ID HSP78_YEAST Reviewed; 811 AA. AC P33416; D6VSN8; Q12137; DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot. DT 23-MAY-2003, sequence version 2. DT 27-MAR-2024, entry version 195. DE RecName: Full=Heat shock protein 78, mitochondrial; DE Flags: Precursor; GN Name=HSP78; OrderedLocusNames=YDR258C; ORFNames=YD9320A.08C; 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], SUBCELLULAR LOCATION, AND INDUCTION. RX PubMed=8413229; DOI=10.1128/mcb.13.10.6304-6313.1993; RA Leonhardt S.A., Fearon K., Danese P.N., Mason T.L.; RT "HSP78 encodes a yeast mitochondrial heat shock protein in the Clp family RT of ATP-dependent proteases."; RL Mol. Cell. Biol. 13:6304-6313(1993). RN [2] 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 [3] 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 [4] RP PROTEIN SEQUENCE OF 85-90, AND FUNCTION. RX PubMed=11231020; DOI=10.1016/s0014-5793(00)02423-6; RA Krzewska J., Langer T., Liberek K.; RT "Mitochondrial Hsp78, a member of the Clp/Hsp100 family in Saccharomyces RT cerevisiae, cooperates with Hsp70 in protein refolding."; RL FEBS Lett. 489:92-96(2001). RN [5] RP FUNCTION. RX PubMed=7628444; DOI=10.1002/j.1460-2075.1995.tb07349.x; RA Schmitt M., Neupert W., Langer T.; RT "Hsp78, a Clp homologue within mitochondria, can substitute for chaperone RT functions of mt-hsp70."; RL EMBO J. 14:3434-3444(1995). RN [6] RP FUNCTION. RX PubMed=7500331; DOI=10.1006/jmbi.1995.0636; RA Moczko M., Schoenfisch B., Voos W., Pfanner N., Rassow J.; RT "The mitochondrial ClpB homolog Hsp78 cooperates with matrix Hsp70 in RT maintenance of mitochondrial function."; RL J. Mol. Biol. 254:538-543(1995). RN [7] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=8830768; DOI=10.1083/jcb.134.6.1375; RA Schmitt M., Neupert W., Langer T.; RT "The molecular chaperone Hsp78 confers compartment-specific thermotolerance RT to mitochondria."; RL J. Cell Biol. 134:1375-1386(1996). RN [8] RP FUNCTION, SUBUNIT, ELECTRON MICROSCOPY, AND MUTAGENESIS OF LYS-149 AND RP LYS-547. RX PubMed=11734006; DOI=10.1006/jmbi.2001.5190; RA Krzewska J., Konopa G., Liberek K.; RT "Importance of two ATP-binding sites for oligomerization, ATPase activity RT and chaperone function of mitochondrial Hsp78 protein."; RL J. Mol. Biol. 314:901-910(2001). RN [9] RP FUNCTION. RX PubMed=12023279; DOI=10.1074/jbc.m201756200; RA Germaniuk A., Liberek K., Marszalek J.; RT "A bichaperone (Hsp70-Hsp78) system restores mitochondrial DNA synthesis RT following thermal inactivation of Mip1p polymerase."; RL J. Biol. Chem. 277:27801-27808(2002). RN [10] RP FUNCTION IN PROTEIN DEGRADATION. RX PubMed=12237310; DOI=10.1074/jbc.m207152200; RA Roettgers K., Zufall N., Guiard B., Voos W.; RT "The ClpB homolog Hsp78 is required for the efficient degradation of RT proteins in the mitochondrial matrix."; RL J. Biol. Chem. 277:45829-45837(2002). 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 SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RC STRAIN=ATCC 76625 / YPH499; RX PubMed=14576278; DOI=10.1073/pnas.2135385100; RA Sickmann A., Reinders J., Wagner Y., Joppich C., Zahedi R.P., Meyer H.E., RA Schoenfisch B., Perschil I., Chacinska A., Guiard B., Rehling P., RA Pfanner N., Meisinger C.; RT "The proteome of Saccharomyces cerevisiae mitochondria."; RL Proc. Natl. Acad. Sci. U.S.A. 100:13207-13212(2003). RN [14] RP INDUCTION. RX PubMed=16339719; DOI=10.1128/ec.4.12.2008-2016.2005; RA Seppae L., Makarow M.; RT "Regulation and recovery of functions of Saccharomyces cerevisiae chaperone RT BiP/Kar2p after thermal insult."; RL Eukaryot. Cell 4:2008-2016(2005). RN [15] RP FUNCTION. RX PubMed=16545993; DOI=10.1016/j.bbamcr.2006.01.007; RA Lewandowska A., Gierszewska M., Marszalek J., Liberek K.; RT "Hsp78 chaperone functions in restoration of mitochondrial network RT following heat stress."; RL Biochim. Biophys. Acta 1763:141-151(2006). RN [16] RP FUNCTION. RX PubMed=16460754; DOI=10.1016/j.jmb.2006.01.008; RA von Janowsky B., Major T., Knapp K., Voos W.; RT "The disaggregation activity of the mitochondrial ClpB homolog Hsp78 RT maintains Hsp70 function during heat stress."; RL J. Mol. Biol. 357:793-807(2006). CC -!