C-type lectin (CTL)/C-type lectin-like (CTLD) domain; CLECT: C-type lectin (CTL)/C-type lectin-like (CTLD) domain; protein domains homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. This group is chiefly comprised of eukaryotic CTLDs, but contains some, as yet functionally uncharacterized, bacterial CTLDs. Many CTLDs are calcium-dependent carbohydrate binding modules; other CTLDs bind protein ligands, lipids, and inorganic surfaces, including CaCO3 and ice. Animal C-type lectins are involved in such functions as extracellular matrix organization, endocytosis, complement activation, pathogen recognition, and cell-cell interactions. For example: mannose-binding lectin and lung surfactant proteins A and D bind carbohydrates on surfaces (e.g. pathogens, allergens, necrotic, and apoptotic cells) and mediate functions associated with killing and phagocytosis; P (platlet)-, E (endothelial)-, and L (leukocyte)- selectins (sels) mediate the initial attachment, tethering, and rolling of lymphocytes on inflamed vascular walls enabling subsequent lymphocyte adhesion and transmigration. CTLDs may bind a variety of carbohydrate ligands including mannose, N-acetylglucosamine, galactose, N-acetylgalactosamine, and fucose. Several CTLDs bind to protein ligands, and only some of these binding interactions are Ca2+-dependent; including the CTLDs of Coagulation Factors IX/X (IX/X) and Von Willebrand Factor (VWF) binding proteins, and natural killer cell receptors. C-type lectins, such as lithostathine, and some type II antifreeze glycoproteins function in a Ca2+-independent manner to bind inorganic surfaces. Many proteins in this group contain a single CTLD; these CTLDs associate with each other through several different surfaces to form dimers, trimers, or tetramers, from which ligand-binding sites project in different orientations. Various vertebrate type 1 transmembrane proteins including macrophage mannose receptor, endo180, phospholipase A2 receptor, and dendritic and epithelial cell receptor (DEC205) have extracellular domains containing 8 or more CTLDs; these CTLDs remain in the parent model. In some members (IX/X and VWF binding proteins), a loop extends to the adjoining domain to form a loop-swapped dimer. A similar conformation is seen in the macrophage mannose receptor CRD4's putative non-sugar bound form of the domain in the acid environment of the endosome. Lineage specific expansions of CTLDs have occurred in several animal lineages including Drosophila melanogaster and Caenorhabditis elegans; these CTLDs also remain in the parent model.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462548642 230 CFMVSSEADTYYRARMKCQRKGGVLAQIKSQKVQDILAFYLgrlettnevidSDFETRNFWIGLTYKTAKDSFRWATGEH 309
Cdd:cd00037     2 CYKFSTEKLTWEEAQEYCRSLGGHLASIHSEEENDFLASLL-----------KKSSSSDVWIGLNDLSSEGTWKWSDGSP 70

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2462548642 310 QA-FTSFAFGQPDNHGFGNCVELQASAAFNWNDQRCKTRNRYICQF 354
Cdd:cd00037    71 LVdYTNWAPGEPNPGGSEDCVVLSSSSDGKWNDVSCSSKLPFICEK 116

CAP (cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins) domain family; The CAP (cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins) domain, also called SCP (sperm-coating glycoprotein), is found in eukaryotes and prokaryotes. This family includes plant pathogenesis-related protein 1 (PR-1), which accumulates after infections with pathogens, and may act as an anti-fungal agent or be involved in cell wall loosening. This family also includes CRISPs (cysteine-rich secretory proteins), which combine the CAP/SCP domain with a C-terminal cysteine rich domain, and allergen 5 from vespid venom. Roles for CRISP, in response to pathogens, fertilization, and sperm maturation have been proposed. One member, Tex31 from the venom duct of Conus textile, has been shown to possess proteolytic activity sensitive to serine protease inhibitors. The human GAPR-1 protein has been reported to dimerize, and such a dimer may form an active site containing a catalytic triad. CAP/SCP has also been proposed to be a Ca++ chelating serine protease. The Ca++-chelating function would fit with various signaling processes that members of this family, such as the CRISPs, are involved in, and is supported by sequence and structural evidence of a conserved pocket containing two histidines and a glutamate. It also may explain how helothermine, a toxic peptide secreted by the beaded lizard, blocks Ca++ transporting ryanodine receptors. Little is known about the biological roles of the bacterial and archaeal CAP/SCP domains.

