ID AHA1_YEAST Reviewed; 350 AA. AC Q12449; D6VSJ8; Q02565; Q7LIE3; DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 27-MAR-2024, entry version 174. DE RecName: Full=Hsp90 co-chaperone AHA1; DE AltName: Full=Activator of Hsp90 ATPase protein 1; GN Name=AHA1; OrderedLocusNames=YDR214W; ORFNames=YD8142.16, YD8142B.06; 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 [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 [2] 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 [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=17322287; DOI=10.1101/gr.6037607; RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F., RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J., RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J., RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D., RA LaBaer J.; RT "Approaching a complete repository of sequence-verified protein-encoding RT clones for Saccharomyces cerevisiae."; RL Genome Res. 17:536-543(2007). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 129-350. RX PubMed=3515197; DOI=10.1038/320283a0; RA Hartshorne T.A., Blumberg H., Young E.T.; RT "Sequence homology of the yeast regulatory protein ADR1 with Xenopus RT transcription factor TFIIIA."; RL Nature 320:283-287(1986). RN [5] RP FUNCTION, INDUCTION, AND INTERACTION WITH HSP82. RX PubMed=12504007; DOI=10.1016/s1097-2765(02)00785-2; RA Panaretou B., Siligardi G., Meyer P., Maloney A., Sullivan J.K., Singh S., RA Millson S.H., Clarke P.A., Naaby-Hansen S., Stein R., Cramer R., RA Mollapour M., Workman P., Piper P.W., Pearl L.H., Prodromou C.; RT "Activation of the ATPase activity of hsp90 by the stress-regulated RT cochaperone aha1."; RL Mol. Cell 10:1307-1318(2002). RN [6] RP FUNCTION, AND INTERACTION WITH HSP82. RX PubMed=12604615; DOI=10.1074/jbc.m212761200; RA Lotz G.P., Lin H., Harst A., Obermann W.M.J.; RT "Aha1 binds to the middle domain of Hsp90, contributes to client protein RT activation, and stimulates the ATPase activity of the molecular RT chaperone."; RL J. Biol. Chem. 278:17228-17235(2003). RN [7] 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 [8] 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 [9] 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 [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE 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 [11] RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 1-156 IN COMPLEX WITH HSP82, AND RP MUTAGENESIS OF ASP-53; ARG-59; LYS-60 AND LYS-62. RX PubMed=14739935; DOI=10.1038/sj.emboj.7600060; RA Meyer P.; RT "Structural basis for recruitment of the ATPase activator Aha1 to the Hsp90 RT chaperone machinery."; RL EMBO J. 23:511-519(2004). RN [12] RP ERRATUM OF PUBMED:14739935. RX PubMed=15039704; DOI=10.1038/sj.emboj.7600141; RA Meyer P., Prodromou C., Liao C., Hu B., Mark Roe S., Vaughan C.K., RA Vlasic I., Panaretou B., Piper P.W., Pearl L.H.; RL EMBO J. 23:1402-1410(2004). CC -!- FUNCTION: Co-chaperone that binds to the molecular chaperone HSP82 and CC stimulates its ATPase activity. Binding to HSP82 promotes a CC conformational switch in the catalytic loop of HSP82, facilitating the CC interaction of the catalytic 'Arg-380' with ATP in the N-terminal CC nucleotide-binding domain. Although not essential, it confers CC thermotolerance when intracellular levels of HSP82 are limiting. CC {ECO:0000269|PubMed:12504007, ECO:0000269|PubMed:12604615}. CC -!