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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2W9L_V        5 LSITTPEEMIEKAKGETAYLPCKFTLSPEDQGPLDIEWLISPADnqKVDQVIILYSGDKIYDDYYPDLKGRVHFTSNDlK 84
Cdd:cd20960   1 LLITSAQTEIKKVAGENVTLPCHHQLGLEDQGTLDIEWLLLPSD--KVEKVVITYSGDRVYNHYYPALKGRVAFTSND-L 77

                        90       100       110
                ....*....|....*....|....*....|....*..
2W9L_V       85 SGDASINVTNLQLSDIGTYQCKVKKAPGVANKKIHLV 121
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2W9L_V        5 LSITTPEEMIEKAKGETAYLPCKFTLSPEDQGPLDIEWLISPADnqKVDQVIILYSGDKIYDDYYPDLKGRVHFTSNDlK 84
Cdd:cd20960   1 LLITSAQTEIKKVAGENVTLPCHHQLGLEDQGTLDIEWLLLPSD--KVEKVVITYSGDRVYNHYYPALKGRVAFTSND-L 77

                        90       100       110
                ....*....|....*....|....*....|....*..
2W9L_V       85 SGDASINVTNLQLSDIGTYQCKVKKAPGVANKKIHLV 121
Cdd:cd20960  78 SGDASLNISNLKLSDTGTYQCKVKKAPGYAWSKITLI 114

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2W9L_V          14 IEKAKGETAYLPCKFTLSPEDQgpldIEWLispadnqKVDQVIILYSGdkiyddyypdlkgRVHFTSNdlkSGDASINVT 93
Cdd:smart00410   4 VTVKEGESVTLSCEASGSPPPE----VTWY-------KQGGKLLAESG-------------RFSVSRS---GSTSTLTIS 56

                           90       100
                   ....*....|....*....|....*....
2W9L_V          94 NLQLSDIGTYQCKVKKAPGVANKKIHLVV 122
Cdd:smart00410  57 NVTPEDSGTYTCAATNSSGSASSGTTLTV 85

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2W9L_V        5 LSITTPEEMIEKAKGETAYLPCKFTLSPEDQGPLDIEWLISPADnqKVDQVIILYSGDKIYDDYYPDLKGRVHFTSNDlK 84
Cdd:cd20960   1 LLITSAQTEIKKVAGENVTLPCHHQLGLEDQGTLDIEWLLLPSD--KVEKVVITYSGDRVYNHYYPALKGRVAFTSND-L 77

                        90       100       110
                ....*....|....*....|....*....|....*..
2W9L_V       85 SGDASINVTNLQLSDIGTYQCKVKKAPGVANKKIHLV 121
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2W9L_V        5 LSITTPEEmIEKAKGETAYLPCKFTLSPEDQGPLDIEWLISPaDNQKVDQVIILYSGDKIYDDYYPDLKGRVHFTSNdLK 84
Cdd:cd05715   1 MEVYTPRE-LNVLNGSDVRLTCTFTSCYTVGDAFSVTWTYQP-EGGNTTESMFHYSKGKPYILKVGRFKDRVSWAGN-PS 77

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
2W9L_V       85 SGDASINVTNLQLSDIGTYQCKVKKAPGVANK--KIHLVV 122
Cdd:cd05715  78 KKDASIVISNLQFSDNGTYTCDVKNPPDIVGGhgEIRLYV 117

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2W9L_V       19 GETAYLPCKFTLSPEDQGpLDIEWLiSPADNQKVDQviiLYSGDKIYDDYYPDLKGRVHFTSNDLKSGDASINVTNLQLS 98
Cdd:cd20984  12 GEDGILSCTFTPDIKLSD-IVIQWL-KEGDSGLVHE---FKEGKDELSRQSPMFRGRTSLFADQVHVGNASLRLKNVQLT 86

                        90       100
                ....*....|....*....|
2W9L_V       99 DIGTYQCKVKKAPGVANKKI 118
Cdd:cd20984  87 DAGTYLCIISNSKGTGNANM 106

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2W9L_V       14 IEKAKGETAYLPCKFTLSPEDQGP----LDIEWLISPADNQKVDQVIILYSGD---KIYDDYypdlKGRVHFTSNDLKSG 86
Cdd:cd05714   7 VFSHLGGNVTLPCKFYRDPTAFGSgihkIRIKWTKLTSDSGYLKEVDVLVAMGnvvYHKKTY----GGRVSVPLKPGSDS 82

                        90       100
                ....*....|....*....|.
2W9L_V       87 DASINVTNLQLSDIGTYQCKV 107
Cdd:cd05714  83 DASLVITDLTASDYGLYRCEV 103

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2W9L_V       14 IEKAKGETAYLPCKFTLSPEDQGPLDIEWlispadnQKVDQVII-LYSGDKiydDYYPDLKGRvhfTSNDLkSGDASINV 92
Cdd:cd16086   4 VTKSVKEKALLSCDYNVSVDELAQVRIYW-------QKDDKMVLtIISGDV---KVWPEYKNR---TLFDI-TNNLSIVI 69

                        90       100
                ....*....|....*....|....*....
2W9L_V       93 TNLQLSDIGTYQCKVKKAPGVANKKIHLV 121
Cdd:cd16086  70 LALRLSDRGTYTCVVQKKERGAYKREHLA 98

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2W9L_V       19 GETAYLPCKFTLSPEDQGP------LDIEWLISPADNQKVDQVIILYSGD---KIYDDYypdlKGRVHFTSNDLKSGDAS 89
Cdd:cd05878  12 GTSVTLPCYFIDPPHPVTPstaplaPRIKWSKVSVDGKKEKEVVLLVATEgrvRVNSAY----QGRVSLPNYPAIPSDAT 87

