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Protein

Heat shock protein HSP 90-beta

Gene

Hsp90ab1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. 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. 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. In the first place, they 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. Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation. Promotes cell differentiation by chaperoning BIRC2 and thereby protecting from auto-ubiquitination and degradation by the proteasomal machinery. Main chaperone that is involved in the phosphorylation/activation of the STAT1 by chaperoning both JAK2 and PRKCE under heat shock and in turn, activates its own transcription.By similarity

Enzyme regulationi

In the resting state, through the dimerization of its C-terminal domain, HSP90 forms a homodimer which is defined as the open conformation. Upon ATP-binding, the N-terminal domain undergoes significant conformational changes and comes in contact to form an active closed conformation. After HSP90 finishes its chaperoning tasks of assisting the proper folding, stabilization and activation of client proteins under the active state, ATP molecule is hydrolyzed to ADP which then dissociates from HSP90 and directs the protein back to the resting state.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei46ATPBy similarity1
Binding sitei88ATPBy similarity1
Binding sitei107ATPBy similarity1
Sitei126 – 127Cleaved under oxidative stressBy similarity2
Binding sitei133ATP; via amide nitrogenBy similarity1
Binding sitei392ATPBy similarity1

GO - Molecular functioni

  • ATP binding Source: RGD
  • ATP-dependent protein binding Source: RGD
  • cadherin binding Source: RGD
  • CTP binding Source: RGD
  • dATP binding Source: RGD
  • disordered domain specific binding Source: RGD
  • DNA polymerase binding Source: RGD
  • double-stranded RNA binding Source: RGD
  • drug binding Source: RGD
  • GTP binding Source: RGD
  • heat shock protein binding Source: RGD
  • histone deacetylase binding Source: RGD
  • histone methyltransferase binding Source: RGD
  • ion channel binding Source: RGD
  • kinase binding Source: RGD
  • MHC class II protein complex binding Source: RGD
  • peptide binding Source: RGD
  • protein dimerization activity Source: UniProtKB
  • protein homodimerization activity Source: RGD
  • protein kinase binding Source: RGD
  • protein kinase regulator activity Source: Ensembl
  • RNA binding Source: RGD
  • sulfonylurea receptor binding Source: RGD
  • unfolded protein binding Source: InterPro
  • UTP binding Source: RGD

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-RNO-2029482. Regulation of actin dynamics for phagocytic cup formation.
R-RNO-3371497. HSP90 chaperone cycle for steroid hormone receptors (SHR).
R-RNO-3371511. HSF1 activation.
R-RNO-3371568. Attenuation phase.
R-RNO-3371571. HSF1-dependent transactivation.
R-RNO-399954. Sema3A PAK dependent Axon repulsion.
R-RNO-6798695. Neutrophil degranulation.
R-RNO-844456. The NLRP3 inflammasome.
R-RNO-8852276. The role of GTSE1 in G2/M progression after G2 checkpoint.
R-RNO-8937144. Aryl hydrocarbon receptor signalling.

Names & Taxonomyi

Protein namesi
Recommended name:
Heat shock protein HSP 90-beta
Alternative name(s):
Heat shock 84 kDa
Short name:
HSP 84
Short name:
HSP84
Gene namesi
Name:Hsp90ab1
Synonyms:Hsp84, Hspcb
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 9

Organism-specific databases

RGDi1303075. Hsp90ab1.

Subcellular locationi

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

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved2 Publications
ChainiPRO_00000629202 – 724Heat shock protein HSP 90-betaAdd BLAST723

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei219N6-succinyllysineBy similarity1
Modified residuei226PhosphoserineCombined sources1
Modified residuei255PhosphoserineCombined sources1
Modified residuei261PhosphoserineCombined sources1
Modified residuei297PhosphothreonineBy similarity1
Modified residuei301PhosphotyrosineBy similarity1
Modified residuei305PhosphotyrosineBy similarity1
Modified residuei307PhosphoserineBy similarity1
Modified residuei399N6-malonyllysineBy similarity1
Glycosylationi434O-linked (GlcNAc) serineBy similarity1
Modified residuei435N6-acetyllysineBy similarity1
Modified residuei445PhosphoserineCombined sources1
Modified residuei452Phosphoserine; alternateBy similarity1
Glycosylationi452O-linked (GlcNAc) serine; alternateBy similarity1
Modified residuei479PhosphothreonineBy similarity1
Modified residuei481N6-acetyllysineBy similarity1
Modified residuei484PhosphotyrosineBy similarity1
Modified residuei531N6-methylated lysine; alternateBy similarity1
Modified residuei531N6-succinyllysine; alternateBy similarity1
Modified residuei532PhosphoserineBy similarity1
Modified residuei574N6-methylated lysineBy similarity1
Modified residuei577N6-succinyllysineBy similarity1
Modified residuei624N6-acetyllysineBy similarity1
Modified residuei669PhosphoserineBy similarity1
Modified residuei718Phosphoserine; by PLK2 and PLK3By similarity1

