P33416 (HSP78_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Heat shock protein 78, mitochondrial

Gene names

Name:	HSP78
Ordered Locus Names:	YDR258C
ORF Names:	YD9320A.08C

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Fungi › Dikarya › Ascomycota › saccharomyceta › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces › Saccharomyces cerevisiae

Protein attributes

Sequence length	811 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Required, in concert with mitochondrial Hsp70 (SSC1), for the dissociation, resolubilization and refolding of aggregates of damaged proteins in the mitochondrial matrix after heat stress. May extract proteins from aggregates by unfolding and threading them in an ATP-dependent process through the axial channel of the protein hexamer, after which they can be refolded by the Hsp70 chaperone system. Required for resumption of mitochondrial respiratory function, DNA synthesis and morphology after heat stress. Its main role may be maintaining the molecular chaperone SSC1 in a soluble and functional state. Also required for the efficient degradation of proteins by matrix protease PIM1, independent on its protein remodeling activity. Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.15 Ref.16
Subunit structure	Homohexamer, forming a ring with a central pore. The hexamer is stabilized by high protein concentrations and by ADP or ATP. Oligomerization influences ATP hydrolysis activity. Ref.8
Subcellular location	Mitochondrion matrix Ref.1 Ref.7 Ref.11 Ref.13.
Induction	By heat stress. Expressed at a higher level in respiring cells than in fermenting cells (at protein level). Ref.1 Ref.14
Domain	Has 2 AAA ATPase type nucleotide-binding domains (NBDs) per monomer. NBD1 is primarily responsible for ATP hydrolysis. NBD2 is crucial for oligomerization.
Miscellaneous	Present with 2990 molecules/cell in log phase SD medium.
Sequence similarities	Belongs to the clpA/clpB family.

Ontologies

Keywords
Biological process	Stress response
Cellular component	Mitochondrion
Domain	Coiled coil Repeat Transit peptide
Ligand	ATP-binding Nucleotide-binding
Molecular function	Chaperone
PTM	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to heat Inferred from mutant phenotype Ref.5Ref.7. Source: SGD mitochondrial genome maintenance Inferred from genetic interaction Ref.6. Source: SGD positive regulation of mitochondrial translation in response to stress Inferred from mutant phenotype Ref.7. Source: SGD protein import into mitochondrial matrix Inferred from genetic interaction Ref.5. Source: SGD protein refolding Inferred from direct assay Ref.8. Source: SGD protein stabilization Inferred from mutant phenotype Ref.16. Source: SGD protein unfolding Inferred from mutant phenotype Ref.16. Source: SGD
Cellular_component	mitochondrial matrix Inferred from direct assay Ref.1. Source: SGD
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ATPase activity Inferred from direct assay Ref.8. Source: SGD misfolded protein binding Inferred from direct assay Ref.5. Source: SGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 44	44	Mitochondrion Potential
	Chain	45 – 811	767	Heat shock protein 78, mitochondrial		PRO_0000005500
Regions
	Nucleotide binding	143 – 150	8	ATP 1 Potential
	Nucleotide binding	541 – 548	8	ATP 2 Potential
	Region	98 – 344	247	NBD1
	Region	467 – 658	192	NBD2
	Coiled coil	345 – 430	86	Potential
Amino acid modifications
	Modified residue	406	1	Phosphoserine Ref.17
Experimental info
	Mutagenesis	149	1	K → T: Abolishes ATPase activity. Ref.8
	Mutagenesis	547	1	K → T: Impairs oligomerization. Reduces ATPase activity by 92%. Ref.8
	Sequence conflict	106	1	T → K in AAC37362. Ref.1
	Sequence conflict	245	1	R → A in AAC37362. Ref.1
	Sequence conflict	429	1	D → V in AAC37362. Ref.1
	Sequence conflict	549	1	E → K in AAC37362. Ref.1
	Sequence conflict	608	1	A → P in AAC37362. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P33416 [UniParc]. Last modified May 23, 2003. Version 2. Checksum: FC080D1874877075	FASTA	811	91,336
	10 20 30 40 50 60 MLRQATKAPI QKYLQRTQLL RRSTPRIYTI VQCKRSICSF NARPRVANKL LSDIKTNALN 70 80 90 100 110 120 EVAISTCALK SSYGLPNFKR TYVQMRMDPN QQPEKPALEQ FGTNLTKLAR DGKLDPVIGR 130 140 150 160 170 180 DEEIARAIQI LSRRTKNNPC LIGRAGVGKT ALIDGLAQRI VAGEVPDSLK DKDLVALDLG 190 200 210 220 230 240 SLIAGAKYRG EFEERLKKVL EEIDKANGKV IVFIDEVHML LGLGKTDGSM DASNILKPKL 250 260 270 280 290 300 ARGLRCISAT TLDEFKIIEK DPALSRRFQP ILLNEPSVSD TISILRGLKE RYEVHHGVRI 310 320 330 340 350 360 TDTALVSAAV LSNRYITDRF LPDKAIDLVD EACAVLRLQH ESKPDEIQKL DRAIMKIQIE 370 380 390 400 410 420 LESLKKETDP VSVERREALE KDLEMKNDEL NRLTKIWDAE RAEIESIKNA KANLEQARIE 430 440 450 460 470 480 LEKCQREGDY TKASELRYSR IPDLEKKVAL SEKSKDGDKV NLLHDSVTSD DISKVVAKMT 490 500 510 520 530 540 GIPTETVMKG DKDRLLYMEN SLKERVVGQD EAIAAISDAV RLQRAGLTSE KRPIASFMFL 550 560 570 580 590 600 GPTGTGKTEL TKALAEFLFD DESNVIRFDM SEFQEKHTVS RLIGAPPGYV LSESGGQLTE 610 620 630 640 650 660 AVRRKPYAVV LFDEFEKAHP DVSKLLLQVL DEGKLTDSLG HHVDFRNTII VMTSNIGQDI 670 680 690 700 710 720 LLNDTKLGDD GKIDTATKNK VIEAMKRSYP PEFINRIDDI LVFNRLSKKV LRSIVDIRIA 730 740 750 760 770 780 EIQDRLAEKR MKIDLTDEAK DWLTDKGYDQ LYGARPLNRL IHRQILNSMA TFLLKGQIRN 790 800 810 GETVRVVVKD TKLVVLPNHE EGEVVEEEAE K

