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Protein

Heat shock protein 104

Gene

HSP104

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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+].25 Publications

Miscellaneous

Present with 32800 molecules/cell in log phase SD medium.1 Publication

Enzyme regulationi

Inhibited by micromolar concentrations of guanidinium chloride. Inhibits the ATPase activity, but does not dissociate the hexameric protein.1 Publication

Kineticsi

  1. KM=170 µM for ATP (at NBD1)5 Publications
  2. KM=4.7 µM for ATP (at NBD2)5 Publications
  1. Vmax=1.25 nmol/min/µg enzyme for ATP5 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi212 – 219ATP 1Sequence analysis8
Nucleotide bindingi614 – 621ATP 2Sequence analysis8

GO - Molecular functioni

  • ADP binding Source: SGD
  • ATPase activity, coupled Source: SGD
  • ATP binding Source: SGD
  • chaperone binding Source: SGD
  • identical protein binding Source: IntAct
  • unfolded protein binding Source: SGD

GO - Biological processi

  • cellular heat acclimation Source: SGD
  • chaperone cofactor-dependent protein refolding Source: SGD
  • inheritance of oxidatively modified proteins involved in replicative cell aging Source: SGD
  • protein folding in endoplasmic reticulum Source: SGD
  • protein metabolic process Source: InterPro
  • protein unfolding Source: SGD
  • stress granule disassembly Source: SGD
  • trehalose metabolism in response to heat stress Source: SGD

Keywordsi

Molecular functionChaperone
Biological processStress response
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciYEAST:G3O-32130-MONOMER
SABIO-RKiP31539

Names & Taxonomyi

Protein namesi
Recommended name:
Heat shock protein 104
Alternative name(s):
Protein aggregation-remodeling factor HSP104
Gene namesi
Name:HSP104
Ordered Locus Names:YLL026W
ORF Names:L0948
OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Taxonomic identifieri559292 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
Proteomesi

Organism-specific databases

EuPathDBiFungiDB:YLL026W
SGDiS000003949 HSP104

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cell wall Cytoskeleton Vacuole Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi184D → A, D, F, N, L, Q or S: Confers resistance to prion-curing by guanidine. 1 Publication1
Mutagenesisi184D → K, W or Y: Impairs prion propagation. 1 Publication1
Mutagenesisi217G → S: Largely reduces ATP hydrolysis. Alters bud morphology and causes septin mislocalization; when associated with I-499. 3 Publications1
Mutagenesisi217G → V: Completely abolishes ATP hydrolysis. 3 Publications1
Mutagenesisi218K → 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. 10 Publications1
Mutagenesisi257Y → A: Reduces thermotolerance 10-fold. 1 Publication1
Mutagenesisi285E → 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. 2 Publications1
Mutagenesisi315A → T: Reduces ATP hydrolysis by 98%; when associated with T-218. 1 Publication1
Mutagenesisi317T → A: Reduces rate of ATP hydrolysis at NBD1 nearly 10-fold. No effect on oligomerization. 2 Publications1
Mutagenesisi334R → M: Reduces ATPase activity by 80%. Impairs oligomerization. 1 Publication1
Mutagenesisi419R → M: Reduces ATPase activity by 80%. 1 Publication1
Mutagenesisi444R → M: Reduces ATPase activity by 80%. 1 Publication1
Mutagenesisi462L → R: Impairs prion propagation, but does not affect thermotolerance. 1 Publication1
Mutagenesisi495R → M: Increases ATPase activity 3-fold. 1 Publication1
Mutagenesisi499T → I: Reduces ATP hydrolysis by 50%. Alters bud morphology and causes septin mislocalization; when associated with S-217. 1 Publication1
Mutagenesisi503A → V: Increases basal level of ATPase activity and abolishes stimulation of ATP hydrolysis upon substrate binding. Inhibits growth at 37 degrees Celsius. 2 Publications1
Mutagenesisi509A → D: Reduces thermotolerance. 1 Publication1
Mutagenesisi557P → L: Impairs prion propagation, but does not affect thermotolerance. 1 Publication1
Mutagenesisi619G → V: Impairs oligomerization at low protein concentrations. 2 Publications1
Mutagenesisi620K → T: Impairs oligomerization at low protein concentrations. Reduces ATP hydrolysis rate. Unable to confer thermotolerance. Comletely abolishes ATPase activity; when associated with T-218. 9 Publications1
Mutagenesisi621T → A: Reduces ATP hydrolysis, but does not affect oligomerization. 1 Publication1
Mutagenesisi645E → K: Abolishes the ability to refold aggregated protein in vitro and to provide thermotolerance in vivo. 1 Publication1
Mutagenesisi662Y → A or K: Abolishes the ability to refold aggregated protein in vitro and to provide thermotolerance in vivo. 1 Publication1
Mutagenesisi662Y → F or W: No effect. 1 Publication1
Mutagenesisi687E → 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. 2 Publications1
Mutagenesisi704D → N: Impairs prion propagation, but does not affect thermotolerance. 1 Publication1
Mutagenesisi728N → 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. 4 Publications1
Mutagenesisi765R → M: Can oligomerize in the absence of nucleotides. 1 Publication1
Mutagenesisi778K → A in NLS17KA; fails to concentrate in the nucleus; when associated with A-782 and A-789. 1 Publication1
Mutagenesisi782K → A in NLS17KA; fails to concentrate in the nucleus; when associated with A-778 and A-789. 1 Publication1
Mutagenesisi789K → A in NLS17KA; fails to concentrate in the nucleus; when associated with A-778 and A-782. 1 Publication1
Mutagenesisi819Y → 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. 1 Publication1
Mutagenesisi826R → M: Reduces ATP and ADP binding at NBD2 6-fold, but does not affect ATP hydrolysis at NBD2. Reduces catalytic rate at NBD1. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001912121 – 908Heat shock protein 104Add BLAST908

