P31539 (HS104_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Heat shock protein 104

Alternative name(s):
Protein aggregation-remodeling factor HSP104

Gene names

Name:	HSP104
Ordered Locus Names:	YLL026W
ORF Names:	L0948

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces

Protein attributes

Sequence length	908 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Required, in concert with Hsp40 (YDJ1) and Hsp70 (SSA1) and small Hsps (HSP26), for the dissociation, resolubilization and refolding of aggregates of damaged proteins after heat or other environmental stresses. Extracts 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 components of the Hsp70/Hsp40 chaperone system. Substrate binding is ATP-dependent, and release of bound polypeptide is triggered by ATP hydrolysis. Also responsible for the maintenance of prions by dissociating prion fibrils into smaller oligomers, thereby producing transmissible seeds that can infect daughter cells during mitosis and meiosis. Loss of HSP104 can cure yeast cells of the prions [PSI+], [URE3] and [PIN+]. Excess HSP104 can also specifically cure cells of [PSI+]. Ref.6 Ref.7 Ref.8 Ref.10 Ref.11 Ref.12 Ref.14 Ref.17 Ref.19 Ref.20 Ref.21 Ref.23 Ref.27 Ref.31 Ref.36 Ref.39 Ref.40 Ref.41 Ref.44 Ref.45 Ref.47 Ref.48 Ref.49 Ref.50 Ref.54
Enzyme regulation	Inhibited by micromolar concentrations of guanidinium chloride. Inhibits the ATPase activity, but does not dissociate the hexameric protein. Ref.35
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 at NBD2. Interacts with YDJ1. Interacts (via C-terminal DDLD tetrapeptide) with CNS1, CPR7 and STI1 (via TPR repeats); under respiratory growth conditions. Ref.9 Ref.14 Ref.17 Ref.22 Ref.24 Ref.43 Ref.46 Ref.52
Subcellular location	Cytoplasm. Nucleus. Note: Shuttles between the cytoplasm and the nucleus in an importin KAP95- and KAP121-dependent and an exportin XPO1-dependent manner. Accumulation in the nucleus is enhanced by severe heat shock. In the cytoplasm, concentrates on a perivacuolar compartment, the 'insoluble protein deposit' (IPOD), in which terminally aggregated proteins are sequestered. It is also found, to a lesser extend, at a 'juxtanuclear quality control' (JUNQ) compartment, where soluble ubiquitinated misfolded proteins accumulate. Ref.13 Ref.18 Ref.32 Ref.55 Ref.56
Induction	By heat stress dependent on the heat shock transcription factor HSF1 and the general stress transcription factors MSN2 and MSN4. Expressed at a higher level in respiring cells than in fermenting cells. Expressed in stationary phase cells and spores (at protein level). Ref.7 Ref.9 Ref.12 Ref.28 Ref.35 Ref.38
Domain	Has 2 AAA ATPase type nucleotide-binding domains (NBDs) per monomer, a low-affinity, high-turnover site (NBD1) and a high-affinity site (NBD2) with a 300-fold slower rate of hydrolysis. There is allosteric regulation between the 2 sites. ATP binding to NBD1 triggers binding of polypeptides and stimulates ATP hydrolysis at NBD2. Nucleotide binding to NBD2 is crucial for oligomerization. The C-terminal extension is involved in oligomerization.
Miscellaneous	Present with 32800 molecules/cell in log phase SD medium. Ref.33
Sequence similarities	Belongs to the clpA/clpB family.
Biophysicochemical properties	Kinetic parameters: KM=170 µM for ATP (at NBD1) Ref.15 Ref.17 Ref.24 Ref.25 Ref.36 KM=4.7 µM for ATP (at NBD2) Vmax=1.25 nmol/min/µg enzyme for ATP