                        90
                ....*....|....*...
2W9L_V       90 INVTNLQLSDIGTYQCKV 107
Cdd:cd05878  88 LEVQSLRASDSGLYRCEV 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2W9L_V       13 MIEKAKGETAYLPCKFTLSPEDQGPLD---IEWL-ISPADNQKvdQVIILYSGDKIYDdYYPDLKGRVHFTSNDLKSGDA 88
Cdd:cd05902   6 PVRRPLSSSVLLPCVFTLPPSASSPPEgprIKWTkLSTSGGQQ--QRPVLVARDNVVR-VAKAFQGRVSLPGYPKNRYNA 82

                        90
                ....*....|....*....
2W9L_V       89 SINVTNLQLSDIGTYQCKV 107
Cdd:cd05902  83 SLVLSRLRYSDSGTYRCEV 101

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2W9L_V        5 LSITTPEEmIEKAKGETAYLPCKFTLSPEDQGPLDIEWLISPaDNQKVDQVIILYSGDKIYDDYYPDLKGRVHFTSNDlK 84
Cdd:cd05879   1 IVVYTDRE-VYGTVGSDVTLSCSFWSSEWISDDISFTWHYQP-DGSRDAISIFHYGKGQPYIDNVGPFKERIEWVGNP-S 77

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
2W9L_V       85 SGDASINVTNLQLSDIGTYQCKVKKAPGVANK--KIHLVV 122
Cdd:cd05879  78 RKDGSIVIHNLDYTDNGTFTCDVKNPPDIVGKssQVTLYV 117

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2W9L_V       24 LPCKFTLSPEDQgpldIEWlISPADNQKVDqviILYSGDKIYDDYYPDLKGRVHFTSNDLKSGDASINVTNLQLSDIGTY 103
Cdd:cd16091  17 LPCSFTPGSEVV----IHW-YKQDSDIKVH---SYYYGKDQLESQDQRYRNRTSLFKDQISNGNASLLLRRVQLQDEGRY 88

                        90
                ....*....|....*....
2W9L_V      104 QCKVKKAPGVANKKIHLVV 122
Cdd:cd16091  89 KCYTSTIIGNQESFVNLKV 107

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2W9L_V       24 LPCKFTLSPEDQGP-------LDIEWLISPADNQKVDQ----VIILYSGD-KIYDDYypdlKGRVHFTSNDLKSGDASIN 91
Cdd:cd05901  17 LPCRFSTLPTLPPSynitsefLRIKWTKIQVDKNGKDHkettVLVAQNGIiKIGQEY----MGRVSVPSHPEDQGDASLT 92

                        90
                ....*....|....*.
2W9L_V       92 VTNLQLSDIGTYQCKV 107
Cdd:cd05901  93 IVKLRASDAGVYRCEV 108

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2W9L_V        7 ITTPEEMIEKAKGETAYLPCKFTLSPE-DQGPLDIEWlispadNQKVDQVIILYSGDKIYDDYYPDLKGRVHFTSNDLKS 85
Cdd:cd20947   1 VTVPKDLYVVEYGSNMTIECKFPVEKQlDLAALIVYW------EMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSL 74

                        90       100       110
                ....*....|....*....|....*....|....*..
2W9L_V       86 GDASINVTNLQLSDIGTYQCKVKKApGVANKKIHLVV 122
Cdd:cd20947  75 GNAALQITDVKLQDAGVYRCMISYG-GADYKRITVKV 110

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
                ....*....|....*....|....*....|....*....|
2W9L_V       83 LKSGDASINVTNLQLSDIGTYQCKVKKAPGVANKKIHLVV 122
Cdd:cd20981  75 LKSGDASLQLPGVQLEEAGEYRCEVVVTPLKAQGTVQLEV 114

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
                ....*....|....*....|....*....|....*....|....*....|...
2W9L_V       70 PDLKGRVHFTSNDLKSGDASINVTNLQLSDIGTYQCKVKKAP-GVANKKIHLV 121
Cdd:cd05889  57 KPYAGRVYFLNSTMASNNMSLSFRNASEDDVGYYSCSLYTYPqGSWEKVIQVV 109

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2W9L_V       10 PEEMIEKAKGETAYLPCKFTLSPE-DQGPLDIEWLISpadNQKvDQVIILYSGDKIYDDYYPDLKGRVHFTSNDLKSGDA 88
Cdd:cd20934   3 PEDPVVALVGTDATLRCSFSPEPGfSLAQLSVFWQLT---DTK-QLVHSFTESQDQGRDQGSAYANRTALFPDLLAQGNA 78

                        90       100
                ....*....|....*....|
2W9L_V       89 SINVTNLQLSDIGTYQCKVK 108
Cdd:cd20934  79 SLRLQRVRVADEGSYTCFVS 98

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2W9L_V          6 SITTPEEMIEKAKGETAYLPCKFTLSPEDQgpldIEWLispadnqKVDQVIIlysgdkiyddyypdlkgRVHFTSNDLKS 85
Cdd:pfam13927   3 VITVSPSSVTVREGETVTLTCEATGSPPPT----ITWY-------KNGEPIS-----------------SGSTRSRSLSG 54

                          90       100
                  ....*....|....*....|...
2W9L_V         86 GDASINVTNLQLSDIGTYQCKVK 108
Cdd:pfam13927  55 SNSTLTISNVTRSDAGTYTCVAS 77