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
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2217489173 315 CFMVSSEADTYYRARMKCQRKGGVLAQIKSQKVQDILAFYLgrlettnevtdSDFETRNFWI 376
Cdd:cd00037     2 CYKFSTEKLTWEEAQEYCRSLGGHLASIHSEEENDFLASLL-----------KKSSSSDVWI 52

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        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217489173   51 LLSLHNRLRS------WVQPPAADMRRLDWSDSLAQLAQARAALCGIPTPSLASGLWRTLQVGWNMQLLPAGLASfvEVV 124
Cdd:smart00198   6 ILDAHNKLRSqvaggfLAAPAASNMLKLTWDCELASSAQNWANQCPFGHSTPRPGYGENLAWWSSSTALPDTYAS--AAV 83

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2217489173  125 SLWFAEGQRYSHAAGECA-RNATCTHYTQVsvlqlVWATSSQLGCGRHLCSAGQTAIEAFVCAYSP 189
Cdd:smart00198  84 QLWYDEFQDYGYSSNTCKdTNGKIGHYTQV-----VWAKTYKVGCGVANCPDGTKKKTVVVCNYDP 144

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2217489173 315 CFMVSSEADTYYRARMKCQRKGGVLAQIKSQKVQDILAFYLgrlettnevtdSDFETRNFWI 376
Cdd:cd00037     2 CYKFSTEKLTWEEAQEYCRSLGGHLASIHSEEENDFLASLL-----------KKSSSSDVWI 52

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        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217489173  50 LLLSLHNRLRSWVQPPAADMRRLDWSDSLAQLAQARAALCgiptpslasgLW----RTLQVGWNMQLLPAGLASFVEVVS 125
Cdd:cd05559     3 LLVDLHNQYRSQVSPSAANMLKMTWDTELEALAKAYARKC----------IWehnpDRGRVGENLFASTGKPLDVELAVE 72

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2217489173 126 LWFAEGQRYSHAAGECARNATCTHYTQVsvlqlVWATSSQLGCGRHLCSAGQ----TAIEAFVCAYS 188
Cdd:cd05559    73 DWHNEKEYYNFETKTCAPGKMCGHYTQV-----VWANTEKIGCGSYFCETLEgvewENATLLVCNYE 134

CAP (cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins) domain of cysteine-rich secretory proteins; Cysteine-rich secretory proteins (CRISPs) are two-domain proteins with an evolutionary diverse and structurally conserved N-terminal CAP domain and a C-terminal cysteine-rich domain, which is comprised of a hinge and an ICR (ion channel regulator) region. CRISPs are involved in response to pathogens, fertilization, and sperm maturation. One member, Tex31 from the venom duct of Conus textile, has been shown to possess proteolytic activity sensitive to serine protease inhibitors. CRISP-1 has been shown to mediate gamete fusion by binding to the egg surface. Other members of the CRISP family secreted in the testis (CRISP2), epididymis (CRISP3-4), or during ejaculation (CRISP3), are also involved in sperm-egg interaction, supporting the existence of a functional redundancy and cooperation between homolog proteins ensuring the success of fertilization. The wider family of CAP domain containing proteins includes plant pathogenesis-related protein 1 (PR-1) and allergen 5 from vespid venom, among others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217489173  44 NRKEsflLLSLHNRLRSWVQPPAADMRRLDWSDSLAQLAQARAALCgIPTPSLASGLWRT-LQVGWNMqLLPAGLASFVE 122
Cdd:cd05383     2 VQQE---IVDLHNALRRSVNPPASNMLKMSWNPEAAENAQRWANRC-NFTHSPPNGRTIPgIRCGENI-FMSSYPASWSE 76

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2217489173 123 VVSLWFAEGQRYSHAAGECARNATCTHYTQVsvlqlVWATSSQLGCGRHLCSAGQTAIEAFVCAYSPG 190
Cdd:cd05383    77 VIQAWYDEYKDFKYGVGAKPPGSVTGHYTQV-----VWYSSYLVGCAVAYCPSQGSLKYFYVCQYCPA 139

CAP (cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins) domain of peptidase inhibitor R3HDML; Peptidase inhibitor R3HDML, also called cysteine-rich secretory protein R3HDML, is a putative serine protease inhibitor. The R3HDML gene may be associated with clinical dimensions of schizophrenia. 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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217489173  50 LLLSLHNRLRSWVQPPAADMRRLDWSDSLAQLAQARAALCgiptpSLASGLWRTLQ-VGWNMQLLPAGLASFVEVVSLWF 128
Cdd:cd18815     3 ALLDYHNRVRSQVFPPAANMEYMVWDERLAKSAEAWAAQC-----VWEHGPPQLMRyIGQNLSIHSGRYRSIVDLVKSWY 77

