N-acetylneuraminic acid mutarotase [Cell wall/membrane/envelope biogenesis];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462518351   1 MLIFGGNTHNDTSlsngakcfsADFLAYDIACDEWKILPKPNLHRdvnRFGHSAVVINGSMYIFGGF-----SSVLLNDI 75
Cdd:COG3055    25 VYVAGGLSGGSAS---------NSFEVYDPATNTWSELAPLPGPP---RHHAAAVAQDGKLYVFGGFtganpSSTPLNDV 92

                  ....*
gi 2462518351  76 LVYKP 80
Cdd:COG3055    93 YVYDP 97

Plexin repeat; A cysteine rich repeat found in several different extracellular receptors. The function of the repeat is unknown. Three copies of the repeat are found Plexin. Two copies of the repeat are found in mahogany protein. A related C. elegans protein contains four copies of the repeat. The Met receptor contains a single copy of the repeat. The Pfam alignment shows 6 conserved cysteine residues that may form three conserved disulphide bridges, whereas some members show 8 conserved cysteines. The pattern of conservation suggests that cysteines 5 and 7 (that are not absolutely conserved) form a disulphide bridge (Personal observation. A Bateman).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2462518351 357 PCSLRTSCSNCT-SNGMECMWCSSTKRCVDSNAYiiSFPYGQCLEWQTATC 406
Cdd:pfam01437   1 RCSQYTSCSSCLaARDPYCGWCSSEGRCVRRSAC--GAPEGNCEEWEQASS 49

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462518351 234 RENYDNAKLYCYNLSGNLASLTTSKEVEFVLDEIQKYtqqKVSPWVGLRKINIS-YWGWEDMSPFTNTTLQWLPGEPNDS 312
Cdd:pfam00059   1 SKTWDEAREACRKLGGHLVSINSAEELDFLSSTLKKS---NKYFWIGLTDRKNEgTWKWVDGSPVNYTNWAPEPNNNGEN 77

                          90       100       110
                  ....*....|....*....|....*....|
gi 2462518351 313 GFCAYLERAAvAGLKANPCTSMaNGLVCEK 342
Cdd:pfam00059  78 EDCVELSSSS-GKWNDENCNSK-NPFVCEK 105

N-acetylneuraminic acid mutarotase [Cell wall/membrane/envelope biogenesis];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462518351   1 MLIFGGNTHNDTSlsngakcfsADFLAYDIACDEWKILPKPNLHRdvnRFGHSAVVINGSMYIFGGF-----SSVLLNDI 75
Cdd:COG3055    25 VYVAGGLSGGSAS---------NSFEVYDPATNTWSELAPLPGPP---RHHAAAVAQDGKLYVFGGFtganpSSTPLNDV 92

                  ....*
gi 2462518351  76 LVYKP 80
Cdd:COG3055    93 YVYDP 97

Plexin repeat; A cysteine rich repeat found in several different extracellular receptors. The function of the repeat is unknown. Three copies of the repeat are found Plexin. Two copies of the repeat are found in mahogany protein. A related C. elegans protein contains four copies of the repeat. The Met receptor contains a single copy of the repeat. The Pfam alignment shows 6 conserved cysteine residues that may form three conserved disulphide bridges, whereas some members show 8 conserved cysteines. The pattern of conservation suggests that cysteines 5 and 7 (that are not absolutely conserved) form a disulphide bridge (Personal observation. A Bateman).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2462518351 357 PCSLRTSCSNCT-SNGMECMWCSSTKRCVDSNAYiiSFPYGQCLEWQTATC 406
Cdd:pfam01437   1 RCSQYTSCSSCLaARDPYCGWCSSEGRCVRRSAC--GAPEGNCEEWEQASS 49

Kelch motif; The kelch motif was initially discovered in Kelch. In this protein there are six copies of the motif. It has been shown that Swiss:Q04652 is related to Galactose Oxidase for which a structure has been solved. The kelch motif forms a beta sheet. Several of these sheets associate to form a beta propeller structure as found in pfam00064, pfam00400 and pfam00415.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 2462518351  49 RFGHSAVVINGSMYIFGGFSS---VLLNDILVYKPPN 82
Cdd:pfam13854   4 RYGHCAVTVGDYIYLYGGYTGgegQPSDDVYVLSLPT 40