Post-translational modificationi

Ubiquitinated in the presence of STUB1-UBE2D1 complex (in vitro).By similarity
ISGylated.By similarity
S-nitrosylated; negatively regulates the ATPase activity.By similarity
Phosphorylation at Tyr-301 by SRC is induced by lipopolysaccharide. Phosphorylation at Ser-226 and Ser-255 inhibits AHR interaction.By similarity
Methylated by SMYD2; facilitates dimerization and chaperone complex formation; promotes cancer cell proliferation.By similarity
Cleaved following oxidative stress resulting in HSP90AB1 protein radicals formation; disrupts the chaperoning function and the degradation of its client proteins.By similarity

Keywords - PTMi

Acetylation, Glycoprotein, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP34058.
PRIDEiP34058.

2D gel databases

World-2DPAGEi0004:P34058.

PTM databases

iPTMnetiP34058.
PhosphoSitePlusiP34058.

Expressioni

Gene expression databases

BgeeiENSRNOG00000019834.
ExpressionAtlasiP34058. baseline and differential.
GenevisibleiP34058. RN.

Interactioni

Subunit structurei

Monomer. Homodimer (By similarity). Forms a complex with CDK6 and CDC37. Interacts with UNC45A; binding to UNC45A involves 2 UNC45A monomers per HSP90AB1 dimer (By similarity). Interacts with CHORDC1 (By similarity). Interacts with DNAJC7. Interacts with FKBP4. May interact with NWD1. Interacts with SGTA. Interacts with HSF1 in an ATP-dependent manner. Interacts with MET; the interaction suppresses MET kinase activity. Interacts with ERBB2 in an ATP-dependent manner; the interaction suppresses ERBB2 kinase activity. Interacts with HIF1A, KEAP1 and RHOBTB2. Interacts with STUB1 and SMAD3. Interacts with XPO1 and AHSA1. Interacts with BIRC2. Interacts with KCNQ4; promotes cell surface expression of KCNQ4. Interacts with BIRC2; prevents auto-ubiquitination and degradation of its client protein BIRC2. Interacts with NOS3. Interacts with AHR; interaction is inhibited by HSP90AB1 phosphorylation on Ser-226 and Ser-255. Interacts with STIP1 and CDC37; upon SMYD2-dependent methylation. Interacts with JAK2 and PRKCE; promotes functional activation in a heat shock-dependent manner. Interacts with HSP90AA1; interaction is constitutive. HSP90AB1-CDC37 chaperone complex interacts with inactive MAPK7 (via N-terminal half) in resting cells; the interaction is MAP2K5-independent and prevents from ubiquitination and proteasomal degradation. Interacts with CDC25A; prevents heat shock-mediated CDC25A degradation and contributes to cell cycle progression (By similarity). Interacts with TP53 (via DNA binding domain); suppresses TP53 aggregation and prevents from irreversible thermal inactivation (PubMed:8663025). Interacts with TGFB1 processed form (LAP); inhibits latent TGFB1 activation (By similarity). Interacts with TRIM8; prevents nucleus translocation of phosphorylated STAT3 and HSP90AB1 (By similarity).By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi256892. 6 interactors.
CORUMiP34058.
IntActiP34058. 5 interactors.
MINTiMINT-4576429.
STRINGi10116.ENSRNOP00000026920.

Structurei

3D structure databases

ProteinModelPortaliP34058.
SMRiP34058.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 527Interaction with TP53By similarityAdd BLAST526
Regioni2 – 214Interaction with BIRC2By similarityAdd BLAST213
Regioni215 – 552Interaction with AHSA1By similarityAdd BLAST338

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi720 – 724TPR repeat-binding5

Domaini

The TPR repeat-binding motif mediates interaction with TPR repeat-containing proteins.By similarity

Sequence similaritiesi

Belongs to the heat shock protein 90 family.Curated

Phylogenomic databases

eggNOGiKOG0019. Eukaryota.
KOG0020. Eukaryota.
COG0326. LUCA.
GeneTreeiENSGT00900000140936.
HOGENOMiHOG000031988.
HOVERGENiHBG007374.
InParanoidiP34058.
KOiK04079.
OMAiLRYHSSQ.
OrthoDBiEOG091G0270.
PhylomeDBiP34058.
TreeFamiTF300686.

