EL52
entrez
3320
canonical
uniprot
P07900
canonical
ensembl
ENSG00000080824
resolver
ensp
ENSP00000216281
resolver
ensp
ENSP00000335153
resolver
genesymbol
EL52
resolver
genesymbol
HSP90AA1
resolver
genesymbol_syn
HEL-S-65p
resolver
genesymbol_syn
HSP90A
resolver
genesymbol_syn
HSPC1
resolver
genesymbol_syn
HSPCA
resolver
hgnc
HGNC:5253
resolver
uniprot
A8K500
resolver
uniprot
B3KPJ9
resolver
uniprot
K9JA46
resolver
uniprot
Q2PP14
resolver
uniprot
Q5CAQ6
resolver
uniprot
Q5CAQ7
resolver
uniprot
Q86SX1
resolver
uniprot
Q9BVQ5
resolver
uniprot_entry
HS90A_HUMAN
resolver
uniprot_entry
K9JA46_HUMAN
resolver
uniprot_entry
Q86SX1_HUMAN
resolver
uniprot_sec
A8K500
resolver
uniprot_sec
B3KPJ9
resolver
uniprot_sec
Q2PP14
resolver
uniprot_sec
Q5CAQ6
resolver
uniprot_sec
Q5CAQ7
resolver
uniprot_sec
Q9BVQ5
resolver
activity_regulation
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:12526792, PubMed:29127155). {ECO:0000269|PubMed:18400751, ECO:0000269|PubMed:29127155}.
uniprot
proteins
amino_acid_sequence
MPEETQTQDQPMEEEEVETFAFQAEIAQLMSLIINTFYSNKEIFLRELISNSSDALDKIRYESLTDPSKLDSGKELHINLIPNKQDRTLTIVDTGIGMTKADLINNLGTIAKSGTKAFMEALQAGADISMIGQFGVGFYSAYLVAEKVTVITKHNDDEQYAWESSAGGSFTVRTDTGEPMGRGTKVILHLKEDQTEYLEERRIKEIVKKHSQFIGYPITLFVEKERDKEVSDDEAEEKEDKEEEKEKEEKESEDKPEIEDVGSDEEEEKKDGDKKKKKKIKEKYIDQEELNKTKPIWTRNPDDITNEEYGEFYKSLTNDWEDHLAVKHFSVEGQLEFRALLFVPRRAPFDLFENRKKKNNIKLYVRRVFIMDNCEELIPEYLNFIRGVVDSEDLPLNISREMLQQSKILKVIRKNLVKKCLELFTELAEDKENYKKFYEQFSKNIKLGIHEDSQNRKKLSELLRYYTSASGDEMVSLKDYCTRMKENQKHIYYITGETKDQVANSAFVERLRKHGLEVIYMIEPIDEYCVQQLKEFEGKTLVSVTKEGLELPEDEEEKKKQEEKKTKFENLCKIMKDILEKKVEKVVVSNRLVTSPCCIVTSTYGWTANMERIMKAQALRDNSTMGYMAAKKHLEINPDHSIIETLRQKAEADKNDKSVKDLVILLYETALLSSGFSLEDPQTHANRIYRMIKLGLGIDEDDPTADDTSAAVTEEMPPLEGDDDTSRMEEVD
uniprot
proteins
ec_number
3.6.4.10
uniprot
proteins
function
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:12526792, PubMed:15577939, PubMed:15937123, PubMed:27353360, PubMed:29127155). 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:26991466, PubMed:27295069). 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}.
