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Protein

Heat shock-related 70 kDa protein 2

Gene

HSPA2

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

Functioni

Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release (PubMed:26865365). Plays a role in spermatogenesis. In association with SHCBP1L may participate in the maintenance of spindle integrity during meiosis in male germ cells (By similarity).1 PublicationBy similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei72ATP1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi13 – 16ATP4
Nucleotide bindingi205 – 207ATP3
Nucleotide bindingi271 – 278ATP8
Nucleotide bindingi342 – 345ATP4

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • chaperone binding Source: Ensembl
  • disordered domain specific binding Source: CAFA
  • enzyme binding Source: BHF-UCL
  • glycolipid binding Source: Ensembl
  • tau protein binding Source: Ensembl
  • unfolded protein binding Source: UniProtKB

GO - Biological processi

  • male meiosis I Source: Ensembl
  • male meiotic nuclear division Source: ProtInc
  • negative regulation of inclusion body assembly Source: UniProtKB
  • positive regulation of calcium-transporting ATPase activity Source: Ensembl
  • positive regulation of G2/M transition of mitotic cell cycle Source: Ensembl
  • positive regulation of protein phosphorylation Source: Ensembl
  • protein refolding Source: UniProtKB
  • response to cold Source: AgBase
  • response to heat Source: AgBase
  • response to unfolded protein Source: ProtInc
  • spermatid development Source: ProtInc
  • spermatogenesis Source: UniProtKB
  • synaptonemal complex disassembly Source: Ensembl

Keywordsi

Molecular functionChaperone
Biological processDifferentiation, Spermatogenesis, Stress response
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-1221632 Meiotic synapsis
R-HSA-3371453 Regulation of HSF1-mediated heat shock response
R-HSA-3371497 HSP90 chaperone cycle for steroid hormone receptors (SHR)
R-HSA-3371568 Attenuation phase
SIGNORiP54652

Names & Taxonomyi

Protein namesi
Recommended name:
Heat shock-related 70 kDa protein 2
Short name:
Heat shock 70 kDa protein 2
Gene namesi
Name:HSPA2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000126803.9
HGNCiHGNC:5235 HSPA2
MIMi140560 gene
neXtProtiNX_P54652

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, Cytoskeleton

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi564K → A: Abolishes methylation by METTL21A. 1 Publication1

Organism-specific databases

DisGeNETi3306
OpenTargetsiENSG00000126803
PharmGKBiPA29501

Chemistry databases

ChEMBLiCHEMBL2062348

Polymorphism and mutation databases

BioMutaiHSPA2
DMDMi1708307

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000782581 – 639Heat shock-related 70 kDa protein 2Add BLAST639

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei403PhosphoserineBy similarity1
Modified residuei408PhosphothreonineBy similarity1
Modified residuei414PhosphothreonineBy similarity1
Modified residuei564N6,N6,N6-trimethyllysine; by METTL21A; in vitro1 Publication1

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

EPDiP54652
MaxQBiP54652
PaxDbiP54652
PeptideAtlasiP54652
PRIDEiP54652
ProteomicsDBi56690

2D gel databases

REPRODUCTION-2DPAGEiIPI00007702

PTM databases

iPTMnetiP54652
PhosphoSitePlusiP54652
SwissPalmiP54652

Expressioni

Gene expression databases

BgeeiENSG00000126803
CleanExiHS_HSPA2
ExpressionAtlasiP54652 baseline and differential
GenevisibleiP54652 HS

Organism-specific databases

HPAiHPA000798
HPA052504

Interactioni

Subunit structurei

Interacts with FKBP6 (PubMed:18529014). Interacts with ZNF541. Component of the CatSper complex. Interacts with RABL2/RABL2A; binds preferentially to GTP-bound RABL2. Interacts with SHCBP1L; this interaction may promote the recruitment of HSPA2 to the spindle (By similarity). Interacts with FKBP6 (PubMed:18529014).By similarity1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • chaperone binding Source: Ensembl
  • disordered domain specific binding Source: CAFA
  • enzyme binding Source: BHF-UCL
  • tau protein binding Source: Ensembl
  • unfolded protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi109538, 90 interactors
CORUMiP54652
ELMiP54652
IntActiP54652, 37 interactors
MINTiP54652
STRINGi9606.ENSP00000247207