                          10        20
                  ....*....|....*....|....*...
gi 2462548642  50 LLLSLHNRLRSWVQPPAADMRRlLVWAT 77
Cdd:cd05559     3 LLVDLHNQYRSQVSPSAANMLK-MTWDT 29

C-type lectin (CTL)/C-type lectin-like (CTLD) domain; CLECT: C-type lectin (CTL)/C-type lectin-like (CTLD) domain; protein domains homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. This group is chiefly comprised of eukaryotic CTLDs, but contains some, as yet functionally uncharacterized, bacterial CTLDs. Many CTLDs are calcium-dependent carbohydrate binding modules; other CTLDs bind protein ligands, lipids, and inorganic surfaces, including CaCO3 and ice. Animal C-type lectins are involved in such functions as extracellular matrix organization, endocytosis, complement activation, pathogen recognition, and cell-cell interactions. For example: mannose-binding lectin and lung surfactant proteins A and D bind carbohydrates on surfaces (e.g. pathogens, allergens, necrotic, and apoptotic cells) and mediate functions associated with killing and phagocytosis; P (platlet)-, E (endothelial)-, and L (leukocyte)- selectins (sels) mediate the initial attachment, tethering, and rolling of lymphocytes on inflamed vascular walls enabling subsequent lymphocyte adhesion and transmigration. CTLDs may bind a variety of carbohydrate ligands including mannose, N-acetylglucosamine, galactose, N-acetylgalactosamine, and fucose. Several CTLDs bind to protein ligands, and only some of these binding interactions are Ca2+-dependent; including the CTLDs of Coagulation Factors IX/X (IX/X) and Von Willebrand Factor (VWF) binding proteins, and natural killer cell receptors. C-type lectins, such as lithostathine, and some type II antifreeze glycoproteins function in a Ca2+-independent manner to bind inorganic surfaces. Many proteins in this group contain a single CTLD; these CTLDs associate with each other through several different surfaces to form dimers, trimers, or tetramers, from which ligand-binding sites project in different orientations. Various vertebrate type 1 transmembrane proteins including macrophage mannose receptor, endo180, phospholipase A2 receptor, and dendritic and epithelial cell receptor (DEC205) have extracellular domains containing 8 or more CTLDs; these CTLDs remain in the parent model. In some members (IX/X and VWF binding proteins), a loop extends to the adjoining domain to form a loop-swapped dimer. A similar conformation is seen in the macrophage mannose receptor CRD4's putative non-sugar bound form of the domain in the acid environment of the endosome. Lineage specific expansions of CTLDs have occurred in several animal lineages including Drosophila melanogaster and Caenorhabditis elegans; these CTLDs also remain in the parent model.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462548642 230 CFMVSSEADTYYRARMKCQRKGGVLAQIKSQKVQDILAFYLgrlettnevidSDFETRNFWIGLTYKTAKDSFRWATGEH 309
Cdd:cd00037     2 CYKFSTEKLTWEEAQEYCRSLGGHLASIHSEEENDFLASLL-----------KKSSSSDVWIGLNDLSSEGTWKWSDGSP 70

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2462548642 310 QA-FTSFAFGQPDNHGFGNCVELQASAAFNWNDQRCKTRNRYICQF 354
Cdd:cd00037    71 LVdYTNWAPGEPNPGGSEDCVVLSSSSDGKWNDVSCSSKLPFICEK 116