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"HSP78 encodes a yeast mitochondrial heat shock protein in the Clp family of ATP-dependent proteases." Leonhardt S.A., Fearon K., Danese P.N., Mason T.L. Mol. Cell. Biol. 13:6304-6313(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], SUBCELLULAR LOCATION, INDUCTION.
[2]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome IV." Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G., Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C., Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F., Delaveau T. , del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M., Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T., Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C., Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S., Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., Paulin L., Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., Prydz H., Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., Rieger M., Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., Scharfe M., Schmidt E.R., Schneider C., Scholler P., Schwarz S., Soler-Mira A., Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., Volckaert G., Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., Harris D.E., Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., Gentles S., Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., Niblett D., Odell C., Oliver K., Rajandream M.A., Richards C., Shore L., Walsh S.V., Barrell B.G., Dietrich F.S., Mulligan J.T., Allen E., Araujo R., Aviles E., Berno A., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M., Hunicke-Smith S., Hyman R.W., Komp C., Lashkari D., Lew H., Lin D., Mosedale D., Nakahara K., Namath A., Oefner P., Oh C., Petel F.X., Roberts D., Schramm S., Schroeder M., Shogren T., Shroff N., Winant A., Yelton M.A., Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R., Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., Greco T., Hallsworth K., Hawkins J., Hillier L.W., Jier M., Johnson D., Johnston L., Kirsten J., Kucaba T., Langston Y., Latreille P., Le T., Mardis E., Menezes S., Miller N., Nhan M., Pauley A., Peluso D., Rifkin L., Riles L., Taich A., Trevaskis E., Vignati D., Wilcox L., Wohldman P., Vaudin M., Wilson R., Waterston R., Albermann K., Hani J., Heumann K., Kleine K., Mewes H.-W., Zollner A., Zaccaria P. Nature 387:75-78(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204511 / S288c / AB972.
[3]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[4]	"Mitochondrial Hsp78, a member of the Clp/Hsp100 family in Saccharomyces cerevisiae, cooperates with Hsp70 in protein refolding." Krzewska J., Langer T., Liberek K. FEBS Lett. 489:92-96(2001) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 85-90, FUNCTION.
[5]	"Hsp78, a Clp homologue within mitochondria, can substitute for chaperone functions of mt-hsp70." Schmitt M., Neupert W., Langer T. EMBO J. 14:3434-3444(1995) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[6]	"The mitochondrial ClpB homolog Hsp78 cooperates with matrix Hsp70 in maintenance of mitochondrial function." Moczko M., Schoenfisch B., Voos W., Pfanner N., Rassow J. J. Mol. Biol. 254:538-543(1995) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[7]	"The molecular chaperone Hsp78 confers compartment-specific thermotolerance to mitochondria." Schmitt M., Neupert W., Langer T. J. Cell Biol. 134:1375-1386(1996) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[8]	"Importance of two ATP-binding sites for oligomerization, ATPase activity and chaperone function of mitochondrial Hsp78 protein." Krzewska J., Konopa G., Liberek K. J. Mol. Biol. 314:901-910(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT, ELECTRON MICROSCOPY, MUTAGENESIS OF LYS-149 AND LYS-547.
