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Protein

Heat shock protein HSP 90-beta

Gene

HSP90AB1

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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

GO - Biological processi

Keywordsi

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

Names & Taxonomyi

Protein namesi
Recommended name:
Heat shock protein HSP 90-beta
Gene namesi
Name:HSP90AB1
Synonyms:HSPCB
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

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
ChainiPRO_00002479331 – 724Heat shock protein HSP 90-betaAdd BLAST724

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei219N6-succinyllysineBy similarity1
Modified residuei226PhosphoserineBy similarity1
Modified residuei255PhosphoserineBy similarity1
Modified residuei261PhosphoserineBy similarity1
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 residuei445PhosphoserineBy similarity1
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

PeptideAtlasiQ76LV1.
PRIDEiQ76LV1.

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. Interacts with TP53 (via DNA binding domain); suppresses TP53 aggregation and prevents from irreversible thermal inactivation. 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 similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi613028. 4 interactors.

Structurei

3D structure databases

ProteinModelPortaliQ76LV1.
SMRiQ76LV1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 527Interaction with TP53By similarityAdd BLAST527
Regioni1 – 214Interaction with BIRC2By similarityAdd BLAST214
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

HOGENOMiHOG000031988.
HOVERGENiHBG007374.
InParanoidiQ76LV1.
KOiK04079.

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.

Q76LV1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPEEVHHGEE EVETFAFQAE IAQLMSLIIN TFYSNKEIFL RELISNASDA
60 70 80 90 100
LDKIRYESLT DPSKLDSGKE LKIDIIPNPQ ERTLTLVDTG IGMTKADLVN
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 DKDDEEKPKI
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):83,253
Last modified:January 23, 2007 - v3
Checksum:iF5C0C65A143CCBD8
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB072369 mRNA. Translation: BAC82488.1.
BT025368 mRNA. Translation: ABF57324.1.
RefSeqiNP_001073105.1. NM_001079637.1.
UniGeneiBt.64721.

Genome annotation databases

GeneIDi767874.
KEGGibta:767874.

Similar proteinsi

Entry informationi

Entry nameiHS90B_BOVIN
AccessioniPrimary (citable) accession number: Q76LV1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: January 23, 2007
Last modified: October 25, 2017
This is version 106 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families