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 568997227  20 LSITTPEQRIEKAKGETAYLPCKFTLSPEDQGPLDIEWLISPSDNqiVDQVIILYSGDKIYDNYYPDLKGRVHFTSNDvK 99
Cdd:cd20960    1 LLITSAQTEIKKVAGENVTLPCHHQLGLEDQGTLDIEWLLLPSDK--VEKVVITYSGDRVYNHYYPALKGRVAFTSND-L 77

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 568997227 100 SGDASINVTNLQLSDIGTYQCKVKKAPGVANKKFLLT 136
Cdd:cd20960   78 SGDASLNISNLKLSDTGTYQCKVKKAPGYAWSKITLI 114

Transmembrane domain of the Epidermal Growth Factor Receptor family of Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER, ErbB) subfamily members include EGFR (HER1, ErbB1), HER2 (ErbB2), HER3 (ErbB3), HER4 (ErbB4), and similar proteins. They are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane (TM) helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. They are activated by ligand-induced dimerization, resulting in the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Collectively, they can recognize a variety of ligands including EGF, TGFalpha, and neuregulins, among others. All four subfamily members can form homo- or heterodimers. HER3 contains an impaired kinase domain and depends on its heterodimerization partner for activation. EGFR subfamily members are involved in signaling pathways leading to a broad range of cellular responses including cell proliferation, differentiation, migration, growth inhibition, and apoptosis. The TM domain not only serves as a membrane anchor, but also plays an important role in receptor dimerization and optimal activation. Mutations in the TM domain of EGFR family RTKs have been associated with increased breast cancer risk.

                         10        20        30
                 ....*....|....*....|....*....|....
gi 568997227 238 TIAGAVIGTLLALVLIGAILFCchRKRREEKYEK 271
Cdd:cd12087    7 SIAAGVVGGLLVLVILGLIVFL--FRRRRHIKRK 38

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 568997227  20 LSITTPEQRIEKAKGETAYLPCKFTLSPEDQGPLDIEWLISPSDNqiVDQVIILYSGDKIYDNYYPDLKGRVHFTSNDvK 99
Cdd:cd20960    1 LLITSAQTEIKKVAGENVTLPCHHQLGLEDQGTLDIEWLLLPSDK--VEKVVITYSGDRVYNHYYPALKGRVAFTSND-L 77

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 568997227 100 SGDASINVTNLQLSDIGTYQCKVKKAPGVANKKFLLT 136
Cdd:cd20960   78 SGDASLNISNLKLSDTGTYQCKVKKAPGYAWSKITLI 114

Sixth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the sixth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997227 147 FVDGSEEIGNDFKLKCEPKEGSLPLQFEWqkLSDSQTMPTPWLAEMT-----SPVISVKNASSEYSGTYSCTVQNRVGSD 221
Cdd:cd20959    9 FGEGAAQVGMRAQLHCGVPGGDLPLNIRW--TLDGQPISDDLGITVSrlgrrSSILSIDSLEASHAGNYTCHARNSAGSA 86

                 ....*...
gi 568997227 222 QCMLRLDV 229
Cdd:cd20959   87 SYTAPLTV 94

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568997227  154 IGNDFKLKCEPKEGSLPLQFEWQK-----LSDSQTMPTPWlaEMTSPVISVKNASSEYSGTYSCTVQNRVGSDQ 222
Cdd:pfam00047  10 EGDSATLTCSASTGSPGPDVTWSKeggtlIESLKVKHDNG--RTTQSSLLISNVTKEDAGTYTCVVNNPGGSAT 81

Transmembrane domain of the Epidermal Growth Factor Receptor family of Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER, ErbB) subfamily members include EGFR (HER1, ErbB1), HER2 (ErbB2), HER3 (ErbB3), HER4 (ErbB4), and similar proteins. They are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane (TM) helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. They are activated by ligand-induced dimerization, resulting in the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Collectively, they can recognize a variety of ligands including EGF, TGFalpha, and neuregulins, among others. All four subfamily members can form homo- or heterodimers. HER3 contains an impaired kinase domain and depends on its heterodimerization partner for activation. EGFR subfamily members are involved in signaling pathways leading to a broad range of cellular responses including cell proliferation, differentiation, migration, growth inhibition, and apoptosis. The TM domain not only serves as a membrane anchor, but also plays an important role in receptor dimerization and optimal activation. Mutations in the TM domain of EGFR family RTKs have been associated with increased breast cancer risk.