- FUNCTION: Required, in concert with mitochondrial Hsp70 (SSC1), for the CC dissociation, resolubilization and refolding of aggregates of damaged CC proteins in the mitochondrial matrix after heat stress. May extract CC proteins from aggregates by unfolding and threading them in an ATP- CC dependent process through the axial channel of the protein hexamer, CC after which they can be refolded by the Hsp70 chaperone system. CC Required for resumption of mitochondrial respiratory function, DNA CC synthesis and morphology after heat stress. Its main role may be CC maintaining the molecular chaperone SSC1 in a soluble and functional CC state. Also required for the efficient degradation of proteins by CC matrix protease PIM1, independent on its protein remodeling activity. CC {ECO:0000269|PubMed:11231020, ECO:0000269|PubMed:11734006, CC ECO:0000269|PubMed:12023279, ECO:0000269|PubMed:12237310, CC ECO:0000269|PubMed:16460754, ECO:0000269|PubMed:16545993, CC ECO:0000269|PubMed:7500331, ECO:0000269|PubMed:7628444, CC ECO:0000269|PubMed:8830768}. CC -!- SUBUNIT: Homohexamer, forming a ring with a central pore. The hexamer CC is stabilized by high protein concentrations and by ADP or ATP. CC Oligomerization influences ATP hydrolysis activity. CC {ECO:0000269|PubMed:11734006}. CC -!- INTERACTION: CC P33416; P10591: SSA1; NbExp=2; IntAct=EBI-8680, EBI-8591; CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix CC {ECO:0000269|PubMed:14562095, ECO:0000269|PubMed:14576278, CC ECO:0000269|PubMed:8413229, ECO:0000269|PubMed:8830768}. CC -!- INDUCTION: By heat stress. Expressed at a higher level in respiring CC cells than in fermenting cells (at protein level). CC {ECO:0000269|PubMed:16339719, ECO:0000269|PubMed:8413229}. CC -!- DOMAIN: Has 2 AAA ATPase type nucleotide-binding domains (NBDs) per CC monomer. NBD1 is primarily responsible for ATP hydrolysis. NBD2 is CC crucial for oligomerization. CC -!- MISCELLANEOUS: Present with 2990 molecules/cell in log phase SD medium. CC {ECO:0000269|PubMed:14562106}. CC -!- SIMILARITY: Belongs to the ClpA/ClpB 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; L16533; AAC37362.1; -; Unassigned_DNA. DR EMBL; Z68329; CAA92715.1; -; Genomic_DNA. DR EMBL; Z70202; CAA94097.1; -; Genomic_DNA. DR EMBL; BK006938; DAA12098.1; -; Genomic_DNA. DR PIR; S67315; S67315. DR RefSeq; NP_010544.3; NM_001180566.3. DR AlphaFoldDB; P33416; -. DR SMR; P33416; -. DR BioGRID; 32308; 328. DR IntAct; P33416; 2. DR STRING; 4932.YDR258C; -. DR iPTMnet; P33416; -. DR MaxQB; P33416; -. DR PaxDb; 4932-YDR258C; -. DR PeptideAtlas; P33416; -. DR TopDownProteomics; P33416; -. DR EnsemblFungi; YDR258C_mRNA; YDR258C; YDR258C. DR GeneID; 851845; -. DR KEGG; sce:YDR258C; -. DR AGR; SGD:S000002666; -. DR SGD; S000002666; HSP78. DR VEuPathDB; FungiDB:YDR258C; -. DR eggNOG; KOG1051; Eukaryota. DR HOGENOM; CLU_005070_4_0_1; -. DR InParanoid; P33416; -. DR OMA; SKMMQGE; -. DR OrthoDB; 35211at2759; -. DR BioCyc; YEAST:G3O-29829-MONOMER; -. DR BioGRID-ORCS; 851845; 0 hits in 10 CRISPR screens. DR PRO; PR:P33416; -. DR Proteomes; UP000002311; Chromosome IV. DR RNAct; P33416; Protein. