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 6857775   20 LSITTPEQRIEKAKGETAYLPCKFTLSPEDQGPLDIEWLISPSDNqiVDQVIILYSGDKIYDNYYPDLKGRVHFTSNDvK 99
Cdd:cd20960   1 LLITSAQTEIKKVAGENVTLPCHHQLGLEDQGTLDIEWLLLPSDK--VEKVVITYSGDRVYNHYYPALKGRVAFTSND-L 77

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 6857775  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 6857775  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 6857775   20 LSITTPEQRIEKAKGETAYLPCKFTLSPEDQGPLDIEWLISPSDNqiVDQVIILYSGDKIYDNYYPDLKGRVHFTSNDvK 99
Cdd:cd20960   1 LLITSAQTEIKKVAGENVTLPCHHQLGLEDQGTLDIEWLLLPSDK--VEKVVITYSGDRVYNHYYPALKGRVAFTSND-L 77

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 6857775  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 6857775  147 FVDGSEEIGNDFKLKCEPKEGSLPLQFEWqkLSDSQTMPTPWLAEMT-----SPVISVKNASSEYSGTYSCTVQNRVGSD 221
Cdd:cd20959   9 FGEGAAQVGMRAQLHCGVPGGDLPLNIRW--TLDGQPISDDLGITVSrlgrrSSILSIDSLEASHAGNYTCHARNSAGSA 86

                ....*...
gi 6857775  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 6857775    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 6857775  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 6857775   20 LSITTPEQRIEKAKGETAYLPCKFTLSPEDQGPLDIEWLISPSDNqiVDQVIILYSGDKIYDNYYPDLKGRVHFTSNDvK 99
Cdd:cd20960   1 LLITSAQTEIKKVAGENVTLPCHHQLGLEDQGTLDIEWLLLPSDK--VEKVVITYSGDRVYNHYYPALKGRVAFTSND-L 77

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 6857775  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 6857775   20 LSITTPEQrIEKAKGETAYLPCKFTLSPEDQGPLDIEWLISPSDNQiVDQVIILYSGDKIYDNYYPDLKGRVHFTSNDVK 99
Cdd:cd05715   1 MEVYTPRE-LNVLNGSDVRLTCTFTSCYTVGDAFSVTWTYQPEGGN-TTESMFHYSKGKPYILKVGRFKDRVSWAGNPSK 78

                        90       100
                ....*....|....*....|....*..
gi 6857775  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 6857775   34 GETAYLPCKFTLSPEDQGpLDIEWLiSPSDNQIVDQviiLYSGDKIYDNYYPDLKGRVHFTSNDVKSGDASINVTNLQLS 113
Cdd:cd20984  12 GEDGILSCTFTPDIKLSD-IVIQWL-KEGDSGLVHE---FKEGKDELSRQSPMFRGRTSLFADQVHVGNASLRLKNVQLT 86

                        90       100
                ....*....|....*....|....
gi 6857775  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 6857775   21 SITTPEQRIEKAKGETAYLPCKftLSPE-DQGPLDIEWLISPSDNqivdqVIILY-SGDKIYDNYYPDLKGRVHFTSNDV 98
Cdd:cd05713   2 SVIGPTEPILALVGEDAELPCH--LSPKmSAEHMEVRWFRSQFSP-----VVHLYrDGQDQEEEQMPEYRGRTELLKDAI 74

                        90       100
                ....*....|....*....|..
gi 6857775   99 KSGDASINVTNLQLSDIGTYQC 120
Cdd:cd05713  75 AEGSVALRIHNVRPSDEGQYTC 96

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 6857775  147 FVDGSEEIGNDFKLKCEPKEGSLPLQFEWqkLSDSQTMPTPWLAEMT-----SPVISVKNASSEYSGTYSCTVQNRVGSD 221
Cdd:cd20959   9 FGEGAAQVGMRAQLHCGVPGGDLPLNIRW--TLDGQPISDDLGITVSrlgrrSSILSIDSLEASHAGNYTCHARNSAGSA 86