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei206PhosphoserineCombined sources1
Modified residuei306PhosphoserineCombined sources1
Cross-linki442Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)Combined sources
Modified residuei499PhosphothreonineCombined sources1
Modified residuei535PhosphoserineCombined sources1
Cross-linki620Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP31539
PaxDbiP31539
PRIDEiP31539

2D gel databases

SWISS-2DPAGEiP31539

PTM databases

CarbonylDBiP31539
iPTMnetiP31539

Expressioni

Inductioni

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).5 Publications

Interactioni

Subunit structurei

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.8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-8050,EBI-8050

GO - Molecular functioni

  • chaperone binding Source: SGD
  • identical protein binding Source: IntAct
  • unfolded protein binding Source: SGD

Protein-protein interaction databases

BioGridi31226, 446 interactors
DIPiDIP-2252N
IntActiP31539, 26 interactors
MINTiP31539
STRINGi4932.YLL026W

Structurei

Secondary structure

1908
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi9 – 24Combined sources16
Beta strandi28 – 30Combined sources3
Helixi32 – 39Combined sources8
Helixi50 – 57Combined sources8
Helixi62 – 73Combined sources12
Helixi90 – 105Combined sources16
Beta strandi109 – 111Combined sources3
Helixi113 – 120Combined sources8
Helixi124 – 132Combined sources9
Helixi137 – 148Combined sources12
Helixi165 – 170Combined sources6
Beta strandi171 – 173Combined sources3
Helixi174 – 179Combined sources6
Helixi190 – 200Combined sources11
Beta strandi203 – 205Combined sources3
Beta strandi207 – 212Combined sources6
Helixi218 – 230Combined sources13
Helixi236 – 238Combined sources3
Beta strandi242 – 246Combined sources5
Helixi248 – 252Combined sources5
Helixi260 – 273Combined sources14
Beta strandi279 – 283Combined sources5
Turni284 – 286Combined sources3
Helixi287 – 290Combined sources4
Helixi298 – 306Combined sources9
Beta strandi311 – 316Combined sources6
Helixi318 – 327Combined sources10
Helixi330 – 334Combined sources5
Beta strandi335 – 339Combined sources5
Turni344 – 346Combined sources3
Helixi347 – 350Combined sources4
Turni351 – 355Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5KNEelectron microscopy5.64A/B/C/D/E/F6-857[»]
5U2UX-ray2.54A/B/C1-166[»]
5VJHelectron microscopy4.00A/B/C/D/E/F1-908[»]
5VY8electron microscopy4.00A/B/C/D/E/F1-908[»]
5VY9electron microscopy4.00A/B/C/D/E/F1-908[»]
5VYAelectron microscopy4.00A/B/C/D/E/F1-908[»]
5WBWX-ray2.60A/B/D4-356[»]
6AMNX-ray2.82A4-352[»]
ProteinModelPortaliP31539
SMRiP31539
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni167 – 411NBD1Add BLAST245
Regioni541 – 731NBD2Add BLAST191
Regioni905 – 908Interaction surface for TPR repeats4

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili412 – 536Sequence analysisAdd BLAST125

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi773 – 789Nuclear localization signalAdd BLAST17

Domaini

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.

Sequence similaritiesi

Belongs to the ClpA/ClpB family.Curated

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

GeneTreeiENSGT00390000012961
HOGENOMiHOG000218211
InParanoidiP31539
KOiK03695
OMAiTQVIRML
OrthoDBiEOG092C0JLO

Family and domain databases

Gene3Di1.10.1780.10, 1 hit
InterProiView protein in InterPro
IPR003593 AAA+_ATPase
IPR003959 ATPase_AAA_core
IPR019489 Clp_ATPase_C
IPR004176 Clp_N
IPR036628 Clp_N_dom_sf
IPR001270 ClpA/B
IPR018368 ClpA/B_CS1
IPR028299 ClpA/B_CS2
IPR027417 P-loop_NTPase
PfamiView protein in Pfam
PF00004 AAA, 1 hit
PF07724 AAA_2, 1 hit
PF02861 Clp_N, 2 hits
PF10431 ClpB_D2-small, 1 hit
PRINTSiPR00300 CLPPROTEASEA
SMARTiView protein in SMART
SM00382 AAA, 2 hits
SM01086 ClpB_D2-small, 1 hit
SUPFAMiSSF52540 SSF52540, 2 hits
SSF81923 SSF81923, 1 hit
PROSITEiView protein in PROSITE
PS00870 CLPAB_1, 1 hit
PS00871 CLPAB_2, 1 hit

Sequencei

Sequence statusi: Complete.

P31539-1 [UniParc]FASTAAdd to basket

« Hide

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

MEIDDDLD
Length:908
Mass (Da):102,035
Last modified:February 1, 1996 - v2
Checksum:i4AD0E7E3AF98E318
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
PIRiS61476
RefSeqiNP_013074.1, NM_001181846.1

Genome annotation databases

EnsemblFungiiYLL026W; YLL026W; YLL026W
GeneIDi850633
KEGGisce:YLL026W

Similar proteinsi

Entry informationi

Entry nameiHS104_YEAST
AccessioniPrimary (citable) accession number: P31539
Secondary accession number(s): D6VXX8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: February 1, 1996
Last modified: May 23, 2018
This is version 169 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Yeast
    Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
  4. Yeast chromosome XII
    Yeast (Saccharomyces cerevisiae) chromosome XII: entries and gene names

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