Ontologies

Keywords
Biological process	Stress response
Cellular component	Cytoplasm Nucleus
Domain	Coiled coil Repeat
Ligand	ATP-binding Nucleotide-binding
Molecular function	Chaperone
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cellular heat acclimation Inferred from mutant phenotype Ref.6. Source: SGD chaperone cofactor-dependent protein refolding Inferred from direct assay Ref.14. Source: SGD inheritance of oxidatively modified proteins involved in replicative cell aging Inferred from mutant phenotype. Source: SGD protein folding in endoplasmic reticulum Inferred from mutant phenotype. Source: SGD protein unfolding Inferred from mutant phenotype Ref.10. Source: SGD trehalose metabolism in response to heat stress Inferred from mutant phenotype. Source: SGD
Cellular component	TRC complex Inferred from direct assay. Source: SGD nucleus Inferred from direct assay Ref.18. Source: SGD
Molecular function	ADP binding Inferred from mutant phenotype Ref.29. Source: SGD ATP binding Inferred from mutant phenotype Ref.29. Source: SGD ATPase activity, coupled Inferred from direct assay Ref.43. Source: SGD chaperone binding Inferred from direct assay Ref.14. Source: SGD unfolded protein binding Inferred from direct assay Ref.43. Source: SGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 908	908	Heat shock protein 104		PRO_0000191212
Regions
	Nucleotide binding	212 – 219	8	ATP 1 Potential
	Nucleotide binding	614 – 621	8	ATP 2 Potential
	Region	167 – 411	245	NBD1
	Region	541 – 731	191	NBD2
	Region	773 – 789	17	Nuclear localization signal
	Region	905 – 908	4	Interaction surface for TPR repeats
	Coiled coil	412 – 536	125	Potential
Amino acid modifications
	Modified residue	87	1	Phosphothreonine Ref.53
	Modified residue	155	1	Phosphoserine Ref.53
	Modified residue	162	1	Phosphothreonine Ref.53
	Modified residue	206	1	Phosphoserine Ref.51 Ref.53
	Modified residue	306	1	Phosphoserine Ref.53
	Modified residue	499	1	Phosphothreonine Ref.53
	Modified residue	535	1	Phosphoserine Ref.53
	Modified residue	577	1	Phosphoserine Ref.53
	Modified residue	578	1	Phosphoserine Ref.53
	Modified residue	768	1	Phosphoserine Ref.53
	Cross-link	620		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.34
Experimental info
	Mutagenesis	184	1	D → A, D, F, N, L, Q or S: Confers resistance to prion-curing by guanidine. Ref.30
	Mutagenesis	184	1	D → K, W or Y: Impairs prion propagation. Ref.30
	Mutagenesis	217	1	G → S: Largely reduces ATP hydrolysis. Alters bud morphology and causes septin mislocalization; when associated with I-499. Ref.15 Ref.24 Ref.37
	Mutagenesis	217	1	G → V: Completely abolishes ATP hydrolysis. Ref.15 Ref.24 Ref.37
	Mutagenesis	218	1	K → T: Abolishes substrate binding. Unable to confer thermotolerance. Reduces ATP hydrolysis by 98%; when associated with T-315. Comletely abolishes ATPase activity; when associated with T-620. Ref.1 Ref.9 Ref.15 Ref.23 Ref.24 Ref.26 Ref.27 Ref.43 Ref.47 Ref.49
	Mutagenesis	257	1	Y → A: Reduces thermotolerance 10-fold. Ref.36
	Mutagenesis	285	1	E → Q in HSP104(TRAP); completely abolishes ATP hydrolysis, but does not affect nucleotide binding, thus keeping HSP104 in an ATP-bound state; when associated with Q-687. Ref.43 Ref.47
