TREA_YEAST
ID TREA_YEAST Reviewed; 751 AA.
AC P32356; D6VRY8; E9P9U7;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 3.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Cytosolic neutral trehalase {ECO:0000305};
DE EC=3.2.1.28 {ECO:0000269|PubMed:22320399, ECO:0000269|PubMed:29087344, ECO:0000305|PubMed:10527941, ECO:0000305|PubMed:8444853};
DE AltName: Full=Alpha,alpha-trehalase;
DE AltName: Full=Alpha,alpha-trehalose glucohydrolase;
GN Name=NTH1 {ECO:0000303|PubMed:8444853}; Synonyms=NTH;
GN OrderedLocusNames=YDR001C; ORFNames=YD8119.07C;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=8444853; DOI=10.1016/s0021-9258(18)53463-3;
RA Kopp M., Mueller H., Holzer H.;
RT "Molecular analysis of the neutral trehalase gene from Saccharomyces
RT cerevisiae.";
RL J. Biol. Chem. 268:4766-4774(1993).
RN [2]
RP SEQUENCE REVISION TO N-TERMINUS.
RX PubMed=7821816; DOI=10.1016/0378-1119(94)90462-6;
RA Kopp M., Nwaka S., Holzer H.;
RT "Corrected sequence of the yeast neutral trehalase-encoding gene (NTH1):
RT biological implications.";
RL Gene 150:403-404(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169867;
RA Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G.,
RA Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C.,
RA Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F.,
RA Delaveau T., del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M.,
RA Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T.,
RA Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C.,
RA Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S.,
RA Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., Paulin L.,
RA Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., Prydz H.,
RA Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., Rieger M.,
RA Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., Scharfe M.,
RA Schmidt E.R., Schneider C., Scholler P., Schwarz S., Soler-Mira A.,
RA Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., Volckaert G.,
RA Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., Harris D.E.,
RA Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., Gentles S.,
RA Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., Niblett D.,
RA Odell C., Oliver K., Rajandream M.A., Richards C., Shore L., Walsh S.V.,
RA Barrell B.G., Dietrich F.S., Mulligan J.T., Allen E., Araujo R., Aviles E.,
RA Berno A., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M.,
RA Hunicke-Smith S., Hyman R.W., Komp C., Lashkari D., Lew H., Lin D.,
RA Mosedale D., Nakahara K., Namath A., Oefner P., Oh C., Petel F.X.,
RA Roberts D., Schramm S., Schroeder M., Shogren T., Shroff N., Winant A.,
RA Yelton M.A., Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R.,
RA Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., Greco T.,
RA Hallsworth K., Hawkins J., Hillier L.W., Jier M., Johnson D., Johnston L.,
RA Kirsten J., Kucaba T., Langston Y., Latreille P., Le T., Mardis E.,
RA Menezes S., Miller N., Nhan M., Pauley A., Peluso D., Rifkin L., Riles L.,
RA Taich A., Trevaskis E., Vignati D., Wilcox L., Wohldman P., Vaudin M.,
RA Wilson R., Waterston R., Albermann K., Hani J., Heumann K., Kleine K.,
RA Mewes H.-W., Zollner A., Zaccaria P.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV.";
RL Nature 387:75-78(1997).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 512-751.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=3537685; DOI=10.1128/mcb.6.1.241-245.1986;
RA Mann C., Davis R.W.;
RT "Structure and sequence of the centromeric DNA of chromosome 4 in
RT Saccharomyces cerevisiae.";
RL Mol. Cell. Biol. 6:241-245(1986).
RN [6]
RP CHARACTERIZATION.
RX PubMed=2507544; DOI=10.1016/s0021-9258(18)71531-7;
RA App H., Holzer H.;
RT "Purification and characterization of neutral trehalase from the yeast
RT ABYS1 mutant.";
RL J. Biol. Chem. 264:17583-17588(1989).