Lectin C-type domain; This family includes both long and short form C-type

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462548642 239 TYYRARMKCQRKGGVLAQIKSQKVQDILAFYLGRlettnevidsdfETRNFWIGLTYKTAKDSFRWATGEHQAFTSFAFG 318
Cdd:pfam00059   3 TWDEAREACRKLGGHLVSINSAEELDFLSSTLKK------------SNKYFWIGLTDRKNEGTWKWVDGSPVNYTNWAPE 70

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 2462548642 319 QPDNHGFGNCVELQASAAFnWNDQRCKTRNRYICQF 354
Cdd:pfam00059  71 PNNNGENEDCVELSSSSGK-WNDENCNSKNPFVCEK 105

SCP / Tpx-1 / Ag5 / PR-1 / Sc7 family of extracellular domains; Human glioma pathogenesis-related protein GliPR and the plant pathogenesis-related protein represent functional links between plant defense systems and human immune system. This family has no known function.

                           10        20        30
                   ....*....|....*....|....*....|..
gi 2462548642   73 LVWATSSQLGCGRHLCSAGQAVIEAFVCAYSP 104
Cdd:smart00198 113 VVWAKTYKVGCGVANCPDGTKKKTVVVCNYDP 144

CAP (cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins) domain of peptidase inhibitor 16 and HrTT-1 protein; Human peptidase inhibitor 16 (PI16) is also called cysteine-rich secretory protein 9 (CRISP-9) or PSP94-binding protein. Mouse PI16 is also called cysteine-rich protease inhibitor. PI16 is predominantly expressed by cardiac fibroblasts and is exposed to the interstitium via a glycophosphatidylinositol (-GPI) membrane anchor. It suppresses the activation of the chemokine chemerin in the myocardium, which may be a part of the cardiac stress response. At high endothelial shear stress, PI16 is an inflammation-regulated inhibitor of matrix metalloproteinase 2 (MMP2). Also included in this subfamily is the HrTT-1 protein, a tail-tip epidermis marker in ascidians. The wider family of CAP domain containing proteins includes plant pathogenesis-related protein 1 (PR-1), cysteine-rich secretory proteins (CRISPs), and allergen 5 from vespid venom, among others.

                          10        20
                  ....*....|....*....|....*...
gi 2462548642  50 LLLSLHNRLRSWVQPPAADMRRlLVWAT 77
Cdd:cd05559     3 LLVDLHNQYRSQVSPSAANMLK-MTWDT 29

C-type lectin (CTL)/C-type lectin-like (CTLD) domain; CLECT: C-type lectin (CTL)/C-type lectin-like (CTLD) domain; protein domains homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. This group is chiefly comprised of eukaryotic CTLDs, but contains some, as yet functionally uncharacterized, bacterial CTLDs. Many CTLDs are calcium-dependent carbohydrate binding modules; other CTLDs bind protein ligands, lipids, and inorganic surfaces, including CaCO3 and ice. Animal C-type lectins are involved in such functions as extracellular matrix organization, endocytosis, complement activation, pathogen recognition, and cell-cell interactions. For example: mannose-binding lectin and lung surfactant proteins A and D bind carbohydrates on surfaces (e.g. pathogens, allergens, necrotic, and apoptotic cells) and mediate functions associated with killing and phagocytosis; P (platlet)-, E (endothelial)-, and L (leukocyte)- selectins (sels) mediate the initial attachment, tethering, and rolling of lymphocytes on inflamed vascular walls enabling subsequent lymphocyte adhesion and transmigration. CTLDs may bind a variety of carbohydrate ligands including mannose, N-acetylglucosamine, galactose, N-acetylgalactosamine, and fucose. Several CTLDs bind to protein ligands, and only some of these binding interactions are Ca2+-dependent; including the CTLDs of Coagulation Factors IX/X (IX/X) and Von Willebrand Factor (VWF) binding proteins, and natural killer cell receptors. C-type lectins, such as lithostathine, and some type II antifreeze glycoproteins function in a Ca2+-independent manner to bind inorganic surfaces. Many proteins in this group contain a single CTLD; these CTLDs associate with each other through several different surfaces to form dimers, trimers, or tetramers, from which ligand-binding sites project in different orientations. Various vertebrate type 1 transmembrane proteins including macrophage mannose receptor, endo180, phospholipase A2 receptor, and dendritic and epithelial cell receptor (DEC205) have extracellular domains containing 8 or more CTLDs; these CTLDs remain in the parent model. In some members (IX/X and VWF binding proteins), a loop extends to the adjoining domain to form a loop-swapped dimer. A similar conformation is seen in the macrophage mannose receptor CRD4's putative non-sugar bound form of the domain in the acid environment of the endosome. Lineage specific expansions of CTLDs have occurred in several animal lineages including Drosophila melanogaster and Caenorhabditis elegans; these CTLDs also remain in the parent model.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462548642 230 CFMVSSEADTYYRARMKCQRKGGVLAQIKSQKVQDILAFYLgrlettnevidSDFETRNFWIGLTYKTAKDSFRWATGEH 309
Cdd:cd00037     2 CYKFSTEKLTWEEAQEYCRSLGGHLASIHSEEENDFLASLL-----------KKSSSSDVWIGLNDLSSEGTWKWSDGSP 70