uniprot
proteins
mass_dalton
84660
uniprot
proteins
mutagenesis
MUTAGEN 47; /note="E->A: Strong ATP-binding. Strong interaction with HSF1, HIF1A, ERBB2, MET, KEAP1 and RHOBTB2. No effect on interaction with TSC1."; /evidence="ECO:0000269|PubMed:26517842, ECO:0000269|PubMed:29127155"; MUTAGEN 93; /note="D->A: Impaired ATP-binding. Strong interaction with HIF1A, MET, KEAP1 and RHOBTB2. Loss of interaction with HSF1 and ERBB2. Los of interaction with TSC1."; /evidence="ECO:0000269|PubMed:26517842, ECO:0000269|PubMed:29127155"; MUTAGEN 97; /note="G->D: Abolishes ATPase activity."; /evidence="ECO:0000269|PubMed:18256191"; MUTAGEN 313; /note="Y->E: Loss of interaction with TSC1 and increases interaction with AHSA1."; /evidence="ECO:0000269|PubMed:29127155"; MUTAGEN 313; /note="Y->F: No deffect on the interaction with TSC1."; /evidence="ECO:0000269|PubMed:29127155"; MUTAGEN 598; /note="C->A,N,D: Reduces ATPase activity and client protein activation."; /evidence="ECO:0000269|PubMed:15937123, ECO:0000269|PubMed:19696785"; MUTAGEN 598; /note="C->S: Loss of S-nitrosylation."; /evidence="ECO:0000269|PubMed:15937123, ECO:0000269|PubMed:19696785"; MUTAGEN 728..732; /note="MEEVD->AAAA: Loss of interaction with TOMM70. No effect on interaction with IRF3."; /evidence="ECO:0000269|PubMed:25609812"; MUTAGEN 728..732; /note="Missing: Loss of interaction with TSC1."; /evidence="ECO:0000269|PubMed:29127155"; MUTAGEN 729..732; /note="Missing: Loss of interaction with TOMM70."; /evidence="ECO:0000269|PubMed:20628368"; MUTAGEN 731..732; /note="VD->AA: Loss of interaction with TOMM70. No effect on interaction with IRF3."; /evidence="ECO:0000269|PubMed:20628368, ECO:0000269|PubMed:25609812
uniprot
proteins
post_translational_modification
PTM: ISGylated. {ECO:0000269|PubMed:16139798}.; PTM: S-nitrosylated; negatively regulates the ATPase activity and the activation of eNOS by HSP90AA1. {ECO:0000269|PubMed:15937123}.; PTM: Ubiquitinated via 'Lys-63'-linked polyubiquitination by HECTD1. Ubiquitination promotes translocation into the cytoplasm away from the membrane and secretory pathways. {ECO:0000250|UniProtKB:P07901}.
uniprot
proteins
protein_family
Heat shock protein 90 family
uniprot
proteins
pubmed
10409742
uniprot
proteins
pubmed
10508479
uniprot
proteins
pubmed
11274138
uniprot
proteins
pubmed
11276205
uniprot
proteins
pubmed
11583998
uniprot
proteins
pubmed
12508121
uniprot
proteins
pubmed
12526792
uniprot
proteins
pubmed
12604615
uniprot
proteins
pubmed
12853476
uniprot
proteins
pubmed
1368637
uniprot
proteins
pubmed
14654843
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15235609
uniprot
proteins
pubmed
15383005
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15577939
uniprot
proteins
pubmed
15708368
uniprot
proteins
pubmed
15937123
uniprot
proteins
pubmed
16139798
uniprot
proteins
pubmed
16269234
uniprot
proteins
pubmed
16307917
uniprot
proteins
pubmed
16531226
uniprot
proteins
pubmed
16807684
uniprot
proteins
pubmed
17028174
uniprot
proteins
pubmed
17081065
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17947705
uniprot
proteins
pubmed
18088087
uniprot
proteins
pubmed
18256191
uniprot
proteins
pubmed
18318008
uniprot
proteins
pubmed
18400751
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19367720
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19696785
uniprot
proteins
pubmed
19875381
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20353823
uniprot
proteins
pubmed
20628368
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
22066472
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23569206
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24613385
uniprot
proteins
pubmed
24681825
uniprot
proteins
pubmed
2469626
uniprot
proteins
pubmed
2492519
uniprot
proteins
pubmed
2507541
uniprot
proteins
pubmed
2527334
uniprot
proteins
pubmed
25609812
uniprot
proteins
pubmed
25738358
uniprot
proteins
pubmed
2591742
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
25973397
uniprot
proteins
pubmed
26517842
uniprot
proteins
pubmed
26754925
uniprot
proteins
pubmed
26991466
uniprot
proteins
pubmed
27295069
uniprot
proteins
pubmed
27353360
uniprot
proteins
pubmed
2780322
uniprot
proteins
pubmed
29127155
uniprot
proteins
pubmed
29743370
uniprot
proteins
pubmed
30559449
uniprot
proteins
pubmed
7588731
uniprot
proteins
pubmed
8289821
uniprot
proteins
pubmed
9108479
uniprot
proteins
pubmed
9195923
uniprot
proteins
pubmed
9660753
uniprot
proteins
pubmed
9817749
uniprot
proteins
sequence_length
732
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P07901}. Cytoplasm {ECO:0000250|UniProtKB:P07901}. Melanosome {ECO:0000269|PubMed:17081065}. Cell membrane {ECO:0000269|PubMed:11276205}. Mitochondrion {ECO:0000269|PubMed:25609812}. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV.
uniprot
proteins