UniProt Accession

 HS90B_HUMAN; P08238; B2R5P0; Q5T9W7; Q9NQW0; Q9NTK6 

Genbank Protein ID

 M16660; J04988; AY359878; AL136543; AK312255; DQ314872; AL139392; CH471081; BC004928; BC009206; BC012807; BC014485; BC016753; BC068474; AH007358; AF275719 

Genbank Nucleotide ID

 AAA36025.1; AAA36026.1; AAQ63401.1; CAB66478.1; BAG35187.1; ABC40731.1; CAI20095.1; EAX04257.1; AAH04928.1; AAH09206.2; AAH12807.1; AAH14485.1; AAH16753.1; AAH68474.1; AAD14062.3; AAF82792.1 

Protein Name

 Heat shock protein HSP 90-beta 

Protein Synonyms/Alias

 HSP 90; Heat shock 84 kDa; HSP 84; HSP84 

Gene Name

 HSP90AB1 

Gene Synonyms/Alias

 HSP90B; HSPC2; HSPCB 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
53	NASDALDKIRYESLT	ubiquitination	[1, 2, 3, 4]
64	ESLTDPSKLDSGKEL	ubiquitination	[1, 3, 4, 5, 6]
69	PSKLDSGKELKIDII	acetylation	[7]
69	PSKLDSGKELKIDII	ubiquitination	[1, 2, 3, 4, 5, 6, 7]
72	LDSGKELKIDIIPNP	ubiquitination	[1, 3, 7]
95	DTGIGMTKADLINNL	ubiquitination	[1, 2, 3, 4, 5, 6, 7, 8]
107	NNLGTIAKSGTKAFM	ubiquitination	[1, 2, 3, 4, 5, 6, 8]
148	EKVVVITKHNDDEQY	ubiquitination	[1, 8]
180	EPIGRGTKVILHLKE	ubiquitination	[1, 2, 3, 4, 6]
186	TKVILHLKEDQTEYL	ubiquitination	[1, 3, 6]
204	RVKEVVKKHSQFIGY	ubiquitination	[2, 3, 4, 5, 6, 7]
219	PITLYLEKEREKEIS	ubiquitination	[2, 4, 5, 6]
237	AEEEKGEKEEEDKDD	acetylation	[9]
237	AEEEKGEKEEEDKDD	ubiquitination	[1]
263	DEEDDSGKDKKKKTK	acetylation	[10, 11]
263	DEEDDSGKDKKKKTK	ubiquitination	[6]
273	KKKTKKIKEKYIDQE	ubiquitination	[3]
275	KTKKIKEKYIDQEEL	ubiquitination	[1, 2, 3, 4, 6]
284	IDQEELNKTKPIWTR	ubiquitination	[1, 2, 3, 4, 6]
286	QEELNKTKPIWTRNP	acetylation	[12, 13]
286	QEELNKTKPIWTRNP	ubiquitination	[1, 2, 3, 4, 6]
306	EEYGEFYKSLTNDWE	acetylation	[11]
306	EEYGEFYKSLTNDWE	ubiquitination	[1, 2, 3, 6, 8]
319	WEDHLAVKHFSVEGQ	ubiquitination	[1, 3, 6, 8]
347	PFDLFENKKKKNNIK	acetylation	[9]
347	PFDLFENKKKKNNIK	ubiquitination	[1, 3, 6, 7, 14]
348	FDLFENKKKKNNIKL	ubiquitination	[3]
354	KKKKNNIKLYVRRVF	ubiquitination	[1, 2, 3, 4, 6]
399	REMLQQSKILKVIRK	malonylation	[15]
399	REMLQQSKILKVIRK	ubiquitination	[1, 2, 3, 4, 6]
411	IRKNIVKKCLELFSE	ubiquitination	[2, 3, 4, 5, 8, 14]
427	AEDKENYKKFYEAFS	ubiquitination	[3]
428	EDKENYKKFYEAFSK	acetylation	[10]
428	EDKENYKKFYEAFSK	ubiquitination	[1, 2, 3, 4, 5, 7]
435	KFYEAFSKNLKLGIH	acetylation	[7, 11, 16]
435	KFYEAFSKNLKLGIH	ubiquitination	[1, 2, 3, 4, 5, 6, 7, 8, 14]
438	EAFSKNLKLGIHEDS	ubiquitination	[1, 3, 4, 5, 6, 7, 8]
477	SEYVSRMKETQKSIY	acetylation	[7]
477	SEYVSRMKETQKSIY	ubiquitination	[8]
481	SRMKETQKSIYYITG	acetylation	[7, 10, 11, 16]
481	SRMKETQKSIYYITG	ubiquitination	[1, 2, 3, 4, 5, 6, 7, 8]
491	YYITGESKEQVANSA	acetylation	[7, 11]
491	YYITGESKEQVANSA	ubiquitination	[1, 3, 6, 7]
505	AFVERVRKRGFEVVY	ubiquitination	[3, 14]
526	EYCVQQLKEFDGKSL	ubiquitination	[8]
531	QLKEFDGKSLVSVTK	ubiquitination	[1, 2, 3, 4, 5, 6, 7]
538	KSLVSVTKEGLELPE	acetylation	[11]
538	KSLVSVTKEGLELPE	ubiquitination	[1, 2, 4, 5, 6]
550	LPEDEEEKKKMEESK	ubiquitination	[1]
552	EDEEEKKKMEESKAK	ubiquitination	[6]
559	KMEESKAKFENLCKL	acetylation	[7]
559	KMEESKAKFENLCKL	ubiquitination	[1, 2, 3, 4, 5, 6, 7, 14]
565	AKFENLCKLMKEILD	acetylation	[7]
565	AKFENLCKLMKEILD	ubiquitination	[1, 2, 3]
568	ENLCKLMKEILDKKV	acetylation	[7, 10, 11, 16]
568	ENLCKLMKEILDKKV	ubiquitination	[2, 3, 4, 5, 7]
573	LMKEILDKKVEKVTI	ubiquitination	[3]
574	MKEILDKKVEKVTIS	acetylation	[7]
574	MKEILDKKVEKVTIS	ubiquitination	[3, 7]
577	ILDKKVEKVTISNRL	ubiquitination	[1, 2, 3, 7]
607	ANMERIMKAQALRDN	ubiquitination	[1, 2, 3, 4, 6]
623	TMGYMMAKKHLEINP	acetylation	[11]
623	TMGYMMAKKHLEINP	methylation	[17]
623	TMGYMMAKKHLEINP	ubiquitination	[1, 3, 4, 5, 6, 7, 8, 14]
624	MGYMMAKKHLEINPD	acetylation	[18, 19]
624	MGYMMAKKHLEINPD	ubiquitination	[1, 2, 3, 4, 5, 6, 7, 14]
649	AEADKNDKAVKDLVV	ubiquitination	[1]
685	NRIYRMIKLGLGIDE	ubiquitination	[1, 8]