RN [7]
RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=7883049; DOI=10.1016/0014-5793(95)00105-i;
RA Nwaka S., Mechler B., Destruelle M., Holzer H.;
RT "Phenotypic features of trehalase mutants in Saccharomyces cerevisiae.";
RL FEBS Lett. 360:286-290(1995).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=7730323; DOI=10.1074/jbc.270.17.10193;
RA Nwaka S., Kopp M., Holzer H.;
RT "Expression and function of the trehalase genes NTH1 and YBR0106 in
RT Saccharomyces cerevisiae.";
RL J. Biol. Chem. 270:10193-10198(1995).
RN [9]
RP INDUCTION.
RX PubMed=9276477; DOI=10.1016/s0014-5793(97)00868-5;
RA Zaehringer H., Burgert M., Holzer H., Nwaka S.;
RT "Neutral trehalase Nth1p of Saccharomyces cerevisiae encoded by the NTH1
RT gene is a multiple stress responsive protein.";
RL FEBS Lett. 412:615-620(1997).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF SER-20; SER-21; THR-58;
RP SER-60; SER-83; THR-135; THR-149; THR-260 AND SER-475.
RX PubMed=10527941; DOI=10.1042/bj3430621;
RA Wera S., De Schrijver E., Geyskens I., Nwaka S., Thevelein J.M.;
RT "Opposite roles of trehalase activity in heat-shock recovery and heat-shock
RT survival in Saccharomyces cerevisiae.";
RL Biochem. J. 343:621-626(1999).
RN [11]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [12]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=YAL6B;
RX PubMed=15665377; DOI=10.1074/mcp.m400219-mcp200;
RA Gruhler A., Olsen J.V., Mohammed S., Mortensen P., Faergeman N.J., Mann M.,
RA Jensen O.N.;
RT "Quantitative phosphoproteomics applied to the yeast pheromone signaling
RT pathway.";
RL Mol. Cell. Proteomics 4:310-327(2005).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-58 AND SER-60, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ADR376;
RX PubMed=17330950; DOI=10.1021/pr060559j;
RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA Elias J.E., Gygi S.P.;
RT "Large-scale phosphorylation analysis of alpha-factor-arrested
RT Saccharomyces cerevisiae.";
RL J. Proteome Res. 6:1190-1197(2007).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-58; SER-60; SER-66 AND
RP SER-83, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=17287358; DOI=10.1073/pnas.0607084104;
RA Chi A., Huttenhower C., Geer L.Y., Coon J.J., Syka J.E.P., Bai D.L.,
RA Shabanowitz J., Burke D.J., Troyanskaya O.G., Hunt D.F.;
RT "Analysis of phosphorylation sites on proteins from Saccharomyces
RT cerevisiae by electron transfer dissociation (ETD) mass spectrometry.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:2193-2198(2007).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-66 AND SER-83, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20; SER-21; SER-23; THR-58;
RP SER-60; SER-66 AND SER-83, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE
RP SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
RN [18]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, INTERACTION WITH BMH1 AND BMH2,
RP PHOSPHORYLATION AT SER-20; SER-21; SER-60 AND SER-83, AND MUTAGENESIS OF
RP SER-20; SER-21; SER-60 AND SER-83.
RX PubMed=22320399; DOI=10.1042/bj20111615;
RA Veisova D., Macakova E., Rezabkova L., Sulc M., Vacha P., Sychrova H.,
RA Obsil T., Obsilova V.;
RT "Role of individual phosphorylation sites for the 14-3-3-protein-dependent
RT activation of yeast neutral trehalase Nth1.";
RL Biochem. J. 443:663-670(2012).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [20] {ECO:0007744|PDB:5JTA, ECO:0007744|PDB:5M4A, ECO:0007744|PDB:5N6N, ECO:0007744|PDB:5NIS}
RP X-RAY CRYSTALLOGRAPHY (2.29 ANGSTROMS) IN COMPLEXES WITH CALCIUM; BMH1 AND
RP SUBSTRATE, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBUNIT, ACTIVE SITE,
RP AND MUTAGENESIS OF GLN-120; ASP-478; GLU-674; ARG-686; GLU-690 AND TYR-691.
RX PubMed=29087344; DOI=10.1073/pnas.1714491114;
RA Alblova M., Smidova A., Docekal V., Vesely J., Herman P., Obsilova V.,
RA Obsil T.;
RT "Molecular basis of the 14-3-3 protein-dependent activation of yeast
RT neutral trehalase Nth1.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:E9811-E9820(2017).