                         10        20        30
                 ....*....|....*....|....*....|....
gi 568997227 238 TIAGAVIGTLLALVLIGAILFCchRKRREEKYEK 271
Cdd:cd12087    7 SIAAGVVGGLLVLVILGLIVFL--FRRRRHIKRK 38

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 568997227  20 LSITTPEQRIEKAKGETAYLPCKFTLSPEDQGPLDIEWLISPSDNqiVDQVIILYSGDKIYDNYYPDLKGRVHFTSNDvK 99
Cdd:cd20960    1 LLITSAQTEIKKVAGENVTLPCHHQLGLEDQGTLDIEWLLLPSDK--VEKVVITYSGDRVYNHYYPALKGRVAFTSND-L 77

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 568997227 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 568997227  20 LSITTPEQrIEKAKGETAYLPCKFTLSPEDQGPLDIEWLISPSDNQiVDQVIILYSGDKIYDNYYPDLKGRVHFTSNDVK 99
Cdd:cd05715    1 MEVYTPRE-LNVLNGSDVRLTCTFTSCYTVGDAFSVTWTYQPEGGN-TTESMFHYSKGKPYILKVGRFKDRVSWAGNPSK 78

                         90       100
                 ....*....|....*....|....*....
gi 568997227 100 SgDASINVTNLQLSDIGTYQCKVKKAPGV 128
Cdd:cd05715   79 K-DASIVISNLQFSDNGTYTCDVKNPPDI 106

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 568997227  34 GETAYLPCKFTLSPEDQGpLDIEWLiSPSDNQIVDQviiLYSGDKIYDNYYPDLKGRVHFTSNDVKSGDASINVTNLQLS 113
Cdd:cd20984   12 GEDGILSCTFTPDIKLSD-IVIQWL-KEGDSGLVHE---FKEGKDELSRQSPMFRGRTSLFADQVHVGNASLRLKNVQLT 86

                         90       100
                 ....*....|....*....|....
gi 568997227 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 568997227  21 SITTPEQRIEKAKGETAYLPCKftLSPE-DQGPLDIEWLISPSDNqivdqVIILY-SGDKIYDNYYPDLKGRVHFTSNDV 98
Cdd:cd05713    2 SVIGPTEPILALVGEDAELPCH--LSPKmSAEHMEVRWFRSQFSP-----VVHLYrDGQDQEEEQMPEYRGRTELLKDAI 74

                         90       100
                 ....*....|....*....|..
gi 568997227  99 KSGDASINVTNLQLSDIGTYQC 120
Cdd:cd05713   75 AEGSVALRIHNVRPSDEGQYTC 96

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 568997227  29 IEKAKGETAYLPCKFTLSPEDQGPLDIEWLISPSDNQiVDQVIILYsgdkiYDNYYPDL----KGRVHFTSNdVKSGDAS 104
Cdd:cd05880    9 VEAVNGTDVRLKCTFSSSAPIGDTLVITWNFRPLDGG-REESVFYY-----HKRPYPPPdgrfKGRVVWDGN-IMRRDAS 81

                         90       100
                 ....*....|....*....|....
gi 568997227 105 INVTNLQLSDIGTYQCKVKKAPGV 128
Cdd:cd05880   82 ILIWQLQPTDNGTYTCQVKNPPDV 105

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 568997227  29 IEKAKGETAYLPCKFTLSPEDQGPLDIEWlisPSDNQIVDQVIilySGDKiydNYYPDLKGRvhfTSNDVkSGDASINVT 108
Cdd:cd16086    4 VTKSVKEKALLSCDYNVSVDELAQVRIYW---QKDDKMVLTII---SGDV---KVWPEYKNR---TLFDI-TNNLSIVIL 70

                         90       100       110
                 ....*....|....*....|....*....|
gi 568997227 109 NLQLSDIGTYQCKV-KKAPGVANKKFLLTV 137
Cdd:cd16086   71 ALRLSDRGTYTCVVqKKERGAYKREHLASV 100

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997227    27 QRIEKAKGETAYLPCKFTLSPEDQgpldIEWLISpsdnqivDQVIILYSGdkiydnyypdlkgRVHFTSNdvkSGDASIN 106
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPE----VTWYKQ-------GGKLLAESG-------------RFSVSRS---GSTSTLT 54

                           90       100       110
                   ....*....|....*....|....*....|.
gi 568997227   107 VTNLQLSDIGTYQCKVKKAPGVANKKFLLTV 137
Cdd:smart00410  55 ISNVTPEDSGTYTCAATNSSGSASSGTTLTV 85

Immunoglobulin variable domain (IgV) in Cluster of Differentiation (CD) 86; The members here are composed of the immunoglobulin variable region (IgV) in the Cluster of Differentiation (CD) 86). Glycoproteins B7-1 (also known as cluster of differentiation (CD) 80) and B7-2 (also known as CD86) are expressed on antigen-presenting cells and deliver the co-stimulatory signal through CD28 and CTLA-4 (also known as CD152) on T cells. signaling through CD28 augments the T-cell response, whereas CTLA-4 signaling attenuates it. The CTLA-4 and B7-2 monomers are both two-layer beta-sandwiches that display the chain topology characteristic of the immunoglobulin variable (V-type) domains present in antigen receptors. The front and back sheets of B7-2 are composed of AGFCC'C" and BED strands, respectively. Members of the IgV family are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 beta-sheets with a tryptophan residue packed against the disulfide bond.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997227  34 GETAYLPCKFTlSPEDQGP--LDIEWlispsDNQiVDQVII-LYSGDKIYDNYYPDLKGRVHFTSNdvksgDASINVTNL 110
Cdd:cd16087    8 NETAYLPCQFK-NPQNISLseLVVFW-----QDQ-KKLVLYeLYLGKEKLDNVNSKYIGRTSFDQE-----NWTLQLHNV 75