	Mutagenesis	315	1	A → T: Reduces ATP hydrolysis by 98%; when associated with T-218. Ref.26
	Mutagenesis	317	1	T → A: Reduces rate of ATP hydrolysis at NBD1 nearly 10-fold. No effect on oligomerization. Ref.25 Ref.49
	Mutagenesis	334	1	R → M: Reduces ATPase activity by 80%. Impairs oligomerization. Ref.46
	Mutagenesis	419	1	R → M: Reduces ATPase activity by 80%. Ref.46
	Mutagenesis	444	1	R → M: Reduces ATPase activity by 80%. Ref.46
	Mutagenesis	462	1	L → R: Impairs prion propagation, but does not affect thermotolerance. Ref.48
	Mutagenesis	495	1	R → M: Increases ATPase activity 3-fold. Ref.46
	Mutagenesis	499	1	T → I: Reduces ATP hydrolysis by 50%. Alters bud morphology and causes septin mislocalization; when associated with S-217. Ref.37
	Mutagenesis	503	1	A → V: Increases basal level of ATPase activity and abolishes stimulation of ATP hydrolysis upon substrate binding. Inhibits growth at 37 degrees Celsius. Ref.26 Ref.37
	Mutagenesis	509	1	A → D: Reduces thermotolerance. Ref.37
	Mutagenesis	557	1	P → L: Impairs prion propagation, but does not affect thermotolerance. Ref.48
	Mutagenesis	619	1	G → V: Impairs oligomerization at low protein concentrations. Ref.15 Ref.24
	Mutagenesis	620	1	K → T: Impairs oligomerization at low protein concentrations. Reduces ATP hydrolysis rate. Unable to confer thermotolerance. Comletely abolishes ATPase activity; when associated with T-218. Ref.1 Ref.9 Ref.15 Ref.23 Ref.24 Ref.27 Ref.43 Ref.47 Ref.49
	Mutagenesis	621	1	T → A: Reduces ATP hydrolysis, but does not affect oligomerization. Ref.24
	Mutagenesis	645	1	E → K: Abolishes the ability to refold aggregated protein in vitro and to provide thermotolerance in vivo. Ref.36
	Mutagenesis	662	1	Y → A or K: Abolishes the ability to refold aggregated protein in vitro and to provide thermotolerance in vivo. Ref.36
	Mutagenesis	662	1	Y → F or W: No effect. Ref.36
	Mutagenesis	687	1	E → Q in HSP104(TRAP); completely abolishes ATP hydrolysis, but does not affect nucleotide binding, thus keeping HSP104 in an ATP-bound state; when associated with Q-285. Ref.43 Ref.47
	Mutagenesis	704	1	D → N: Impairs prion propagation, but does not affect thermotolerance. Ref.48
	Mutagenesis	728	1	N → A: Almost completely abolishes ATP hydrolysis at NBD2, but does not affect nucleotide binding, thus keeping NBD2 in an ATP-bound state. Reduces stimulation of ATP hydrolysis upon substrate binding. Ref.25 Ref.26 Ref.46 Ref.49
	Mutagenesis	765	1	R → M: Can oligomerize in the absence of nucleotides. Ref.46
	Mutagenesis	778	1	K → A in NLS17KA; fails to concentrate in the nucleus; when associated with A-782 and A-789. Ref.56
	Mutagenesis	782	1	K → A in NLS17KA; fails to concentrate in the nucleus; when associated with A-778 and A-789. Ref.56
	Mutagenesis	789	1	K → A in NLS17KA; fails to concentrate in the nucleus; when associated with A-778 and A-782. Ref.56
	Mutagenesis	819	1	Y → W: Site-specific fluorescent probe in an otherwise Trp-less HSP104. Fluorescence of this Trp changes in response to ATP and ADP binding at NBD2. Has no effect on ATP hydrolysis or protein stability. Ref.29
	Mutagenesis	826	1	R → M: Reduces ATP and ADP binding at NBD2 6-fold, but does not affect ATP hydrolysis at NBD2. Reduces catalytic rate at NBD1. Ref.29