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2462548642 310 QA-FTSFAFGQPDNHGFGNCVELQASAAFNWNDQRCKTRNRYICQF 354
Cdd:cd00037    71 LVdYTNWAPGEPNPGGSEDCVVLSSSSDGKWNDVSCSSKLPFICEK 116

Lectin C-type domain; This family includes both long and short form C-type

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462548642 239 TYYRARMKCQRKGGVLAQIKSQKVQDILAFYLGRlettnevidsdfETRNFWIGLTYKTAKDSFRWATGEHQAFTSFAFG 318
Cdd:pfam00059   3 TWDEAREACRKLGGHLVSINSAEELDFLSSTLKK------------SNKYFWIGLTDRKNEGTWKWVDGSPVNYTNWAPE 70

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 2462548642 319 QPDNHGFGNCVELQASAAFnWNDQRCKTRNRYICQF 354
Cdd:pfam00059  71 PNNNGENEDCVELSSSSGK-WNDENCNSKNPFVCEK 105

C-type lectin-like domain (CTLD) of the type found in human dendritic cell (DC)-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) and the related receptor, DC-SIGN receptor (DC-SIGNR); CLECT_DC-SIGN_like: C-type lectin-like domain (CTLD) of the type found in human dendritic cell (DC)-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) and the related receptor, DC-SIGN receptor (DC-SIGNR). This group also contains proteins similar to hepatic asialoglycoprotein receptor (ASGP-R) and langerin in human. These proteins are type II membrane proteins with a CTLD ectodomain. CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. DC-SIGN is thought to mediate the initial contact between dendritic cells and resting T cells, and may also mediate the rolling of DCs on epithelium. DC-SIGN and DC-SIGNR bind to oligosaccharides present on human tissues, as well as, on pathogens including parasites, bacteria, and viruses. DC-SIGN and DC-SIGNR bind to HIV enhancing viral infection of T cells. DC-SIGN and DC-SIGNR are homotetrameric, and contain four CTLDs stabilized by a coiled coil of alpha helices. The hepatic ASGP-R is an endocytic recycling receptor which binds and internalizes desialylated glycoproteins having a terminal galactose or N-acetylgalactosamine residues on their N-linked carbohydrate chains, via the clathrin-coated pit mediated endocytic pathway, and delivers them to lysosomes for degradation. It has been proposed that glycoproteins bearing terminal Sia (sialic acid) alpha2, 6GalNAc and Sia alpha2, 6Gal are endogenous ligands for ASGP-R and that ASGP-R participates in regulating the relative concentration of serum glycoproteins bearing alpha 2,6-linked Sia. The human ASGP-R is a hetero-oligomer composed of two subunits, both of which are found within this group. Langerin is expressed in a subset of dendritic leukocytes, the Langerhans cells (LC). Langerin induces the formation of Birbeck Granules (BGs) and associates with these BGs following internalization. Langerin binds, in a calcium-dependent manner, to glyco-conjugates containing mannose and related sugars mediating their uptake and degradation. Langerin molecules oligomerize as trimers with three CTLDs held together by a coiled-coil of alpha helices.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462548642 230 CFMVSSEADTYYRARMKCQRKGGVLAQIKSQKVQDILafylgrlettNEVIDSDfetRNFWIGLTYKTAKDSFRWA--TG 307
Cdd:cd03590    12 CYFFSTEKKSWEESRQFCEDMGAHLVIINSQEEQEFI----------SKILSGN---RSYWIGLSDEETEGEWKWVdgTP 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 2462548642 308 EHQAFTSFAFGQPDNHGFGN--CVELQASAAfNWNDQRCKTRNRYICQ 353
Cdd:cd03590    79 LNSSKTFWHPGEPNNWGGGGedCAELVYDSG-GWNDVPCNLEYRWICE 125

