BioPAX pathway converted from "DT fragment B transports DT fragment A from target cell endosome membrane" in the Reactome database.DT fragment B transports DT fragment A from target cell endosome membrane

DT fragment B transports DT fragment A from target cell endosome membrane

The normal process of acidification of the endocytic vesicle containing diphtheria toxin (DT A:B) associated with target cell proteins HBEGF and CD9 is thought to cause a conformational change in the toxin. Its B fragment forms a channel in the endocytic vesicle membrane through which the A fragment is extruded into the target cell cytosol. There, reduction of the disulfide bond connecting the A and B fragments releases the A fragment to refold. The process requires participation of target cell heat shock proteins (HSP90AA1 and HSP90AB1) and thioredoxin reductase 1 (TXNRD1), which may mediate disulfide bond cleavage (Ratts et al. 2003; Murphy 2011).

Authored: D'Eustachio, Peter, 2014-03-04Reviewed: Liu, Shihui, 2014-11-18Edited: D'Eustachio, Peter, 2014-03-04

Reactome DB_ID: 5334780

endocytic vesicle membraneGO0030666DT:HBEGF:CD9 [endocytic vesicle membrane]

DT:HBEGF:CD9

Reactome DB_ID: 5334776

UniProt:Q99075 HBEGF

HBEGF

DTSDTRHEGFLHBEGFFUNCTION Growth factor that mediates its effects via EGFR, ERBB2 and ERBB4. Required for normal cardiac valve formation and normal heart function. Promotes smooth muscle cell proliferation. May be involved in macrophage-mediated cellular proliferation. It is mitogenic for fibroblasts, but not endothelial cells. It is able to bind EGF receptor/EGFR with higher affinity than EGF itself and is a far more potent mitogen for smooth muscle cells than EGF. Also acts as a diphtheria toxin receptor.SUBUNIT Interacts with FBLN1 (By similarity). Interacts with EGFR and ERBB4.PTM Several N-termini have been identified by direct sequencing. The forms with N-termini 63, 73 and 74 have been tested and found to be biologically active.PTM O-glycosylated with core 1 or possibly core 8 glycans. Thr-47 is a minor glycosylation site compared to Thr-44.

Reactomehttp://www.reactome.orgHomo sapiens

NCBI Taxonomy9606UniProtQ99075

Chain Coordinates

EQUAL

208

EQUAL

Reactome DB_ID: 5334774

UniProt:P21926 CD9

CD9

TSPAN29MIC3CD9GIG2FUNCTION Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion (PubMed:8478605, PubMed:14575715, PubMed:18541721). Present at the cell surface of oocytes and plays a key role in sperm-egg fusion, possibly by organizing multiprotein complexes and the morphology of the membrane required for the fusion (By similarity). In myoblasts, associates with CD81 and PTGFRN and inhibits myotube fusion during muscle regeneration (By similarity). In macrophages, associates with CD81 and beta-1 and beta-2 integrins, and prevents macrophage fusion into multinucleated giant cells specialized in ingesting complement-opsonized large particles (PubMed:12796480). Also prevents the fusion between mononuclear cell progenitors into osteoclasts in charge of bone resorption (By similarity). Acts as a receptor for PSG17 (By similarity). Involved in platelet activation and aggregation (PubMed:18541721). Regulates paranodal junction formation (By similarity). Involved in cell adhesion, cell motility and tumor metastasis (PubMed:8478605, PubMed:7511626).SUBUNIT Forms both disulfide-linked homodimers and higher homooligomers as well as heterooligomers with other members of the tetraspanin family (PubMed:14556650). Interacts (via the second extracellular domain) with integrin ITGAV:ITGB3 (PubMed:19640571, PubMed:27993971). Interacts with integrin ITGA6:ITGB1; interaction takes place in oocytes and is involved in sperm-egg fusion (By similarity). Part of integrin-tetraspanin complexes composed of CD81, beta-1 and beta-2 integrins in the membrane of monocyte/macrophages (PubMed:12796480). Interacts with CD63; identified in a complex with CD63 and ITGB3 (PubMed:19640571). Associates with CR2/CD21 and with PTGFRN/CD9P1 (PubMed:11278880). Part of a complex composed of CD9, CD81, PTGFRN and IGSF8 (By similarity). Interacts directly with IGSF8 (PubMed:11504738). Interacts with PDPN; this interaction is homophilic and attenuates platelet aggregation and pulmonary metastasis induced by PDPN (PubMed:18541721). Interacts (on T cell side) with CD81 at immunological synapses between antigen-presenting cells and T cells (PubMed:23858057).TISSUE SPECIFICITY Detected in platelets (at protein level) (PubMed:19640571). Expressed by a variety of hematopoietic and epithelial cells (PubMed:19640571).PTM Palmitoylated at a low, basal level in unstimulated platelets. The level of palmitoylation increases when platelets are activated by thrombin (in vitro). The protein exists in three forms with molecular masses between 22 and 27 kDa, and is known to carry covalently linked fatty acids (PubMed:11959120). Palmitoylation by ZDHHC2 regulates CD9 expression, association with other tetraspanin family proteins and function in cell adhesion (PubMed:18508921).SIMILARITY Belongs to the tetraspanin (TM4SF) family.