Structurei

Secondary structure

1639
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi8 – 12Combined sources5
Beta strandi14 – 23Combined sources10
Beta strandi26 – 29Combined sources4
Beta strandi37 – 40Combined sources4
Beta strandi43 – 45Combined sources3
Beta strandi50 – 52Combined sources3
Helixi54 – 58Combined sources5
Turni59 – 62Combined sources4
Helixi64 – 66Combined sources3
Helixi71 – 73Combined sources3
Turni74 – 76Combined sources3
Helixi82 – 88Combined sources7
Beta strandi92 – 98Combined sources7
Beta strandi101 – 108Combined sources8
Beta strandi111 – 115Combined sources5
Helixi117 – 136Combined sources20
Beta strandi142 – 147Combined sources6
Helixi153 – 166Combined sources14
Beta strandi169 – 175Combined sources7
Helixi176 – 183Combined sources8
Turni184 – 187Combined sources4
Beta strandi191 – 194Combined sources4
Beta strandi197 – 203Combined sources7
Beta strandi208 – 216Combined sources9
Beta strandi219 – 228Combined sources10
Helixi233 – 252Combined sources20
Helixi260 – 276Combined sources17
Turni277 – 279Combined sources3
Beta strandi280 – 291Combined sources12
Beta strandi294 – 301Combined sources8
Helixi302 – 308Combined sources7
Helixi310 – 315Combined sources6
Helixi317 – 327Combined sources11
Helixi331 – 333Combined sources3
Beta strandi336 – 341Combined sources6
Helixi342 – 345Combined sources4
Helixi347 – 356Combined sources10
Turni357 – 359Combined sources3
Turni368 – 370Combined sources3
Helixi371 – 383Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3I33X-ray1.30A6-386[»]
4FSVX-ray1.80A2-387[»]
5FPDX-ray1.97A/B4-386[»]
5FPEX-ray1.96A/B4-386[»]
5FPMX-ray1.96A/B4-386[»]
5FPNX-ray1.96A/B4-639[»]
ProteinModelPortaliP54652
SMRiP54652
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP54652

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 389Nucleotide-binding domain (NBD)By similarityAdd BLAST388
Regioni397 – 512Substrate-binding domain (SBD)By similarityAdd BLAST116

Domaini

The N-terminal nucleotide binding domain (NBD) (also known as the ATPase domain) is responsible for binding and hydrolyzing ATP. The C-terminal substrate-binding domain (SBD) (also known as peptide-binding domain) binds to the client/substrate proteins. The two domains are allosterically coupled so that, when ATP is bound to the NBD, the SBD binds relatively weakly to clients. When ADP is bound in the NBD, a conformational change enhances the affinity of the SBD for client proteins.1 Publication

Sequence similaritiesi

Belongs to the heat shock protein 70 family.Curated

Phylogenomic databases

eggNOGiKOG0101 Eukaryota
COG0443 LUCA
GeneTreeiENSGT00910000144045
HOGENOMiHOG000228135
HOVERGENiHBG051845
InParanoidiP54652
KOiK03283
OMAiEAYLGCK
OrthoDBiEOG091G03SF
PhylomeDBiP54652
TreeFamiTF105042

Family and domain databases

Gene3Di1.20.1270.10, 1 hit
2.60.34.10, 1 hit
InterProiView protein in InterPro
IPR018181 Heat_shock_70_CS
IPR029048 HSP70_C_sf
IPR029047 HSP70_peptide-bd_sf
IPR013126 Hsp_70_fam
PANTHERiPTHR19375 PTHR19375, 1 hit
PfamiView protein in Pfam
PF00012 HSP70, 1 hit
PRINTSiPR00301 HEATSHOCK70
SUPFAMiSSF100920 SSF100920, 1 hit
SSF100934 SSF100934, 1 hit
PROSITEiView protein in PROSITE
PS00297 HSP70_1, 1 hit
PS00329 HSP70_2, 1 hit
PS01036 HSP70_3, 1 hit

Sequencei

Sequence statusi: Complete.