Family and domain databases

CDDicd00075. HATPase_c. 1 hit.
Gene3Di3.30.565.10. 1 hit.
HAMAPiMF_00505. HSP90. 1 hit.
InterProiView protein in InterPro
IPR003594. HATPase_C.
IPR036890. HATPase_C_sf.
IPR019805. Heat_shock_protein_90_CS.
IPR037196. HSP90_C.
IPR001404. Hsp90_fam.
IPR020575. Hsp90_N.
IPR020568. Ribosomal_S5_D2-typ_fold.
PANTHERiPTHR11528. PTHR11528. 1 hit.
PfamiView protein in Pfam
PF02518. HATPase_c. 1 hit.
PF00183. HSP90. 1 hit.
PIRSFiPIRSF002583. Hsp90. 1 hit.
PRINTSiPR00775. HEATSHOCK90.
SMARTiView protein in SMART
SM00387. HATPase_c. 1 hit.
SUPFAMiSSF110942. SSF110942. 1 hit.
SSF54211. SSF54211. 1 hit.
SSF55874. SSF55874. 1 hit.
PROSITEiView protein in PROSITE
PS00298. HSP90. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P34058-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPEEVHHGEE EVETFAFQAE IAQLMSLIIN TFYSNKEIFL RELISNASDA
60 70 80 90 100
LDKIRYESLT DPSKLDSGKE LKIDIIPNPQ ERTLTLVDTG IGMTKADLIN
110 120 130 140 150
NLGTIAKSGT KAFMEALQAG ADISMIGQFG VGFYSAYLVA EKVVVITKHN
160 170 180 190 200
DDEQYAWESS AGGSFTVRAD HGEPIGRGTK VILHLKEDQT EYLEERRVKE
210 220 230 240 250
VVKKHSQFIG YPITLYLEKE REKEISDDEA EEEKGEKEEE DKEDEEKPKI
260 270 280 290 300
EDVGSDEEDD SGKDKKKKTK KIKEKYIDQE ELNKTKPIWT RNPDDITQEE
310 320 330 340 350
YGEFYKSLTN DWEDHLAVKH FSVEGQLEFR ALLFIPRRAP FDLFENKKKK
360 370 380 390 400
NNIKLYVRRV FIMDSCDELI PEYLNFIRGV VDSEDLPLNI SREMLQQSKI
410 420 430 440 450
LKVIRKNIVK KCLELFSELA EDKENYKKFY EAFSKNLKLG IHEDSTNRRR
460 470 480 490 500
LSELLRYHTS QSGDEMTSLS EYVSRMKETQ KSIYYITGES KEQVANSAFV
510 520 530 540 550
ERVRKRGFEV VYMTEPIDEY CVQQLKEFDG KSLVSVTKEG LELPEDEEEK
560 570 580 590 600
KKMEESKAKF ENLCKLMKEI LDKKVEKVTI SNRLVSSPCC IVTSTYGWTA
610 620 630 640 650
NMERIMKAQA LRDNSTMGYM MAKKHLEINP DHPIVETLRQ KAEADKNDKA
660 670 680 690 700
VKDLVVLLFE TALLSSGFSL EDPQTHSNRI YRMIKLGLGI DEDEVTAEEP
710 720
SAAVPDEIPP LEGDEDASRM EEVD
Length:724
Mass (Da):83,281
Last modified:January 23, 2007 - v4
Checksum:iCE323E81CE173ECB
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti6 – 7HH → QK AA sequence (PubMed:3189818).Curated2
Sequence conflicti11E → P AA sequence (PubMed:3189818).Curated1
Sequence conflicti17F → T AA sequence (PubMed:3189818).Curated1
Sequence conflicti20E → F AA sequence (PubMed:3189818).Curated1
Sequence conflicti26S → F in AAH82009 (PubMed:15489334).Curated1
Sequence conflicti82R → A in AAB23369 (PubMed:1525042).Curated1
Sequence conflicti368E → D in AAB23369 (PubMed:1525042).Curated1
Sequence conflicti375N → D in ABE27999 (Ref. 3) Curated1
Sequence conflicti559K → R in AAB23369 (PubMed:1525042).Curated1
Sequence conflicti664 – 674LSSGFSLEDPQ → SSLASHFRRPK in AAB23369 (PubMed:1525042).CuratedAdd BLAST11

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S45392 mRNA. Translation: AAB23369.1.
AY695392 mRNA. Translation: AAT99568.1.
AY695393 mRNA. Translation: AAT99569.1.
DQ022068 Genomic DNA. Translation: ABE27999.1.
BC082009 mRNA. Translation: AAH82009.1.
PIRiS71306.
RefSeqiNP_001004082.3. NM_001004082.3.
UniGeneiRn.98667.

Genome annotation databases

EnsembliENSRNOT00000026920; ENSRNOP00000026920; ENSRNOG00000019834.
GeneIDi301252.
KEGGirno:301252.
UCSCiRGD:1303075. rat.

Similar proteinsi

Entry informationi

Entry nameiHS90B_RAT
AccessioniPrimary (citable) accession number: P34058
Secondary accession number(s): Q1PSW2
, Q66H55, Q68GV5, Q9QWC6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: January 23, 2007
Last modified: November 22, 2017
This is version 174 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families