HSP72_RAT
ID HSP72_RAT Reviewed; 633 AA.
AC P14659; Q66HL1;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 12-JUN-2007, sequence version 2.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Heat shock-related 70 kDa protein 2;
DE Short=Heat shock protein 70.2;
DE AltName: Full=Testis-specific heat shock protein-related;
DE Short=HST;
GN Name=Hspa2; Synonyms=Hst70;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=1688714; DOI=10.1016/0167-4781(90)90027-y;
RA Wisniewski J., Kordula T., Krawczyk Z.;
RT "Isolation and nucleotide sequence analysis of the rat testis-specific
RT major heat-shock protein (HSP70)-related gene.";
RL Biochim. Biophys. Acta 1048:93-99(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-403; THR-408 AND THR-414, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Molecular chaperone implicated in a wide variety of cellular
CC processes, including protection of the proteome from stress, folding
CC and transport of newly synthesized polypeptides, activation of
CC proteolysis of misfolded proteins and the formation and dissociation of
CC protein complexes. Plays a pivotal role in the protein quality control
CC system, ensuring the correct folding of proteins, the re-folding of
CC misfolded proteins and controlling the targeting of proteins for
CC subsequent degradation. This is achieved through cycles of ATP binding,
CC ATP hydrolysis and ADP release, mediated by co-chaperones. In the ATP-
CC bound form, it has a low affinity for substrate proteins. However, upon
CC hydrolysis of the ATP to ADP, it undergoes a conformational change that
CC increases its affinity for substrate proteins. It goes through repeated
CC cycles of ATP hydrolysis and nucleotide exchange, which permits cycles
CC of substrate binding and release. Plays a role in spermatogenesis. In
CC association with SHCBP1L may participate in the maintenance of spindle
CC integrity during meiosis in male germ cells.
CC {ECO:0000250|UniProtKB:P17156, ECO:0000250|UniProtKB:P54652}.
CC -!- SUBUNIT: Interacts with FKBP6. Interacts with ZNF541. Component of the
CC CatSper complex. Interacts with RABL2/RABL2A; binds preferentially to
CC GTP-bound RABL2. Interacts with SHCBP1L; this interaction may promote
CC the recruitment of HSPA2 to the spindle. Interacts with MOV10L1 (By
CC similarity). {ECO:0000250|UniProtKB:P17156,
CC ECO:0000250|UniProtKB:P54652}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, spindle
CC {ECO:0000250|UniProtKB:P17156}. Note=Colocalizes with SHCBP1L at
CC spindle during the meiosis process. {ECO:0000250|UniProtKB:P17156}.
CC -!- DOMAIN: The N-terminal nucleotide binding domain (NBD) (also known as
CC the ATPase domain) is responsible for binding and hydrolyzing ATP. The
CC C-terminal substrate-binding domain (SBD) (also known as peptide-
CC binding domain) binds to the client/substrate proteins. The two domains
CC are allosterically coupled so that, when ATP is bound to the NBD, the
CC SBD binds relatively weakly to clients. When ADP is bound in the NBD, a
CC conformational change enhances the affinity of the SBD for client
CC proteins. {ECO:0000250|UniProtKB:P54652}.
CC -!- SIMILARITY: Belongs to the heat shock protein 70 family. {ECO:0000305}.
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DR EMBL; X15705; CAA33735.1; -; Genomic_DNA.
DR EMBL; BC081803; AAH81803.1; -; mRNA.
DR PIR; S08211; S08211.
DR RefSeq; NP_068635.1; NM_021863.3.
DR RefSeq; XP_006240309.1; XM_006240247.3.
DR AlphaFoldDB; P14659; -.
DR SMR; P14659; -.
DR BioGRID; 248845; 1.
DR ELM; P14659; -.
DR IntAct; P14659; 1.
DR MINT; P14659; -.
DR STRING; 10116.ENSRNOP00000008504; -.
DR iPTMnet; P14659; -.
DR PhosphoSitePlus; P14659; -.
DR jPOST; P14659; -.
DR PaxDb; P14659; -.
DR PRIDE; P14659; -.
DR Ensembl; ENSRNOT00000008504; ENSRNOP00000008504; ENSRNOG00000006472.
DR GeneID; 60460; -.
DR KEGG; rno:60460; -.
DR UCSC; RGD:620664; rat.
DR CTD; 3306; -.
DR RGD; 620664; Hspa2.
DR eggNOG; KOG0101; Eukaryota.
DR GeneTree; ENSGT00940000154813; -.
DR InParanoid; P14659; -.
DR OMA; GCKVQNA; -.
DR OrthoDB; 288077at2759; -.
DR PhylomeDB; P14659; -.
DR TreeFam; TF105042; -.
DR Reactome; R-RNO-3371453; Regulation of HSF1-mediated heat shock response.
DR Reactome; R-RNO-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand.
DR Reactome; R-RNO-3371568; Attenuation phase.
DR PRO; PR:P14659; -.
DR Proteomes; UP000002494; Chromosome 6.
DR Bgee; ENSRNOG00000006472; Expressed in testis and 18 other tissues.
DR ExpressionAtlas; P14659; baseline and differential.
DR Genevisible; P14659; RN.
DR GO; GO:0036128; C:CatSper complex; ISS:UniProtKB.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0001673; C:male germ cell nucleus; ISO:RGD.
DR GO; GO:0072687; C:meiotic spindle; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0000795; C:synaptonemal complex; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; IBA:GO_Central.