C-type lectin-like domain (CTLD) of the type found in natural killer cell receptors (NKRs); CLECT_NK_receptors_like: C-type lectin-like domain (CTLD) of the type found in natural killer cell receptors (NKRs), including proteins similar to oxidized low density lipoprotein (OxLDL) receptor (LOX-1), CD94, CD69, NKG2-A and -D, osteoclast inhibitory lectin (OCIL), dendritic cell-associated C-type lectin-1 (dectin-1), human myeloid inhibitory C-type lectin-like receptor (MICL), mast cell-associated functional antigen (MAFA), killer cell lectin-like receptors: subfamily F, member 1 (KLRF1) and subfamily B, member 1 (KLRB1), and lys49 receptors. CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. NKRs are variously associated with activation or inhibition of natural killer (NK) cells. Activating NKRs stimulate cytolysis by NK cells of virally infected or transformed cells; inhibitory NKRs block cytolysis upon recognition of markers of healthy self cells. Most Lys49 receptors are inhibitory; some are stimulatory. OCIL inhibits NK cell function via binding to the receptor NKRP1D. Murine OCIL in addition to inhibiting NK cell function inhibits osteoclast differentiation. MAFA clusters with the type I Fc epsilon receptor (FcepsilonRI) and inhibits the mast cells secretory response to FcepsilonRI stimulus. CD72 is a negative regulator of B cell receptor signaling. NKG2D is an activating receptor for stress-induced antigens; human NKG2D ligands include the stress induced MHC-I homologs, MICA, MICB, and ULBP family of glycoproteins Several NKRs have a carbohydrate-binding capacity which is not mediated through calcium ions (e.g. OCIL binds a range of high molecular weight sulfated glycosaminoglycans including dextran sulfate, fucoidan, and gamma-carrageenan sugars). Dectin-1 binds fungal beta-glucans and in involved in the innate immune responses to fungal pathogens. MAFA binds saccharides having terminal alpha-D mannose residues in a calcium-dependent manner. LOX-1 is the major receptor for OxLDL in endothelial cells and thought to play a role in the pathology of atherosclerosis. Some NKRs exist as homodimers (e.g.Lys49, NKG2D, CD69, LOX-1) and some as heterodimers (e.g. CD94/NKG2A). Dectin-1 can function as a monomer in vitro.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462548642 230 CFMVSSEADTYYRARMKCQRKGGVLAQIKSQKVQDILAFYLGRlettnevidsdfetRNFWIGLTYKTAKDSFRWatgEH 309
Cdd:cd03593    12 CYYFSMEKKTWNESKEACSSKNSSLLKIDDEEELEFLQSQIGS--------------SSYWIGLSREKSEKPWKW---ID 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 2462548642 310 QAFTSFAFGQPDNHGFGNCVELQASAAFNwndQRCKTRNRYICQ 353
Cdd:cd03593    75 GSPLNNLFNIRGSTKSGNCAYLSSTGIYS---EDCSTKKRWICE 115

