DegronMD - P08238(HSP90AB1)

FUNCTION: 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). {ECO:0000269|PubMed:16478993, ECO:0000269|PubMed:18239673, ECO:0000269|PubMed:19696785, ECO:0000269|PubMed:20353823, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:32272059, ECO:0000303|PubMed:25973397, ECO:0000303|PubMed:26991466, ECO:0000303|PubMed:27295069}.; FUNCTION: (Microbial infection) Binding to N.meningitidis NadA stimulates monocytes (PubMed:21949862). Seems to interfere with N.meningitidis NadA-mediated invasion of human cells (Probable). {ECO:0000269|PubMed:21949862, ECO:0000305|PubMed:22066472}. View more >>

GO - Biological processes (BP): axon extension [GO:0048675]; cellular response to heat [GO:0034605]; cellular response to interleukin-4 [GO:0071353]; cellular response to organic cyclic compound [GO:0071407]; central nervous system neuron axonogenesis [GO:0021955]; chaperone-mediated protein complex assembly [GO:0051131]; establishment of cell polarity [GO:0030010]; negative regulation of complement-dependent cytotoxicity [GO:1903660]; negative regulation of neuron apoptotic process [GO:0043524]; negative regulation of proteasomal protein catabolic process [GO:1901799]; negative regulation of proteasomal ubiquitin-dependent protein catabolic process [GO:0032435]; negative regulation of protein metabolic process [GO:0051248]; negative regulation of transforming growth factor beta activation [GO:1901389]; placenta development [GO:0001890]; positive regulation of cell differentiation [GO:0045597]; positive regulation of cell size [GO:0045793]; positive regulation of cyclin-dependent protein kinase activity [GO:1904031]; positive regulation of nitric oxide biosynthetic process [GO:0045429]; positive regulation of peptidyl-serine phosphorylation [GO:0033138]; positive regulation of phosphoprotein phosphatase activity [GO:0032516]; positive regulation of protein binding [GO:0032092]; positive regulation of protein import into nucleus [GO:0042307]; positive regulation of protein kinase B signaling [GO:0051897]; positive regulation of protein localization to cell surface [GO:2000010]; positive regulation of protein serine/threonine kinase activity [GO:0071902]; positive regulation of tau-protein kinase activity [GO:1902949]; positive regulation of telomerase activity [GO:0051973]; positive regulation of transforming growth factor beta receptor signaling pathway [GO:0030511]; protein folding [GO:0006457]; protein stabilization [GO:0050821]; regulation of cell cycle [GO:0051726]; regulation of protein localization [GO:0032880]; regulation of protein ubiquitination [GO:0031396]; response to cocaine [GO:0042220]; response to salt stress [GO:0009651]; response to unfolded protein [GO:0006986]; response to xenobiotic stimulus [GO:0009410]; supramolecular fiber organization [GO:0097435]; telomerase holoenzyme complex assembly [GO:1905323]; telomere maintenance via telomerase [GO:0007004]; virion attachment to host cell [GO:0019062] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.R449H	TCGA-2W-A8YY	CESC	TCGA	NRRRLSELL	DEG_APCC_DBOX_1	447:455	Mutation altering degron motif	0.7133
p.R449H	DO223732	CESC	ICGC	NRRRLSELL	DEG_APCC_DBOX_1	447:455	Mutation altering degron motif	0.7133
p.R449H	DO233746	GACA	ICGC	NRRRLSELL	DEG_APCC_DBOX_1	447:455	Mutation altering degron motif	0.7133
p.R448H	TCGA-CR-6478	HNSC	TCGA	NRRRLSELL	DEG_APCC_DBOX_1	447:455	Mutation altering degron motif	0.8244
p.R448H	DO233855	GACA	ICGC	NRRRLSELL	DEG_APCC_DBOX_1	447:455	Mutation altering degron motif	0.8244
p.R448H	DO15839	HNSC	ICGC	NRRRLSELL	DEG_APCC_DBOX_1	447:455	Mutation altering degron motif	0.8244
p.R448C	TCGA-D7-A6EV	STAD	TCGA	NRRRLSELL	DEG_APCC_DBOX_1	447:455	Mutation altering degron motif	0.8301
p.R448C	DO50116	STAD	ICGC	NRRRLSELL	DEG_APCC_DBOX_1	447:455	Mutation altering degron motif	0.8301
p.R456L	TCGA-E2-A1IJ	BRCA	TCGA	NRRRLSELL	DEG_APCC_DBOX_1	447:455	Mutation rewiring degron network	0.3056
p.R456L	DO2761	BRCA	ICGC	NRRRLSELL	DEG_APCC_DBOX_1	447:455	Mutation rewiring degron network	0.3056
p.Q461H	DO229041	LICA	ICGC	NRRRLSELL	DEG_APCC_DBOX_1	447:455	Mutation rewiring degron network	0.1667
p.Y457C	DO48888	PBCA	ICGC	NRRRLSELL	DEG_APCC_DBOX_1	447:455	Mutation blocking phosphorylation signal	0.7222
p.R450H	SIDM01307	Colorectal Carcinoma	GDSC	NRRRLSELL	DEG_APCC_DBOX_1	447:455	Mutation altering degron motif	0.7133
p.E443K	SIDM00118	Colorectal Carcinoma	GDSC	NRRRLSELL	DEG_APCC_DBOX_1	447:455	Mutation rewiring degron network	0.2222
p.E443K	ACH-001081	Colon/Colorectal Cancer	CCLE	NRRRLSELL	DEG_APCC_DBOX_1	447:455	Mutation rewiring degron network	0.2222
p.E443K	HCC2998	large intestine	COSMIC	NRRRLSELL	DEG_APCC_DBOX_1	447:455	Mutation rewiring degron network	0.2222

DegronMD: protein-targeted degradation, mutation and drug response to degrons

HSP90AB1

UniProt ID: P08238

Entrez ID: 3326

Protein name: Heat shock protein HSP 90-beta (HSP 90) (Heat shock 84 kDa) (HSP 84) (HSP84)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for HSP90AB1 in