DR GO; GO:0016887; F:ATP hydrolysis activity; IBA:GO_Central.
DR GO; GO:0140662; F:ATP-dependent protein folding chaperone; IEA:InterPro.
DR GO; GO:0051087; F:chaperone binding; IPI:ARUK-UCL.
DR GO; GO:0097718; F:disordered domain specific binding; ISO:RGD.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0051861; F:glycolipid binding; ISO:RGD.
DR GO; GO:0031072; F:heat shock protein binding; IBA:GO_Central.
DR GO; GO:0051787; F:misfolded protein binding; IBA:GO_Central.
DR GO; GO:0044183; F:protein folding chaperone; IBA:GO_Central.
DR GO; GO:0048156; F:tau protein binding; IPI:ARUK-UCL.
DR GO; GO:0051082; F:unfolded protein binding; ISO:RGD.
DR GO; GO:0034620; P:cellular response to unfolded protein; IBA:GO_Central.
DR GO; GO:0051085; P:chaperone cofactor-dependent protein refolding; IBA:GO_Central.
DR GO; GO:0007141; P:male meiosis I; ISO:RGD.
DR GO; GO:0007140; P:male meiotic nuclear division; ISO:RGD.
DR GO; GO:0090084; P:negative regulation of inclusion body assembly; ISO:RGD.
DR GO; GO:0032781; P:positive regulation of ATP-dependent activity; ISO:RGD.
DR GO; GO:1901896; P:positive regulation of ATPase-coupled calcium transmembrane transporter activity; ISO:RGD.
DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; ISO:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0042026; P:protein refolding; ISO:RGD.
DR GO; GO:0009409; P:response to cold; ISS:AgBase.
DR GO; GO:0009408; P:response to heat; ISS:AgBase.
DR GO; GO:0007286; P:spermatid development; ISO:RGD.
DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR GO; GO:0070194; P:synaptonemal complex disassembly; ISO:RGD.
DR GO; GO:0016192; P:vesicle-mediated transport; IBA:GO_Central.
DR Gene3D; 1.20.1270.10; -; 1.
DR Gene3D; 2.60.34.10; -; 1.
DR InterPro; IPR043129; ATPase_NBD.
DR InterPro; IPR018181; Heat_shock_70_CS.
DR InterPro; IPR029048; HSP70_C_sf.
DR InterPro; IPR029047; HSP70_peptide-bd_sf.
DR InterPro; IPR013126; Hsp_70_fam.
DR PANTHER; PTHR19375; PTHR19375; 1.
DR Pfam; PF00012; HSP70; 1.
DR SUPFAM; SSF100920; SSF100920; 1.
DR SUPFAM; SSF100934; SSF100934; 1.
DR SUPFAM; SSF53067; SSF53067; 2.
DR PROSITE; PS00297; HSP70_1; 1.
DR PROSITE; PS00329; HSP70_2; 1.
DR PROSITE; PS01036; HSP70_3; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Chaperone; Cytoplasm; Cytoskeleton; Developmental protein;
KW Differentiation; Methylation; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Spermatogenesis; Stress response.
FT CHAIN 1..633
FT /note="Heat shock-related 70 kDa protein 2"
FT /id="PRO_0000078260"
FT REGION 2..389
FT /note="Nucleotide-binding domain (NBD)"
FT /evidence="ECO:0000250|UniProtKB:P11142"
FT REGION 397..512
FT /note="Substrate-binding domain (SBD)"
FT /evidence="ECO:0000250|UniProtKB:P11142"
FT REGION 613..633
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 13..16
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 72
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 205..207
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 271..278
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 342..345
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 403
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 408
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 414
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 564
FT /note="N6,N6,N6-trimethyllysine; by METTL21A; in vitro"
FT /evidence="ECO:0000250|UniProtKB:P54652"
FT CONFLICT 526..527
FT /note="ER -> DG (in Ref. 1; CAA33735)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 633 AA; 69642 MW; 6F65773C7EFFA69F CRC64;
MSARGPAIGI DLGTTYSCVG VFQHGKVEII ANDQGNRTTP SYVAFTDTER LIGDAAKNQV
AMNPTNTIFD AKRLIGRKFE DATVQSDMKH WPFRVVSEGG KPKVQVEYKG EMKTFFPEEI
SSMVLTKMKE IAEAYLGGKV QSAVITVPAY FNDSQRQATK DAGTITGLNV LRIINEPTAA
AIAYGLDKKG CAGGEKNVLI FDLGGGTFDV SILTIEDGIF EVKSTAGDTH LGGEDFDNRM
VSHLAEEFKR KHKKDIGPNK RAVRRLRTAC ERAKRTLSSS TQASIEIDSL YEGVDFYTSI
TRARFEELNA DLFRGTLEPV EKALRDAKLD KGQIQEIVLV GGSTRIPKIQ KLLQDFFNGK
ELNKSINPDE AVAYGAAVQA AILIGDKSEN VQDLLLLDVT PLSLGIETAG GVMTPLIKRN
TTIPTKQTQT FTTYSDNQSS VLVQVYEGER AMTKDNNLLG KFDLTGIPPA PRGVPQIEVT
FDIDANGILN VTAADKSTGK ENKITITNDK GRLSKDDIDR MVQEAERYKS EDEANRDRVA
AKNAVESYTY NIKQTVEDEK LRGKISEQDK NKILDKCQEV INWLDRNQMA EKDEYEHKQK
ELERVCNPII SKLYQGGPGG GGSSGGPTIE EVD