UniProtP21926

EQUAL

228

EQUAL

Reactome DB_ID: 5334767

DT A:B [endocytic vesicle membrane]

DT A:B

DT(33-225):DT(226-567)Diphtheria toxin fragment A:fragment B dimer

Reactome DB_ID: 5334094

UniProt:P00588 Diphtheria toxin

Diphtheria toxin

FUNCTION Diphtheria toxin, produced by a phage infecting Corynebacterium diphtheriae, is a proenzyme that, after activation, catalyzes the covalent attachment of the ADP ribose moiety of NAD to eukaryotic elongation factor 2 (eEF-2). Fragment A is the catalytic portion responsible for enzymatic ADP-ribosylation of elongation factor 2, while fragment B is responsible for binding of toxin to cell receptors and entry of fragment A.ACTIVITY REGULATION Partially inhibited by 1,8-naphthalimide (NAP).SUBUNIT Homodimer.

Corynephage beta

NCBI Taxonomy10703UniProtP00588

Inter-chain Crosslink via L-cystine (cross-link) at 218 and 233

218

EQUAL

L-cystine (cross-link)ChEBI50058

modification

EQUAL

225

EQUAL

Reactome DB_ID: 5334082

Inter-chain Crosslink via L-cystine (cross-link) at 233 and 218

233

EQUAL

226

EQUAL

567

EQUAL

Reactome Database ID Release 765334767Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5334767ReactomeR-CPH-5334767

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CPH-5334767.6Reactome Database ID Release 765334780Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5334780ReactomeR-HSA-5334780

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5334780.7

Reactome DB_ID: 5334084

226

EQUAL

567

EQUAL

Reactome DB_ID: 5334776

EQUAL

208

EQUAL

Reactome DB_ID: 5334774

EQUAL

228

EQUAL

Reactome DB_ID: 5334080

cytosolGO0005829

EQUAL

225

EQUAL

PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Reactome DB_ID: 5334780

GO0008320

GO molecular function

Reactome Database ID Release 765336418Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5336418Reactome Database ID Release 765336420Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5336420ReactomeR-HSA-5336420

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5336420.422069710Pubmed2011Mechanism of diphtheria toxin catalytic domain delivery to the eukaryotic cell cytosol and the cellular factors that directly participate in the processMurphy, John RToxins (Basel) 3:294-30812668662Pubmed2003The cytosolic entry of diphtheria toxin catalytic domain requires a host cell cytosolic translocation factor complexRatts, RyanZeng, HuiyanBerg, Eric ABlue, ClareMcComb, Mark ECostello, Cathy EvanderSpek, Johanna CMurphy, John RJ. Cell Biol. 160:1139-50

ACTIVATION

Reactome Database ID Release 765339491Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5339491ReactomeR-HSA-5339491