Sequences

	Sequence		Length	Mass (Da)
	P31539 [UniParc]. Last modified February 1, 1996. Version 2. Checksum: 4AD0E7E3AF98E318	FASTA	908	102,035
	10 20 30 40 50 60 MNDQTQFTER ALTILTLAQK LASDHQHPQL QPIHILAAFI ETPEDGSVPY LQNLIEKGRY 70 80 90 100 110 120 DYDLFKKVVN RNLVRIPQQQ PAPAEITPSY ALGKVLQDAA KIQKQQKDSF IAQDHILFAL 130 140 150 160 170 180 FNDSSIQQIF KEAQVDIEAI KQQALELRGN TRIDSRGADT NTPLEYLSKY AIDMTEQARQ 190 200 210 220 230 240 GKLDPVIGRE EEIRSTIRVL ARRIKSNPCL IGEPGIGKTA IIEGVAQRII DDDVPTILQG 250 260 270 280 290 300 AKLFSLDLAA LTAGAKYKGD FEERFKGVLK EIEESKTLIV LFIDEIHMLM GNGKDDAANI 310 320 330 340 350 360 LKPALSRGQL KVIGATTNNE YRSIVEKDGA FERRFQKIEV AEPSVRQTVA ILRGLQPKYE 370 380 390 400 410 420 IHHGVRILDS ALVTAAQLAK RYLPYRRLPD SALDLVDISC AGVAVARDSK PEELDSKERQ 430 440 450 460 470 480 LQLIQVEIKA LERDEDADST TKDRLKLARQ KEASLQEELE PLRQRYNEEK HGHEELTQAK 490 500 510 520 530 540 KKLDELENKA LDAERRYDTA TAADLRYFAI PDIKKQIEKL EDQVAEEERR AGANSMIQNV 550 560 570 580 590 600 VDSDTISETA ARLTGIPVKK LSESENEKLI HMERDLSSEV VGQMDAIKAV SNAVRLSRSG 610 620 630 640 650 660 LANPRQPASF LFLGLSGSGK TELAKKVAGF LFNDEDMMIR VDCSELSEKY AVSKLLGTTA 670 680 690 700 710 720 GYVGYDEGGF LTNQLQYKPY SVLLFDEVEK AHPDVLTVML QMLDDGRITS GQGKTIDCSN 730 740 750 760 770 780 CIVIMTSNLG AEFINSQQGS KIQESTKNLV MGAVRQHFRP EFLNRISSIV IFNKLSRKAI 790 800 810 820 830 840 HKIVDIRLKE IEERFEQNDK HYKLNLTQEA KDFLAKYGYS DDMGARPLNR LIQNEILNKL 850 860 870 880 890 900 ALRILKNEIK DKETVNVVLK KGKSRDENVP EEAEECLEVL PNHEATIGAD TLGDDDNEDS MEIDDDLD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Hsp104 is a highly conserved protein with two essential nucleotide-binding sites." Parsell D.A., Sanchez Y., Stitzel J.D., Lindquist S.L. Nature 353:270-273(1991) [PubMed: 1896074] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], MUTAGENESIS OF LYS-218 AND LYS-620. Strain: ATCC 26109 / X2180 / NCYC 826.
[2]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome XII." Johnston M., Hillier L.W., Riles L., Albermann K., Andre B., Ansorge W., Benes V., Brueckner M., Delius H., Dubois E., Duesterhoeft A., Entian K.-D., Floeth M., Goffeau A., Hebling U., Heumann K., Heuss-Neitzel D., Hilbert H. , Hilger F., Kleine K., Koetter P., Louis E.J., Messenguy F., Mewes H.-W., Miosga T., Moestl D., Mueller-Auer S., Nentwich U., Obermaier B., Piravandi E., Pohl T.M., Portetelle D., Purnelle B., Rechmann S., Rieger M., Rinke M., Rose M., Scharfe M., Scherens B., Scholler P., Schwager C., Schwarz S., Underwood A.P., Urrestarazu L.A., Vandenbol M., Verhasselt P., Vierendeels F., Voet M., Volckaert G., Voss H., Wambutt R., Wedler E., Wedler H., Zimmermann F.K., Zollner A., Hani J., Hoheisel J.D. Nature 387:87-90(1997) [PubMed: 9169871] [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]	"Approaching a complete repository of sequence-verified protein-encoding clones for Saccharomyces cerevisiae." Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F., Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J., Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J. , Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D., LaBaer J. Genome Res. 17:536-543(2007) [PubMed: 17322287] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[5]	"The sequence of 32kb on the left arm of yeast chromosome XII reveals six known genes, a new member of the seripauperins family and a new ABC transporter homologous to the human multidrug resistance protein." Purnelle B., Goffeau A. Yeast 13:183-188(1997) [PubMed: 9046100] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 749-908. Strain: ATCC 204508 / S288c.
[6]	"HSP104 required for induced thermotolerance." Sanchez Y., Lindquist S.L. Science 248:1112-1115(1990) [PubMed: 2188365] [Abstract] Cited for: FUNCTION.
