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 1937867459  30 CEGTACYTAHWGKLSAAEAQHRCNENGGNLATVKSEEEARHVQEALAQLLktkAPSETKIGKFWIGLQREKGKCTYHDLP 109
Cdd:cd03600     1 CVSDACYTLHPQKLTFLEAQRSCIELGGNLATVRSGEEADVVSLLLAAGP---GRHGRGSLRLWIGLQREPRQCSDPSLP 77

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1937867459 110 MKGFSWVGGGEDTTYSNWYKASKSSCISKRCVSLILDLSLkphpSHLPKWHESPCGTPdapgnsIEGFLCKFNF 183
Cdd:cd03600    78 LRGFSWVTGDQDTDFSNWLQEPAGTCTSPRCVALSAAGST----PDNLKWKDGPCSAR------ADGYLCKFSF 141

Calcium-binding EGF-like domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1937867459  382 DVDECtAAYSPCAQG--CTNTDGSFYCSCKEGYimsgEDSTQCE 423
Cdd:smart00179   1 DIDEC-ASGNPCQNGgtCVNTVGSYRCECPPGY----TDGRNCE 39

Coagulation Factor Xa inhibitory site; This short domain on coagulation enzyme factor Xa is found to be the target for a potent inhibitor of coagulation, TAK-442.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1937867459 261 CSFNNGGCQQDCfEGGDGSFRCGCRPGFRLLDDLVTC 297
Cdd:pfam14670   1 CSVNNGGCSHLC-LNTPGGYTCSCPEGYELQDDGRTC 36

EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very similar, but has 8 instead of 6 conserved cysteines. Includes some cytokine receptors. The EGF domain misses the N-terminus regions of the Ca2+ binding EGF domains (this is the main reason of discrepancy between swiss-prot domain start/end and Pfam). The family is hard to model due to many similar but different sub-types of EGF domains. Pfam certainly misses a number of EGF domains.

                          10        20
                  ....*....|....*....|....*....
gi 1937867459 303 CSSNPCTGGGMCHSVPlsENYTCHCPRGY 331
Cdd:pfam00008   1 CAPNPCSNGGTCVDTP--GGYTCICPEGY 27

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 1937867459  30 CEGTACYTAHWGKLSAAEAQHRCNENGGNLATVKSEEEARHVQEALAQLLktkAPSETKIGKFWIGLQREKGKCTYHDLP 109
Cdd:cd03600     1 CVSDACYTLHPQKLTFLEAQRSCIELGGNLATVRSGEEADVVSLLLAAGP---GRHGRGSLRLWIGLQREPRQCSDPSLP 77

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1937867459 110 MKGFSWVGGGEDTTYSNWYKASKSSCISKRCVSLILDLSLkphpSHLPKWHESPCGTPdapgnsIEGFLCKFNF 183
Cdd:cd03600    78 LRGFSWVTGDQDTDFSNWLQEPAGTCTSPRCVALSAAGST----PDNLKWKDGPCSAR------ADGYLCKFSF 141

Calcium-binding EGF-like domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1937867459  424 DIDECL-GNPCD--TLCINTDGSFRCGCPAGFElapNGVSCT 462
Cdd:smart00179   1 DIDECAsGNPCQngGTCVNTVGSYRCECPPGYT---DGRNCE 39

Calcium-binding EGF-like domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1937867459  382 DVDECtAAYSPCAQG--CTNTDGSFYCSCKEGYimsgEDSTQCE 423
Cdd:smart00179   1 DIDEC-ASGNPCQNGgtCVNTVGSYRCECPPGY----TDGRNCE 39

Calcium-binding EGF-like domain;

                           10        20        30
                   ....*....|....*....|....*....|....
gi 1937867459  342 DIDECE-DSPCDQ--ECINTPGGFHCECWVGYQS 372
Cdd:smart00179   1 DIDECAsGNPCQNggTCVNTVGSYRCECPPGYTD 34

Calcium-binding EGF domain;

                          10        20        30
                  ....*....|....*....|....*....|..
gi 1937867459 424 DIDECL--GNPCD--TLCINTDGSFRCGCPAG 451
Cdd:pfam07645   1 DVDECAtgTHNCPanTVCVNTIGSFECRCPDG 32

Calcium-binding EGF domain;

                          10        20        30
                  ....*....|....*....|....*....|..
gi 1937867459 382 DVDECTAAYSPCAQG--CTNTDGSFYCSCKEG 411
Cdd:pfam07645   1 DVDECATGTHNCPANtvCVNTIGSFECRCPDG 32