P54652-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSARGPAIGI DLGTTYSCVG VFQHGKVEII ANDQGNRTTP SYVAFTDTER
60 70 80 90 100
LIGDAAKNQV AMNPTNTIFD AKRLIGRKFE DATVQSDMKH WPFRVVSEGG
110 120 130 140 150
KPKVQVEYKG ETKTFFPEEI SSMVLTKMKE IAEAYLGGKV HSAVITVPAY
160 170 180 190 200
FNDSQRQATK DAGTITGLNV LRIINEPTAA AIAYGLDKKG CAGGEKNVLI
210 220 230 240 250
FDLGGGTFDV SILTIEDGIF EVKSTAGDTH LGGEDFDNRM VSHLAEEFKR
260 270 280 290 300
KHKKDIGPNK RAVRRLRTAC ERAKRTLSSS TQASIEIDSL YEGVDFYTSI
310 320 330 340 350
TRARFEELNA DLFRGTLEPV EKALRDAKLD KGQIQEIVLV GGSTRIPKIQ
360 370 380 390 400
KLLQDFFNGK ELNKSINPDE AVAYGAAVQA AILIGDKSEN VQDLLLLDVT
410 420 430 440 450
PLSLGIETAG GVMTPLIKRN TTIPTKQTQT FTTYSDNQSS VLVQVYEGER
460 470 480 490 500
AMTKDNNLLG KFDLTGIPPA PRGVPQIEVT FDIDANGILN VTAADKSTGK
510 520 530 540 550
ENKITITNDK GRLSKDDIDR MVQEAERYKS EDEANRDRVA AKNALESYTY
560 570 580 590 600
NIKQTVEDEK LRGKISEQDK NKILDKCQEV INWLDRNQMA EKDEYEHKQK
610 620 630
ELERVCNPII SKLYQGGPGG GSGGGGSGAS GGPTIEEVD
Length:639
Mass (Da):70,021
Last modified:October 1, 1996 - v1
Checksum:i3851755494E7B729
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti14T → P in AAH36107 (PubMed:15489334).Curated1
Sequence conflicti54Missing in AAC50076 (PubMed:7849706).Curated1
Sequence conflicti80E → G in AAH36107 (PubMed:15489334).Curated1
Sequence conflicti266L → S in AAD11466 (Ref. 2) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_032706191C → S1 PublicationCorresponds to variant dbSNP:rs45456191Ensembl.1
Natural variantiVAR_032707496K → E1 PublicationCorresponds to variant dbSNP:rs45447398Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L26336 Genomic DNA Translation: AAA52698.1
U56725 mRNA Translation: AAD11466.1
BT009815 mRNA Translation: AAP88817.1
DQ489378 Genomic DNA Translation: ABE96830.1
BC001752 mRNA Translation: AAH01752.1
BC036107 mRNA Translation: AAH36107.1
AH006615 Genomic DNA Translation: AAC50076.1
CCDSiCCDS9766.1
PIRiA55719
I37564
RefSeqiNP_068814.2, NM_021979.3
UniGeneiHs.432648

Genome annotation databases

EnsembliENST00000247207; ENSP00000247207; ENSG00000126803
ENST00000394709; ENSP00000378199; ENSG00000126803
GeneIDi3306
KEGGihsa:3306
UCSCiuc001xhj.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiHSP72_HUMAN
AccessioniPrimary (citable) accession number: P54652
Secondary accession number(s): Q15508, Q53XM3, Q9UE78
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: June 20, 2018
This is version 177 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

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