HS90B_PONAB
ID HS90B_PONAB Reviewed; 724 AA.
AC Q5R710;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=Heat shock protein HSP 90-beta;
GN Name=HSP90AB1;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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 linked to its ATPase activity. This cycle probably
CC induces conformational changes in the client proteins, thereby causing
CC their 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. They first alter the steady-state levels of
CC certain transcription factors in response to various physiological
CC cues. Second, they modulate the activity of certain epigenetic
CC modifiers, such as histone deacetylases or DNA methyl transferases, and
CC thereby respond to the change in the environment. Third, they
CC participate in the eviction of histones from the promoter region of
CC certain genes and thereby turn on gene expression. Antagonizes STUB1-
CC mediated inhibition of TGF-beta signaling via inhibition of STUB1-
CC mediated SMAD3 ubiquitination and degradation. Promotes cell
CC differentiation by chaperoning BIRC2 and thereby protecting from auto-
CC ubiquitination and degradation by the proteasomal machinery. Main
CC chaperone involved in the phosphorylation/activation of the STAT1 by
CC chaperoning both JAK2 and PRKCE under heat shock and in turn, activates
CC its own transcription. Involved in the translocation into ERGIC
CC (endoplasmic reticulum-Golgi intermediate compartment) of leaderless
CC cargos (lacking the secretion signal sequence) such as the interleukin
CC 1/IL-1; the translocation process is mediated by the cargo receptor
CC TMED10. {ECO:0000250|UniProtKB:P08238}.
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. {ECO:0000250|UniProtKB:P08238}.
CC -!- SUBUNIT: Monomer. Homodimer (By similarity). Forms a complex with CDK6
CC and CDC37. Interacts with UNC45A; binding to UNC45A involves 2 UNC45A
CC monomers per HSP90AB1 dimer (By similarity). Interacts with CHORDC1 (By
CC similarity). Interacts with DNAJC7. Interacts with FKBP4. May interact
CC with NWD1. Interacts with SGTA. Interacts with HSF1 in an ATP-dependent
CC manner. Interacts with MET; the interaction suppresses MET kinase
CC activity. Interacts with ERBB2 in an ATP-dependent manner; the
CC interaction suppresses ERBB2 kinase activity. Interacts with HIF1A,
CC KEAP1 and RHOBTB2. Interacts with STUB1 and SMAD3. Interacts with XPO1
CC and AHSA1. Interacts with BIRC2. Interacts with KCNQ4; promotes cell
CC surface expression of KCNQ4. Interacts with BIRC2; prevents auto-
CC ubiquitination and degradation of its client protein BIRC2. Interacts
CC with NOS3. Interacts with AHR; interaction is inhibited by HSP90AB1
CC phosphorylation on Ser-226 and Ser-255. Interacts with STIP1 and CDC37;
CC upon SMYD2-dependent methylation. Interacts with JAK2 and PRKCE;
CC promotes functional activation in a heat shock-dependent manner.
CC Interacts with HSP90AA1; interaction is constitutive. HSP90AB1-CDC37
CC chaperone complex interacts with inactive MAPK7 (via N-terminal half)
CC in resting cells; the interaction is MAP2K5-independent and prevents
CC from ubiquitination and proteasomal degradation. Interacts with CDC25A;
CC prevents heat shock-mediated CDC25A degradation and contributes to cell
CC cycle progression. Interacts with TP53 (via DNA binding domain);
CC suppresses TP53 aggregation and prevents from irreversible thermal
CC inactivation. Interacts with TGFB1 processed form (LAP); inhibits
CC latent TGFB1 activation (By similarity). Interacts with TRIM8; prevents
CC nucleus translocation of phosphorylated STAT3 and HSP90AB1 (By
CC similarity). Interacts with NR3C1 (via domain NR LBD) and NR1D1 (via
CC domain NR LBD) (By similarity). Interacts with PDCL3 (By similarity).