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2217489173 129 AEGQRYSHAAG-EC-------ARNATCTHYTqvsvlQLVWATSSQLGCGRHLCSA----GQTAIEA--FVCAYS 188
Cdd:cd18815    78 DERQHYSFPHPrECnprcpskCSGAVCSHYT-----QMVWASSNRIGCAVHTCSNinvwGSTWRRAtyLVCNYA 146

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        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217489173  51 LLSLHNRLRSWVQPPAADMRRLDWSDSLAQLAQARAALCGIPTPSLASGlwrtLQVGWNMQLLPAGLASfVEVVSLWFAE 130
Cdd:cd00168     4 ILDLHNSYRSSVSPPASNMPLMAWDQELADVAIGYAKDCIFSHSSPTSR----QLAGENIAASSYDMDG-VAALQAWHNE 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2217489173 131 GQRYSHAAGECARNATCTHYTqvsvlQLVWATSSQLGCGRHLCSAGqtaIEAFVCAY 187
Cdd:cd00168    79 IKNYNFGTAQPGFNSGTGHYT-----QMVWEKTTKLGCGVADCSDN---SKFVVCNY 127

CAP (cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins) domain of cysteine-rich secretory protein LCCL domain-containing 2; Cysteine-rich secretory protein LCCL domain-containing 2 (CRISPLD2) is also called cysteine-rich secretory protein 11 (CRSIP-11), LCCL domain-containing cysteine-rich secretory protein 2 (LCRISP2), or CAP and LCCL domain containing protein 2 (CAPLD2). It plays a role in the etiology of NSCLP (non-syndromic cleft lip with or without cleft palate). It is required for neural crest cell migration and cell viability during craniofacial development. The CRISPLD2 gene has been identified a glucocorticoid responsive gene that modulates cytokine function in airway smooth muscle cells. 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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217489173  51 LLSLHNRLRSWVQPPAADMRRLDWSDSLAQLAQARAALCGI---PTPSLASgLWRTLQVGWNMQLLPAglasfvEVVSLW 127
Cdd:cd18816     4 ILQLHNKLRGQVYPSASNMEYMTWDDELERSAEAWAQQCIWehgPTSLLPS-IGQNLAVHWGRYRSPA------FHVQSW 76

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2217489173 128 FAEGQRYSHA-AGEC-------ARNATCTHYTqvsvlQLVWATSSQLGCGRHLCSA----GQTAIEA--FVCAYS 188
Cdd:cd18816    77 YDEVKDYTYPyPHECnpwcperCSGPMCTHYT-----QIVWATTNKVGCAVNVCRRmnvwGEIWENAvyLVCNYS 146

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        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217489173 113 LPAGLASFVEVVSLWFAEGQRY-------SHAAGecarnatctHYTQvsvlqLVWATSSQLGCGRHLCSAGQTAIeaFVC 185
Cdd:cd05384    56 LALGYSSGAAAVDAWYDEISDYdysnpgfSESTG---------HFTQ-----LVWKSTTQVGCAYKDCGGAWGLY--IVC 119

                  ....*....
gi 2217489173 186 AYSPGGNWE 194
Cdd:cd05384   120 EYDPAGNVI 128

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217489173  52 LSLHNRLRswvqpPAADMRRLDWSDSLAQ------LAQARAALCGIPTPSLASGLWRTLQVGWNmqLLPAGLASFVEVVS 125
Cdd:pfam00188   1 LDLHNEYR-----AAAGLPPLSWDNELAAaaqdhaKYCADNGSHNHRSPYGGNIYARVVAAGYA--LGDAGPDSAEDAVD 73

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2217489173 126 LWFAEGQRYShaagecarnatCTHYTqvsvlQLVWATSSQLGCGRHLCSAGQTaiEAFVCAY 187
Cdd:pfam00188  74 GWYDSPGTYN-----------CGHRT-----NLLWPKSTKVGCAVAKCGDGGT--YYFVCNY 117

CAP (cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins) domain of Golgi-associated plant pathogenesis-related protein 1 and similar proteins; Golgi-associated plant pathogenesis related protein 1 (GAPR1), also called Golgi-associated PR-1 protein or glioma pathogenesis-related protein 2 (GLIPR-2), forms amyloid-like fibrils in the presence of liposomes containing acidic phospholipids. It has been identified in mice as an up-regulated protein in kidney fibrosis, and is involved in epithelial to mesenchymal transition and in generating a pool of myofibroblasts contributing to fibrosis. 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        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2217489173 122 EVVSLWFAEGQRY-------SHAAGecarnatctHYTQVsvlqlVWATSSQLGCGRHLCSAGQTAIeafVCAYSPGGNW 193
Cdd:cd05382    71 EAVDSWYNEIKNYnfnkpgfQSGTG---------HFTQV-----VWKSSTELGVGVAKSKDGCVYV---VARYSPAGNV 132

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 2217489173 235 NPCRMS--CQNHGR-LN-ISTCHCHCPPGYTGRYCQ 266
Cdd:cd00054     3 DECASGnpCQNGGTcVNtVGSYRCSCPPGYTGRNCE 38