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005759; C:mitochondrial matrix; IDA:SGD. DR GO; GO:0005739; C:mitochondrion; HDA:SGD. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:SGD. DR GO; GO:0051787; F:misfolded protein binding; IDA:SGD. DR GO; GO:0034605; P:cellular response to heat; IMP:SGD. DR GO; GO:0000002; P:mitochondrial genome maintenance; IGI:SGD. DR GO; GO:0042026; P:protein refolding; IDA:SGD. DR GO; GO:0050821; P:protein stabilization; IMP:SGD. DR GO; GO:0043335; P:protein unfolding; IMP:SGD. DR CDD; cd00009; AAA; 1. DR CDD; cd19499; RecA-like_ClpB_Hsp104-like; 1. DR Gene3D; 1.10.8.60; -; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 3. DR InterPro; IPR003593; AAA+_ATPase. DR InterPro; IPR003959; ATPase_AAA_core. DR InterPro; IPR019489; Clp_ATPase_C. DR InterPro; IPR001270; ClpA/B. DR InterPro; IPR018368; ClpA/B_CS1. DR InterPro; IPR028299; ClpA/B_CS2. DR InterPro; IPR041546; ClpA/ClpB_AAA_lid. DR InterPro; IPR027417; P-loop_NTPase. DR PANTHER; PTHR11638; ATP-DEPENDENT CLP PROTEASE; 1. DR PANTHER; PTHR11638:SF18; HEAT SHOCK PROTEIN 78, MITOCHONDRIAL; 1. DR Pfam; PF00004; AAA; 1. DR Pfam; PF07724; AAA_2; 1. DR Pfam; PF17871; AAA_lid_9; 1. DR Pfam; PF10431; ClpB_D2-small; 1. DR PRINTS; PR00300; CLPPROTEASEA. DR SMART; SM00382; AAA; 2. DR SMART; SM01086; ClpB_D2-small; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 2. DR PROSITE; PS00870; CLPAB_1; 1. DR PROSITE; PS00871; CLPAB_2; 1. PE 1: Evidence at protein level; KW ATP-binding; Chaperone; Coiled coil; Direct protein sequencing; KW Mitochondrion; Nucleotide-binding; Reference proteome; Repeat; KW Stress response; Transit peptide. FT TRANSIT 1..44 FT /note="Mitochondrion" FT /evidence="ECO:0000255" FT CHAIN 45..811 FT /note="Heat shock protein 78, mitochondrial" FT /id="PRO_0000005500" FT REGION 98..344 FT /note="NBD1" FT REGION 467..658 FT /note="NBD2" FT COILED 345..430 FT /evidence="ECO:0000255" FT BINDING 143..150 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000255" FT BINDING 541..548 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000255" FT MUTAGEN 149 FT /note="K->T: Abolishes ATPase activity." FT /evidence="ECO:0000269|PubMed:11734006" FT MUTAGEN 547 FT /note="K->T: Impairs oligomerization. Reduces ATPase FT activity by 92%." FT /evidence="ECO:0000269|PubMed:11734006" FT CONFLICT 106 FT /note="T -> K (in Ref. 1; AAC37362)" FT /evidence="ECO:0000305" FT CONFLICT 245 FT /note="R -> A (in Ref. 1; AAC37362)" FT /evidence="ECO:0000305" FT CONFLICT 429 FT /note="D -> V (in Ref. 1; AAC37362)" FT /evidence="ECO:0000305" FT CONFLICT 549 FT /note="E -> K (in Ref. 1; AAC37362)" FT /evidence="ECO:0000305" FT CONFLICT 608 FT /note="A -> P (in Ref. 1; AAC37362)" FT /evidence="ECO:0000305" SQ SEQUENCE 811 AA; 91336 MW; FC080D1874877075 CRC64; MLRQATKAPI QKYLQRTQLL RRSTPRIYTI VQCKRSICSF NARPRVANKL LSDIKTNALN EVAISTCALK SSYGLPNFKR TYVQMRMDPN QQPEKPALEQ FGTNLTKLAR DGKLDPVIGR DEEIARAIQI LSRRTKNNPC LIGRAGVGKT ALIDGLAQRI VAGEVPDSLK DKDLVALDLG SLIAGAKYRG EFEERLKKVL EEIDKANGKV IVFIDEVHML LGLGKTDGSM DASNILKPKL ARGLRCISAT TLDEFKIIEK DPALSRRFQP ILLNEPSVSD TISILRGLKE RYEVHHGVRI TDTALVSAAV LSNRYITDRF LPDKAIDLVD EACAVLRLQH ESKPDEIQKL DRAIMKIQIE LESLKKETDP VSVERREALE KDLEMKNDEL NRLTKIWDAE RAEIESIKNA KANLEQARIE LEKCQREGDY TKASELRYSR IPDLEKKVAL SEKSKDGDKV NLLHDSVTSD DISKVVAKMT GIPTETVMKG DKDRLLYMEN SLKERVVGQD EAIAAISDAV RLQRAGLTSE KRPIASFMFL GPTGTGKTEL TKALAEFLFD DESNVIRFDM SEFQEKHTVS RLIGAPPGYV LSESGGQLTE AVRRKPYAVV LFDEFEKAHP DVSKLLLQVL DEGKLTDSLG HHVDFRNTII VMTSNIGQDI LLNDTKLGDD GKIDTATKNK VIEAMKRSYP PEFINRIDDI LVFNRLSKKV LRSIVDIRIA EIQDRLAEKR MKIDLTDEAK DWLTDKGYDQ LYGARPLNRL IHRQILNSMA TFLLKGQIRN GETVRVVVKD TKLVVLPNHE EGEVVEEEAE K //