UniProt Accession

 HS90A_HUMAN; P07900; A8K500; B3KPJ9; Q2PP14; Q5CAQ6; Q5CAQ7; Q9BVQ5 

Genbank Protein ID

 X15183; M27024; AJ890082; AJ890083; DQ314871; AK056446; AK291115; AK291607; AL133223; CH471061; X07270; M30626; BC000987; BC121062; D87666; D87666 

Genbank Nucleotide ID

 CAA33259.1; AAA63194.1; CAI64495.1; CAI64496.1; ABC40730.1; BAG51711.1; BAF83804.1; BAF84296.1; EAW81765.1; CAA30255.1; AAA36023.1; AAH00987.1; AAI21063.1; BAA13430.1; BAA13431.1 

Protein Name

 Heat shock protein HSP 90-alpha 

Protein Synonyms/Alias

 Heat shock 86 kDa; HSP 86; HSP86; Renal carcinoma antigen NY-REN-38 

Gene Name

 HSP90AA1 

Gene Synonyms/Alias

 HSP90A; HSPC1; HSPCA 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
58	NSSDALDKIRYESLT	ubiquitination	[1]
69	ESLTDPSKLDSGKEL	acetylation	[2]
74	PSKLDSGKELHINLI	ubiquitination	[1, 3]
84	HINLIPNKQDRTLTI	ubiquitination	[3]
100	DTGIGMTKADLINNL	ubiquitination	[4, 5]
112	NNLGTIAKSGTKAFM	acetylation	[6]
112	NNLGTIAKSGTKAFM	ubiquitination	[1, 3, 5, 7, 8, 9, 10]
153	EKVTVITKHNDDEQY	ubiquitination	[7, 10]
191	TKVILHLKEDQTEYL	ubiquitination	[1]
209	RIKEIVKKHSQFIGY	ubiquitination	[3]
224	PITLFVEKERDKEVS	acetylation	[2]
224	PITLFVEKERDKEVS	ubiquitination	[1, 3]
228	FVEKERDKEVSDDEA	ubiquitination	[1]
274	EEKKDGDKKKKKKIK	acetylation	[11]
275	EKKDGDKKKKKKIKE	ubiquitination	[3]
276	KKDGDKKKKKKIKEK	acetylation	[11]
281	KKKKKKIKEKYIDQE	ubiquitination	[8, 10]
283	KKKKIKEKYIDQEEL	acetylation	[2, 6, 10, 12]
283	KKKKIKEKYIDQEEL	ubiquitination	[1, 3, 8, 10]
292	IDQEELNKTKPIWTR	acetylation	[2, 6, 10, 12, 13]
292	IDQEELNKTKPIWTR	ubiquitination	[1, 3, 8, 9, 10]
294	QEELNKTKPIWTRNP	acetylation	[13, 14]
294	QEELNKTKPIWTRNP	ubiquitination	[1, 3, 5, 7, 8, 9, 10]
314	EEYGEFYKSLTNDWE	acetylation	[6]
314	EEYGEFYKSLTNDWE	ubiquitination	[1, 3, 5, 7, 9, 10]
327	WEDHLAVKHFSVEGQ	acetylation	[13]
327	WEDHLAVKHFSVEGQ	ubiquitination	[1, 7, 8, 9, 10]
362	RKKKNNIKLYVRRVF	acetylation	[2, 6, 12]
362	RKKKNNIKLYVRRVF	ubiquitination	[1, 3, 5, 7, 8, 9, 10]
407	REMLQQSKILKVIRK	acetylation	[2, 6, 10, 12]
407	REMLQQSKILKVIRK	ubiquitination	[1, 3, 4, 5, 7, 8, 9, 10]
410	LQQSKILKVIRKNLV	acetylation	[2, 13]
419	IRKNLVKKCLELFTE	ubiquitination	[3, 5, 7, 8]
436	EDKENYKKFYEQFSK	acetylation	[13]
436	EDKENYKKFYEQFSK	ubiquitination	[1, 3, 8, 10]
443	KFYEQFSKNIKLGIH	acetylation	[2, 6, 10]
443	KFYEQFSKNIKLGIH	ubiquitination	[1, 3, 5, 7, 8, 9, 10]
446	EQFSKNIKLGIHEDS	ubiquitination	[3, 5, 8, 10]
457	HEDSQNRKKLSELLR	ubiquitination	[8]
458	EDSQNRKKLSELLRY	acetylation	[2, 10, 12]
458	EDSQNRKKLSELLRY	ubiquitination	[8, 10]
478	GDEMVSLKDYCTRMK	ubiquitination	[5, 7, 8, 10]
485	KDYCTRMKENQKHIY	acetylation	[10, 13]
485	KDYCTRMKENQKHIY	ubiquitination	[8]
489	TRMKENQKHIYYITG	acetylation	[2, 6, 10, 12, 13]
489	TRMKENQKHIYYITG	ubiquitination	[1, 3, 9]
499	YYITGETKDQVANSA	acetylation	[6, 10]
499	YYITGETKDQVANSA	ubiquitination	[1, 3, 7, 8, 9]
513	AFVERLRKHGLEVIY	methylation	[15]
539	QLKEFEGKTLVSVTK	acetylation	[6]
539	QLKEFEGKTLVSVTK	ubiquitination	[3, 8, 10]
546	KTLVSVTKEGLELPE	acetylation	[6]
546	KTLVSVTKEGLELPE	ubiquitination	[1, 9]
558	LPEDEEEKKKQEEKK	acetylation	[2, 6, 10, 12]
558	LPEDEEEKKKQEEKK	ubiquitination	[1, 3, 10]
559	PEDEEEKKKQEEKKT	acetylation	[10]
559	PEDEEEKKKQEEKKT	ubiquitination	[10]
565	KKKQEEKKTKFENLC	acetylation	[10]
565	KKKQEEKKTKFENLC	ubiquitination	[1, 3, 8]
567	KQEEKKTKFENLCKI	acetylation	[10]
567	KQEEKKTKFENLCKI	ubiquitination	[8, 10]
573	TKFENLCKIMKDILE	acetylation	[2, 12]
576	ENLCKIMKDILEKKV	acetylation	[2, 6, 10]
576	ENLCKIMKDILEKKV	ubiquitination	[8, 10]
581	IMKDILEKKVEKVVV	acetylation	[10]
581	IMKDILEKKVEKVVV	ubiquitination	[8, 10]
582	MKDILEKKVEKVVVS	ubiquitination	[8]
585	ILEKKVEKVVVSNRL	acetylation	[2]
585	ILEKKVEKVVVSNRL	ubiquitination	[8, 16]
615	ANMERIMKAQALRDN	methylation	[15]
615	ANMERIMKAQALRDN	ubiquitination	[1, 3, 5, 7, 8, 9, 10, 17]
631	TMGYMAAKKHLEINP	acetylation	[10]
631	TMGYMAAKKHLEINP	ubiquitination	[1, 5, 8, 9, 10]
632	MGYMAAKKHLEINPD	ubiquitination	[3, 8, 10]