CC -!- FUNCTION: Hydrolyzes intracellular trehalose to glucose
CC (PubMed:22320399, PubMed:29087344) (Probable). The disaccharide
CC trehalose serves as a storage carbohydrate that is mobilized during
CC nutrient stress (Probable). Regulates the level of trehalose as a
CC protectant for cell integrity during heat stress (PubMed:7883049,
CC PubMed:7730323). {ECO:0000269|PubMed:22320399,
CC ECO:0000269|PubMed:29087344, ECO:0000269|PubMed:7730323,
CC ECO:0000269|PubMed:7883049, ECO:0000305|PubMed:10527941,
CC ECO:0000305|PubMed:24374639, ECO:0000305|PubMed:8444853}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=alpha,alpha-trehalose + H2O = alpha-D-glucose + beta-D-
CC glucose; Xref=Rhea:RHEA:32675, ChEBI:CHEBI:15377, ChEBI:CHEBI:15903,
CC ChEBI:CHEBI:16551, ChEBI:CHEBI:17925; EC=3.2.1.28;
CC Evidence={ECO:0000269|PubMed:22320399, ECO:0000269|PubMed:29087344,
CC ECO:0000305|PubMed:10527941, ECO:0000305|PubMed:8444853};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:22320399, ECO:0000269|PubMed:29087344};
CC -!- ACTIVITY REGULATION: Activated by calcium (PubMed:22320399). Activated
CC by protein kinase A (PKA)-mediated phosphorylation (PubMed:22320399).
CC {ECO:0000269|PubMed:22320399}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=8 mM for trehalose (in the presence of BMH1, at pH 7.5 and 30
CC degrees Celsius) {ECO:0000269|PubMed:22320399};
CC KM=6 mM for trehalose (in the presence of 5 mM calcium, at pH 7.5 and
CC 30 degrees Celsius) {ECO:0000269|PubMed:22320399};
CC KM=3.6 mM for trehalose (in the presence of 5 mM calcium and BMH1, at
CC pH 7.5 and 30 degrees Celsius) {ECO:0000269|PubMed:22320399};
CC Note=kcat is 71 sec(-1) for trehalose (in the presence of BMH1, at pH
CC 7.5 and 30 degrees Celsius). kcat is 6.2 sec(-1) for trehalose (in
CC the presence of 5 mM calcium, at pH 7.5 and 30 degrees Celsius). kcat
CC is 42 sec(-1) for trehalose (in the presence of 5 mM calcium and
CC BMH1, at pH 7.5 and 30 degrees Celsius).;
CC -!- PATHWAY: Carbohydrate degradation. {ECO:0000305}.
CC -!- SUBUNIT: Monomer (PubMed:22320399, PubMed:29087344). Interacts with
CC BMH1 dimers; the interaction is direct and activates NTH1
CC (PubMed:29087344, PubMed:22320399). Interacts with BMH2
CC (PubMed:22320399). {ECO:0000269|PubMed:22320399,
CC ECO:0000269|PubMed:29087344}.
CC -!- INTERACTION:
CC P32356; P29311: BMH1; NbExp=7; IntAct=EBI-19509, EBI-3661;
CC P32356; P34730: BMH2; NbExp=8; IntAct=EBI-19509, EBI-3672;
CC P32356; Q06151: DCS1; NbExp=3; IntAct=EBI-19509, EBI-38973;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}.
CC -!- INDUCTION: Induced during thermal stress (at protein level)
CC (PubMed:7883049, PubMed:9276477). Induced by oxidative stress (hydrogen
CC peroxide, sodium arsenite) (at protein level) (PubMed:9276477). Induced
CC by copper stress (at protein level) (PubMed:9276477). Induced by
CC protein synthesis inhibitor (cycloheximide) (PubMed:9276477).
CC {ECO:0000269|PubMed:7883049, ECO:0000269|PubMed:9276477}.