CC Interacts with TTC4 (via TPR repeats) (By similarity). Interacts with
CC IL1B; the interaction facilitates cargo translocation into the ERGIC
CC (By similarity). {ECO:0000250|UniProtKB:P08238,
CC ECO:0000250|UniProtKB:P11499, ECO:0000250|UniProtKB:P34058}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P08238}.
CC Melanosome {ECO:0000250|UniProtKB:P08238}. Nucleus
CC {ECO:0000250|UniProtKB:P08238}. Secreted
CC {ECO:0000250|UniProtKB:P08238}. Cell membrane
CC {ECO:0000250|UniProtKB:P08238}. Dynein axonemal particle
CC {ECO:0000250|UniProtKB:Q6AZV1}. Note=Translocates with BIRC2 from the
CC nucleus to the cytoplasm during differentiation. Secreted when
CC associated with TGFB1 processed form (LAP).
CC {ECO:0000250|UniProtKB:P08238}.
CC -!- DOMAIN: The TPR repeat-binding motif mediates interaction with TPR
CC repeat-containing proteins. {ECO:0000250|UniProtKB:P07900}.
CC -!- PTM: Ubiquitinated in the presence of STUB1-UBE2D1 complex (in vitro).
CC {ECO:0000250|UniProtKB:P08238}.
CC -!- PTM: ISGylated. {ECO:0000250|UniProtKB:P08238}.
CC -!- PTM: S-nitrosylated; negatively regulates the ATPase activity.
CC {ECO:0000250|UniProtKB:P08238}.
CC -!- PTM: Phosphorylation at Tyr-301 by SRC is induced by
CC lipopolysaccharide. Phosphorylation at Ser-226 and Ser-255 inhibits AHR
CC interaction. {ECO:0000250|UniProtKB:P08238}.
CC -!- PTM: Methylated by SMYD2; facilitates dimerization and chaperone
CC complex formation; promotes cancer cell proliferation.
CC {ECO:0000250|UniProtKB:P08238}.
CC -!- PTM: Cleaved following oxidative stress resulting in HSP90AB1 protein
CC radicals formation; disrupts the chaperoning function and the
CC degradation of its client proteins. {ECO:0000250|UniProtKB:P08238}.
CC -!- SIMILARITY: Belongs to the heat shock protein 90 family. {ECO:0000305}.
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DR EMBL; CR860313; CAH92450.1; -; mRNA.
DR RefSeq; NP_001126444.1; NM_001132972.2.
DR AlphaFoldDB; Q5R710; -.
DR SMR; Q5R710; -.
DR STRING; 9601.ENSPPYP00000018631; -.
DR PRIDE; Q5R710; -.
DR GeneID; 100173428; -.
DR KEGG; pon:100173428; -.
DR CTD; 3326; -.
DR eggNOG; KOG0019; Eukaryota.
DR InParanoid; Q5R710; -.
DR OrthoDB; 924636at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0034751; C:aryl hydrocarbon receptor complex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0120293; C:dynein axonemal particle; ISS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0019899; F:enzyme binding; IEA:UniProt.
DR GO; GO:0046983; F:protein dimerization activity; ISS:UniProtKB.
DR GO; GO:0051082; F:unfolded protein binding; IEA:InterPro.
DR GO; GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:1901389; P:negative regulation of transforming growth factor beta activation; ISS:UniProtKB.
DR GO; GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0006457; P:protein folding; IEA:InterPro.
DR GO; GO:0051726; P:regulation of cell cycle; ISS:UniProtKB.
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;
KW Glycoprotein; Membrane; Methylation; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; S-nitrosylation; Secreted;
KW Stress response; Ubl conjugation.