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 2462518351 227 CLRVNSSRENYDNAKLYCYNLSGNLASLTTSKEVEFVLDEIQKYTQQKVspWVGLRKINI-SYWGWEDMSPFTNTTlQWL 305
Cdd:cd00037     2 CYKFSTEKLTWEEAQEYCRSLGGHLASIHSEEENDFLASLLKKSSSSDV--WIGLNDLSSeGTWKWSDGSPLVDYT-NWA 78

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2462518351 306 PGEPN--DSGFCAYLERAAVAGLKANPCTSMaNGLVCEK 342
Cdd:cd00037    79 PGEPNpgGSEDCVVLSSSSDGKWNDVSCSSK-LPFICEK 116

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 2462518351  216 CGEGWSHIGDACLRVNSSRENYDNAKLYCYNLSGNLASLTTSKEVEFVLDEIQKYTQQKvSPWVGLRKINISY-WGWEDM 294
Cdd:smart00034   1 CPSGWISYGGKCYKFSTEKKTWEDAQAFCQSLGGHLASIHSEAENDFVASLLKNSGSSD-YYWIGLSDPDSNGsWQWSDG 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 2462518351  295 SPFTNTTLqWLPGEPNDS-GFCAYLeRAAVAGLKANPCTSmANGLVCE 341
Cdd:smart00034  80 SGPVSYSN-WAPGEPNNSsGDCVVL-STSGGKWNDVSCTS-KLPFVCE 124

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 2462518351 216 CGEGWSHIGDACLRVNSSRENYDNAKLYCYNLSGNLASLTTSKEVEFvldeIQKYTQQKvSPWVGLRKINISY-WGWEDM 294
Cdd:cd03593     1 CPKDWICYGNKCYYFSMEKKTWNESKEACSSKNSSLLKIDDEEELEF----LQSQIGSS-SYWIGLSREKSEKpWKWIDG 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 2462518351 295 SPFTNttlqWL-PGEPNDSGFCAYLERaavAGLKANPCtSMANGLVCEK 342
Cdd:cd03593    76 SPLNN----LFnIRGSTKSGNCAYLSS---TGIYSEDC-STKKRWICEK 116

Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation; the laminin-type epidermal growth factor-like module occurs in tandem arrays; the domain contains 4 disulfide bonds (loops a-d) the first three resemble epidermal growth factor (EGF); the number of copies of this domain in the different forms of laminins is highly variable ranging from 3 up to 22 copies

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2462518351 481 ACQCNGHSTciNNNVCEQ------CKNLTTGKQCQDCMPGYYGDPTNGGQCT 526
Cdd:cd00055     1 PCDCNGHGS--LSGQCDPgtgqceCKPNTTGRRCDRCAPGYYGLPSQGGGCQ 50

Plexin repeat; A cysteine rich repeat found in several different extracellular receptors. The function of the repeat is unknown. Three copies of the repeat are found Plexin. Two copies of the repeat are found in mahogany protein. A related C. elegans protein contains four copies of the repeat. The Met receptor contains a single copy of the repeat. The Pfam alignment shows 6 conserved cysteine residues that may form three conserved disulphide bridges, whereas some members show 8 conserved cysteines. The pattern of conservation suggests that cysteines 5 and 7 (that are not absolutely conserved) form a disulphide bridge (Personal observation. A Bateman).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2462518351 357 PCSLRTSCSNCT-SNGMECMWCSSTKRCVDSNAYiiSFPYGQCLEWQTATC 406
Cdd:pfam01437   1 RCSQYTSCSSCLaARDPYCGWCSSEGRCVRRSAC--GAPEGNCEEWEQASS 49

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 2462518351 216 CGEGWSHIGDACLRVNSSRENYDNAKLYC--YNLSGNLASLTTSKEVEFVLDEIQKYTQQKVSPWVGLRKINISY-WGWE 292
Cdd:cd03594     1 CPKGWLPYKGNCYGYFRQPLSWSDAELFCqkYGPGAHLASIHSPAEAAAIASLISSYQKAYQPVWIGLHDPQQSRgWEWS 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2462518351 293 DMSPFTNTTlqWLPGEP-NDSGFCAYLER-AAVAGLKANPCTSMaNGLVCE 341
Cdd:cd03594    81 DGSKLDYRS--WDRNPPyARGGYCAELSRsTGFLKWNDANCEER-NPFICK 128

