HS90A_PANTR
ID HS90A_PANTR Reviewed; 733 AA.
AC A5A6K9;
DT 21-AUG-2007, integrated into UniProtKB/Swiss-Prot.
DT 12-JUN-2007, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Heat shock protein HSP 90-alpha;
GN Name=HSP90AA1;
OS Pan troglodytes (Chimpanzee).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pan.
OX NCBI_TaxID=9598;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=17574350; DOI=10.1016/j.gene.2007.04.013;
RA Sakate R., Suto Y., Imanishi T., Tanoue T., Hida M., Hayasaka I.,
RA Kusuda J., Gojobori T., Hashimoto K., Hirai M.;
RT "Mapping of chimpanzee full-length cDNAs onto the human genome unveils
RT large potential divergence of the transcriptome.";
RL Gene 399:1-10(2007).
CC -!- FUNCTION: Molecular chaperone that promotes the maturation, structural
CC maintenance and proper regulation of specific target proteins involved
CC for instance in cell cycle control and signal transduction. Undergoes a
CC functional cycle that is linked to its ATPase activity which is
CC essential for its chaperone activity. This cycle probably induces
CC conformational changes in the client proteins, thereby causing their
CC activation. Interacts dynamically with various co-chaperones that
CC modulate its substrate recognition, ATPase cycle and chaperone
CC function. Engages with a range of client protein classes via its
CC interaction with various co-chaperone proteins or complexes, that act
CC as adapters, simultaneously able to interact with the specific client
CC and the central chaperone itself. Recruitment of ATP and co-chaperone
CC followed by client protein forms a functional chaperone. After the
CC completion of the chaperoning process, properly folded client protein
CC and co-chaperone leave HSP90 in an ADP-bound partially open
CC conformation and finally, ADP is released from HSP90 which acquires an
CC open conformation for the next cycle. Apart from its chaperone
CC activity, it also plays a role in the regulation of the transcription
CC machinery. HSP90 and its co-chaperones modulate transcription at least
CC at three different levels. In the first place, they alter the steady-
CC state levels of certain transcription factors in response to various
CC physiological cues. Second, they modulate the activity of certain
CC epigenetic modifiers, such as histone deacetylases or DNA methyl
CC transferases, and thereby respond to the change in the environment.
CC Third, they participate in the eviction of histones from the promoter
CC region of certain genes and thereby turn on gene expression. Binds
CC bacterial lipopolysaccharide (LPS) and mediates LPS-induced
CC inflammatory response, including TNF secretion by monocytes.
CC {ECO:0000250|UniProtKB:P07900}.
CC -!- ACTIVITY REGULATION: In the resting state, through the dimerization of
CC its C-terminal domain, HSP90 forms a homodimer which is defined as the
CC open conformation. Upon ATP-binding, the N-terminal domain undergoes
CC significant conformational changes and comes in contact to form an
CC active closed conformation. After HSP90 finishes its chaperoning tasks
CC of assisting the proper folding, stabilization and activation of client
CC proteins under the active state, ATP molecule is hydrolyzed to ADP
CC which then dissociates from HSP90 and directs the protein back to the
CC resting state. Co-chaperone TSC1 promotes ATP binding and inhibits
CC HSP90AA1 ATPase activity. Binding to phosphorylated AHSA1 promotes
CC HSP90AA1 ATPase activity. Inhibited by Ganetespib (STA-9090) and SNX-
CC 2112. {ECO:0000250|UniProtKB:P07900}.
CC -!- SUBUNIT: Homodimer. Identified in NR3C1/GCR steroid receptor-chaperone
CC complexes formed at least by NR3C1, HSP90AA1 and a variety of proteins
CC containing TPR repeats such as FKBP4, FKBP5, PPID, PPP5C or STIP1.
CC Forms a complex containing HSP90AA1, TSC1 and TSC2; TSC1 is required to
CC recruit TCS2 to the complex. The closed form interacts (via the middle
CC domain and TPR repeat-binding motif) with co-chaperone TSC1 (via C-
CC terminus). Interacts with TOM34. Interacts with TERT; the interaction,
CC together with PTGES3, is required for correct assembly and
CC stabilization of the TERT holoenzyme complex. Interacts with CHORDC1
CC and DNAJC7. Interacts with STUB1 and UBE2N; may couple the chaperone
CC and ubiquitination systems. Interacts (via TPR repeat-binding motif)
CC with PPP5C (via TPR repeats); the interaction is direct and activates
CC PPP5C phosphatase activity. Following LPS binding, may form a complex
CC with CXCR4, GDF5 and HSPA8. Interacts with KSR1. Interacts with co-
CC chaperone CDC37 (via C-terminus); the interaction inhibits HSP90AA1
CC ATPase activity. May interact with NWD1. Interacts with FNIP1 and
CC FNIP2; the interaction inhibits HSP90AA1 ATPase activity. Interacts
CC with co-chaperone AHSA1 (phosphorylated on 'Tyr-223'); the interaction
CC activates HSP90AA1 ATPase activity and results in the dissociation of
CC TSC1 from HSP90AA1. Interacts with FLCN in the presence of FNIP1.