[7]	"Hsp104 is required for tolerance to many forms of stress." Sanchez Y., Taulien J., Borkovich K.A., Lindquist S.L. EMBO J. 11:2357-2364(1992) [PubMed: 1600951] [Abstract] Cited for: FUNCTION, INDUCTION.
[8]	"Genetic evidence for a functional relationship between Hsp104 and Hsp70." Sanchez Y., Parsell D.A., Taulien J., Vogel J.L., Craig E.A., Lindquist S.L. J. Bacteriol. 175:6484-6491(1993) [PubMed: 8407824] [Abstract] Cited for: FUNCTION.
[9]	"Saccharomyces cerevisiae Hsp104 protein. Purification and characterization of ATP-induced structural changes." Parsell D.A., Kowal A.S., Lindquist S.L. J. Biol. Chem. 269:4480-4487(1994) [PubMed: 8308017] [Abstract] Cited for: INDUCTION, MUTAGENESIS OF LYS-218 AND LYS-620, SUBUNIT, ELECTRON MICROSCOPY.
[10]	"Protein disaggregation mediated by heat-shock protein Hsp104." Parsell D.A., Kowal A.S., Singer M.A., Lindquist S.L. Nature 372:475-478(1994) [PubMed: 7984243] [Abstract] Cited for: FUNCTION.
[11]	"Role of the chaperone protein Hsp104 in propagation of the yeast prion-like factor [psi+]." Chernoff Y.O., Lindquist S.L., Ono B., Inge-Vechtomov S.G., Liebman S.W. Science 268:880-884(1995) [PubMed: 7754373] [Abstract] Cited for: FUNCTION IN PRION MAINTENANCE.
[12]	"Heat-shock protein 104 expression is sufficient for thermotolerance in yeast." Lindquist S.L., Kim G. Proc. Natl. Acad. Sci. U.S.A. 93:5301-5306(1996) [PubMed: 8643570] [Abstract] Cited for: FUNCTION, INDUCTION.
[13]	"Hsp104 responds to heat and oxidative stress with different intracellular localization in Saccharomyces cerevisiae." Fujita K., Kawai R., Iwahashi H., Komatsu Y. Biochem. Biophys. Res. Commun. 248:542-547(1998) [PubMed: 9703962] [Abstract] Cited for: SUBCELLULAR LOCATION.
[14]	"Hsp104, Hsp70, and Hsp40: a novel chaperone system that rescues previously aggregated proteins." Glover J.R., Lindquist S.L. Cell 94:73-82(1998) [PubMed: 9674429] [Abstract] Cited for: FUNCTION, INTERACTION WITH YDJ1.
[15]	"The ATPase activity of Hsp104, effects of environmental conditions and mutations." Schirmer E.C., Queitsch C., Kowal A.S., Parsell D.A., Lindquist S.L. J. Biol. Chem. 273:15546-15552(1998) [PubMed: 9624144] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF GLY-217; LYS-218; GLY-619 AND LYS-620.
[16]	Erratum Schirmer E.C., Queitsch C., Kowal A.S., Parsell D.A., Lindquist S.L. J. Biol. Chem. 273:19922-19922(1998)
[17]	"Purification and properties of Hsp104 from yeast." Schirmer E.C., Lindquist S.L. Methods Enzymol. 290:430-444(1998) [PubMed: 9534180] [Abstract] Cited for: FUNCTION, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES.
[18]	"Direct evidence for the intracellular localization of Hsp104 in Saccharomyces cerevisiae by immunoelectron microscopy." Kawai R., Fujita K., Iwahashi H., Komatsu Y. Cell Stress Chaperones 4:46-53(1999) [PubMed: 10467108] [Abstract] Cited for: SUBCELLULAR LOCATION.
[19]	"Rnq1: an epigenetic modifier of protein function in yeast." Sondheimer N., Lindquist S.L. Mol. Cell 5:163-172(2000) [PubMed: 10678178] [Abstract] Cited for: FUNCTION IN PRION PROPAGATION.
[20]	"[URE3] prion propagation in Saccharomyces cerevisiae: requirement for chaperone Hsp104 and curing by overexpressed chaperone Ydj1p." Moriyama H., Edskes H.K., Wickner R.B. Mol. Cell. Biol. 20:8916-8922(2000) [PubMed: 11073991] [Abstract] Cited for: FUNCTION IN PRION PROPAGATION.
[21]	"Guanidine hydrochloride inhibits Hsp104 activity in vivo: a possible explanation for its effect in curing yeast prions." Jung G., Masison D.C. Curr. Microbiol. 43:7-10(2001) [PubMed: 11375656] [Abstract] Cited for: FUNCTION IN PRION PROPAGATION.