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] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [3] 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]
 [4] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [5] 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]
 [6] 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]
 [7] 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]
 [8] 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]
 [9] Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome.
 Morselli E, Mariño G, Bennetzen MV, Eisenberg T, Megalou E, Schroeder S, Cabrera S, Bénit P, Rustin P, Criollo A, Kepp O, Galluzzi L, Shen S, Malik SA, Maiuri MC, Horio Y, López-Otín C, Andersen JS, Tavernarakis N, Madeo F, Kroemer G.
 J Cell Biol. 2011 Feb 21;192(4):615-29. [PMID: 21339330]
 [10] 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]
 [11] 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]
 [12] 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]
 [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] 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]
 [15] The first identification of lysine malonylation substrates and its regulatory enzyme.
 Peng C, Lu Z, Xie Z, Cheng Z, Chen Y, Tan M, Luo H, Zhang Y, He W, Yang K, Zwaans BM, Tishkoff D, Ho L, Lombard D, He TC, Dai J, Verdin E, Ye Y, Zhao Y.
 Mol Cell Proteomics. 2011 Dec;10(12):M111.012658. [PMID: 21908771]
 [16] 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]
 [17] Mass spectrometry-based identification and characterisation of lysine and arginine methylation in the human proteome.
 Bremang M, Cuomo A, Agresta AM, Stugiewicz M, Spadotto V, Bonaldi T.
 Mol Biosyst. 2013 Jul 30;9(9):2231-47. [PMID: 23748837]
 [18] Substrate and functional diversity of lysine acetylation revealed by a proteomics survey.
 Kim SC, Sprung R, Chen Y, Xu Y, Ball H, Pei J, Cheng T, Kho Y, Xiao H, Xiao L, Grishin NV, White M, Yang XJ, Zhao Y.
 Mol Cell. 2006 Aug;23(4):607-18. [PMID: 16916647]
 [19] Proteome-wide prediction of acetylation substrates.
 Basu A, Rose KL, Zhang J, Beavis RC, Ueberheide B, Garcia BA, Chait B, Zhao Y, Hunt DF, Segal E, Allis CD, Hake SB.
 Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13785-90. [PMID: 19666589] 