[9]	"A bichaperone (Hsp70-Hsp78) system restores mitochondrial DNA synthesis following thermal inactivation of Mip1p polymerase." Germaniuk A., Liberek K., Marszalek J. J. Biol. Chem. 277:27801-27808(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"The ClpB homolog Hsp78 is required for the efficient degradation of proteins in the mitochondrial matrix." Roettgers K., Zufall N., Guiard B., Voos W. J. Biol. Chem. 277:45829-45837(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PROTEIN DEGRADATION.
[11]	"Global analysis of protein localization in budding yeast." Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., Weissman J.S., O'Shea E.K. Nature 425:686-691(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
[12]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed] [Europe PMC] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[13]	"The proteome of Saccharomyces cerevisiae mitochondria." Sickmann A., Reinders J., Wagner Y., Joppich C., Zahedi R.P., Meyer H.E., Schoenfisch B., Perschil I., Chacinska A., Guiard B., Rehling P., Pfanner N., Meisinger C. Proc. Natl. Acad. Sci. U.S.A. 100:13207-13212(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. Strain: ATCC 76625 / YPH499.
[14]	"Regulation and recovery of functions of Saccharomyces cerevisiae chaperone BiP/Kar2p after thermal insult." Seppae L., Makarow M. Eukaryot. Cell 4:2008-2016(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[15]	"Hsp78 chaperone functions in restoration of mitochondrial network following heat stress." Lewandowska A., Gierszewska M., Marszalek J., Liberek K. Biochim. Biophys. Acta 1763:141-151(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[16]	"The disaggregation activity of the mitochondrial ClpB homolog Hsp78 maintains Hsp70 function during heat stress." von Janowsky B., Major T., Knapp K., Voos W. J. Mol. Biol. 357:793-807(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[17]	"A multidimensional chromatography technology for in-depth phosphoproteome analysis." Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H. Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-406, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L16533 Unassigned DNA. Translation: AAC37362.1. Z68329 Genomic DNA. Translation: CAA92715.1. Z70202 Genomic DNA. Translation: CAA94097.1. BK006938 Genomic DNA. Translation: DAA12098.1.
PIR	S67315.
RefSeq	NP_010544.3. NM_001180566.3.
3D structure databases
ProteinModelPortal	P33416.
SMR	P33416. Positions 97-794.
ModBase	Search...
Protein-protein interaction databases
IntAct	P33416. 2 interactions.
STRING	4932.YDR258C.
Proteomic databases
PaxDb	P33416.
PeptideAtlas	P33416.
PRIDE	P33416.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblFungi	YDR258C; YDR258C; YDR258C.
GeneID	851845.
KEGG	sce:YDR258C. sce:YDR261W-B.
Organism-specific databases
CYGD	YDR258c.
SGD	S000002666. HSP78.
Phylogenomic databases
eggNOG	COG0542.
GeneTree	ENSGT00390000012961.
HOGENOM	HOG000218211.
OMA	RAGLHSH.
OrthoDB	EOG4RR9RF.
Gene expression databases
Genevestigator	P33416.
GermOnline	YDR258C. Saccharomyces cerevisiae.
Family and domain databases
InterPro	IPR003593. AAA+_ATPase. IPR013093. ATPase_AAA-2. IPR003959. ATPase_AAA_core. IPR018368. Chaperonin_ClpA/B_CS. IPR001270. Chaprnin_ClpA/B. IPR019489. Clp_ATPase_C. [Graphical view]
Pfam	PF00004. AAA. 1 hit. PF07724. AAA_2. 1 hit. PF10431. ClpB_D2-small. 1 hit. [Graphical view]
PRINTS	PR00300. CLPPROTEASEA.
SMART	SM00382. AAA. 2 hits. SM01086. ClpB_D2-small. 1 hit. [Graphical view]
PROSITE	PS00870. CLPAB_1. 1 hit. PS00871. CLPAB_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	969757.

Entry information

Entry name

HSP78_YEAST

Accession

Primary (citable) accession number: P33416
Secondary accession number(s): D6VSN8, Q12137

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	May 23, 2003
Last modified:	May 1, 2013
This is version 122 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program