UniProtKB - P17156 (HSP72_MOUSE)
Protein
Heat shock-related 70 kDa protein 2
Gene
Hspa2
Organism
Mus musculus (Mouse)
Status
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 (By similarity). Plays a role in spermatogenesis (PubMed:24557841). In association with SHCBP1L may participate in the maintenance of spindle integrity during meiosis in male germ cells (PubMed:24557841).By similarity1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 72 | ATPBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 13 – 16 | ATPBy similarity | 4 | |
Nucleotide bindingi | 205 – 207 | ATPBy similarity | 3 | |
Nucleotide bindingi | 271 – 278 | ATPBy similarity | 8 | |
Nucleotide bindingi | 342 – 345 | ATPBy similarity | 4 |
GO - Molecular functioni
- ATPase activity Source: GO_Central
- ATP binding Source: GO_Central
- chaperone binding Source: MGI
- disordered domain specific binding Source: MGI
- enzyme binding Source: MGI
- glycolipid binding Source: MGI
- heat shock protein binding Source: GO_Central
- misfolded protein binding Source: GO_Central
- protein folding chaperone Source: GO_Central
- tau protein binding Source: MGI
- unfolded protein binding Source: MGI
GO - Biological processi
- cellular response to unfolded protein Source: GO_Central
- chaperone cofactor-dependent protein refolding Source: GO_Central
- male meiosis I Source: MGI
- male meiotic nuclear division Source: MGI
- negative regulation of inclusion body assembly Source: MGI
- positive regulation of ATPase activity Source: CACAO
- positive regulation of ATPase-coupled calcium transmembrane transporter activity Source: CACAO
- positive regulation of G2/M transition of mitotic cell cycle Source: MGI
- positive regulation of protein phosphorylation Source: MGI
- protein refolding Source: MGI
- response to cold Source: AgBase
- response to heat Source: AgBase
- response to unfolded protein Source: GO_Central
- spermatid development Source: MGI
- spermatogenesis Source: UniProtKB
- synaptonemal complex disassembly Source: MGI
- vesicle-mediated transport Source: GO_Central
Keywordsi
Molecular function | Chaperone |
Biological process | Differentiation, Spermatogenesis, Stress response |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
Reactomei | R-MMU-3371453, Regulation of HSF1-mediated heat shock response R-MMU-3371497, HSP90 chaperone cycle for steroid hormone receptors (SHR) R-MMU-3371568, Attenuation phase |
Names & Taxonomyi
Protein namesi | Recommended name: Heat shock-related 70 kDa protein 2Short name: Heat shock protein 70.2 |
Gene namesi | Name:Hspa2 Synonyms:Hcp70.2, Hsp70-2 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:96243, Hspa2 |
Subcellular locationi
Cytoskeleton
- meiotic spindle Source: UniProtKB
Cytosol
- cytosol Source: MGI
Mitochondrion
- mitochondrion Source: MGI
Nucleus
- male germ cell nucleus Source: MGI
- nucleoplasm Source: Reactome
- nucleus Source: GO_Central
- synaptonemal complex Source: MGI
Plasma Membrane
- CatSper complex Source: UniProtKB
- plasma membrane Source: GO_Central
Other locations
- cell surface Source: MGI
- cytoplasm Source: GO_Central
- myelin sheath Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, CytoskeletonPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000078259 | 1 – 633 | Heat shock-related 70 kDa protein 2Add BLAST | 633 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 403 | PhosphoserineBy similarity | 1 | |
Modified residuei | 408 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 414 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 564 | N6,N6,N6-trimethyllysine; by METTL21A; in vitroBy similarity | 1 |
Keywords - PTMi
Methylation, PhosphoproteinProteomic databases
EPDi | P17156 |
jPOSTi | P17156 |
MaxQBi | P17156 |
PaxDbi | P17156 |
PeptideAtlasi | P17156 |
PRIDEi | P17156 |
2D gel databases
REPRODUCTION-2DPAGEi | IPI00331546 P17156 |
UCD-2DPAGEi | P17156 |
PTM databases
iPTMneti | P17156 |
PhosphoSitePlusi | P17156 |
SwissPalmi | P17156 |
Expressioni
Tissue specificityi
Expressed in male germ cells (at protein level) (PubMed:24557841, PubMed:23055941, PubMed:3405224).3 Publications
Developmental stagei
Specifically expressed in prophage stage of meiosis (PubMed:3405224).1 Publication
Gene expression databases
Bgeei | ENSMUSG00000059970, Expressed in testis and 260 other tissues |
Genevisiblei | P17156, MM |
Interactioni
Subunit structurei
Interacts with FKBP6 (By similarity).