- SUBUNIT: Monomer. Interacts with HSP82. {ECO:0000269|PubMed:12504007, CC ECO:0000269|PubMed:12604615, ECO:0000269|PubMed:14739935}. CC -!- INTERACTION: CC Q12449; P39009: DUN1; NbExp=2; IntAct=EBI-37072, EBI-6194; CC Q12449; P15108: HSC82; NbExp=3; IntAct=EBI-37072, EBI-8666; CC Q12449; P02829: HSP82; NbExp=13; IntAct=EBI-37072, EBI-8659; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. CC -!- INDUCTION: By heat shock. {ECO:0000269|PubMed:12504007}. CC -!- MISCELLANEOUS: Present with 13939 molecules/cell in log phase SD CC medium. {ECO:0000269|PubMed:14562106}. CC -!- SIMILARITY: Belongs to the AHA1 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Z68194; CAA92357.1; -; Genomic_DNA. DR EMBL; Z68195; CAA92365.1; -; Genomic_DNA. DR EMBL; AY557694; AAS56020.1; -; Genomic_DNA. DR EMBL; U28414; AAA73862.1; -; Genomic_DNA. DR EMBL; BK006938; DAA12058.1; -; Genomic_DNA. DR PIR; S61581; S61581. DR RefSeq; NP_010500.3; NM_001180522.3. DR PDB; 1USU; X-ray; 2.15 A; B=1-156. DR PDB; 1USV; X-ray; 2.70 A; B/D/F/H=1-156. DR PDB; 6XLB; EM; 3.80 A; C1/D1=1-350. DR PDB; 6XLD; EM; 3.66 A; C=1-350. DR PDB; 6XLE; EM; 2.74 A; C/D=1-350. DR PDB; 6XLF; EM; 3.15 A; C/D=1-350. DR PDB; 6XLG; EM; 2.71 A; C/D=1-350. DR PDB; 6XLH; EM; 2.83 A; C/D=1-350. DR PDBsum; 1USU; -. DR PDBsum; 1USV; -. DR PDBsum; 6XLB; -. DR PDBsum; 6XLD; -. DR PDBsum; 6XLE; -. DR PDBsum; 6XLF; -. DR PDBsum; 6XLG; -. DR PDBsum; 6XLH; -. DR AlphaFoldDB; Q12449; -. DR BMRB; Q12449; -. DR EMDB; EMD-22238; -. DR EMDB; EMD-22240; -. DR EMDB; EMD-22241; -. DR EMDB; EMD-22242; -. DR EMDB; EMD-22243; -. DR EMDB; EMD-22244; -. DR SMR; Q12449; -. DR BioGRID; 32268; 165. DR DIP; DIP-1831N; -. DR IntAct; Q12449; 55. DR MINT; Q12449; -. DR STRING; 4932.YDR214W; -. DR CarbonylDB; Q12449; -. DR iPTMnet; Q12449; -. DR MaxQB; Q12449; -. DR PaxDb; 4932-YDR214W; -. DR PeptideAtlas; Q12449; -. DR EnsemblFungi; YDR214W_mRNA; YDR214W; YDR214W. DR GeneID; 851800; -. DR KEGG; sce:YDR214W; -. DR AGR; SGD:S000002622; -. DR SGD; S000002622; AHA1. DR VEuPathDB; FungiDB:YDR214W; -. DR eggNOG; KOG2936; Eukaryota. DR GeneTree; ENSGT00940000173240; -. DR HOGENOM; CLU_049046_1_0_1; -. DR InParanoid; Q12449; -. DR OMA; CEVNQRK; -. DR OrthoDB; 5473696at2759; -. DR BioCyc; YEAST:G3O-29796-MONOMER; -. DR BioGRID-ORCS; 851800; 4 hits in 10 CRISPR screens. DR EvolutionaryTrace; Q12449; -. DR PRO; PR:Q12449; -. DR Proteomes; UP000002311; Chromosome IV. DR RNAct; Q12449; Protein. DR GO; GO:0005737; C:cytoplasm; IPI:SGD. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0001671; F:ATPase activator activity; IDA:UniProtKB. DR GO; GO:0051087; F:protein-folding chaperone binding; IDA:SGD. DR GO; GO:0006457; P:protein folding; IMP:SGD. DR CDD; cd08892; SRPBCC_Aha1; 1. DR Gene3D; 3.30.530.20; -; 1. DR Gene3D; 3.15.10.20; Activator of Hsp90 ATPase Aha1, N-terminal domain; 1. DR InterPro; IPR036338; Aha1. DR InterPro; IPR015310; AHSA1-like_N. DR InterPro; IPR013538; ASHA1-like_C. DR InterPro; IPR023393; START-like_dom_sf. DR PANTHER; PTHR13009; HEAT SHOCK PROTEIN 90 HSP90 CO-CHAPERONE AHA-1; 1. DR PANTHER; PTHR13009:SF8; LD43819P; 1. DR Pfam; PF09229; Aha1_N; 1. DR Pfam; PF08327; AHSA1; 1. DR SMART; SM01000; Aha1_N; 1. DR SUPFAM; SSF103111; Activator of Hsp90 ATPase, Aha1; 1. DR SUPFAM; SSF55961; Bet v1-like; 1. PE 1: Evidence at protein level; KW 3D-structure; Chaperone; Cytoplasm; Reference proteome; Stress response. FT CHAIN 1..350 FT /note="Hsp90 co-chaperone AHA1" FT /id="PRO_0000215822" FT REGION 158..212 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 