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 1937867459 342 DIDECED-SPC--DQECINTPGGFHCECWVGYQ 371
Cdd:cd00054     1 DIDECASgNPCqnGGTCVNTVGSYRCSCPPGYT 33

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 1937867459  30 CEGTACYTAHWGKLSAAEAQHRCNENGGNLATVKSEEEARHVQEALAQLLktkAPSETKIGKFWIGLQREKGKCTYHDLP 109
Cdd:cd03600     1 CVSDACYTLHPQKLTFLEAQRSCIELGGNLATVRSGEEADVVSLLLAAGP---GRHGRGSLRLWIGLQREPRQCSDPSLP 77

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1937867459 110 MKGFSWVGGGEDTTYSNWYKASKSSCISKRCVSLILDLSLkphpSHLPKWHESPCGTPdapgnsIEGFLCKFNF 183
Cdd:cd03600    78 LRGFSWVTGDQDTDFSNWLQEPAGTCTSPRCVALSAAGST----PDNLKWKDGPCSAR------ADGYLCKFSF 141

C-type lectin (CTL) or carbohydrate-recognition domain (CRD); Many of these domains function as calcium-dependent carbohydrate binding modules.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937867459   35 CYTAHWGKLSAAEAQHRCNENGGNLATVKSEEEARHVQEalaqllktKAPSETKIGKFWIGLQREKGKCTyhdlpmkgFS 114
Cdd:smart00034  12 CYKFSTEKKTWEDAQAFCQSLGGHLASIHSEAENDFVAS--------LLKNSGSSDYYWIGLSDPDSNGS--------WQ 75

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1937867459  115 WVGGGEDTTYSNWYKASKSScISKRCVSLIldlslkphpSHLPKWHESPCGTPdapgnsiEGFLCK 180
Cdd:smart00034  76 WSDGSGPVSYSNWAPGEPNN-SSGDCVVLS---------TSGGKWNDVSCTSK-------LPFVCE 124

Calcium-binding EGF-like domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1937867459  424 DIDECL-GNPCD--TLCINTDGSFRCGCPAGFElapNGVSCT 462
Cdd:smart00179   1 DIDECAsGNPCQngGTCVNTVGSYRCECPPGYT---DGRNCE 39

Calcium-binding EGF-like domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1937867459  382 DVDECtAAYSPCAQG--CTNTDGSFYCSCKEGYimsgEDSTQCE 423
Cdd:smart00179   1 DIDEC-ASGNPCQNGgtCVNTVGSYRCECPPGY----TDGRNCE 39

C-type lectin-like domain (CTLD) of the type found in Human REG-1 (lithostathine), REG-4, and avian eggshell-specific proteins: ansocalcin, structhiocalcin-1(SCA-1), and -2(SCA-2); CLECT_REG-1_like: C-type lectin-like domain (CTLD) of the type found in Human REG-1 (lithostathine), REG-4, and avian eggshell-specific proteins: ansocalcin, structhiocalcin-1(SCA-1), and -2(SCA-2). CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. REG-1 is a proliferating factor which participates in various kinds of tissue regeneration including pancreatic beta-cell regeneration, regeneration of intestinal mucosa, regeneration of motor neurons, and perhaps in tissue regeneration of damaged heart. REG-1 may play a role on the pathophysiology of Alzheimer's disease and in the development of gastric cancers. Its expression is correlated with reduced survival from early-stage colorectal cancer. REG-1 also binds and aggregates several bacterial strains from the intestinal flora and it has been suggested that it is involved in the control of the intestinal bacterial ecosystem. Rat lithostathine has calcium carbonate crystal inhibitor activity in vitro. REG-IV is unregulated in pancreatic, gastric, hepatocellular, and prostrate adenocarcinomas. REG-IV activates the EGF receptor/Akt/AP-1 signaling pathway in colorectal carcinoma. Ansocalcin, SCA-1 and -2 are found at high concentration in the calcified egg shell layer of goose and ostrich, respectively and tend to form aggregates. Ansocalcin nucleates calcite crystal aggregates in vitro.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937867459  46 AEAQHRCNENGGNLATVKSEEEARhvqeALAQLLKTKAPSETKIgkfWIGLqrekgkctyHDlPMKGFSWV-GGGEDTTY 124
Cdd:cd03594    25 AELFCQKYGPGAHLASIHSPAEAA----AIASLISSYQKAYQPV---WIGL---------HD-PQQSRGWEwSDGSKLDY 87

