Database: UniProt/SWISS-PROT
Entry: HS90B_RABIT
Original site: HS90B_RABIT 
ID   HS90B_RABIT             Reviewed;         726 AA.
AC   P30947; G1T8Q6;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   12-APR-2017, sequence version 2.
DT   31-JUL-2019, entry version 104.
DE   RecName: Full=Heat shock protein HSP 90-beta;
GN   Name=HSP90AB1; Synonyms=HSPCB;
OS   Oryctolagus cuniculus (Rabbit).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae;
OC   Oryctolagus.
OX   NCBI_TaxID=9986;
RN   [1]
RC   STRAIN=Thorbecke;
RX   PubMed=21993624; DOI=10.1038/nature10530;
RA   Lindblad-Toh K., Garber M., Zuk O., Lin M.F., Parker B.J.,
RA   Washietl S., Kheradpour P., Ernst J., Jordan G., Mauceli E.,
RA   Ward L.D., Lowe C.B., Holloway A.K., Clamp M., Gnerre S., Alfoldi J.,
RA   Beal K., Chang J., Clawson H., Cuff J., Di Palma F., Fitzgerald S.,
RA   Flicek P., Guttman M., Hubisz M.J., Jaffe D.B., Jungreis I.,
RA   Kent W.J., Kostka D., Lara M., Martins A.L., Massingham T., Moltke I.,
RA   Raney B.J., Rasmussen M.D., Robinson J., Stark A., Vilella A.J.,
RA   Wen J., Xie X., Zody M.C., Baldwin J., Bloom T., Chin C.W., Heiman D.,
RA   Nicol R., Nusbaum C., Young S., Wilkinson J., Worley K.C., Kovar C.L.,
RA   Muzny D.M., Gibbs R.A., Cree A., Dihn H.H., Fowler G., Jhangiani S.,
RA   Joshi V., Lee S., Lewis L.R., Nazareth L.V., Okwuonu G.,
RA   Santibanez J., Warren W.C., Mardis E.R., Weinstock G.M., Wilson R.K.,
RA   Delehaunty K., Dooling D., Fronik C., Fulton L., Fulton B., Graves T.,
RA   Minx P., Sodergren E., Birney E., Margulies E.H., Herrero J.,
RA   Green E.D., Haussler D., Siepel A., Goldman N., Pollard K.S.,
RA   Pedersen J.S., Lander E.S., Kellis M.;
RT   "A high-resolution map of human evolutionary constraint using 29
RT   mammals.";
RL   Nature 478:476-482(2011).
RN   [2]
RX   PubMed=2507541;
RA   Lees-Miller S.P., Anderson C.W.;
RT   "The human double-stranded DNA-activated protein kinase phosphorylates
RT   the 90-kDa heat-shock protein, hsp90 alpha at two NH2-terminal
RT   threonine residues.";
RL   J. Biol. Chem. 264:17275-17280(1989).
CC   -!- FUNCTION: Molecular chaperone that promotes the maturation,
CC       structural maintenance and proper regulation of specific target
CC       proteins involved for instance in cell cycle control and signal
CC       transduction. Undergoes a functional cycle that is linked to its
CC       ATPase activity. This cycle probably induces conformational
CC       changes in the client proteins, thereby causing their activation.
CC       Interacts dynamically with various co-chaperones that modulate its
CC       substrate recognition, ATPase cycle and chaperone function.
CC       Engages with a range of client protein classes via its interaction
CC       with various co-chaperone proteins or complexes, that act as
CC       adapters, simultaneously able to interact with the specific client
CC       and the central chaperone itself. Recruitment of ATP and co-
CC       chaperone followed by client protein forms a functional chaperone.
CC       After the completion of the chaperoning process, properly folded
CC       client protein and co-chaperone leave HSP90 in an ADP-bound
CC       partially open conformation and finally, ADP is released from
CC       HSP90 which acquires an open conformation for the next cycle.
CC       Apart from its chaperone activity, it also plays a role in the
CC       regulation of the transcription machinery. HSP90 and its co-
CC       chaperones modulate transcription at least at three different
CC       levels. In the first place, they 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
CC       transferases, and thereby respond to the change in the
CC       environment. Third, they participate in the eviction of histones
CC       from the promoter region of certain genes and thereby turn on gene
CC       expression. Antagonizes STUB1-mediated inhibition of TGF-beta
CC       signaling via inhibition of STUB1-mediated SMAD3 ubiquitination
CC       and degradation. Promotes cell differentiation by chaperoning
CC       BIRC2 and thereby protecting from auto-ubiquitination and
CC       degradation by the proteasomal machinery. Main chaperone that is
CC       involved in the phosphorylation/activation of the STAT1 by
CC       chaperoning both JAK2 and PRKCE under heat shock and in turn,
CC       activates its own transcription. {ECO:0000250|UniProtKB:P08238}.