Interacts with ZNF541 (PubMed:18849567).
Component of the CatSper complex (PubMed:21224844).
Interacts with RABL2/RABL2A; binds preferentially to GTP-bound RABL2 (PubMed:23055941).
Interacts with SHCBP1L; this interaction may promote the recruitment of HSPA2 to the spindle (PubMed:24557841).
Interacts with MOV10L1 (PubMed:20547853).
By similarity5 PublicationsGO - Molecular functioni
- chaperone binding Source: MGI
- disordered domain specific binding Source: MGI
- enzyme binding Source: MGI
- heat shock protein binding Source: GO_Central
- misfolded protein binding Source: GO_Central
- tau protein binding Source: MGI
- unfolded protein binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 200453, 38 interactors |
CORUMi | P17156 |
DIPi | DIP-42071N |
ELMi | P17156 |
IntActi | P17156, 10 interactors |
MINTi | P17156 |
STRINGi | 10090.ENSMUSP00000079306 |
Miscellaneous databases
RNActi | P17156, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 2 – 389 | Nucleotide-binding domain (NBD)By similarityAdd BLAST | 388 | |
Regioni | 397 – 512 | Substrate-binding domain (SBD)By similarityAdd BLAST | 116 |
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.By similarity
Sequence similaritiesi
Belongs to the heat shock protein 70 family.Curated
Phylogenomic databases
eggNOGi | KOG0101, Eukaryota |
GeneTreei | ENSGT00940000154813 |
HOGENOMi | CLU_005965_3_0_1 |
InParanoidi | P17156 |
OMAi | EAYLGCK |
OrthoDBi | 288077at2759 |
TreeFami | TF105042 |
Family and domain databases
Gene3Di | 1.20.1270.10, 1 hit 2.60.34.10, 1 hit |
InterProi | View protein in InterPro IPR043129, ATPase_NBD IPR018181, Heat_shock_70_CS IPR029048, HSP70_C_sf IPR029047, HSP70_peptide-bd_sf IPR013126, Hsp_70_fam |
PANTHERi | PTHR19375, PTHR19375, 1 hit |
Pfami | View protein in Pfam PF00012, HSP70, 1 hit |
SUPFAMi | SSF100920, SSF100920, 1 hit SSF100934, SSF100934, 1 hit SSF53067, SSF53067, 2 hits |
PROSITEi | View protein in PROSITE PS00297, HSP70_1, 1 hit PS00329, HSP70_2, 1 hit PS01036, HSP70_3, 1 hit |
i Sequence
Sequence statusi: Complete.