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1937867459 125 SNWYKASKSSCiSKRCVSLildlslkPHPSHLPKWHESPCGTPDApgnsiegFLCKF 181
Cdd:cd03594    88 RSWDRNPPYAR-GGYCAEL-------SRSTGFLKWNDANCEERNP-------FICKY 129

Coagulation Factor Xa inhibitory site; This short domain on coagulation enzyme factor Xa is found to be the target for a potent inhibitor of coagulation, TAK-442.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1937867459 261 CSFNNGGCQQDCfEGGDGSFRCGCRPGFRLLDDLVTC 297
Cdd:pfam14670   1 CSVNNGGCSHLC-LNTPGGYTCSCPEGYELQDDGRTC 36

VWA_Matrilin: In cartilaginous plate, extracellular matrix molecules mediate cell-matrix and matrix-matrix interactions thereby providing tissue integrity. Some members of the matrilin family are expressed specifically in developing cartilage rudiments. The matrilin family consists of at least four members. All the members of the matrilin family contain VWA domains, EGF-like domains and a heptad repeat coiled-coiled domain at the carboxy terminus which is responsible for the oligomerization of the matrilins. The VWA domains have been shown to be essential for matrilin network formation by interacting with matrix ligands.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1937867459 376 KEEACEDVDECTAAYSPCAQGCTNTDGSFYCSCKEGYIMSgEDS 419
Cdd:cd01475   180 QGKICVVPDLCATLSHVCQQVCISTPGSYLCACTEGYALL-EDN 222

Coagulation Factor Xa inhibitory site; This short domain on coagulation enzyme factor Xa is found to be the target for a potent inhibitor of coagulation, TAK-442.

                          10        20
                  ....*....|....*....|....*....
gi 1937867459 433 CDTLCINTDGSFRCGCPAGFELAPNGVSC 461
Cdd:pfam14670   8 CSHLCLNTPGGYTCSCPEGYELQDDGRTC 36

Complement Clr-like EGF-like; cEGF, or complement Clr-like EGF, domains have six conserved cysteine residues disulfide-bonded into the characteriztic pattern 'ababcc'. They are found in blood coagulation proteins such as fibrillin, Clr and Cls, thrombomodulin, and the LDL receptor. The core fold of the EGF domain consists of two small beta-hairpins packed against each other. Two major structural variants have been identified based on the structural context of the C-terminal cysteine residue of disulfide 'c' in the C-terminal hairpin: hEGFs and cEGFs. In cEGFs the C-terminal thiol resides on the C-terminal beta-sheet, resulting in long loop-lengths between the cysteine residues of disulfide 'c', typically C[10+]XC. These longer loop-lengths may have arisen by selective cysteine loss from a four-disulfide EGF template such as laminin or integrin. Tandem cEGF domains have five linking residues between terminal cysteines of adjacent domains. cEGF domains may or may not bind calcium in the linker region. cEGF domains with the consensus motif CXN4X[F,Y]XCXC are hydroxylated exclusively on the asparagine residue.

                          10        20
                  ....*....|....*....|..
gi 1937867459 324 TCHCPRGYQLDSSQVHCVDIDE 345
Cdd:pfam12662   1 TCSCPPGYQLDPDGRTCVDIDE 22

C-type lectin (CTL)/C-type lectin-like (CTLD) domain subgroup 1; a subgroup of protein domains homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins; CLECT_1: C-type lectin (CTL)/C-type lectin-like (CTLD) domain subgroup 1; a subgroup of 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. 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937867459  47 EAQHRCNENGGNLATVKSEEEarhvqeaLAQLLKTkapSETKIGKFWIGLQREKGkctyhdlpmkGFSWvGGGEDTTYSN 126
Cdd:cd03602    14 EAQQYCRENYTDLATVQNQED-------NALLSNL---SRVSNSAAWIGLYRDVD----------SWRW-SDGSESSFRN 72

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1937867459 127 WykASKSSCISKRCVSLILDlslkphpshlPKWHESPC 164
Cdd:cd03602    73 W--NTFQPFGQGDCATMYSS----------GRWYAALC 98

EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very similar, but has 8 instead of 6 conserved cysteines. Includes some cytokine receptors. The EGF domain misses the N-terminus regions of the Ca2+ binding EGF domains (this is the main reason of discrepancy between swiss-prot domain start/end and Pfam). The family is hard to model due to many similar but different sub-types of EGF domains. Pfam certainly misses a number of EGF domains.

                          10        20
                  ....*....|....*....|....*....
gi 1937867459 303 CSSNPCTGGGMCHSVPlsENYTCHCPRGY 331
Cdd:pfam00008   1 CAPNPCSNGGTCVDTP--GGYTCICPEGY 27