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

 MOTIF 720 724 TPR repeat-binding.
 BINDING 46 46 ATP (By similarity).
 BINDING 88 88 ATP.
 BINDING 107 107 ATP (By similarity).
 BINDING 133 133 ATP; via amide nitrogen (By similarity).
 BINDING 392 392 ATP (By similarity).
 MOD_RES 226 226 Phosphoserine.
 MOD_RES 255 255 Phosphoserine.
 MOD_RES 261 261 Phosphoserine.
 MOD_RES 275 275 N6-acetyllysine.
 MOD_RES 284 284 N6-acetyllysine.
 MOD_RES 297 297 Phosphothreonine.
 MOD_RES 305 305 Phosphotyrosine (By similarity).
 MOD_RES 307 307 Phosphoserine.
 MOD_RES 354 354 N6-acetyllysine.
 MOD_RES 399 399 N6-acetyllysine; alternate.
 MOD_RES 399 399 N6-malonyllysine; alternate.
 MOD_RES 402 402 N6-acetyllysine.
 MOD_RES 435 435 N6-acetyllysine.
 MOD_RES 452 452 Phosphoserine; alternate.
 MOD_RES 481 481 N6-acetyllysine.
 MOD_RES 484 484 Phosphotyrosine.
 MOD_RES 532 532 Phosphoserine.
 MOD_RES 568 568 N6-acetyllysine.
 MOD_RES 590 590 S-nitrosocysteine (Probable).
 MOD_RES 624 624 N6-acetyllysine.
 MOD_RES 718 718 Phosphoserine.
 CARBOHYD 434 434 O-linked (GlcNAc...) (By similarity).
 CARBOHYD 452 452 O-linked (GlcNAc...); alternate (By  

Keyword

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

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 724 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; TAS:Reactome.
 GO:0016234; C:inclusion body; IEA:Compara.
 GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
 GO:0005739; C:mitochondrion; IEA:Compara.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0002135; F:CTP binding; IEA:Compara.
 GO:0032564; F:dATP binding; IEA:Compara.
 GO:0005525; F:GTP binding; IEA:Compara.
 GO:0030235; F:nitric-oxide synthase regulator activity; ISS:UniProtKB.
 GO:0030911; F:TPR domain binding; ISS:UniProtKB.
 GO:0002134; F:UTP binding; IEA:Compara.
 GO:0007411; P:axon guidance; TAS:Reactome.
 GO:0071407; P:cellular response to organic cyclic compound; IEA:Compara.
 GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Compara.
 GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:MGI.
 GO:0035872; P:nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway; TAS:Reactome.
 GO:0001890; P:placenta development; IEA:Compara.
 GO:0045793; P:positive regulation of cell size; IEA:Compara.
 GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISS:UniProtKB.
 GO:0032092; P:positive regulation of protein binding; IEA:Compara.
 GO:0033160; P:positive regulation of protein import into nucleus, translocation; IEA:Compara.
 GO:0071902; P:positive regulation of protein serine/threonine kinase activity; IEA:Compara.
 GO:0006457; P:protein folding; IEA:InterPro.
 GO:0060334; P:regulation of interferon-gamma-mediated signaling pathway; IMP:MGI.
 GO:0060338; P:regulation of type I interferon-mediated signaling pathway; IMP:MGI.
 GO:0009651; P:response to salt stress; IEA:Compara.
 GO:0006986; P:response to unfolded protein; NAS:UniProtKB. 

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.