P17156-1 [UniParc]FASTAAdd to basket
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 EMKTFFPEEI SSMVLTKMKE IAEAYLGGKV QSAVITVPAY
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 AKNAVESYTY
560 570 580 590 600
NIKQTVEDEK LRGKISEQDK NKILDKCQEV INWLDRNQMA EKDEYEHKQK
610 620 630
ELERVCNPII SKLYQGGPGG GGSSGGPTIE EVD
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 71 | A → R in AAA37859 (PubMed:3405224).Curated | 1 | |
Sequence conflicti | 222 | V → L in AAA37859 (PubMed:3405224).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M20567 Genomic DNA Translation: AAA37859.1 CH466526 Genomic DNA Translation: EDL36460.1 BC004714 mRNA Translation: AAH04714.1 BC052350 mRNA Translation: AAH52350.1 |
CCDSi | CCDS25993.1 |
PIRi | S10859 |
RefSeqi | NP_001002012.1, NM_001002012.1 NP_032327.2, NM_008301.4 XP_006515547.1, XM_006515484.3 |
Genome annotation databases
Ensembli | ENSMUST00000080449; ENSMUSP00000079306; ENSMUSG00000059970 ENSMUST00000219555; ENSMUSP00000151408; ENSMUSG00000059970 |
GeneIDi | 15512 |
KEGGi | mmu:15512 |
UCSCi | uc007nyf.1, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M20567 Genomic DNA Translation: AAA37859.1 CH466526 Genomic DNA Translation: EDL36460.1 BC004714 mRNA Translation: AAH04714.1 BC052350 mRNA Translation: AAH52350.1 |
CCDSi | CCDS25993.1 |
PIRi | S10859 |
RefSeqi | NP_001002012.1, NM_001002012.1 NP_032327.2, NM_008301.4 XP_006515547.1, XM_006515484.3 |
3D structure databases
SMRi | P17156 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 200453, 38 interactors |
CORUMi | P17156 |
DIPi | DIP-42071N |
ELMi | P17156 |
IntActi | P17156, 10 interactors |
MINTi | P17156 |
STRINGi | 10090.ENSMUSP00000079306 |
PTM databases
iPTMneti | P17156 |
PhosphoSitePlusi | P17156 |
SwissPalmi | P17156 |
2D gel databases
REPRODUCTION-2DPAGEi | IPI00331546 P17156 |
UCD-2DPAGEi | P17156 |
Proteomic databases
EPDi | P17156 |
jPOSTi | P17156 |
MaxQBi | P17156 |
PaxDbi | P17156 |
PeptideAtlasi | P17156 |
PRIDEi | P17156 |
Protocols and materials databases
Antibodypediai | 6, 259 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000080449; ENSMUSP00000079306; ENSMUSG00000059970 ENSMUST00000219555; ENSMUSP00000151408; ENSMUSG00000059970 |
GeneIDi | 15512 |
KEGGi | mmu:15512 |
UCSCi | uc007nyf.1, mouse |
Organism-specific databases
CTDi | 3306 |
MGIi | MGI:96243, Hspa2 |
Phylogenomic databases
eggNOGi | KOG0101, Eukaryota |
GeneTreei | ENSGT00940000154813 |
HOGENOMi | CLU_005965_3_0_1 |
InParanoidi | P17156 |
OMAi | EAYLGCK |
OrthoDBi | 288077at2759 |
TreeFami | TF105042 |
Enzyme and pathway databases
Reactomei | R-MMU-3371453, Regulation of HSF1-mediated heat shock response R-MMU-3371497, HSP90 chaperone cycle for steroid hormone receptors (SHR) R-MMU-3371568, Attenuation phase |
Miscellaneous databases
BioGRID-ORCSi | 15512, 1 hit in 17 CRISPR screens |
ChiTaRSi | Hspa2, mouse |
PROi | PR:P17156 |
RNActi | P17156, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000059970, Expressed in testis and 260 other tissues |
Genevisiblei | P17156, MM |
Family and domain databases
Gene3Di | 1.20.1270.10, 1 hit 2.60.34.10, 1 hit |
InterProi | View protein in InterPro IPR043129, ATPase_NBD IPR018181, Heat_shock_70_CS IPR029048, HSP70_C_sf IPR029047, HSP70_peptide-bd_sf IPR013126, Hsp_70_fam |
PANTHERi | PTHR19375, PTHR19375, 1 hit |
Pfami | View protein in Pfam PF00012, HSP70, 1 hit |
SUPFAMi | SSF100920, SSF100920, 1 hit SSF100934, SSF100934, 1 hit SSF53067, SSF53067, 2 hits |
PROSITEi | View protein in PROSITE PS00297, HSP70_1, 1 hit PS00329, HSP70_2, 1 hit PS01036, HSP70_3, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | HSP72_MOUSE | |
Accessioni | P17156Primary (citable) accession number: P17156 Secondary accession number(s): Q99KD7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 1, 1990 |
Last sequence update: | July 27, 2011 | |
Last modified: | December 2, 2020 | |
This is version 178 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families