CC -!- PTM: Phosphorylated by protein kinase A (PKA); phosphorylation at Ser-
CC 60 and Ser-83 is required for activation by the 14-3-3 proteins BMH1
CC and BMH2. {ECO:0000269|PubMed:22320399}.
CC -!- DISRUPTION PHENOTYPE: Increases cellular trehalase level during thermal
CC stress (PubMed:7730323). Increases sensitivity to heat shock
CC (PubMed:7730323, PubMed:7883049). Decreases growth on the non-
CC fermentable carbon source glycerol; simultaneous knockout of ATH1
CC exacerbates the effect (PubMed:7883049). {ECO:0000269|PubMed:7730323,
CC ECO:0000269|PubMed:7883049}.
CC -!- MISCELLANEOUS: Present with 1840 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 37 family. {ECO:0000305}.
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DR EMBL; X65925; CAA46718.1; -; Genomic_DNA.
DR EMBL; Z48008; CAA88061.1; -; Genomic_DNA.
DR EMBL; M13000; AAA66896.1; -; Genomic_DNA.
DR EMBL; BK006938; DAA11848.1; -; Genomic_DNA.
DR PIR; S50982; S50982.
DR RefSeq; NP_010284.1; NM_001180309.1.
DR PDB; 5JTA; X-ray; 2.72 A; A=1-751.
DR PDB; 5M4A; X-ray; 2.90 A; A=153-751.
DR PDB; 5N6N; X-ray; 2.29 A; C=1-751.
DR PDB; 5NIS; X-ray; 3.15 A; A=100-751.
DR PDBsum; 5JTA; -.
DR PDBsum; 5M4A; -.
DR PDBsum; 5N6N; -.
DR PDBsum; 5NIS; -.
DR AlphaFoldDB; P32356; -.
DR SMR; P32356; -.
DR BioGRID; 32054; 99.
DR DIP; DIP-1479N; -.
DR IntAct; P32356; 16.
DR MINT; P32356; -.
DR STRING; 4932.YDR001C; -.
DR CAZy; GH37; Glycoside Hydrolase Family 37.
DR iPTMnet; P32356; -.
DR MaxQB; P32356; -.
DR PaxDb; P32356; -.
DR PRIDE; P32356; -.
DR EnsemblFungi; YDR001C_mRNA; YDR001C; YDR001C.
DR GeneID; 851564; -.
DR KEGG; sce:YDR001C; -.
DR SGD; S000002408; NTH1.
DR VEuPathDB; FungiDB:YDR001C; -.
DR eggNOG; KOG0602; Eukaryota.
DR GeneTree; ENSGT00390000006949; -.
DR HOGENOM; CLU_006451_1_1_1; -.
DR InParanoid; P32356; -.
DR OMA; GLERPNR; -.
DR BioCyc; MetaCyc:YDR001C-MON; -.
DR BioCyc; YEAST:YDR001C-MON; -.
DR BRENDA; 3.2.1.28; 984.
DR PRO; PR:P32356; -.
DR Proteomes; UP000002311; Chromosome IV.
DR RNAct; P32356; protein.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR GO; GO:0004555; F:alpha,alpha-trehalase activity; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0015927; F:trehalase activity; IDA:UniProtKB.
DR GO; GO:0071465; P:cellular response to desiccation; IMP:SGD.
DR GO; GO:0005993; P:trehalose catabolic process; IDA:UniProtKB.
DR Gene3D; 1.50.10.10; -; 1.
DR InterPro; IPR008928; 6-hairpin_glycosidase_sf.
DR InterPro; IPR012341; 6hp_glycosidase-like_sf.
DR InterPro; IPR001661; Glyco_hydro_37.
DR InterPro; IPR018232; Glyco_hydro_37_CS.
DR InterPro; IPR011120; Trehalase_Ca-bd.
DR PANTHER; PTHR23403; PTHR23403; 1.
DR Pfam; PF01204; Trehalase; 1.
DR Pfam; PF07492; Trehalase_Ca-bi; 1.
DR PRINTS; PR00744; GLHYDRLASE37.
DR SUPFAM; SSF48208; SSF48208; 1.