FT CHAIN 1..724
FT /note="Heat shock protein HSP 90-beta"
FT /id="PRO_0000271478"
FT REGION 1..527
FT /note="Interaction with TP53"
FT /evidence="ECO:0000250|UniProtKB:P08238"
FT REGION 1..214
FT /note="Interaction with BIRC2"
FT /evidence="ECO:0000250|UniProtKB:P08238"
FT REGION 9..231
FT /note="Interaction with NR3C1"
FT /evidence="ECO:0000250|UniProtKB:P11499"
FT REGION 215..552
FT /note="Interaction with AHSA1"
FT /evidence="ECO:0000250|UniProtKB:P08238"
FT REGION 222..270
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 264..608
FT /note="Interaction with NR3C1"
FT /evidence="ECO:0000250|UniProtKB:P11499"
FT REGION 620..723
FT /note="Interaction with NR1D1"
FT /evidence="ECO:0000250|UniProtKB:P11499"
FT REGION 695..724
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 720..724
FT /note="TPR repeat-binding"
FT COMPBIAS 241..270
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 46
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 88
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 107
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 133
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 392
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT SITE 126..127
FT /note="Cleaved under oxidative stress"
FT /evidence="ECO:0000250|UniProtKB:P08238"
FT MOD_RES 219
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P11499"
FT MOD_RES 226
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P08238"
FT MOD_RES 255
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P08238"
FT MOD_RES 261
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11499"
FT MOD_RES 297
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P08238"
FT MOD_RES 301
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P08238"
FT MOD_RES 305
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P11499"
FT MOD_RES 307
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P08238"
FT MOD_RES 399
FT /note="N6-malonyllysine"
FT /evidence="ECO:0000250"
FT MOD_RES 435
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P08238"
FT MOD_RES 445
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P08238"
FT MOD_RES 479
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P08238"
FT MOD_RES 481
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P08238"
FT MOD_RES 484
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P11499"
FT MOD_RES 531
FT /note="N6-methylated lysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P08238"
FT MOD_RES 531
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P11499"
FT MOD_RES 574
FT /note="N6-methylated lysine"
FT /evidence="ECO:0000250|UniProtKB:P08238"
FT MOD_RES 590
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:P08238"
FT MOD_RES 624
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P11499"
FT MOD_RES 669
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P08238"
FT MOD_RES 718
FT /note="Phosphoserine; by PLK2 and PLK3"
FT /evidence="ECO:0000250|UniProtKB:P08238"
FT CARBOHYD 434
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000250"
FT CARBOHYD 452
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000250"
SQ SEQUENCE 724 AA; 83238 MW; 08F2F828F49438A5 CRC64;
MPEEVHHGEE EVETFAFQAE IAQLMSLIIN TFYSNKEIFL RELISNASDA LDKIRYESLT
DPSKLDSGKE LKIDIIPNPQ ERTLTLVDTG IGMTKADLIN NLGTIAKSGT KAFMEALQAG
ADISMIGQFG VGFYSAYLVA EKVVVITKHN DDEQYAWESS AGGSFTVRAD HGEPIGRGTK
VILHLKEDQT EYLEERRVKE VVKKHSQFIG YPITLYLEKE REKEISDDEA EEEKGEKEEE
DKDDEEKPKI EDVGSDEEDD SGKDKKKKTK KIKEKYIDQE ELNKTKPIWT RNPDDITQEE
YGEFYKSLTN DWEDHLAVKH FSVEGQLEFR ALLFIPRRAP FDLFENKKKK NNIKLYVRRV
FIMDSCDELI PEYLNFIRGV VDSEDLPLNI SREMLQQSKI LKVIRKNIVK KCLELFSELA
EDKENYKKFY EAFSKNLKLG IHEDSTNRRR LSELLRYHTS QSGDEMTSLS EYVSRMKETQ
KSIYYITGES KEQVANSAFV ERVRKRGFEV VYMTEPIDEY CVQQLKEFDG KSLVSVTKEG
LELPEDEEEK KKMEESKAKF ENLCKLMKEI LDKKVEEVTI SNRLVSSPCC IVTSTYGWTA
NMERIMKAQA LRDNSTMGYM MAKKHLEINP DHPIVETLRQ KAEADKNDKA VKDLVVLLFE
TALLSSGFSL EDPQTHSNRI YRMIKLGLGI DEDEVAAEEP SAAVPDEIPP LEGDEDASRM
EEVD