C-type lectin-like domain (CTLD) of the type found in the human type-1A transmembrane proteins chondrolectin (CHODL) and layilin; CLECT_chondrolectin_like: C-type lectin-like domain (CTLD) of the type found in the human type-1A transmembrane proteins chondrolectin (CHODL) and layilin. CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. CHODL is predominantly expressed in muscle cells and is associated with T-cell maturation. Various alternatively spliced isoforms have been of CHODL have been identified. The transmembrane form of CHODL is localized in the ER-Golgi apparatus. Layilin is widely expressed in different cell types. The extracellular CTLD of layilin binds hyaluronan (HA), a major constituent of the extracellular matrix (ECM). The cytoplasmic tail of layilin binds various members of the band 4.1/ERM superfamily (talin, radixin, and merlin). The ERM proteins are cytoskeleton-membrane linker molecules which link actin to receptors in the plasma membrane. Layilin co-localizes in with talin in membrane ruffles and may mediate signals from the ECM to the cell cytoskeleton.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462548642 230 CFMVSSEADTYYR-----ARMKCQRKGGVLAQIKSQKVQDILAFYLGRLETTneviDSDFetrnfWIGL--------TYK 296
Cdd:cd03595    12 CYKIAYFQDSRRRlnfeeARQACREDGGELLSIESENEQKLIERFIQTLRAS----DGDF-----WIGLrrssqynvTSS 82

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462548642 297 TAKDSFRWATGEHQAFTSFAFGQPdNHGFGNCVEL--QASAA--------FNWNDQRCKTRNRYICQF 354
Cdd:cd03595    83 ACSSLYYWLDGSISTFRNWYVDEP-SCGSEVCVVMyhQPSAPagqggpylFQWNDDNCNMKNNFICKY 149

C-type lectin-like domain (CTLD) of the type found in the human proteins, eosinophil major basic protein (EMBP) and prepro major basic protein homolog (MBPH); CLECT_EMBP_like: C-type lectin-like domain (CTLD) of the type found in the human proteins, eosinophil major basic protein (EMBP) and prepro major basic protein homolog (MBPH). CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. Eosinophils and basophils carry out various functions in allergic, parasitic, and inflammatory diseases. EMBP is stored in eosinophil crystalloid granules and is released upon degranulation. EMBP is also expressed in basophils. The proform of EMBP is expressed in placental X cells and breast tissue and increases significantly during human pregnancy. EMBP has cytotoxic properties and damages bacteria and mammalian cells, in vitro, as well as, helminth parasites. EMBP deposition has been observed in the inflamed tissue of allergy patients in a variety of diseases including asthma, atopic dermatitis, and rhinitis. In addition to its cytotoxic functions, EMBP activates cells and stimulates cytokine production. EMBP has been shown to bind the proteoglycan heparin. The binding site is similar to the carbohydrate binding site of other classical CTLD, such as mannose-binding protein (MBP1), however, heparin binding to EMBP is calcium ion independent. MBPH has reduced potency in cytotoxic and cytostimulatory assays compared with EMBP.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462548642 228 GDCFMVSSEADTYYRARMKCQR-KGGVLAQIKSQKVQDILAFYLGRLETTNevidsdfetrnFWIG--LTYKTAKDSFRW 304
Cdd:cd03598     1 GRCYRFVKSPRTFRDAQVICRRcYRGNLASIHSFAFNYRVQRLVSTLNQAQ-----------VWIGgiITGKGRCRRFSW 69