[22]	"Hsp104 interacts with Hsp90 cochaperones in respiring yeast." Abbas-Terki T., Donze O., Briand P.-A., Picard D. Mol. Cell. Biol. 21:7569-7575(2001) [PubMed: 11604493] [Abstract] Cited for: INTERACTION WITH CNS1; CPR7 AND STI1.
[23]	"The elimination of the yeast [PSI+] prion by guanidine hydrochloride is the result of Hsp104 inactivation." Ferreira P.C., Ness F., Edwards S.R., Cox B.S., Tuite M.F. Mol. Microbiol. 40:1357-1369(2001) [PubMed: 11442834] [Abstract] Cited for: FUNCTION IN PRION PROPAGATION, MUTAGENESIS OF LYS-218 AND LYS-620.
[24]	"Subunit interactions influence the biochemical and biological properties of Hsp104." Schirmer E.C., Ware D.M., Queitsch C., Kowal A.S., Lindquist S.L. Proc. Natl. Acad. Sci. U.S.A. 98:914-919(2001) [PubMed: 11158570] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, MUTAGENESIS OF GLY-217; LYS-218; GLY-619; LYS-620 AND THR-621.
[25]	"Cooperative kinetics of both Hsp104 ATPase domains and interdomain communication revealed by AAA sensor-1 mutants." Hattendorf D.A., Lindquist S.L. EMBO J. 21:12-21(2002) [PubMed: 11782421] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF THR-317 AND ASN-728.
[26]	"Defining a pathway of communication from the C-terminal peptide binding domain to the N-terminal ATPase domain in a AAA protein." Cashikar A.G., Schirmer E.C., Hattendorf D.A., Glover J.R., Ramakrishnan M.S., Ware D.M., Lindquist S.L. Mol. Cell 9:751-760(2002) [PubMed: 11983167] [Abstract] Cited for: SUBSTRATE-BINDING, MUTAGENESIS OF LYS-218; ALA-315; ALA-503 AND ASN-728.
[27]	"Guanidine hydrochloride inhibits the generation of prion 'seeds' but not prion protein aggregation in yeast." Ness F., Ferreira P.C., Cox B.S., Tuite M.F. Mol. Cell. Biol. 22:5593-5605(2002) [PubMed: 12101251] [Abstract] Cited for: FUNCTION IN PRION PROPAGATION, MUTAGENESIS OF LYS-218 AND LYS-620.
[28]	"HSF and Msn2/4p can exclusively or cooperatively activate the yeast HSP104 gene." Grably M.R., Stanhill A., Tell O., Engelberg D. Mol. Microbiol. 44:21-35(2002) [PubMed: 11967066] [Abstract] Cited for: INDUCTION.
[29]	"Analysis of the AAA sensor-2 motif in the C-terminal ATPase domain of Hsp104 with a site-specific fluorescent probe of nucleotide binding." Hattendorf D.A., Lindquist S.L. Proc. Natl. Acad. Sci. U.S.A. 99:2732-2737(2002) [PubMed: 11867765] [Abstract] Cited for: MUTAGENESIS OF TYR-819 AND ARG-826, ATP-BINDING.
[30]	"Amino acid residue 184 of yeast Hsp104 chaperone is critical for prion-curing by guanidine, prion propagation, and thermotolerance." Jung G., Jones G., Masison D.C. Proc. Natl. Acad. Sci. U.S.A. 99:9936-9941(2002) [PubMed: 12105276] [Abstract] Cited for: MUTAGENESIS OF ASP-184.
[31]	"Yeast [PSI+] prion aggregates are formed by small Sup35 polymers fragmented by Hsp104." Kryndushkin D.S., Alexandrov I.M., Ter-Avanesyan M.D., Kushnirov V.V. J. Biol. Chem. 278:49636-49643(2003) [PubMed: 14507919] [Abstract] Cited for: FUNCTION IN PRION FRAGMENTATION.
[32]	"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: 14562095] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
[33]	"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: 14562106] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[34]	"A subset of membrane-associated proteins is ubiquitinated in response to mutations in the endoplasmic reticulum degradation machinery." Hitchcock A.L., Auld K., Gygi S.P., Silver P.A. Proc. Natl. Acad. Sci. U.S.A. 100:12735-12740(2003) [PubMed: 14557538] [Abstract] Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-620, MASS SPECTROMETRY.
[35]	"The prion curing agent guanidinium chloride specifically inhibits ATP hydrolysis by Hsp104." Grimminger V., Richter K., Imhof A., Buchner J., Walter S. J. Biol. Chem. 279:7378-7383(2004) [PubMed: 14668331] [Abstract] Cited for: ENZYME REGULATION.