                ....*...
gi 6857775  222 QCMLRLDV 229
Cdd:cd20959  87 SYTAPLTV 94

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 6857775   29 IEKAKGETAYLPCKFTLSPEDQGPLDIEWlisPSDNQIVDQVIilySGDKiydNYYPDLKGRvhfTSNDVkSGDASINVT 108
Cdd:cd16086   4 VTKSVKEKALLSCDYNVSVDELAQVRIYW---QKDDKMVLTII---SGDV---KVWPEYKNR---TLFDI-TNNLSIVIL 70

                        90       100       110
                ....*....|....*....|....*....|
gi 6857775  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 6857775      27 QRIEKAKGETAYLPCKFTLSPEDQgpldIEWLISpsdnqivDQVIILYSGdkiydnyypdlkgRVHFTSNdvkSGDASIN 106
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPE----VTWYKQ-------GGKLLAESG-------------RFSVSRS---GSTSTLT 54

                           90       100       110
                   ....*....|....*....|....*....|.
gi 6857775     107 VTNLQLSDIGTYQCKVKKAPGVANKKFLLTV 137
Cdd:smart00410  55 ISNVTPEDSGTYTCAATNSSGSASSGTTLTV 85

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 6857775   34 GETAYLPCKFTLSPEDQGP------LDIEWL-ISPSDNQIVDQVIILYSGDKIYDNyyPDLKGRVHFTSNDVKSGDASIN 106
Cdd:cd05878  12 GTSVTLPCYFIDPPHPVTPstaplaPRIKWSkVSVDGKKEKEVVLLVATEGRVRVN--SAYQGRVSLPNYPAIPSDATLE 89

                        90       100       110
                ....*....|....*....|....*....|....
gi 6857775  107 VTNLQLSDIGTYQCKVKKapGVANKKFLLTVLVK 140
Cdd:cd05878  90 VQSLRASDSGLYRCEVMH--GIEDSQDTVELVVK 121

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 6857775   27 QRIEKAKGETAYLPCKFTLSPEDQGPLD---IEWL-ISPSDNQivDQVIILYSGDKIYdNYYPDLKGRVHFTSNDVKSGD 102
Cdd:cd05902   5 PPVRRPLSSSVLLPCVFTLPPSASSPPEgprIKWTkLSTSGGQ--QQRPVLVARDNVV-RVAKAFQGRVSLPGYPKNRYN 81

                        90       100
                ....*....|....*....|
gi 6857775  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 6857775   21 SITTPE-QRIEKAKGETAYLPCKFTLSPEDQGPLdIEWL--ISPSDNQIV---DQVIILYSGDkiYDNYYPDLKGRVHFT 94
Cdd:cd20963   3 TVTVPSyTRTDPTWGNRVELPCSYTISPAAQPPT-ITWLkgISVDRAEVVfkgFKYWNETSSS--GEVYFGDYAGRASVA 79

                        90       100
                ....*....|....*....|....*...
gi 6857775   95 SNDvksgDASINVTNLQLSDIGTYQCKV 122
Cdd:cd20963  80 SLT----QPTLVLTDLKFDDWGRYWCRV 103

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 6857775   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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 6857775  158 FKLKCEPkEGSLPLQFEWQKLSDSQTMPTPWLAEMTSP--VISVKNASSEYSGTYSCTVQNRVG 219
Cdd:cd00096   1 VTLTCSA-SGNPPPTITWYKNGKPLPPSSRDSRRSELGngTLTISNVTLEDSGTYTCVASNSAG 63