CC   -!- ACTIVITY REGULATION: In the resting state, through the
CC       dimerization of its C-terminal domain, HSP90 forms a homodimer
CC       which is defined as the open conformation. Upon ATP-binding, the
CC       N-terminal domain undergoes significant conformational changes and
CC       comes in contact to form an active closed conformation. After
CC       HSP90 finishes its chaperoning tasks of assisting the proper
CC       folding, stabilization and activation of client proteins under the
CC       active state, ATP molecule is hydrolyzed to ADP which then
CC       dissociates from HSP90 and directs the protein back to the resting
CC       state. {ECO:0000250|UniProtKB:P08238}.
CC   -!- SUBUNIT: Monomer. Homodimer (By similarity). Forms a complex with
CC       CDK6 and CDC37. Interacts with UNC45A; binding to UNC45A involves
CC       2 UNC45A monomers per HSP90AB1 dimer (By similarity). Interacts
CC       with CHORDC1 (By similarity). Interacts with DNAJC7. Interacts
CC       with FKBP4. May interact with NWD1. Interacts with SGTA. Interacts
CC       with HSF1 in an ATP-dependent manner. Interacts with MET; the
CC       interaction suppresses MET kinase activity. Interacts with ERBB2
CC       in an ATP-dependent manner; the interaction suppresses ERBB2
CC       kinase activity. Interacts with HIF1A, KEAP1 and RHOBTB2.
CC       Interacts with STUB1 and SMAD3. Interacts with XPO1 and AHSA1.
CC       Interacts with BIRC2. Interacts with KCNQ4; promotes cell surface
CC       expression of KCNQ4. Interacts with BIRC2; prevents auto-
CC       ubiquitination and degradation of its client protein BIRC2.
CC       Interacts with NOS3. Interacts with AHR; interaction is inhibited
CC       by HSP90AB1 phosphorylation on Ser-226 and Ser-257. Interacts with
CC       STIP1 and CDC37; upon SMYD2-dependent methylation. Interacts with
CC       JAK2 and PRKCE; promotes functional activation in a heat shock-
CC       dependent manner. Interacts with HSP90AA1; interaction is
CC       constitutive. HSP90AB1-CDC37 chaperone complex interacts with
CC       inactive MAPK7 (via N-terminal half) in resting cells; the
CC       interaction is MAP2K5-independent and prevents from ubiquitination
CC       and proteasomal degradation. Interacts with CDC25A; prevents heat
CC       shock-mediated CDC25A degradation and contributes to cell cycle
CC       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;
CC       prevents nucleus translocation of phosphorylated STAT3 and
CC       HSP90AB1 (By similarity). Interacts with NR3C1 (via domain NR LBD)
CC       and NR1D1 (via domain NR LBD) (By similarity).
CC       {ECO:0000250|UniProtKB:P08238, ECO:0000250|UniProtKB:P11499}.
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}. Note=Translocates with BIRC2 from
CC       the 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
CC       vitro). {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-303 by SRC is induced by
CC       lipopolysaccharide. Phosphorylation at Ser-226 and Ser-257
CC       inhibits AHR 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
CC       protein radicals formation; disrupts the chaperoning function and
CC       the degradation of its client proteins.
CC       {ECO:0000250|UniProtKB:P08238}.
CC   -!- SIMILARITY: Belongs to the heat shock protein 90 family.
CC       {ECO:0000305}.
DR   EMBL; AAGW02018042; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   PIR; B34461; B34461.
DR   RefSeq; XP_002714493.1; XM_002714447.2.
DR   SMR; P30947; -.
DR   STRING; 9986.ENSOCUP00000012976; -.
DR   ChEMBL; CHEMBL3317338; -.
DR   PRIDE; P30947; -.
DR   GeneID; 100358690; -.
DR   KEGG; ocu:100358690; -.
DR   CTD; 3326; -.
DR   eggNOG; KOG0020; Eukaryota.
DR   eggNOG; COG0326; LUCA.
DR   HOGENOM; HOG000031988; -.
DR   KO; K04079; -.
DR   OrthoDB; 924636at2759; -.
DR   TreeFam; TF300686; -.
DR   Proteomes; UP000001811; Unplaced.
DR   Bgee; ENSOCUG00000012842; Expressed in 3 organ(s), highest expression level in prefrontal cortex.
DR   GO; GO:0034751; C:aryl hydrocarbon receptor complex; ISS:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; 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:0046983; F:protein dimerization activity; ISS:UniProtKB.