CC Interacts with HSP70, STIP1 and PTGES3. Interacts with SMYD3; this
CC interaction enhances SMYD3 histone-lysine N-methyltransferase.
CC Interacts with SGTA (via TPR repeats). Interacts with TTC1 (via TPR
CC repeats). Interacts with HSF1 in an ATP-dependent manner. Interacts
CC with MET; the interaction suppresses MET kinase activity. Interacts
CC with ERBB2 in an ATP-dependent manner; the interaction suppresses ERBB2
CC kinase activity. Interacts with HIF1A, KEAP1 and RHOBTB2. Interacts
CC with HIF1A, KEAP1 and RHOBTB2 (By similarity). Interacts with HSF1;
CC this interaction is decreased in a IER5-dependent manner, promoting
CC HSF1 accumulation in the nucleus, homotrimerization and DNA-binding
CC activities. Interacts with STUB1 and SMAD3. Interacts with HSP90AB1;
CC interaction is constitutive (By similarity). Interacts with NR3C1 (via
CC domain NR LBD) and NR1D1 (via domain NR LBD) (By similarity). Interacts
CC with NLPR12. Interacts with PDCL3 (By similarity). Forms a complex with
CC ASL, ASS1, SLC7A1, and NOS2; the complex regulates cell-autonomous L-
CC arginine synthesis and citrulline recycling while channeling
CC extracellular L-arginine to nitric oxide synthesis pathway.
CC {ECO:0000250|UniProtKB:P07900, ECO:0000250|UniProtKB:P07901,
CC ECO:0000250|UniProtKB:P82995}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P07901}. Cytoplasm
CC {ECO:0000250|UniProtKB:P07901}. Melanosome
CC {ECO:0000250|UniProtKB:P07900}. Cell membrane
CC {ECO:0000250|UniProtKB:P07900}.
CC -!- DOMAIN: The TPR repeat-binding motif mediates interaction with TPR
CC repeat-containing proteins like the co-chaperone STUB1.
CC {ECO:0000250|UniProtKB:P07900}.
CC -!- PTM: ISGylated. {ECO:0000250|UniProtKB:P07900}.
CC -!- PTM: S-nitrosylated; negatively regulates the ATPase activity and the
CC activation of eNOS by HSP90AA1. {ECO:0000250|UniProtKB:P07900}.
CC -!- PTM: Ubiquitinated via 'Lys-63'-linked polyubiquitination by HECTD1.
CC Ubiquitination promotes translocation into the cytoplasm away from the
CC membrane and secretory pathways. {ECO:0000250|UniProtKB:P07901}.
CC -!- SIMILARITY: Belongs to the heat shock protein 90 family. {ECO:0000305}.
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DR EMBL; AB222137; BAF62382.1; -; mRNA.
DR RefSeq; NP_001092042.1; NM_001098572.1.
DR AlphaFoldDB; A5A6K9; -.
DR BMRB; A5A6K9; -.
DR SMR; A5A6K9; -.
DR STRING; 9598.ENSPTRP00000058433; -.
DR PaxDb; A5A6K9; -.
DR PRIDE; A5A6K9; -.
DR GeneID; 743883; -.
DR KEGG; ptr:743883; -.
DR CTD; 3320; -.
DR eggNOG; KOG0019; Eukaryota.
DR InParanoid; A5A6K9; -.
DR Proteomes; UP000002277; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:AgBase.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0043209; C:myelin sheath; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; ISS:AgBase.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0097718; F:disordered domain specific binding; IBA:GO_Central.
DR GO; GO:0019899; F:enzyme binding; IEA:UniProt.
DR GO; GO:0051082; F:unfolded protein binding; IBA:GO_Central.
DR GO; GO:0034605; P:cellular response to heat; IBA:GO_Central.
DR GO; GO:0006457; P:protein folding; IBA:GO_Central.
DR GO; GO:0050821; P:protein stabilization; IBA:GO_Central.
DR GO; GO:0046677; P:response to antibiotic; ISS:AgBase.
DR GO; GO:0009409; P:response to cold; ISS:AgBase.
DR GO; GO:0009408; P:response to heat; ISS:AgBase.
DR Gene3D; 1.20.120.790; -; 1.
DR Gene3D; 3.30.565.10; -; 1.
DR HAMAP; MF_00505; HSP90; 1.
DR InterPro; IPR003594; HATPase_C.
DR InterPro; IPR036890; HATPase_C_sf.