C-type lectin-like domain (CTLD) of the type found in chondroitin sulfate proteoglycan core proteins; CLECT_CSPGs: C-type lectin-like domain (CTLD) of the type found in chondroitin sulfate proteoglycan core proteins (CSPGs) in human and chicken aggrecan, frog brevican, and zebra fish dermacan. CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. In cartilage, aggrecan forms cartilage link protein stabilized aggregates with hyaluronan (HA). These aggregates contribute to the tissue's load bearing properties. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. Xenopus brevican is expressed in the notochord and the brain during early embryogenesis. Zebra fish dermacan is expressed in dermal bones and may play a role in dermal bone development. CSPGs do contain LINK domain(s) which bind HA. These LINK domains are considered by one classification system to be a variety of CTLD, but are omitted from this hierarchical classification based on insignificant sequence similarity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462518351 216 CGEGWSHIGDACLRVNSSRENYDNAKLYCYNLSGNLASLTTSKEVEFVLDEIQKYTqqkvspWVGLRKINISY-WGWEDM 294
Cdd:cd03588     1 CEEGWDKFQGHCYRHFPDRETWEDAERRCREQQGHLSSIVTPEEQEFVNNNAQDYQ------WIGLNDRTIEGdFRWSDG 74

                          90       100
                  ....*....|....*....|....
gi 2462518351 295 SP--FTNttlqWLPGEPnDSGFCA 316
Cdd:cd03588    75 HPlqFEN----WRPNQP-DNFFAT 93

N-acetylneuraminic acid mutarotase [Cell wall/membrane/envelope biogenesis];

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 2462518351  17 GAKCFSADFLAYDIACDEWKILPKPNlhrdVNRFGHSAVVINGSMYIFGG 66
Cdd:COG3055   214 GESGFSDEVEAYDPATNTWTALGELP----TPRHGHAAVLTDGKVYVIGG 259

C-type lectin-like domain (CTLD) of the type found in the type 1 transmembrane proteins: P(platlet)-, E(endothelial)-, and L(leukocyte)- selectins (sels); CLECT_selectins_like: C-type lectin-like domain (CTLD) of the type found in the type 1 transmembrane proteins: P(platlet)-, E(endothelial)-, and L(leukocyte)- selectins (sels). CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. P- E- and L-sels are cell adhesion receptors that mediate the initial attachment, tethering, and rolling of lymphocytes on inflamed vascular walls enabling subsequent lymphocyte adhesion and transmigration. L- sel is expressed constitutively on most leukocytes. P-sel is stored in the Weibel-Palade bodies of endothelial cells and in the alpha granules of platlets. E- sels are present on endothelial cells. Following platelet and/or endothelial cell activation P- sel is rapidly translocated to the cell surface and E-sel expression is induced. The initial step in leukocyte migration involves interactions of selectins with fucosylated, sialylated, and sulfated carbohydrate moieties on target ligands displayed on glycoprotein scaffolds on endothelial cells and leucocytes. A major ligand of P- E- and L-sels is PSGL-1 (P-sel glycoprotein ligand). Interactions of E- and P- sels with tumor cells may promote extravasation of cancer cells. Regulation of L-sel and P-sel function includes proteolytic shedding of the most extracellular portion (containing the CTLD) from the cell surface. Increased levels of the soluble form of P-sel in the plasma have been found in a number of diseases including coronary disease and diabetes. E- and P- sel also play roles in the development of synovial inflammation in inflammatory arthritis. Platelet P-sel, but not endothelial P-sel, plays a role in the inflammatory response and neointimal formation after arterial injury. Selectins may also function as signal-transducing receptors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462518351 228 LRVNSSRENYDNAKLYCYNLSGNLASLTTSKEVEFVLDEIQKYTQQKVspWVGLRKINISyWGWEDMSPFTNTTLQWLPG 307
Cdd:cd03592     3 YHYSTEKMTFNEAVKYCKSRGTDLVAIQNAEENALLNGFALKYNLGYY--WIDGNDINNE-GTWVDTDKKELEYKNWAPG 79

                  ....*.
gi 2462518351 308 EPNDSG 313
Cdd:cd03592    80 EPNNGR 85

Kelch motif; The kelch motif was initially discovered in Kelch. In this protein there are six copies of the motif. It has been shown that Swiss:Q04652 is related to Galactose Oxidase for which a structure has been solved. The kelch motif forms a beta sheet. Several of these sheets associate to form a beta propeller structure as found in pfam00064, pfam00400 and pfam00415.

                          10        20        30
                  ....*....|....*....|....*....|...
gi 2462518351  49 RFGHSAVVINGSMYIFGGF-SSVLLNDILVYKP 80
Cdd:pfam01344   2 RSGAGVVVVGGKIYVIGGFdGNQSLNSVEVYDP 34