                         90
                 ....*....|
gi 568997227 111 QLSDIGTYQC 120
Cdd:cd16087   76 QIKDQGTYQC 85

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997227   155 GNDFKLKCEPKeGSLPLQFEWQKlsDSQTMPTP-----WLAEMTSPVISVKNASSEYSGTYSCTVQNRVGSDQCMLRLDV 229
Cdd:smart00410   9 GESVTLSCEAS-GSPPPEVTWYK--QGGKLLAEsgrfsVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTLTV 85

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997227   21 SITTPEQRIEKAKGETAYLPCKFTLSPedqgPLDIEWL-----ISPSDnqivdqviilysgdkiydnyypdlkgRVHFTS 95
Cdd:pfam07679   2 KFTQKPKDVEVQEGESARFTCTVTGTP----DPEVSWFkdgqpLRSSD--------------------------RFKVTY 51

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 568997227   96 NDvksGDASINVTNLQLSDIGTYQCKVKKAPGVANKKFLLTV 137
Cdd:pfam07679  52 EG---GTYTLTISNVQPDDSGKYTCVATNSAGEAEASAELTV 90

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997227  84 YPDLKG----RVHFTSNDvKSGDASINVTNLQLSDIGTYQCKVKKAPGVANKKFLLTVLV 139
Cdd:cd05879   59 YIDNVGpfkeRIEWVGNP-SRKDGSIVIHNLDYTDNGTFTCDVKNPPDIVGKSSQVTLYV 117

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568997227 158 FKLKCEPkEGSLPLQFEWQKLSDSQTMPTPWLAEMTSP--VISVKNASSEYSGTYSCTVQNRVG 219
Cdd:cd00096    1 VTLTCSA-SGNPPPTITWYKNGKPLPPSSRDSRRSELGngTLTISNVTLEDSGTYTCVASNSAG 63

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997227  154 IGNDFKLKCEpKEGSLPLQFEWQK----LSDSQTMPTPWLAEMTSPVISvkNASSEYSGTYSCTVQNRVGSDQCMLRLDV 229
Cdd:pfam07679  14 EGESARFTCT-VTGTPDPEVSWFKdgqpLRSSDRFKVTYEGGTYTLTIS--NVQPDDSGKYTCVATNSAGEAEASAELTV 90

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 568997227  39 LPCKFTLSPEDQgpldIEWlISPSDNQIVDqviILYSGDKIYDNYYPDLKGRVHFTSNDVKSGDASINVTNLQLSDIGTY 118
Cdd:cd16091   17 LPCSFTPGSEVV----IHW-YKQDSDIKVH---SYYYGKDQLESQDQRYRNRTSLFKDQISNGNASLLLRRVQLQDEGRY 88

                         90
                 ....*....|....*....
gi 568997227 119 QCKVKKAPGVANKKFLLTV 137
Cdd:cd16091   89 KCYTSTIIGNQESFVNLKV 107

Transmembrane domain of the Epidermal Growth Factor Receptor family of Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER, ErbB) subfamily members include EGFR (HER1, ErbB1), HER2 (ErbB2), HER3 (ErbB3), HER4 (ErbB4), and similar proteins. They are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane (TM) helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. They are activated by ligand-induced dimerization, resulting in the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Collectively, they can recognize a variety of ligands including EGF, TGFalpha, and neuregulins, among others. All four subfamily members can form homo- or heterodimers. HER3 contains an impaired kinase domain and depends on its heterodimerization partner for activation. EGFR subfamily members are involved in signaling pathways leading to a broad range of cellular responses including cell proliferation, differentiation, migration, growth inhibition, and apoptosis. The TM domain not only serves as a membrane anchor, but also plays an important role in receptor dimerization and optimal activation. Mutations in the TM domain of EGFR family RTKs have been associated with increased breast cancer risk.

                         10        20        30
                 ....*....|....*....|....*....|....
gi 568997227 238 TIAGAVIGTLLALVLIGAILFCchRKRREEKYEK 271
Cdd:cd12087    7 SIAAGVVGGLLVLVILGLIVFL--FRRRRHIKRK 38

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568997227 154 IGNDFKLKCEPKEGSLPlQFEWQKlsDSQTMPTPWLAEMTSP--VISVKNASSEYSGTYSCTVQNRVGSDQCMLRLDV 229
Cdd:cd05856   18 VGSSVRLKCVASGNPRP-DITWLK--DNKPLTPPEIGENKKKkwTLSLKNLKPEDSGKYTCHVSNRAGEINATYKVDV 92

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568997227  154 IGNDFKLKCEPKeGSLPLQFEWQKlsDSQTMPTpwlaemtSPVISVKNASSEYSGTYSCTVQNRVGS 220
Cdd:pfam13895  13 EGEPVTLTCSAP-GNPPPSYTWYK--DGSAISS-------SPNFFTLSVSAEDSGTYTCVARNGRGG 69