DR   GO; GO:0051082; F:unfolded protein binding; IEA:InterPro.
DR   GO; GO:0071157; P:negative regulation of cell cycle arrest; ISS:UniProtKB.
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   Gene3D;; -; 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   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   1: Evidence at protein level;
KW   Acetylation; ATP-binding; Cell membrane; Chaperone; Complete proteome;
KW   Cytoplasm; Direct protein sequencing; Glycoprotein; Membrane;
KW   Methylation; Nucleotide-binding; Nucleus; Phosphoprotein;
KW   Reference proteome; S-nitrosylation; Secreted; Stress response;
KW   Ubl conjugation.
FT   INIT_MET      1      1       Removed. {ECO:0000269|PubMed:2507541}.
FT   CHAIN         2    726       Heat shock protein HSP 90-beta.
FT                                /FTId=PRO_0000062919.
FT   REGION        2    529       Interaction with TP53.
FT                                {ECO:0000250|UniProtKB:P08238}.
FT   REGION        2    214       Interaction with BIRC2.
FT                                {ECO:0000250|UniProtKB:P08238}.
FT   REGION        9    231       Interaction with NR3C1.
FT                                {ECO:0000250|UniProtKB:P11499}.
FT   REGION      215    554       Interaction with AHSA1.
FT                                {ECO:0000250|UniProtKB:P08238}.
FT   REGION      266    610       Interaction with NR3C1.
FT                                {ECO:0000250|UniProtKB:P11499}.
FT   REGION      622    725       Interaction with NR1D1.
FT                                {ECO:0000250|UniProtKB:P11499}.
FT   MOTIF       722    726       TPR repeat-binding.
FT                                {ECO:0000250|UniProtKB:P08238}.
FT   COMPBIAS    234    288       Lys-rich. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00012}.
FT   BINDING      46     46       ATP. {ECO:0000250}.
FT   BINDING      88     88       ATP. {ECO:0000250|UniProtKB:P08238}.
FT   BINDING     107    107       ATP. {ECO:0000250}.
FT   BINDING     133    133       ATP; via amide nitrogen. {ECO:0000250}.
FT   BINDING     394    394       ATP. {ECO:0000250}.
FT   SITE        126    127       Cleaved under oxidative stress.
FT                                {ECO:0000250|UniProtKB:P08238}.
FT   MOD_RES     219    219       N6-succinyllysine.
FT                                {ECO:0000250|UniProtKB:P11499}.
FT   MOD_RES     226    226       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P08238}.
FT   MOD_RES     257    257       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P08238}.
FT   MOD_RES     263    263       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P11499}.
FT   MOD_RES     299    299       Phosphothreonine.
FT                                {ECO:0000250|UniProtKB:P08238}.
FT   MOD_RES     303    303       Phosphotyrosine.
FT                                {ECO:0000250|UniProtKB:P08238}.
FT   MOD_RES     307    307       Phosphotyrosine.
FT                                {ECO:0000250|UniProtKB:P11499}.
FT   MOD_RES     309    309       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P08238}.
FT   MOD_RES     401    401       N6-malonyllysine.
FT                                {ECO:0000250|UniProtKB:P08238}.
FT   MOD_RES     437    437       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:P08238}.
FT   MOD_RES     447    447       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P08238}.
FT   MOD_RES     481    481       Phosphothreonine.
FT                                {ECO:0000250|UniProtKB:P08238}.
FT   MOD_RES     483    483       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:P08238}.
FT   MOD_RES     486    486       Phosphotyrosine.
FT                                {ECO:0000250|UniProtKB:P11499}.
FT   MOD_RES     533    533       N6-methylated lysine; alternate.
FT                                {ECO:0000250|UniProtKB:P08238}.
FT   MOD_RES     533    533       N6-succinyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:P11499}.
FT   MOD_RES     576    576       N6-methylated lysine.
FT                                {ECO:0000250|UniProtKB:P08238}.
FT   MOD_RES     579    579       N6-succinyllysine.
FT                                {ECO:0000250|UniProtKB:P11499}.
FT   MOD_RES     592    592       S-nitrosocysteine.
FT                                {ECO:0000250|UniProtKB:P08238}.
FT   MOD_RES     626    626       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:P11499}.
FT   MOD_RES     671    671       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P08238}.
FT   MOD_RES     720    720       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P08238}.
FT   CARBOHYD    436    436       O-linked (GlcNAc) serine. {ECO:0000250}.
FT   CARBOHYD    454    454       O-linked (GlcNAc) serine. {ECO:0000250}.
SQ   SEQUENCE   726 AA;  83467 MW;  1C597A8FD867D533 CRC64;
DBGET integrated database retrieval system