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442796434    36 TAYLPCKFTLSpeDQGPLDIEWLISPSDNQivdqVIILYSGDKIYDNYYPD-LKGRVHFTSNDVKSgDASINVTNLQLSD 114
Cdd:smart00406   1 SVTLSCKFSGS--TFSSYYVSWVRQPPGKG----LEWLGYIGSNGSSYYQEsYKGRFTISKDTSKN-DVSLTISNLRVED 73

                   ....*...
gi 442796434   115 IGTYQCKV 122
Cdd:smart00406  74 TGTYYCAV 81

Immunoglobulin (Ig)-like domain of the aggrecan-like chondroitin sulfate proteoglycan core protein (CSPG); The members here are composed of the immunoglobulin (Ig)-like domain of the aggrecan-like chondroitin sulfate proteoglycan core proteins (CSPGs). Included in this group are the Ig domains of other CSPGs: 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. 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 442796434  34 GETAYLPCKFTLSPEDQGP------LDIEWL-ISPSDNQIVDQVIILYSGDKIYDNyyPDLKGRVHFTSNDVKSGDASIN 106
Cdd:cd05878   12 GTSVTLPCYFIDPPHPVTPstaplaPRIKWSkVSVDGKKEKEVVLLVATEGRVRVN--SAYQGRVSLPNYPAIPSDATLE 89

                         90
                 ....*....|....*.
gi 442796434 107 VTNLQLSDIGTYQCKV 122
Cdd:cd05878   90 VQSLRASDSGLYRCEV 105

Immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), neurocan; The members here are composed of the immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), neurocan. 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. Unlike aggrecan which is widely distributed 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. 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 442796434  27 QRIEKAKGETAYLPCKFTLSPEDQGPLD---IEWL-ISPSDNQivDQVIILYSGDKIYdNYYPDLKGRVHFTSNDVKSGD 102
Cdd:cd05902    5 PPVRRPLSSSVLLPCVFTLPPSASSPPEgprIKWTkLSTSGGQ--QQRPVLVARDNVV-RVAKAFQGRVSLPGYPKNRYN 81

                         90       100
                 ....*....|....*....|
gi 442796434 103 ASINVTNLQLSDIGTYQCKV 122
Cdd:cd05902   82 ASLVLSRLRYSDSGTYRCEV 101

Immunoglobulin Variable region-containing chitin-binding proteins; an immunoglobulin V-set domain; The members here are composed of the immunoglobulin variable (IgV) region-containing chitin-binding proteins (VCBPs). VCBPs are secreted, immune-type molecules that have been identified in both amphioxus and sea squirt (Ciona intestinalis). VCBPs, which consist of a leader peptide, two tandem N-terminal immunoglobulin V-type domains and a single C-terminal chitin-binding domain, belong to a multigene family encoding secreted proteins. The VCBPs were identified first in the cephalochordate Branchiostoma floridae and show structural similarities with V-type domains of immunoglobulins and T cell receptors, suggesting that VCBPs represent a unique gut-associated form of innate immune proteins. 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. 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. 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 442796434  21 SITTPE-QRIEKAKGETAYLPCKFTLSPEDQGPLdIEWL--ISPSDNQIV---DQVIILYSGDkiYDNYYPDLKGRVHFT 94
Cdd:cd20963    3 TVTVPSyTRTDPTWGNRVELPCSYTISPAAQPPT-ITWLkgISVDRAEVVfkgFKYWNETSSS--GEVYFGDYAGRASVA 79

                         90       100
                 ....*....|....*....|....*...
gi 442796434  95 SNDvksgDASINVTNLQLSDIGTYQCKV 122
Cdd:cd20963   80 SLT----QPTLVLTDLKFDDWGRYWCRV 103

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 442796434  34 GETAYLPCKFTlSPEDQGPLDIEWLISPSDNQivdQVIILYS---GDKIYDNYypdlKGRVHFTSNDVKSGDASINVTNL 110
Cdd:cd05718   14 GGSVTLPCSLT-SPGTTKITQVTWMKIGAGSS---QNVAVFHpqyGPSVPNPY----AERVEFLAARLGLRNATLRIRNL 85

                         90
                 ....*....|....*..
gi 442796434 111 QLSDIGTYQCKVKKAPG 127
Cdd:cd05718   86 RVEDEGNYICEFATFPQ 102

Immunoglobulin (Ig)-like variable (V) domain of the Signal-Regulatory Protein (SIRP); The members here are composed of the immunoglobulin (Ig)-like domain of the Signal-Regulatory Protein (SIRP). The SIRPs belong to the "paired receptors" class of membrane proteins that comprise several genes coding for proteins with similar extracellular regions, but very different transmembrane/cytoplasmic regions with different (activating or inhibitory) signaling potentials. They are commonly on NK cells, but are also on many myeloid cells. Their extracellular region contains three immunoglobulin superfamily domains, a single V-set, and two C1-set IgSF domains. Their cytoplasmic tails that contain either ITIMs or transmembrane regions have positively charged residues that allow an association with adaptor proteins, such as DAP12/KARAP, containing ITAMs. There are 3 distinct SIRP members: alpha, beta, and gamma. SIRP alpha (also known as CD172a or SRC homology 2 domain-containing protein tyrosine phosphatase substrate 1/Shps-1) is a membrane receptor that interacts with a ligand CD47 expressed on many cells and gives an inhibitory signal through immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic region that interact with phosphatases SHP-1 and SHP-2. SIRP beta has a short cytoplasmic region and associates with a transmembrane adapter protein DAP12 containing immunoreceptor tyrosine-based activation motifs to give an activating signal. SIRP gamma contains a very short cytoplasmic region lacking obvious signaling motifs, but also binds CD47 with much less affinity. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442796434  22 ITTPEQRIEKAKGETAYLPCKFT-LSPedQGPldIEWL--ISPSDNQIVDQviilysgdkiYDNYYPdlkgRVHFTSNDV 98
Cdd:cd16097    2 VIQPEKSVSVAAGESATLHCTVTsLIP--VGP--IQWFrgAGPGRELIYNQ----------KEGHFP----RVTTVSDLT 63