DR PROSITE; PS00927; TREHALASE_1; 1.
DR PROSITE; PS00928; TREHALASE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Calcium; Cytoplasm; Glycosidase; Hydrolase;
KW Metal-binding; Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..751
FT /note="Cytosolic neutral trehalase"
FT /id="PRO_0000173798"
FT REGION 1..59
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 73..92
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..28
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 478
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000305|PubMed:29087344,
FT ECO:0007744|PDB:5M4A"
FT ACT_SITE 674
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000305|PubMed:29087344,
FT ECO:0007744|PDB:5M4A"
FT BINDING 114
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:29087344,
FT ECO:0007744|PDB:5N6N"
FT BINDING 116
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:29087344,
FT ECO:0007744|PDB:5N6N"
FT BINDING 118
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:29087344,
FT ECO:0007744|PDB:5N6N"
FT BINDING 120
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:29087344,
FT ECO:0007744|PDB:5N6N"
FT BINDING 125
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:29087344,
FT ECO:0007744|PDB:5N6N"
FT BINDING 302
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P13482"
FT BINDING 309..310
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:29087344,
FT ECO:0007744|PDB:5M4A, ECO:0007744|PDB:5N6N"
FT BINDING 346
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:29087344,
FT ECO:0007744|PDB:5M4A, ECO:0007744|PDB:5N6N"
FT BINDING 355..357
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:29087344,
FT ECO:0007744|PDB:5M4A, ECO:0007744|PDB:5N6N"
FT BINDING 424
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:29087344,
FT ECO:0007744|PDB:5M4A, ECO:0007744|PDB:5N6N"
FT BINDING 473
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:29087344,
FT ECO:0007744|PDB:5M4A, ECO:0007744|PDB:5N6N"
FT BINDING 476
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:29087344,
FT ECO:0007744|PDB:5M4A, ECO:0007744|PDB:5N6N"
FT SITE 55
FT /note="BMH1 binding"
FT /evidence="ECO:0000269|PubMed:29087344,
FT ECO:0007744|PDB:5N6N"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 20
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:22320399,
FT ECO:0007744|PubMed:19779198"
FT MOD_RES 21
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:22320399,
FT ECO:0007744|PubMed:19779198"
FT MOD_RES 23
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 58
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17287358,
FT ECO:0007744|PubMed:17330950, ECO:0007744|PubMed:19779198"
FT MOD_RES 60
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:22320399,
FT ECO:0007744|PubMed:15665377, ECO:0007744|PubMed:17287358,
FT ECO:0007744|PubMed:17330950, ECO:0007744|PubMed:19779198"
FT MOD_RES 66
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17287358,
FT ECO:0007744|PubMed:18407956, ECO:0007744|PubMed:19779198"
FT MOD_RES 83
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:22320399,
FT ECO:0007744|PubMed:17287358, ECO:0007744|PubMed:18407956,
FT ECO:0007744|PubMed:19779198"
FT MUTAGEN 20
FT /note="S->A: Abolishes activity; when associated with A-21;
FT A-58; A-60; A-83; A-135; A-149; A-260 and A-475. Abolishes
FT activation by BMH1 and BMH2; when associated with A-21; A-
FT 60 and A-83."
FT /evidence="ECO:0000269|PubMed:10527941,
FT ECO:0000269|PubMed:22320399"
FT MUTAGEN 21
FT /note="S->A: Abolishes activity; when associated with A-20;
FT A-58; A-60; A-83; A-135; A-149; A-260 and A-475. Abolishes
FT activation by BMH1 and BMH2; when associated with A-20; A-
FT 60 and A-83."
FT /evidence="ECO:0000269|PubMed:10527941,
FT ECO:0000269|PubMed:22320399"
FT MUTAGEN 58
FT /note="T->A: Abolishes activity; when associated with A-20;
FT A-21; A-60; A-83; A-135; A-149; A-260 and A-475."
FT /evidence="ECO:0000269|PubMed:10527941"
FT MUTAGEN 60
FT /note="S->A: Abolishes activity; when associated with A-20;
FT A-21; A-58; A-83; A-135; A-149; A-260 and A-475. Abolishes
FT activation by BMH1 and BMH2; when associated with A-20; A-
FT 21 and A-83."