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5339491.1

Reactome DB_ID: 73531

UniProt:Q16881 TXNRD1

TXNRD1

TXNRD1GRIM12KDRFFUNCTION Isoform 1 may possess glutaredoxin activity as well as thioredoxin reductase activity and induces actin and tubulin polymerization, leading to formation of cell membrane protrusions. Isoform 4 enhances the transcriptional activity of estrogen receptors alpha and beta while isoform 5 enhances the transcriptional activity of the beta receptor only. Isoform 5 also mediates cell death induced by a combination of interferon-beta and retinoic acid.SUBUNIT Homodimer. Isoform 4 interacts with ESR1 and ESR2. Interacts with HERC5.TISSUE SPECIFICITY Isoform 1 is expressed predominantly in Leydig cells (at protein level). Also expressed in ovary, spleen, heart, liver, kidney and pancreas and in a number of cancer cell lines. Isoform 4 is widely expressed with highest levels in kidney, testis, uterus, ovary, prostate, placenta and fetal liver.INDUCTION Isoform 5 is induced by a combination of interferon-beta and retinoic acid (at protein level). Isoform 1 is induced by estradiol or testosterone in HeLa cells.DOMAIN The N-terminal glutaredoxin domain found in isoform 1 does not contain the C-P-Y-C redox-active motif normally found in glutaredoxins and has been found to be inactive in classical glutaredoxin assays.PTM The N-terminus of isoform 5 is blocked.PTM ISGylated.MISCELLANEOUS The thioredoxin reductase active site is a redox-active disulfide bond. The selenocysteine residue is also essential for catalytic activity.SIMILARITY Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.

UniProtQ16881

EQUAL

649

EQUAL

ACTIVATION

Reactome Database ID Release 765336424Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5336424ReactomeR-HSA-5336424

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5336424.1

Reactome DB_ID: 5228597

endocytic vesicle lumenGO0071682

hydron [ChEBI:15378]

hydron

ChEBI15378

ACTIVATION

Reactome Database ID Release 765339496Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5339496ReactomeR-HSA-5339496