[36]	"Evidence for an unfolding/threading mechanism for protein disaggregation by Saccharomyces cerevisiae Hsp104." Lum R., Tkach J.M., Vierling E., Glover J.R. J. Biol. Chem. 279:29139-29146(2004) [PubMed: 15128736] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF TYR-257; GLU-645 AND TYR-662, BIOPHYSICOCHEMICAL PROPERTIES.
[37]	"Dominant gain-of-function mutations in Hsp104p reveal crucial roles for the middle region." Schirmer E.C., Homann O.R., Kowal A.S., Lindquist S.L. Mol. Biol. Cell 15:2061-2072(2004) [PubMed: 14978213] [Abstract] Cited for: MUTAGENESIS OF GLY-217; THR-499; ALA-503 AND ALA-509.
[38]	"Upregulation of the Hsp104 chaperone at physiological temperature during recovery from thermal insult." Seppae L., Haenninen A.-L., Makarow M. Mol. Microbiol. 52:217-225(2004) [PubMed: 15049822] [Abstract] Cited for: INDUCTION.
[39]	"Hsp104 catalyzes formation and elimination of self-replicating Sup35 prion conformers." Shorter J., Lindquist S.L. Science 304:1793-1797(2004) [PubMed: 15155912] [Abstract] Cited for: FUNCTION IN PRION PROPAGATION.
[40]	"Disassembling protein aggregates in the yeast cytosol. The cooperation of Hsp26 with Ssa1 and Hsp104." Haslbeck M., Miess A., Stromer T., Walter S., Buchner J. J. Biol. Chem. 280:23861-23868(2005) [PubMed: 15843375] [Abstract] Cited for: FUNCTION.
[41]	"A chaperone pathway in protein disaggregation. Hsp26 alters the nature of protein aggregates to facilitate reactivation by Hsp104." Cashikar A.G., Duennwald M., Lindquist S.L. J. Biol. Chem. 280:23869-23875(2005) [PubMed: 15845535] [Abstract] Cited for: FUNCTION.
[42]	Erratum Cashikar A.G., Duennwald M., Lindquist S.L. J. Biol. Chem. 281:8996-8996(2006)
[43]	"Substrate binding to the molecular chaperone Hsp104 and its regulation by nucleotides." Boesl B., Grimminger V., Walter S. J. Biol. Chem. 280:38170-38176(2005) [PubMed: 16135516] [Abstract] Cited for: SUBUNIT, MUTAGENESIS OF LYS-218; GLU-285; LYS-620 AND GLU-687.
[44]	"Yeast prion-protein, sup35, fibril formation proceeds by addition and substraction of oligomers." Narayanan S., Walter S., Reif B. ChemBioChem 7:757-765(2006) [PubMed: 16570324] [Abstract] Cited for: FUNCTION IN PRION DISASSEMBLY.
[45]	"Destruction or potentiation of different prions catalyzed by similar Hsp104 remodeling activities." Shorter J., Lindquist S.L. Mol. Cell 23:425-438(2006) [PubMed: 16885031] [Abstract] Cited for: FUNCTION IN PRION DISASSEMBLY.
[46]	"Atypical AAA+ subunit packing creates an expanded cavity for disaggregation by the protein-remodeling factor Hsp104." Wendler P., Shorter J., Plisson C., Cashikar A.G., Lindquist S.L., Saibil H.R. Cell 131:1366-1377(2007) [PubMed: 18160044] [Abstract] Cited for: SUBUNIT, ELECTRON MICROSCOPY, MUTAGENESIS OF ARG-334; ARG-419; ARG-444; ARG-495; ASN-728 AND ARG-765.
[47]	"Processing of proteins by the molecular chaperone Hsp104." Schaupp A., Marcinowski M., Grimminger V., Boesl B., Walter S. J. Mol. Biol. 370:674-686(2007) [PubMed: 17543332] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF LYS-218; GLU-285; LYS-620 AND GLU-687.
[48]	"Channel mutations in Hsp104 hexamer distinctively affect thermotolerance and prion-specific propagation." Kurahashi H., Nakamura Y. Mol. Microbiol. 63:1669-1683(2007) [PubMed: 17367387] [Abstract] Cited for: FUNCTION IN PRION PROPAGATION, MUTAGENESIS OF LEU-462; PRO-557 AND ASP-704.
[49]	"Asymmetric deceleration of ClpB or Hsp104 ATPase activity unleashes protein-remodeling activity." Doyle S.M., Shorter J., Zolkiewski M., Hoskins J.R., Lindquist S.L., Wickner S. Nat. Struct. Mol. Biol. 14:114-122(2007) [PubMed: 17259993] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF LYS-218; THR-317; LYS-620 AND ASN-728.