158..177 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 185..212 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MUTAGEN 53 FT /note="D->A: No effect on Hsp90 ATPase activity but reduces FT Hsp90 binding affinity." FT /evidence="ECO:0000269|PubMed:14739935" FT MUTAGEN 53 FT /note="D->K: Decreases activation of Hsp90 ATPase activity FT and substantially reduces Hsp90 binding affinity." FT /evidence="ECO:0000269|PubMed:14739935" FT MUTAGEN 59 FT /note="R->A: Decreases activation of Hsp90 ATPase activity FT with a small reduction in Hsp90 binding affinity." FT /evidence="ECO:0000269|PubMed:14739935" FT MUTAGEN 60 FT /note="K->A: Decreased activation of Hsp90 ATPase activity FT with a small reduction in Hsp90 binding affinity." FT /evidence="ECO:0000269|PubMed:14739935" FT MUTAGEN 62 FT /note="K->A: Decreased activation of Hsp90 ATPase activity FT with a small reduction in Hsp90 binding affinity." FT /evidence="ECO:0000269|PubMed:14739935" FT CONFLICT 28 FT /note="L -> I (in Ref. 11)" FT /evidence="ECO:0000305" FT HELIX 6..8 FT /evidence="ECO:0007829|PDB:6XLH" FT STRAND 12..15 FT /evidence="ECO:0007829|PDB:6XLH" FT HELIX 17..28 FT /evidence="ECO:0007829|PDB:1USU" FT STRAND 32..34 FT /evidence="ECO:0007829|PDB:1USV" FT STRAND 36..39 FT /evidence="ECO:0007829|PDB:6XLH" FT STRAND 41..44 FT /evidence="ECO:0007829|PDB:1USU" FT STRAND 49..53 FT /evidence="ECO:0007829|PDB:1USU" FT STRAND 55..57 FT /evidence="ECO:0007829|PDB:1USV" FT STRAND 63..65 FT /evidence="ECO:0007829|PDB:6XLH" FT STRAND 68..78 FT /evidence="ECO:0007829|PDB:1USU" FT STRAND 82..85 FT /evidence="ECO:0007829|PDB:1USV" FT STRAND 88..99 FT /evidence="ECO:0007829|PDB:1USU" FT HELIX 104..106 FT /evidence="ECO:0007829|PDB:1USU" FT STRAND 110..113 FT /evidence="ECO:0007829|PDB:1USU" FT HELIX 118..122 FT /evidence="ECO:0007829|PDB:6XLH" FT HELIX 123..130 FT /evidence="ECO:0007829|PDB:1USU" FT HELIX 132..150 FT /evidence="ECO:0007829|PDB:1USU" FT TURN 151..153 FT /evidence="ECO:0007829|PDB:6XLF" FT HELIX 158..160 FT /evidence="ECO:0007829|PDB:6XLH" FT HELIX 164..169 FT /evidence="ECO:0007829|PDB:6XLH" FT STRAND 213..218 FT /evidence="ECO:0007829|PDB:6XLG" FT STRAND 221..224 FT /evidence="ECO:0007829|PDB:6XLE" FT HELIX 226..232 FT /evidence="ECO:0007829|PDB:6XLG" FT HELIX 236..243 FT /evidence="ECO:0007829|PDB:6XLG" FT STRAND 246..248 FT /evidence="ECO:0007829|PDB:6XLG" FT STRAND 252..254 FT /evidence="ECO:0007829|PDB:6XLG" FT STRAND 259..263 FT /evidence="ECO:0007829|PDB:6XLG" FT TURN 264..267 FT /evidence="ECO:0007829|PDB:6XLG" FT STRAND 268..275 FT /evidence="ECO:0007829|PDB:6XLG" FT STRAND 277..283 FT /evidence="ECO:0007829|PDB:6XLG" FT STRAND 297..305 FT /evidence="ECO:0007829|PDB:6XLG" FT TURN 306..309 FT /evidence="ECO:0007829|PDB:6XLG" FT STRAND 310..321 FT /evidence="ECO:0007829|PDB:6XLG" FT HELIX 322..324 FT /evidence="ECO:0007829|PDB:6XLG" FT HELIX 325..330 FT /evidence="ECO:0007829|PDB:6XLG" FT HELIX 332..335 FT /evidence="ECO:0007829|PDB:6XLG" FT HELIX 338..343 FT /evidence="ECO:0007829|PDB:6XLG" SQ SEQUENCE 350 AA; 39436 MW; 06DF6B40EB5050BE CRC64; MVVNNPNNWH WVDKNCIGWA KEYFKQKLVG VEAGSVKDKK YAKIKSVSSI EGDCEVNQRK GKVISLFDLK ITVLIEGHVD SKDGSALPFE GSINVPEVAF DSEASSYQFD ISIFKETSEL SEAKPLIRSE LLPKLRQIFQ QFGKDLLATH GNDIQVPESQ VKSNYTRGNQ KSSFTEIKDS ASKPKKNALP SSTSTSAPVS STNKVPQNGS GNSTSIYLEP TFNVPSSELY ETFLDKQRIL AWTRSAQFFN SGPKLETKEK FELFGGNVIS ELVSCEKDKK LVFHWKLKDW SAPFNSTIEM TFHESQEFHE TKLQVKWTGI PVGEEDRVRA NFEEYYVRSI KLTFGFGAVL //