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5339496.1

Reactome DB_ID: 192864

UniProt:P07900 HSP90AA1

HSP90AA1

HSP90AA1HSP90AHSPC1HSPCAFUNCTION 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 which is essential for its chaperone 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 (PubMed:11274138, PubMed:15577939, PubMed:15937123, PubMed:27353360, PubMed:29127155, PubMed:12526792). 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 (PubMed:29127155). 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 (PubMed:27295069, PubMed:26991466). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). 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 (PubMed:25973397). In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues(PubMed:25973397). 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 (PubMed:25973397). Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Mediates the association of TOMM70 with IRF3 or TBK1 in mitochodria outer membrane which promotes host antiviral response (PubMed:20628368, PubMed:25609812).ACTIVITY REGULATION In the resting state, through the dimerization of its C-terminal domain, HSP90 forms a homodimer which is defined as the open conformation (PubMed:18400751). Upon ATP-binding, the N-terminal domain undergoes significant conformational changes and comes in contact to form an active closed conformation (PubMed:18400751). 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 (PubMed:18400751). Co-chaperone TSC1 promotes ATP binding and inhibits HSP90AA1 ATPase activity (PubMed:29127155). Binding to phosphorylated AHSA1 promotes HSP90AA1 ATPase activity (PubMed:29127155). Inhibited by geldanamycin, Ganetespib (STA-9090) and SNX-2112 (PubMed:29127155, PubMed:12526792).SUBUNIT Homodimer (PubMed:7588731, PubMed:8289821, PubMed:18400751, PubMed:29127155). Identified in NR3C1/GCR steroid receptor-chaperone complexes formed at least by NR3C1, HSP90AA1 and a variety of proteins containing TPR repeats such as FKBP4, FKBP5, PPID, PPP5C or STIP1 (PubMed:15383005, PubMed:9195923). Forms a complex containing HSP90AA1, TSC1 and TSC2; TSC1 is required to recruit TCS2 to the complex (PubMed:29127155). The closed form interacts (via the middle domain and TPR repeat-binding motif) with co-chaperone TSC1 (via C-terminus) (PubMed:29127155). Interacts with TOM34 (PubMed:9660753). Interacts with TERT; the interaction, together with PTGES3, is required for correct assembly and stabilization of the TERT holoenzyme complex (PubMed:11274138, PubMed:9817749). Interacts with CHORDC1 and DNAJC7 (PubMed:12853476, PubMed:19875381). Interacts with STUB1 and UBE2N; may couple the chaperone and ubiquitination systems (PubMed:16307917, PubMed:27353360). Interacts (via TPR repeat-binding motif) with PPP5C (via TPR repeats); the interaction is direct and activates PPP5C phosphatase activity (PubMed:15383005, PubMed:15577939, PubMed:16531226, PubMed:27353360). Following LPS binding, may form a complex with CXCR4, GDF5 and HSPA8 (PubMed:11276205). Interacts with KSR1 (PubMed:10409742). Interacts with co-chaperone CDC37 (via C-terminus); the interaction inhibits HSP90AA1 ATPase activity (PubMed:23569206, PubMed:27353360). May interact with NWD1 (PubMed:24681825). Interacts with FNIP1 and FNIP2; the interaction inhibits HSP90AA1 ATPase activity (PubMed:17028174, PubMed:27353360). Interacts with co-chaperone AHSA1 (phosphorylated on 'Tyr-223'); the interaction activates HSP90AA1 ATPase activity and results in the dissociation of TSC1 from HSP90AA1 (PubMed:12604615, PubMed:27353360, PubMed:29127155). Interacts with FLCN in the presence of FNIP1 (PubMed:27353360). Interacts with HSP70, STIP1 and PTGES3 (PubMed:27353360). Interacts with SMYD3; this interaction enhances SMYD3 histone-lysine N-methyltransferase (PubMed:15235609, PubMed:25738358). Interacts with SGTA (via TPR repeats) (PubMed:15708368). Interacts with TTC1 (via TPR repeats) (PubMed:15708368). Interacts with HSF1 in an ATP-dependent manner (PubMed:11583998. PubMed:26517842). Interacts with MET; the interaction suppresses MET kinase activity (PubMed:26517842). Interacts with ERBB2 in an ATP-dependent manner; the interaction suppresses ERBB2 kinase activity (PubMed:26517842). Interacts with HIF1A, KEAP1 and RHOBTB2 (PubMed:26517842). Interacts with HSF1; this interaction is decreased in a IER5-dependent manner, promoting HSF1 accumulation in the nucleus, homotrimerization and DNA-binding activities (PubMed:26754925). Interacts with STUB1 and SMAD3 (PubMed:24613385). Interacts with HSP90AB1; interaction is constitutive (PubMed:20353823). Interacts with HECTD1 (via N-terminus) (By similarity). Interacts with NR3C1 (via domain NR LBD) and NR1D1 (via domain NR LBD) (By similarity). Interacts with NLPR12 (PubMed:30559449, PubMed:17947705). Interacts with PDCL3 (By similarity). Interacts with TOMM70; the interaction is required for preprotein mitochondrial import (PubMed:12526792). Interacts with TOMM70, IRF3 and TBK1; the interactions are direct and mediate the association of TOMM70 with IRF3 and TBK1 (PubMed:20628368).SUBUNIT (Microbial infection) Interacts with herpes simplex virus 1 protein US11; this interaction inhibits TBK1-induced interferon production.DOMAIN The TPR repeat-binding motif mediates interaction with TPR repeat-containing proteins like the co-chaperone STUB1.PTM ISGylated.PTM S-nitrosylated; negatively regulates the ATPase activity and the activation of eNOS by HSP90AA1.PTM Ubiquitinated via 'Lys-63'-linked polyubiquitination by HECTD1. Ubiquitination promotes translocation into the cytoplasm away from the membrane and secretory pathways.SIMILARITY Belongs to the heat shock protein 90 family.

