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Protein

Activator of 90 kDa heat shock protein ATPase homolog 1

Gene

AHSA1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Acts as a co-chaperone of HSP90AA1 (PubMed:29127155). Activates the ATPase activity of HSP90AA1 leading to increase in its chaperone activity (PubMed:29127155). Competes with the inhibitory co-chaperone FNIP1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:27353360). Competes with the inhibitory co-chaperone TSC1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:29127155).2 Publications

GO - Molecular functioni

  • ATPase activator activity Source: UniProtKB
  • cadherin binding Source: BHF-UCL
  • chaperone binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionChaperone
Biological processStress response

Enzyme and pathway databases

SIGNORiO95433

Names & Taxonomyi

Protein namesi
Recommended name:
Activator of 90 kDa heat shock protein ATPase homolog 1
Short name:
AHA1
Alternative name(s):
p38
Gene namesi
Name:AHSA1
Synonyms:C14orf3
ORF Names:HSPC322
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000100591.7
HGNCiHGNC:1189 AHSA1
MIMi608466 gene
neXtProtiNX_O95433

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi223Y → E: Phosphomimetic mutant. Increases the binding to HSP90AA1 resulting in TSC1 dissociation from HSP90AA1. 1 Publication1

Organism-specific databases

DisGeNETi10598
OpenTargetsiENSG00000100591
PharmGKBiPA25515

Chemistry databases

ChEMBLiCHEMBL3309113

Polymorphism and mutation databases

BioMutaiAHSA1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002158201 – 338Activator of 90 kDa heat shock protein ATPase homolog 1Add BLAST338

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei3N6-acetyllysineCombined sources1
Cross-linki182Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)Combined sources
Modified residuei193PhosphoserineCombined sources1
Cross-linki203Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei212N6-acetyllysineCombined sources1
Modified residuei223Phosphotyrosine; by ABL1 Publication1
Modified residuei258PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylation at Tyr-223 enhances binding to chaperone HSP90AA1.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO95433
MaxQBiO95433
PaxDbiO95433
PeptideAtlasiO95433
PRIDEiO95433

2D gel databases

REPRODUCTION-2DPAGEiIPI00030706

PTM databases

iPTMnetiO95433
PhosphoSitePlusiO95433
SwissPalmiO95433

Expressioni

Tissue specificityi

Expressed in numerous tissues, including brain, heart, skeletal muscle and kidney and, at lower levels, liver and placenta.1 Publication

Inductioni

By heat shock and treatment with the HSP90 inhibitor 17-demethoxygeldanamycin (17AAG).1 Publication

Gene expression databases

BgeeiENSG00000100591
CleanExiHS_AHSA1
ExpressionAtlasiO95433 baseline and differential
GenevisibleiO95433 HS

Organism-specific databases

HPAiCAB006244
HPA000903

Interactioni

Subunit structurei

Interacts with HSPCA/HSP90 (PubMed:12504007, PubMed:12604615). Interacts (phosphorylated on Tyr-223) with HSP90AA1; the interaction activates HSP90AA1 ATPase activity (PubMed:27353360, PubMed:29127155). Interacts with HSP90AB1 (By similarity). Interacts with GCH1 (PubMed:16696853). Interacts with SRPK1 (PubMed:19240134). Interacts with FLCN (PubMed:27353360).By similarity6 Publications
(Microbial infection) Interacts with vesicular stomatitis virus glycoprotein (VSV G) (via cytoplasmic tail).1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • chaperone binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115846, 176 interactors
IntActiO95433, 38 interactors
MINTiO95433
STRINGi9606.ENSP00000216479

Structurei

Secondary structure

1338
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi206 – 217Combined sources12
Helixi219 – 225Combined sources7
Helixi229 – 235Combined sources7
Turni253 – 256Combined sources4
Beta strandi261 – 265Combined sources5
Turni266 – 268Combined sources3
Beta strandi269 – 276Combined sources8
Beta strandi285 – 290Combined sources6
Beta strandi298 – 308Combined sources11
Helixi309 – 317Combined sources9
Turni318 – 323Combined sources6
Helixi324 – 330Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1X53NMR-A204-335[»]
ProteinModelPortaliO95433
SMRiO95433
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO95433