Immunoglobulin variable (IgV)-like domain in complement receptor of the immunoglobulin superfamily (CRIg); The members here are composed of the immunoglobulin variable (IgV) region of the complement receptor of the immunoglobulin superfamily (CRIg). The N-terminal domain of CRIg (also known as Z39Ig and V-set and Ig domain-containing 4 (VSIG4) belongs to the IgV family of immunoglobulin-like domains while the C-terminal domain of CRIg belongs to the IgC family of immunoglobulin-like domains. Like all members of this family, the CRIg domain contains two beta-sheets: one composed of strands A', G, F, C, C' and C", and the other of strands B, E and D. The complement system is an important part of the innate immune system and is required for removal of pathogens from the bloodstream. After exposure to pathogens, the third component of the complement system, C3, is cleaved to C3b which, after recruitment of factor B, initiates formation of the alternative pathway convertases. CRIg, a complement receptor expressed on macrophages, binds to C3b and iC3b mediating phagocytosis of the particles. It is also a potent inhibitor of the alternative pathway convertases and a negative regulator of T cell activation. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as, T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as, butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6857775   22 ITTPEQRIEKAKGETAyLPCkfTLSPE-DQGPLDIEWLISPSDNQIVdqvIILY--SGDKIYDNYYpdlKGRVHfTSNDV 98
Cdd:cd16089   3 LEGPESITGPWKGSVN-LPC--TYVPEeGYTQVLVKWLVQRDSDPVT---IFLRdsSGDHIQQAKY---RGRLE-VSKDT 72

                        90       100
                ....*....|....*....|....
gi 6857775   99 kSGDASINVTNLQLSDIGTYQCKV 122
Cdd:cd16089  73 -PGDVSLQLDTLEMDDRGHYTCQV 95

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6857775  155 GNDFKLKCEPKEGSLPlQFEW-------QKLSDSQTMpTPWLAEMTspvisVKNASSEYSGTYSCTVQNRVGSDQCMLRL 227
Cdd:cd20976  16 GQDFVAQCSARGKPVP-RITWirnaqplQYAADRSTC-EAGVGELH-----IQDVLPEDHGTYTCLAKNAAGQVSCSAWV 88

                ..
gi 6857775  228 DV 229
Cdd:cd20976  89 TV 90

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 6857775  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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 6857775  154 IGNDFKLKCEPKEGSLPlQFEWQKlsDSQTMPTPWLAEMTSP--VISVKNASSEYSGTYSCTVQNRVGSDQCMLRLDV 229
Cdd:cd05856  18 VGSSVRLKCVASGNPRP-DITWLK--DNKPLTPPEIGENKKKkwTLSLKNLKPEDSGKYTCHVSNRAGEINATYKVDV 92

First (N-terminal) immunoglobulin (Ig)-like domain of the nectin-like molecules; member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 (CADM3)), Necl-2 (CADM1), Necl-3 (CADM2), and similar proteins. At least five nectin-like molecules have been identified (Necl-1 to Necl-5). They all have an extracellular region containing three Ig-like domains, a transmembrane region, and a cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1, Necl-2, and Necl-3 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue, and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues and is a putative tumour suppressor gene which is downregulated in aggressive neuroblastoma. Necl-3 accumulates in central and peripheral nervous system tissue and has been shown to selectively interact with oligodendrocytes. This group also contains Class-I MHC-restricted T-cell-associated molecule (CRTAM), whose expression pattern is consistent with its expression in Class-I MHC-restricted T-cells.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6857775   34 GETAYLPCKFTLSPEDQgpldIEWLiSPSdnqivdqviilysGDKIYDNYYPDLKGR----VHFTSNDVksgdaSINVTN 109
Cdd:cd05717  11 GETLTLKCQVSLRDDSS----LQWL-NPN-------------GQTIYFNDKRALRDSryqlLNHSASEL-----SISVSN 67

                        90       100
                ....*....|....*....|....*...
gi 6857775  110 LQLSDIGTYQCKVKKAPgVANKKFLLTV 137
Cdd:cd05717  68 VTLSDEGVYTCLHYTDP-VSTKKVTVTV 94