Reference

 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [3] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [4] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [5] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [6] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [7] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [8] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [9] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [10] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [11] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [12] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [13] Monoclonal antibody cocktail as an enrichment tool for acetylome analysis.
 Shaw PG, Chaerkady R, Zhang Z, Davidson NE, Pandey A.
 Anal Chem. 2011 May 15;83(10):3623-6. [PMID: 21466224]
 [14] An acetylation site in the middle domain of Hsp90 regulates chaperone function.
 Scroggins BT, Robzyk K, Wang D, Marcu MG, Tsutsumi S, Beebe K, Cotter RJ, Felts S, Toft D, Karnitz L, Rosen N, Neckers L.
 Mol Cell. 2007 Jan 12;25(1):151-9. [PMID: 17218278]
 [15] Large-scale global identification of protein lysine methylation in vivo.
 Cao XJ, Arnaudo AM, Garcia BA.
 Epigenetics. 2013 May 1;8(5):477-85. [PMID: 23644510]
 [16] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
 [17] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
 Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
 Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048] 

Functional Description

 Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function. 

Sequence Annotation

 REGION 682 732 Required for homodimerization.
 MOTIF 728 732 TPR repeat-binding.
 BINDING 51 51 ATP.
 BINDING 93 93 ATP.
 BINDING 112 112 ATP (By similarity).
 BINDING 138 138 ATP; via amide nitrogen.
 BINDING 400 400 ATP (By similarity).
 MOD_RES 5 5 Phosphothreonine; by PRKDC.
 MOD_RES 7 7 Phosphothreonine; by PRKDC.
 MOD_RES 224 224 N6-acetyllysine.
 MOD_RES 231 231 Phosphoserine.
 MOD_RES 252 252 Phosphoserine.
 MOD_RES 263 263 Phosphoserine.
 MOD_RES 313 313 Phosphotyrosine (By similarity).
 MOD_RES 399 399 Phosphoserine.
 MOD_RES 410 410 N6-acetyllysine.
 MOD_RES 443 443 N6-acetyllysine.
 MOD_RES 458 458 N6-acetyllysine.
 MOD_RES 489 489 N6-acetyllysine.
 MOD_RES 492 492 Phosphotyrosine (By similarity).
 MOD_RES 576 576 N6-acetyllysine.
 MOD_RES 585 585 N6-acetyllysine.
 MOD_RES 598 598 S-nitrosocysteine.  