Family & Domainsi

Sequence similaritiesi

Belongs to the AHA1 family.Curated

Phylogenomic databases

eggNOGiKOG2936 Eukaryota
COG5580 LUCA
GeneTreeiENSGT00390000006429
HOGENOMiHOG000242852
HOVERGENiHBG065806
InParanoidiO95433
OMAiEYYVRSI
OrthoDBiEOG091G0BRP
PhylomeDBiO95433
TreeFamiTF313680

Family and domain databases

Gene3Di3.15.10.20, 1 hit
3.30.530.20, 1 hit
InterProiView protein in InterPro
IPR013538 Activator_of_Hsp90_ATPase
IPR036338 Aha1
IPR015310 AHSA1_N
IPR023393 START-like_dom_sf
PfamiView protein in Pfam
PF09229 Aha1_N, 1 hit
PF08327 AHSA1, 1 hit
SMARTiView protein in SMART
SM01000 Aha1_N, 1 hit
SUPFAMiSSF103111 SSF103111, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O95433-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAKWGEGDPR WIVEERADAT NVNNWHWTER DASNWSTDKL KTLFLAVQVQ
60 70 80 90 100
NEEGKCEVTE VSKLDGEASI NNRKGKLIFF YEWSVKLNWT GTSKSGVQYK
110 120 130 140 150
GHVEIPNLSD ENSVDEVEIS VSLAKDEPDT NLVALMKEEG VKLLREAMGI
160 170 180 190 200
YISTLKTEFT QGMILPTMNG ESVDPVGQPA LKTEERKAKP APSKTQARPV
210 220 230 240 250
GVKIPTCKIT LKETFLTSPE ELYRVFTTQE LVQAFTHAPA TLEADRGGKF
260 270 280 290 300
HMVDGNVSGE FTDLVPEKHI VMKWRFKSWP EGHFATITLT FIDKNGETEL
310 320 330
CMEGRGIPAP EEERTRQGWQ RYYFEGIKQT FGYGARLF
Length:338
Mass (Da):38,274
Last modified:May 1, 1999 - v1
Checksum:iE6B686DDD8D7D729
GO
Isoform 2 (identifier: O95433-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     283-338: HFATITLTFIDKNGETELCMEGRGIPAPEEERTRQGWQRYYFEGIKQTFGYGARLF → SHCHSG

Note: No experimental confirmation available.
Show »
Length:288
Mass (Da):32,340
Checksum:i4ACB777F0ED29F4E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti67 – 68EA → CL in AAF29000 (PubMed:11042152).Curated2

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_055797283 – 338HFATI…GARLF → SHCHSG in isoform 2. 1 PublicationAdd BLAST56

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ243310 mRNA Translation: CAB45684.1
AF164791 mRNA Translation: AAF80755.1
AK300766 mRNA Translation: BAG62431.1
AK313824 mRNA Translation: BAG36559.1
AF111168 Genomic DNA Translation: AAD09623.1
CH471061 Genomic DNA Translation: EAW81291.1
BC000321 mRNA Translation: AAH00321.1
BC007398 mRNA Translation: AAH07398.2
AF161440 mRNA Translation: AAF29000.1
CCDSiCCDS9863.1 [O95433-1]
PIRiJC7769
RefSeqiNP_001308370.1, NM_001321441.1
NP_036243.1, NM_012111.2 [O95433-1]
UniGeneiHs.204041

Genome annotation databases

EnsembliENST00000216479; ENSP00000216479; ENSG00000100591 [O95433-1]
ENST00000535854; ENSP00000440108; ENSG00000100591 [O95433-2]
GeneIDi10598
KEGGihsa:10598
UCSCiuc001xtw.4 human [O95433-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiAHSA1_HUMAN
AccessioniPrimary (citable) accession number: O95433
Secondary accession number(s): B2R9L2
, B4DUR9, Q96IL6, Q9P060
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: May 1, 1999
Last modified: April 25, 2018
This is version 167 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health