                         90       100       110
                 ....*....|....*....|....*....|.
gi 442796434  99 KSG--DASINVTNLQLSDIGTYQC-KVKKAP 126
Cdd:cd16097   64 KRNnmDFSIRISNITPADAGTYYCvKFRKGS 94

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 442796434  39 LPCKFTLSPEDQgpldIEWlISPSDNQIVDqviILYSGDKIYDNYYPDLKGRVHFTSNDVKSGDASINVTNLQLSDIGTY 118
Cdd:cd16091   17 LPCSFTPGSEVV----IHW-YKQDSDIKVH---SYYYGKDQLESQDQRYRNRTSLFKDQISNGNASLLLRRVQLQDEGRY 88

                         90
                 ....*....|....*....
gi 442796434 119 QCKVKKAPGVANKKFLLTV 137
Cdd:cd16091   89 KCYTSTIIGNQESFVNLKV 107

Immunoglobulin variable (IgV) domain of B7-H6; The members here are composed of the immunoglobulin variable (IgV) domain of B7-H6 (also known as NCR3LG1). B7-H6 contains one IgV domain and one IgC domain (IgV-IgC) and belongs to the B7-family, which consists of structurally related cell-surface protein ligands which bind to receptors on lymphocytes that regulate immune responses. B7-H6 is a ligand of NKp30, which is a member of CD28 family and an activating receptor of natural killer (NK) cells. The expression of NKp30 has been found in most of NK cells, which is involved in the process of tumor cell killing and interaction with antigen presenting cells (APCs) such as dendritic cells. Studies showed that NK cells eliminate B7-H6-expressing tumor cells either directly via cytotoxicity or indirectly by cytokine secretion. For instance, chimeric NKp30-expressing T cells responded to B7-H6(+) tumor cells and those T cells produced IFN-gamma and killed B7-H6-expressing tumor cells in vivo. B7-H6 mRNA is not found in normal cells, while high expression of B7-H6 is found in certain type tumor cells, such as lymphoma, leukemia, ovarian cancer, brain tumors, breast cancers, and various sarcomas. Since B7-H6 can bind NKp30 to exert anti-tumor effects by NK cells, which are able to recognize the difference between cancer cells and normal cells, B7-H6 may serve as a promising target for cancer immunotherapy.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 442796434  98 VKSGDASINVTNLQLSDIGTYQCKVKKAPGVANKKFLLTV 137
Cdd:cd20981   75 LKSGDASLQLPGVQLEEAGEYRCEVVVTPLKAQGTVQLEV 114

First immunoglobulin variable (IgV) domain of nectin-3 (also known as poliovirus receptor related protein 3), and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of nectin-3 (also known as poliovirus receptor related protein 3 (PVRL3) or cluster of differentiation (CD) 113). Nectin-3 belongs to the nectin family 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, during spermatid development, the nectin-3,-2 trans-interaction is required for the formation of Sertoli cell-spermatid junctions in testis, and during morphogenesis of the ciliary body, the nectin-3,-1 trans-interaction is important for apex-apex adhesion between the pigment and non-pigment layers of the ciliary epithelia. Nectins also heterophilically trans-interact with other CAMs such as nectin-like molecules (Necls); nectin-3 for example, trans-interacts with Necl-5, regulating cell movement and proliferation. Other proteins with which nectin-3 interacts include the actin filament-binding protein, afadin, integrin alpha-beta3, Par-3, and PDGF receptor; its interaction with PDGF receptor regulates the latter's signaling for anti-apoptosis.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 442796434  85 PDLKGRVHFTSNDVKsgDASINVTNLQLSDIGTYQCKVKKAP-GVANKKFLLTVL 138
Cdd:cd05887   58 GEYQGRVSFKNYSLN--DATITLHNVGFSDSGKYICKAVTFPlGNAQSSTTVTVL 110

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442796434  22 ITTPEQRIEKAKGETAYLPCKFTLSPEDQgpldIEWLispsdnqivdqviilYSGDKIYDNyypdlKGRVHFTSNdvksg 101
Cdd:cd20978    4 IQKPEKNVVVKGGQDVTLPCQVTGVPQPK----ITWL---------------HNGKPLQGP-----MERATVEDG----- 54

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 442796434 102 daSINVTNLQLSDIGTYQCKVKKAPGVANKKFLLTV 137
Cdd:cd20978   55 --TLTIINVQPEDTGYYGCVATNEIGDIYTETLLHV 88