[50]	"Hsp104-dependent remodeling of prion complexes mediates protein-only inheritance." Satpute-Krishnan P., Langseth S.X., Serio T.R. PLoS Biol. 5:251-262(2007) [PubMed: 17253904] [Abstract] Cited for: FUNCTION IN PRION PROPAGATION.
[51]	"Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases." Smolka M.B., Albuquerque C.P., Chen S.H., Zhou H. Proc. Natl. Acad. Sci. U.S.A. 104:10364-10369(2007) [PubMed: 17563356] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-206, MASS SPECTROMETRY.
[52]	"The C-terminal extension of Saccharomyces cerevisiae Hsp104 plays a role in oligomer assembly." Mackay R.G., Helsen C.W., Tkach J.M., Glover J.R. Biochemistry 47:1918-1927(2008) [PubMed: 18197703] [Abstract] Cited for: INTERACTION WITH CPR7.
[53]	"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: 18407956] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-87; SER-155; THR-162; SER-206; SER-306; THR-499; SER-535; SER-577; SER-578 AND SER-768, MASS SPECTROMETRY.
[54]	"Substrate threading through the central pore of the Hsp104 chaperone as a common mechanism for protein disaggregation and prion propagation." Tessarz P., Mogk A., Bukau B. Mol. Microbiol. 68:87-97(2008) [PubMed: 18312264] [Abstract] Cited for: FUNCTION.
[55]	"Misfolded proteins partition between two distinct quality control compartments." Kaganovich D., Kopito R., Frydman J. Nature 454:1088-1095(2008) [PubMed: 18756251] [Abstract] Cited for: SUBCELLULAR LOCATION.
[56]	"Nucleocytoplasmic trafficking of the molecular chaperone Hsp104 in unstressed and heat-shocked cells." Tkach J.M., Glover J.R. Traffic 9:39-56(2008) [PubMed: 17973656] [Abstract] Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-778; LYS-782 AND LYS-789.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M67479 Genomic DNA. Translation: AAA50477.1. Z73131 Genomic DNA. Translation: CAA97475.1. Z73130 Genomic DNA. Translation: CAA97474.1. AY693002 Genomic DNA. Translation: AAT93021.1. X97560 Genomic DNA. Translation: CAA66164.1. BK006945 Genomic DNA. Translation: DAA09294.1.
PIR	S61476.
RefSeq	NP_013074.1. NM_001181846.1.
3D structure databases
ProteinModelPortal	P31539.
SMR	P31539. Positions 5-869.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-2252N.
IntAct	P31539. 19 interactions.
MINT	MINT-530773.
STRING	P31539.
2D gel databases
SWISS-2DPAGE	P31539.
Proteomic databases
PeptideAtlas	P31539.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblFungi	YLL026W; YLL026W; YLL026W.
GeneID	850633.
KEGG	sce:YLL026W.
NMPDR	fig|4932.3.peg.4065.
Organism-specific databases
CYGD	YLL026w.
SGD	S000003949. HSP104.
Phylogenomic databases
eggNOG	fuNOG04091.
GeneTree	EFGT00050000005150.
HOGENOM	HBG413133.
OMA	QPLANAM.
OrthoDB	EOG4T4H3H.
Gene expression databases
ArrayExpress	P31539.
Genevestigator	P31539.
GermOnline	YLL026W. Saccharomyces cerevisiae.
Family and domain databases
InterPro	IPR003593. ATPase_AAA+_core. IPR013093. ATPase_AAA-2. IPR003959. ATPase_AAA_core. IPR018368. Chaperonin_ClpA/B_CS. IPR001270. Chaprnin_ClpA/B. IPR019489. Clp_ATPase_C. IPR004176. Clp_N. IPR023150. Dbl_Clp-N. [Graphical view]
Gene3D	G3DSA:1.10.1780.10. Dbl_Clp-N. 1 hit.
Pfam	PF00004. AAA. 1 hit. PF07724. AAA_2. 1 hit. PF02861. Clp_N. 2 hits. 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	966553.

Entry information

Entry name

HS104_YEAST

Accession

Primary (citable) accession number: P31539
Secondary accession number(s): D6VXX8

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	February 1, 1996
Last modified:	January 25, 2012
This is version 113 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program