DegronMD - P07900(HSP90AA1)

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 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 mitochondrial outer membrane which promotes host antiviral response (PubMed:20628368, PubMed:25609812). {ECO:0000269|PubMed:11274138, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:12526792, ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:15937123, ECO:0000269|PubMed:20628368, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:29127155, ECO:0000303|PubMed:25973397, ECO:0000303|PubMed:26991466, ECO:0000303|PubMed:27295069}.; FUNCTION: (Microbial infection) Seems to interfere with N.meningitidis NadA-mediated invasion of human cells. Decreasing HSP90 levels increases adhesion and entry of E.coli expressing NadA into human Chang cells; increasing its levels leads to decreased adhesion and invasion. {ECO:0000305|PubMed:22066472}. View more >>

GO - Biological processes (BP): 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.R477K	TCGA-B5-A3FA	UCEC	TCGA	MKENQ	DEG_APCC_KENBOX_2	484:488	Mutation rewiring degron network	0.1389
p.V487I	TCGA-FI-A2D0	UCEC	TCGA	MKENQ	DEG_APCC_KENBOX_2	484:488	Mutation altering degron motif	0.7076
p.C496Y	TCGA-VQ-A8P2	STAD	TCGA	MKENQ	DEG_APCC_KENBOX_2	484:488	Mutation rewiring degron network	0.1111
p.R489T	TCGA-ZF-AA4W	BLCA	TCGA	MKENQ	DEG_APCC_KENBOX_2	484:488	Mutation blocking ubiquitination signal	0.75
p.K485N	DO217864	BTCA	ICGC	MKENQ	DEG_APCC_KENBOX_2	484:488	Mutation altering degron motif	0.6918
p.K485E	DO48676	KIRC	ICGC	MKENQ	DEG_APCC_KENBOX_2	484:488	Mutation altering degron motif	0.7022
p.T495K	DO229026	LICA	ICGC	MKENQ	DEG_APCC_KENBOX_2	484:488	Mutation rewiring degron network	0.1389
p.Y480H	DO229213	THCA	ICGC	MKENQ	DEG_APCC_KENBOX_2	484:488	Mutation blocking phosphorylation signal	0.6667
p.G496C	DO41235	UCEC	ICGC	MKENQ	DEG_APCC_KENBOX_2	484:488	Mutation rewiring degron network	0.1111
p.I491T	ACH-000095	Brain Cancer	CCLE	MKENQ	DEG_APCC_KENBOX_2	484:488	Mutation rewiring degron network	0.25
p.E497D	ACH-000716	Thyroid Cancer	CCLE	MKENQ	DEG_APCC_KENBOX_2	484:488	Mutation rewiring degron network	0.0833
p.E497D	TT2609-C02	thyroid	COSMIC	MKENQ	DEG_APCC_KENBOX_2	484:488	Mutation rewiring degron network	0.0833
p.M484I	ACH-001961	Gallbladder Cancer	CCLE	MKENQ	DEG_APCC_KENBOX_2	484:488	Mutation altering degron motif	0.6507
p.D479N	ACH-001961	Gallbladder Cancer	CCLE	MKENQ	DEG_APCC_KENBOX_2	484:488	Mutation rewiring degron network	0.1944
p.V475L	ACH-002710	Sarcoma	CCLE	MKENQ	DEG_APCC_KENBOX_2	484:488	Mutation rewiring degron network	0.0833
p.H490N	COLO-829	skin	COSMIC	MKENQ	DEG_APCC_KENBOX_2	484:488	Mutation rewiring degron network	0.2778

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

HSP90AA1

UniProt ID: P07900

Entrez ID: 3320

Protein name: Heat shock protein HSP 90-alpha (EC 3.6.4.10) (Heat shock 86 kDa) (HSP 86) (HSP86) (Lipopolysaccharide-associated protein 2) (LAP-2) (LPS-associated protein 2) (Renal carcinoma antigen NY-REN-38)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for HSP90AA1 in