UniProtP07900

EQUAL

732

EQUAL

ACTIVATION

Reactome Database ID Release 765339504Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5339504ReactomeR-HSA-5339504

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5339504.1

Reactome DB_ID: 419617

UniProt:P08238 HSP90AB1

HSP90AB1

HSP90AB1HSP90BHSPC2HSPCBFUNCTION 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 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 (PubMed:16478993, PubMed:19696785). 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 (PubMed:27295069, PubMed:26991466). 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. They first 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 (PubMed:25973397). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Promotes cell differentiation by chaperoning BIRC2 and thereby protecting from auto-ubiquitination and degradation by the proteasomal machinery (PubMed:18239673). Main chaperone involved in the phosphorylation/activation of the STAT1 by chaperoning both JAK2 and PRKCE under heat shock and in turn, activates its own transcription (PubMed:20353823). Involved in the translocation into ERGIC (endoplasmic reticulum-Golgi intermediate compartment) of leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1; the translocation process is mediated by the cargo receptor TMED10 (PubMed:32272059).ACTIVITY REGULATION 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.SUBUNIT Monomer (PubMed:24880080). Homodimer (PubMed:7588731, PubMed:18400751). Forms a complex with CDK6 and CDC37 (PubMed:9482106, PubMed:25486457). Interacts with UNC45A; binding to UNC45A involves 2 UNC45A monomers per HSP90AB1 dimer (PubMed:16478993). Interacts with CHORDC1 (By similarity). Interacts with DNAJC7 (PubMed:18620420). Interacts with FKBP4 (PubMed:15159550). May interact with NWD1 (PubMed:24681825). Interacts with SGTA (PubMed:16580629). 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 (PubMed:26517842). Interacts with STUB1 and SMAD3 (PubMed:24613385). Interacts with XPO1 and AHSA1 (PubMed:22022502, PubMed:25486457). Interacts with BIRC2 (PubMed:25486457). Interacts with KCNQ4; promotes cell surface expression of KCNQ4 (PubMed:23431407). Interacts with BIRC2; prevents auto-ubiquitination and degradation of its client protein BIRC2 (PubMed:18239673). Interacts with NOS3 (PubMed:23585225). Interacts with AHR; interaction is inhibited by HSP90AB1 phosphorylation on Ser-226 and Ser-255 (PubMed:15581363). Interacts with STIP1 and CDC37; upon SMYD2-dependent methylation (PubMed:24880080). Interacts with JAK2 and PRKCE; promotes functional activation in a heat shock-dependent manner (PubMed:20353823). Interacts with HSP90AA1; interaction is constitutive (PubMed:20353823). 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 (PubMed:23428871). Interacts with CDC25A; prevents heat shock-mediated CDC25A degradation and contributes to cell cycle progression (PubMed:22843495). Interacts with TP53 (via DNA binding domain); suppresses TP53 aggregation and prevents from irreversible thermal inactivation (PubMed:15358771). Interacts with TGFB1 processed form (LAP); inhibits latent TGFB1 activation (PubMed:20599762). Interacts with TRIM8; prevents nucleus translocation of phosphorylated STAT3 and HSP90AB1 (By similarity). Interacts with NR3C1 (via domain NR LBD) and NR1D1 (via domain NR LBD) (By similarity). Interacts with PDCL3 (By similarity). Interacts with TTC4 (via TPR repeats) (PubMed:18320024). Interacts with IL1B; the interaction facilitates cargo translocation into the ERGIC (PubMed:32272059).INDUCTION By heat shock.DOMAIN The TPR repeat-binding motif mediates interaction with TPR repeat-containing proteins.PTM Ubiquitinated in the presence of STUB1-UBE2D1 complex (in vitro).PTM ISGylated.PTM S-nitrosylated; negatively regulates the ATPase activity.PTM Phosphorylation at Tyr-301 by SRC is induced by lipopolysaccharide (PubMed:23585225). Phosphorylation at Ser-226 and Ser-255 inhibits AHR interaction (PubMed:15581363).PTM Methylated by SMYD2; facilitates dimerization and chaperone complex formation; promotes cancer cell proliferation.PTM Cleaved following oxidative stress resulting in HSP90AB1 protein radicals formation; disrupts the chaperoning function and the degradation of its client proteins.SIMILARITY Belongs to the heat shock protein 90 family.

UniProtP08238

EQUAL

724

EQUAL