FT /evidence="ECO:0000269|PubMed:10527941,
FT ECO:0000269|PubMed:22320399"
FT MUTAGEN 83
FT /note="S->A: Abolishes activity; when associated with A-20;
FT A-21; A-58; A-60; A-135; A-149; A-260 and A-475. Abolishes
FT activation by BMH1 and BMH2; when associated with A-20; A-
FT 21 and A-60."
FT /evidence="ECO:0000269|PubMed:10527941,
FT ECO:0000269|PubMed:22320399"
FT MUTAGEN 120
FT /note="Q->A: Decreases catalytic activity."
FT /evidence="ECO:0000269|PubMed:29087344"
FT MUTAGEN 135
FT /note="T->A: Abolishes activity; when associated with A-20;
FT A-21; A-58; A-60; A-83; A-149; A-260 and A-475."
FT /evidence="ECO:0000269|PubMed:10527941"
FT MUTAGEN 149
FT /note="T->A: Abolishes activity; when associated with A-20;
FT A-21; A-58; A-60; A-83; A-135; A-260 and A-475."
FT /evidence="ECO:0000269|PubMed:10527941"
FT MUTAGEN 260
FT /note="T->A: Abolishes activity; when associated with A-20;
FT A-21; A-58; A-60; A-83; A-135; A-149 and A-475."
FT /evidence="ECO:0000269|PubMed:10527941"
FT MUTAGEN 475
FT /note="S->A: Abolishes activity; when associated with A-20;
FT A-21; A-58; A-60; A-83; A-135; A-149 and A-260."
FT /evidence="ECO:0000269|PubMed:10527941"
FT MUTAGEN 478
FT /note="D->A: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:29087344"
FT MUTAGEN 674
FT /note="E->A: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:29087344"
FT MUTAGEN 686
FT /note="R->A: Decreases catalytic activity."
FT /evidence="ECO:0000269|PubMed:29087344"
FT MUTAGEN 690
FT /note="E->A: Severely decreases catalytic activity."
FT /evidence="ECO:0000269|PubMed:29087344"
FT MUTAGEN 691
FT /note="Y->A: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:29087344"
FT CONFLICT 514..515
FT /note="CD -> NN (in Ref. 5; AAA66896)"
FT /evidence="ECO:0000305"
FT CONFLICT 712
FT /note="S -> R (in Ref. 1; CAA46718 and 5; AAA66896)"
FT /evidence="ECO:0000305"
FT CONFLICT 723..724
FT /note="HA -> YE (in Ref. 1; CAA46718 and 5; AAA66896)"
FT /evidence="ECO:0000305"
FT CONFLICT 727..728
FT /note="AL -> EI (in Ref. 1; CAA46718 and 5; AAA66896)"
FT /evidence="ECO:0000305"
FT HELIX 32..35
FT /evidence="ECO:0007829|PDB:5N6N"
FT TURN 55..57
FT /evidence="ECO:0007829|PDB:5N6N"
FT TURN 67..73
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 87..92
FT /evidence="ECO:0007829|PDB:5N6N"
FT STRAND 96..100
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 102..113
FT /evidence="ECO:0007829|PDB:5N6N"
FT STRAND 129..135
FT /evidence="ECO:0007829|PDB:5N6N"
FT TURN 136..140
FT /evidence="ECO:0007829|PDB:5N6N"
FT STRAND 141..148
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 149..164
FT /evidence="ECO:0007829|PDB:5N6N"
FT STRAND 168..173
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 174..176
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 181..191
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 193..197
FT /evidence="ECO:0007829|PDB:5N6N"
FT TURN 203..205
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 206..210
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 218..220
FT /evidence="ECO:0007829|PDB:5N6N"
FT STRAND 224..227
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 232..244
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 246..248
FT /evidence="ECO:0007829|PDB:5N6N"
FT STRAND 251..254
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 261..266
FT /evidence="ECO:0007829|PDB:5N6N"
