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Overview

Uniprot IDP08238
Protein NameHeat shock protein HSP 90-beta
Gene NameHSP90AB1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
107 NNLGTIAKSGTKAFM
180 EPIGRGTKVILHLKE
186 TKVILHLKEDQTEYL
204 RVKEVVKKHSQFIGY
247 EDKDDEEKPKIEDVG
263 DEEDDSGKDKKKKTK
273 KKKTKKIKEKYIDQE
275 KTKKIKEKYIDQEEL
284 IDQEELNKTKPIWTR
286 QEELNKTKPIWTRNP
347 PFDLFENKKKKNNIK
348 FDLFENKKKKNNIKL
354 KKKKNNIKLYVRRVF
399 REMLQQSKILKVIRK
411 IRKNIVKKCLELFSE
428 EDKENYKKFYEAFSK
435 KFYEAFSKNLKLGIH
438 EAFSKNLKLGIHEDS
481 SRMKETQKSIYYITG
53 NASDALDKIRYESLT
531 QLKEFDGKSLVSVTK
538 KSLVSVTKEGLELPE
559 KMEESKAKFENLCKL
568 ENLCKLMKEILDKKV
577 ILDKKVEKVTISNRL
607 ANMERIMKAQALRDN
623 TMGYMMAKKHLEINP
624 MGYMMAKKHLEINPD
64 ESLTDPSKLDSGKEL
641 IVETLRQKAEADKND
69 PSKLDSGKELKIDII
72 LDSGKELKIDIIPNP

Function

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 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 (PubMed:16478993, PubMed:19696785). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself. Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:26991466, PubMed:27295069). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels. They first alter the steady-state levels of certain transcription factors in response to various physiological cues. Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment. Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Promotes cell differentiation by chaperoning BIRC2 and thereby protecting from auto-ubiquitination and degradation by the proteasomal machinery (PubMed:18239673). Main chaperone involved in the phosphorylation/activation of the STAT1 by chaperoning both JAK2 and PRKCE under heat shock and in turn, activates its own transcription (PubMed:20353823). Involved in the translocation into ERGIC (endoplasmic reticulum-Golgi intermediate compartment) of leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1; the translocation process is mediated by the cargo receptor TMED10 (PubMed:32272059)

Protein Sequence

10 MPEEVHHGEE 20 EVETFAFQAE 30 IAQLMSLIIN 40 TFYSNKEIFL 50 RELISNASDA 60 LDKIRYESLT 70 DPSKLDSGKE 80 LKIDIIPNPQ 90 ERTLTLVDTG 100 IGMTKADLIN 110 NLGTIAKSGT 120 KAFMEALQAG 130 ADISMIGQFG 140 VGFYSAYLVA 150 EKVVVITKHN 160 DDEQYAWESS 170 AGGSFTVRAD 180 HGEPIGRGTK 190 VILHLKEDQT 200 EYLEERRVKE 210 VVKKHSQFIG 220 YPITLYLEKE 230 REKEISDDEA 240 EEEKGEKEEE 250 DKDDEEKPKI 260 EDVGSDEEDD 270 SGKDKKKKTK 280 KIKEKYIDQE 290 ELNKTKPIWT 300 RNPDDITQEE 310 YGEFYKSLTN 320 DWEDHLAVKH 330 FSVEGQLEFR 340 ALLFIPRRAP 350 FDLFENKKKK 360 NNIKLYVRRV 370 FIMDSCDELI 380 PEYLNFIRGV 390 VDSEDLPLNI 400 SREMLQQSKI 410 LKVIRKNIVK 420 KCLELFSELA 430 EDKENYKKFY 440 EAFSKNLKLG 450 IHEDSTNRRR 460 LSELLRYHTS 470 QSGDEMTSLS 480 EYVSRMKETQ 490 KSIYYITGES 500 KEQVANSAFV 510 ERVRKRGFEV 520 VYMTEPIDEY 530 CVQQLKEFDG 540 KSLVSVTKEG 550 LELPEDEEEK 560 KKMEESKAKF 570 ENLCKLMKEI 580 LDKKVEKVTI 590 SNRLVSSPCC 600 IVTSTYGWTA 610 NMERIMKAQA 620 LRDNSTMGYM 630 MAKKHLEINP 640 DHPIVETLRQ 650 KAEADKNDKA 660 VKDLVVLLFE 670 TALLSSGFSL 680 EDPQTHSNRI 690 YRMIKLGLGI 700 DEDEVAAEEP 710 NAAVPDEIPP 720 LEGDEDASRM EEVD