Keyword

 3D-structure; Acetylation; Alternative splicing; ATP-binding; Chaperone; Complete proteome; Cytoplasm; Direct protein sequencing; Nucleotide-binding; Phosphoprotein; Reference proteome; S-nitrosylation; Stress response; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 732 AA 

Protein Sequence

Gene Ontology

 GO:0016324; C:apical plasma membrane; IEA:Compara.
 GO:0016323; C:basolateral plasma membrane; IEA:Compara.
 GO:0031526; C:brush border membrane; IEA:Compara.
 GO:0009986; C:cell surface; IEA:Compara.
 GO:0005829; C:cytosol; NAS:UniProtKB.
 GO:0031012; C:extracellular matrix; IEA:Compara.
 GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
 GO:0043005; C:neuron projection; IEA:Compara.
 GO:0043025; C:neuronal cell body; IEA:Compara.
 GO:0048471; C:perinuclear region of cytoplasm; IEA:Compara.
 GO:0005886; C:plasma membrane; TAS:Reactome.
 GO:0043234; C:protein complex; IEA:Compara.
 GO:0005524; F:ATP binding; TAS:UniProtKB.
 GO:0016887; F:ATPase activity; IDA:UniProtKB.
 GO:0002135; F:CTP binding; IEA:Compara.
 GO:0032564; F:dATP binding; IEA:Compara.
 GO:0005525; F:GTP binding; IEA:Compara.
 GO:0003729; F:mRNA binding; IEA:Compara.
 GO:0030235; F:nitric-oxide synthase regulator activity; IDA:UniProtKB.
 GO:0042803; F:protein homodimerization activity; TAS:UniProtKB.
 GO:0030911; F:TPR domain binding; IDA:UniProtKB.
 GO:0002134; F:UTP binding; IEA:Compara.
 GO:0007411; P:axon guidance; TAS:Reactome.
 GO:0010659; P:cardiac muscle cell apoptotic process; IEA:Compara.
 GO:0051131; P:chaperone-mediated protein complex assembly; IDA:BHF-UCL.
 GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
 GO:0000086; P:G2/M transition of mitotic cell cycle; TAS:Reactome.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0001764; P:neuron migration; IEA:Compara.
 GO:0046209; P:nitric oxide metabolic process; TAS:Reactome.
 GO:0060452; P:positive regulation of cardiac muscle contraction; IEA:Compara.
 GO:0045793; P:positive regulation of cell size; IEA:Compara.
 GO:0010592; P:positive regulation of lamellipodium assembly; IEA:Compara.
 GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISS:UniProtKB.
 GO:0033160; P:positive regulation of protein import into nucleus, translocation; IEA:Compara.
 GO:0045040; P:protein import into mitochondrial outer membrane; IDA:BHF-UCL.
 GO:0042026; P:protein refolding; TAS:UniProtKB.
 GO:0050999; P:regulation of nitric-oxide synthase activity; TAS:Reactome.
 GO:0043627; P:response to estrogen stimulus; IEA:Compara.
 GO:0009408; P:response to heat; IEA:Compara.
 GO:0009651; P:response to salt stress; IEA:Compara.
 GO:0006986; P:response to unfolded protein; NAS:UniProtKB.
 GO:0003009; P:skeletal muscle contraction; IEA:Compara. 

Interpro

 IPR003594; HATPase_ATP-bd.
 IPR019805; Heat_shock_protein_90_CS.
 IPR001404; Hsp90.
 IPR020575; Hsp90_N.
 IPR020568; Ribosomal_S5_D2-typ_fold. 

Pfam

 PF02518; HATPase_c
 PF00183; HSP90 

SMART

 SM00387; HATPase_c 

PROSITE

 PS00298; HSP90 

PRINTS

 PR00775; HEATSHOCK90.