FT TURN 267..269
FT /evidence="ECO:0007829|PDB:5N6N"
FT STRAND 278..282
FT /evidence="ECO:0007829|PDB:5N6N"
FT TURN 284..286
FT /evidence="ECO:0007829|PDB:5N6N"
FT STRAND 289..293
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 309..320
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 324..341
FT /evidence="ECO:0007829|PDB:5N6N"
FT STRAND 346..349
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 350..352
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 361..371
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 374..376
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 378..397
FT /evidence="ECO:0007829|PDB:5N6N"
FT TURN 398..400
FT /evidence="ECO:0007829|PDB:5N6N"
FT TURN 402..404
FT /evidence="ECO:0007829|PDB:5N6N"
FT TURN 407..409
FT /evidence="ECO:0007829|PDB:5N6N"
FT TURN 427..430
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 431..433
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 449..453
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 460..474
FT /evidence="ECO:0007829|PDB:5N6N"
FT TURN 481..486
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 487..489
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 493..513
FT /evidence="ECO:0007829|PDB:5N6N"
FT TURN 514..516
FT /evidence="ECO:0007829|PDB:5M4A"
FT TURN 521..523
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 529..547
FT /evidence="ECO:0007829|PDB:5N6N"
FT TURN 550..553
FT /evidence="ECO:0007829|PDB:5N6N"
FT TURN 560..563
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 571..574
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 575..578
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 584..593
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 595..598
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 609..612
FT /evidence="ECO:0007829|PDB:5N6N"
FT STRAND 617..619
FT /evidence="ECO:0007829|PDB:5N6N"
FT STRAND 623..625
FT /evidence="ECO:0007829|PDB:5M4A"
FT HELIX 631..643
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 647..667
FT /evidence="ECO:0007829|PDB:5N6N"
FT TURN 668..670
FT /evidence="ECO:0007829|PDB:5N6N"
FT STRAND 674..677
FT /evidence="ECO:0007829|PDB:5N6N"
FT STRAND 699..701
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 707..717
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 722..729
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 734..740
FT /evidence="ECO:0007829|PDB:5N6N"
FT HELIX 745..749
FT /evidence="ECO:0007829|PDB:5N6N"
SQ SEQUENCE 751 AA; 85879 MW; E6687F2E9377E49F CRC64;
MSQVNTSQGP VAQGRQRRLS SLSEFNDPFS NAEVYYGPPT DPRKQKQAKP AKINRTRTMS
VFDNVSPFKK TGFGKLQQTR RGSEDDTYSS SQGNRRFFIE DVDKTLNELL AAEDTDKNYQ
ITIEDTGPKV LKVGTANSYG YKHINIRGTY MLSNLLQELT IAKSFGRHQI FLDEARINEN
PVNRLSRLIN TQFWNSLTRR VDLNNVGEIA KDTKIDTPGA KNPRIYVPYD CPEQYEFYVQ
ASQMHPSLKL EVEYLPKKIT AEYVKSVNDT PGLLALAMEE HFNPSTGEKT LIGYPYAVPG
GRFNELYGWD SYMMALGLLE ANKTDVARGM VEHFIFEINH YGKILNANRS YYLCRSQPPF
LTEMALVVFK KLGGRSNPDA VDLLKRAFQA SIKEYKTVWT ASPRLDPETG LSRYHPNGLG
IPPETESDHF DTVLLPYASK HGVTLDEFKQ LYNDGKIKEP KLDEFFLHDR GVRESGHDTT
YRFEGVCAYL ATIDLNSLLY KYEIDIADFI KEFCDDKYED PLDHSITTSA MWKEMAKIRQ
EKITKYMWDD ESGFFFDYNT KIKHRTSYES ATTFWALWAG LATKEQAQKM VEKALPKLEM
LGGLAACTER SRGPISISRP IRQWDYPFGW APHQILAWEG LRSYGYLTVT NRLAYRWLFM
MTKAFVDYNG IVVEKYDVTR GTDPHRVEAE YGNQGADFKG AATEGFGWVN ASYILGLKYM
NSHARRALGA CIPPISFFSS LRPQERNLYG L