Gene Ontology

Classification GO ID Description
Cellular Component GO:0034751 aryl hydrocarbon receptor complex
Cellular Component GO:0044295 axonal growth cone
Cellular Component GO:0009986 cell surface
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0044294 dendritic growth cone
Cellular Component GO:0120293 dynein axonemal particle
Cellular Component GO:0070062 extracellular exosome
Cellular Component GO:0005576 extracellular region
Cellular Component GO:1904813 ficolin-1-rich granule lumen
Cellular Component GO:1990565 HSP90-CDC37 chaperone complex
Cellular Component GO:0042470 melanosome
Cellular Component GO:0016020 membrane
Cellular Component GO:0005739 mitochondrion
Cellular Component GO:0043025 neuronal cell body
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0048471 perinuclear region of cytoplasm
Cellular Component GO:0005886 plasma membrane
Cellular Component GO:0101031 protein folding chaperone complex
Cellular Component GO:0032991 protein-containing complex
Cellular Component GO:0034774 secretory granule lumen
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0016887 ATP hydrolysis activity
Molecular Function GO:0043008 ATP-dependent protein binding
Molecular Function GO:0140662 ATP-dependent protein folding chaperone
Molecular Function GO:0045296 cadherin binding
Molecular Function GO:0097718 disordered domain specific binding
Molecular Function GO:0070182 DNA polymerase binding
Molecular Function GO:0003725 double-stranded RNA binding
Molecular Function GO:0031072 heat shock protein binding
Molecular Function GO:0042826 histone deacetylase binding
Molecular Function GO:1990226 histone methyltransferase binding
Molecular Function GO:0042802 identical protein binding
Molecular Function GO:0019900 kinase binding
Molecular Function GO:0023026 MHC class II protein complex binding
Molecular Function GO:0030235 nitric-oxide synthase regulator activity
Molecular Function GO:0042277 peptide binding
Molecular Function GO:0046983 protein dimerization activity
Molecular Function GO:0044183 protein folding chaperone
Molecular Function GO:0042803 protein homodimerization activity
Molecular Function GO:0019901 protein kinase binding
Molecular Function GO:0019887 protein kinase regulator activity
Molecular Function GO:0072542 protein phosphatase activator activity
Molecular Function GO:0141069 receptor ligand inhibitor activity
Molecular Function GO:0003723 RNA binding
Molecular Function GO:0048156 tau protein binding
Molecular Function GO:0030911 TPR domain binding
Molecular Function GO:0031625 ubiquitin protein ligase binding
Molecular Function GO:0051082 unfolded protein binding
Biological Process GO:0034605 cellular response to heat
Biological Process GO:0051131 chaperone-mediated protein complex assembly
Biological Process GO:1901799 negative regulation of proteasomal protein catabolic process
Biological Process GO:0032435 negative regulation of proteasomal ubiquitin-dependent protein catabolic process
Biological Process GO:0045597 positive regulation of cell differentiation
Biological Process GO:0045429 positive regulation of nitric oxide biosynthetic process
Biological Process GO:2000010 positive regulation of protein localization to cell surface
Biological Process GO:0030511 positive regulation of transforming growth factor beta receptor signaling pathway
Biological Process GO:0006457 protein folding
Biological Process GO:0050821 protein stabilization
Biological Process GO:0051726 regulation of cell cycle
Biological Process GO:0032880 regulation of protein localization
Biological Process GO:0031396 regulation of protein ubiquitination
Biological Process GO:0006986 response to unfolded protein
Biological Process GO:0097435 supramolecular fiber organization
Biological Process GO:1905323 telomerase holoenzyme complex assembly
Biological Process GO:0007004 telomere maintenance via telomerase
Biological Process GO:0019062 virion attachment to host cell

Reference

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[2] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[3] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.

[4] Lin Y, Chen M, Wang D, Yu Y, Chen R et al.. Multi-Proteomic Analysis Reveals the Effect of Protein Lactylation on Matrix and Cholesterol Metabolism in Tendinopathy.. J Proteome Res 22(6):1712-1722. 2023 Jun 2. PMID: 37159428.

[5] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.

[6] Bao Q, Wan N, He Z, Cao J, Yuan W et al.. Subcellular Proteomic Mapping of Lysine Lactylation.. J Am Soc Mass Spectrom 35(12):3221-3232. 2024 Dec 4. PMID: 39569522.

[7] Shi CM, Wang QC, Li XL, Yang YH, Tang XY et al.. Global Profiling of Protein Lactylation in Human Hippocampi.. Proteomics Clin Appl 19(2):e202400061. 2025 Mar. PMID: 39610256.

[8] Guo X, Ren X, Yan C, Huang H. Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells.. ACS Chem Biol 20(7):1728-1738. 2025 Jul 18. PMID: 40590393.

[9] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.

[10] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.