UniProt Accession

 HS104_YEAST; P31539; D6VXX8 

Genbank Protein ID

 M67479; Z73131; Z73130; AY693002; X97560; BK006945 

Genbank Nucleotide ID

 AAA50477.1; CAA97475.1; CAA97474.1; AAT93021.1; CAA66164.1; DAA09294.1 

Protein Name

 Heat shock protein 104 

Protein Synonyms/Alias

 Protein aggregation-remodeling factor HSP104 

Gene Name

 HSP104 

Gene Synonyms/Alias

 YLL026W; L0948 

Created Date

 July 27, 2013 

Organism

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

NCBI Taxa ID

 559292 

Lysine Modification

Position	Peptide	Type	References
101	KVLQDAAKIQKQQKD	acetylation	[1]
218	IGEPGIGKTAIIEGV	ubiquitination	[2]
256	AALTAGAKYKGDFEE	ubiquitination	[3]
258	LTAGAKYKGDFEERF	ubiquitination	[2]
327	EYRSIVEKDGAFERR	ubiquitination	[2]
358	ILRGLQPKYEIHHGV	acetylation	[1]
410	VAVARDSKPEELDSK	ubiquitination	[2]
442	EDADSTTKDRLKLAR	acetylation	[1]
442	EDADSTTKDRLKLAR	ubiquitination	[3]
470	RQRYNEEKHGHEELT	acetylation	[1]
470	RQRYNEEKHGHEELT	ubiquitination	[2]
514	YFAIPDIKKQIEKLE	acetylation	[1]
620	LGLSGSGKTELAKKV	ubiquitination	[4, 5, 6]
649	DCSELSEKYAVSKLL	ubiquitination	[2, 3]
782	LSRKAIHKIVDIRLK	acetylation	[1]
803	EQNDKHYKLNLTQEA	acetylation	[1]
811	LNLTQEAKDFLAKYG	acetylation	[1]
816	EAKDFLAKYGYSDDM	acetylation	[1]
839	IQNEILNKLALRILK	acetylation	[1]
839	IQNEILNKLALRILK	ubiquitination	[2]

Reference

 [1] Proteome-wide analysis of lysine acetylation suggests its broad regulatory scope in Saccharomyces cerevisiae.
 Henriksen P, Wagner SA, Weinert BT, Sharma S, Bacinskaja G, Rehman M, Juffer AH, Walther TC, Lisby M, Choudhary C.
 Mol Cell Proteomics. 2012 Nov;11(11):1510-22. [PMID: 22865919]
 [2] Global analysis of phosphorylation and ubiquitylation cross-talk in protein degradation.
 Swaney DL, Beltrao P, Starita L, Guo A, Rush J, Fields S, Krogan NJ, Villén J.
 Nat Methods. 2013 Jul;10(7):676-82. [PMID: 23749301]
 [3] Sites of ubiquitin attachment in Saccharomyces cerevisiae.
 Starita LM, Lo RS, Eng JK, von Haller PD, Fields S.
 Proteomics. 2012 Jan;12(2):236-40. [PMID: 22106047]
 [4] A subset of membrane-associated proteins is ubiquitinated in response to mutations in the endoplasmic reticulum degradation machinery.
 Hitchcock AL, Auld K, Gygi SP, Silver PA.
 Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12735-40. [PMID: 14557538]
 [5] Computational identification of ubiquitylation sites from protein sequences.
 Tung CW, Ho SY.
 BMC Bioinformatics. 2008 Jul 15;9:310. [PMID: 18625080]
 [6] Identification, analysis, and prediction of protein ubiquitination sites.
 Radivojac P, Vacic V, Haynes C, Cocklin RR, Mohan A, Heyen JW, Goebl MG, Iakoucheva LM.
 Proteins. 2010 Feb 1;78(2):365-80. [PMID: 19722269] 

Functional Description

 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+]. 

Sequence Annotation

 NP_BIND 212 219 ATP 1 (Potential).
 NP_BIND 614 621 ATP 2 (Potential).
 REGION 167 411 NBD1.
 REGION 541 731 NBD2.
 REGION 773 789 Nuclear localization signal.
 REGION 905 908 Interaction surface for TPR repeats.
 MOD_RES 206 206 Phosphoserine.
 MOD_RES 306 306 Phosphoserine.
 MOD_RES 499 499 Phosphothreonine.
 MOD_RES 535 535 Phosphoserine.
 CROSSLNK 620 620 Glycyl lysine isopeptide (Lys-Gly)  

Keyword

 ATP-binding; Chaperone; Coiled coil; Complete proteome; Cytoplasm; Isopeptide bond; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat; Stress response; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 908 AA 

Protein Sequence

Gene Ontology

 GO:0005634; C:nucleus; IDA:SGD.
 GO:0072380; C:TRC complex; IDA:SGD.
 GO:0043531; F:ADP binding; IMP:SGD.
 GO:0005524; F:ATP binding; IMP:SGD.
 GO:0042623; F:ATPase activity, coupled; IMP:SGD.
 GO:0051087; F:chaperone binding; IDA:SGD.
 GO:0051082; F:unfolded protein binding; IDA:SGD.
 GO:0070370; P:cellular heat acclimation; IMP:SGD.
 GO:0070389; P:chaperone cofactor-dependent protein refolding; IDA:SGD.
 GO:0001319; P:inheritance of oxidatively modified proteins involved in replicative cell aging; IMP:SGD.
 GO:0034975; P:protein folding in endoplasmic reticulum; IMP:SGD.
 GO:0043335; P:protein unfolding; IMP:SGD.
 GO:0070414; P:trehalose metabolism in response to heat stress; IMP:SGD. 

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.
 IPR004176; Clp_N.
 IPR023150; Dbl_Clp-N.
 IPR027417; P-loop_NTPase. 

Pfam

 PF00004; AAA
 PF07724; AAA_2
 PF02861; Clp_N
 PF10431; ClpB_D2-small 

SMART

 SM00382; AAA
 SM01086; ClpB_D2-small 

PROSITE

 PS00870; CLPAB_1
 PS00871; CLPAB_2 

PRINTS

 PR00300; CLPPROTEASEA.