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 2462548642 305 ATGEHQAFTSFAFGQPDNhGFGNCVELQASAAFnWNDQRCKTRNRYICQF 354
Cdd:cd03598    70 VDGSVWNYAYWAPGQPGN-RRGHCVELCTRGGH-WRRAHCKLRRPFICSY 117

C-type lectin-like domain (CTLD) of the type found in human thrombomodulin(TM), Endosialin, C14orf27, and C1qR; CLECT_thrombomodulin_like: C-type lectin-like domain (CTLD) of the type found in human thrombomodulin(TM), Endosialin, C14orf27, and C1qR. CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. In these thrombomodulin-like proteins the residues involved in coordinating Ca2+ in the classical MBP-A CTLD are not conserved. TM exerts anti-fibrinolytic and anti-inflammatory activity. TM also regulates blood coagulation in the anticoagulant protein C pathway. In this pathway, the procoagulant properties of thrombin (T) are lost when it binds TM. TM also plays a key role in tumor biology. It is expressed on endothelial cells and on several type of tumor cell including squamous cell carcinoma. Loss of TM expression correlates with advanced stage and poor prognosis. Loss of function of TM function may be associated with arterial or venous thrombosis and with late fetal loss. Soluble molecules of TM retaining the CTLD are detected in human plasma and urine where higher levels indicate injury and/or enhanced turnover of the endothelium. C1qR is expressed on endothelial cells and stem cells. It is also expressed on monocots and neutrophils, where it is subject to ectodomain shedding. Soluble forms of C1qR retaining the CTLD is detected in human plasma. C1qR modulates the phagocytosis of apoptotic cells in vivo. C1qR-deficient mice are defective in clearance of apoptotic cells in vivo. The cytoplasmic tail of C1qR, C-terminal to the CTLD of CD93, contains a PDZ binding domain which interacts with the PDZ domain-containing adaptor protein, GIPC. The juxtamembrane region of this tail interacts with the ezrin/radixin/moesin family. Endosialin functions in the growth and progression of abdominal tumors and is expressed in the stroma of several tumors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462548642 226 IDGDCFMVSSEADTYYRARMKCQRKGGVLAQIKSQKVQDILAFYLGRLETTNEVIDsdfetRNFWIGLTYKTAKDS---- 301
Cdd:cd03600     2 VSDACYTLHPQKLTFLEAQRSCIELGGNLATVRSGEEADVVSLLLAAGPGRHGRGS-----LRLWIGLQREPRQCSdpsl 76

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462548642 302 ----FRWATG-EHQAFTSFAFGQPDNHGFGNCVELQASAA----FNWNDQRCKTR-NRYICQFA 355
Cdd:cd03600    77 plrgFSWVTGdQDTDFSNWLQEPAGTCTSPRCVALSAAGStpdnLKWKDGPCSARaDGYLCKFS 140

CAP (cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins) domain of pathogen-related yeast 1 (PRY1) protein and similar fungal proteins; PRY1, also called pathogenesis-related protein 1, is a yeast protein that is up-regulated in core ESCRT mutants. It is a secreted protein required for efficient export of lipids such as acetylated sterols, and acts in detoxification of hydrophobic compounds. This PRY1-like group also contains fruiting body proteins SC7/14 from Schizophyllum commune. The wider family of CAP domain containing proteins includes plant pathogenesis-related protein 1 (PR-1), cysteine-rich secretory proteins (CRISPs), and allergen 5 from vespid venom, among others.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 2462548642  73 LVWATSSQLGCGRHLCSAGQAVIeaFVCAYSPGGNWE 109
Cdd:cd05384    94 LVWKSTTQVGCAYKDCGGAWGLY--IVCEYDPAGNVI 128