DR InterPro; IPR019805; Heat_shock_protein_90_CS.
DR InterPro; IPR037196; HSP90_C.
DR InterPro; IPR001404; Hsp90_fam.
DR InterPro; IPR020575; Hsp90_N.
DR InterPro; IPR020568; Ribosomal_S5_D2-typ_fold.
DR PANTHER; PTHR11528; PTHR11528; 1.
DR Pfam; PF02518; HATPase_c; 1.
DR Pfam; PF00183; HSP90; 1.
DR PIRSF; PIRSF002583; Hsp90; 1.
DR PRINTS; PR00775; HEATSHOCK90.
DR SMART; SM00387; HATPase_c; 1.
DR SUPFAM; SSF110942; SSF110942; 1.
DR SUPFAM; SSF54211; SSF54211; 1.
DR SUPFAM; SSF55874; SSF55874; 1.
DR PROSITE; PS00298; HSP90; 1.
PE 2: Evidence at transcript level;
KW Acetylation; ATP-binding; Cell membrane; Chaperone; Cytoplasm; Membrane;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW S-nitrosylation; Stress response; Ubl conjugation.
FT CHAIN 1..733
FT /note="Heat shock protein HSP 90-alpha"
FT /id="PRO_0000297556"
FT REGION 9..236
FT /note="Interaction with NR3C1"
FT /evidence="ECO:0000250|UniProtKB:P07901"
FT REGION 225..279
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 272..617
FT /note="Interaction with NR3C1"
FT /evidence="ECO:0000250|UniProtKB:P07901"
FT REGION 285..733
FT /note="Interaction with FLCN and FNIP1"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT REGION 285..621
FT /note="Interaction with FNIP2 and TSC1"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT REGION 629..732
FT /note="Interaction with NR1D1"
FT /evidence="ECO:0000250|UniProtKB:P07901"
FT REGION 683..733
FT /note="Required for homodimerization"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT REGION 701..733
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 729..733
FT /note="Essential for interaction with SMYD3, TSC1 and
FT STIP1/HOP"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT REGION 730..733
FT /note="Essential for interaction with SGTA and TTC1"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT MOTIF 724..733
FT /note="TPR repeat-binding"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT COMPBIAS 243..257
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 51
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 93
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 112
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 138
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 401
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 5
FT /note="Phosphothreonine; by PRKDC"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT MOD_RES 7
FT /note="Phosphothreonine; by PRKDC"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT MOD_RES 58
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P07901"
FT MOD_RES 84
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P07901"
FT MOD_RES 231
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT MOD_RES 252
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT MOD_RES 263
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT MOD_RES 314
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P07901"
FT MOD_RES 444
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT MOD_RES 454
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P82995"
FT MOD_RES 459
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT MOD_RES 477
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT MOD_RES 490
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT MOD_RES 493
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P07901"
FT MOD_RES 586
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT MOD_RES 599
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:P07900"
FT MOD_RES 642
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P07900"
SQ SEQUENCE 733 AA; 84773 MW; 4DF02752EEE820C5 CRC64;
MPEETQTQDQ PMEEEEVETF AFQAEIAQLM SLIINTFYSN KEIFLRELIS NSSDALDKIR
YESLTDPSKL DSGKELHINL IPNKQDRTLT IVDTGIGMTK ADLINNLGTI AKSGTKAFME
ALQAGADISM IGQFGVGFYS AYLVAEKVTV ITKHNDDEQY AWESSAGGSF TVRTDTGEPM
GRGTKVIPHL KEDQTEYLEE RRIKEIVKKH SQFIGYPITL FVEKERDKEV SDDEAEEKED
KEEEKEKEEK ESEDKPEIED VGSDEEEEEK KDGDKKKKKK IKEKYIDQEE LNKTKPIWTR
NPDDITNEEY GEFYKSLTND WEDHLAVKHF SVEGQLEFRA LLFVPRRAPF DLFENRKKKN
NIKLYVRRVF IMDNCEELIP EYLNFIRGVV DSEDLPLNIS REMLQQSKIL KVIRKNLVKK
CLELFTELAE DKENYKKFYE QFSKNIKLGI HEDSQNRKKL SELLRYYTSA SGDEMVSLKD
YCTRMKENQK HIYYITGETK DQVANSAFVE RLRKHGLEVI YMIEPIDEYC VQQLKEFEGK
TLVSVTKEGL ELPEDEEEKK KQEEKKTKFE NLCKIMKDIL EKKVEKVVVS NRLVTSPCCI
VTSTYGWTAN MERIMKAQAL RDNSTMGYMA AKKHLEINPD HSIIETLRQK AEADKNDKSV
KDLVILLYET ALLSSGFSLE DPQTHANRIY RMIKLGLGID EDDPTADDTS AAVTEEMPPL
EGDDDTSRME EVD