A bacterial subgroup of the C-type lectin-like (CTLD) domain; a subgroup of bacterial protein domains homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins; CLECT_VCBS: A bacterial subgroup of the C-type lectin-like (CTLD) domain; a subgroup of bacterial protein domains homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. Many CTLDs are calcium-dependent carbohydrate binding modules; other CTLDs bind protein ligands, lipids, and inorganic surfaces including CaCO3 and ice. Bacterial CTLDs within this group are functionally uncharacterized. Animal C-type lectins are involved in such functions as extracellular matrix organization, endocytosis, complement activation, pathogen recognition, and cell-cell interactions. CTLDs may bind a variety of carbohydrate ligands including mannose, N-acetylglucosamine, galactose, N-acetylgalactosamine, and fucose. CTLDs associate with each other through several different surfaces to form dimers, trimers, or tetramers from which ligand-binding sites project in different orientations. In some CTLDs a loop extends to the adjoining domain to form a loop-swapped dimer.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462548642 251 GGVLAQIKSQKVQDILafylGRLETTNEvidsdfetrNFWIGLTYKTAKDSFRWATGEHQAFTSFAFGQPDNHGFGN 327
Cdd:cd03603    23 GGHLVTINSAEENDWL----LSNFGGYG---------ASWIGASDAATEGTWKWSDGEESTYTNWGSGEPHNNGGGN 86

CAP (cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins) domain of glioma pathogenesis-related protein 1 and similar proteins; Glioma pathogenesis-related protein 1 (GLIPR1) is also called related to testes-specific, vespid, and pathogenesis protein 1 (RTVP-1). The GLIPR1 gene has been identified as a p53 target gene and was shown to be methylated and down-regulated in prostate cancer. It is a novel broad-spectrum tumor suppressor whose proapoptotic properties are exerted in part through ROS-JNK signaling. GLIPR1 is composed of a signal peptide that directs its secretion, a CAP domain, and a transmembrane domain. The wider family of CAP domain containing proteins includes plant pathogenesis-related protein 1 (PR-1), cysteine-rich secretory proteins (CRISPs), and allergen 5 from vespid venom, among others.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 2462548642  73 LVWATSSQLGCGRHLCSAG-------QAVIeaFVCAYSPGG 106
Cdd:cd05385   110 VVWADSYKVGCAVHVCPNGggffsgsSSAI--FVCNYGPAG 148

Cysteine-rich secretory protein family; This is a large family of cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins (CAP) that are found in a wide range of organizms, including prokaryotes and non-vertebrate eukaryotes, The nine subfamilies of the mammalian CAP 'super'family include: the human glioma pathogenesis-related 1 (GLIPR1), Golgi associated pathogenesis related-1 (GAPR1) proteins, peptidase inhibitor 15 (PI15), peptidase inhibitor 16 (PI16), cysteine-rich secretory proteins (CRISPs), CRISP LCCL domain containing 1 (CRISPLD1), CRISP LCCL domain containing 2 (CRISPLD2), mannose receptor like and the R3H domain containing like proteins. Members are most often secreted and have an extracellular endocrine or paracrine function and are involved in processes including the regulation of extracellular matrix and branching morphogenesis, potentially as either proteases or protease inhibitors; in ion channel regulation in fertility; as tumour suppressor or pro-oncogenic genes in tissues including the prostate; and in cell-cell adhesion during fertilization. The overall protein structural conservation within the CAP 'super'family results in fundamentally similar functions for the CAP domain in all members, yet the diversity outside of this core region dramatically alters the target specificity and, thus, the biological consequences. The Ca++-chelating function would fit with the various signalling processes (e.g. the CRISP proteins) that members of this family are involved in, and also the sequence and structural evidence of a conserved pocket containing two histidines and a glutamate. It also may explain how Swiss:Q91055 blocks the Ca++ transporting ryanodine receptors.

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gi 2462548642  70 RRLLVWATSSQLGCGRHLCSAGQAVIeaFVCAY 102
Cdd:pfam00188  87 RTNLLWPKSTKVGCAVAKCGDGGTYY--FVCNY 117