HSP72_MOUSE
ID HSP72_MOUSE Reviewed; 633 AA.
AC P17156; Q99KD7;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Heat shock-related 70 kDa protein 2;
DE Short=Heat shock protein 70.2;
GN Name=Hspa2; Synonyms=Hcp70.2, Hsp70-2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=3405224; DOI=10.1128/mcb.8.7.2925-2932.1988;
RA Zakeri Z.F., Wolgemuth D.J., Hunt C.R.;
RT "Identification and sequence analysis of a new member of the mouse HSP70
RT gene family and characterization of its unique cellular and developmental
RT pattern of expression in the male germ line.";
RL Mol. Cell. Biol. 8:2925-2932(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor, and 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 [4]
RP INTERACTION WITH ZNF541.
RX PubMed=18849567; DOI=10.1074/jbc.m805590200;
RA Choi E., Han C., Park I., Lee B., Jin S., Choi H., Kim do H., Park Z.Y.,
RA Eddy E.M., Cho C.;
RT "A novel germ cell-specific protein, SHIP1, forms a complex with chromatin
RT remodeling activity during spermatogenesis.";
RL J. Biol. Chem. 283:35283-35294(2008).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP INTERACTION WITH MOV10L1.
RX PubMed=20547853; DOI=10.1073/pnas.1007158107;
RA Frost R.J., Hamra F.K., Richardson J.A., Qi X., Bassel-Duby R., Olson E.N.;
RT "MOV10L1 is necessary for protection of spermatocytes against
RT retrotransposons by Piwi-interacting RNAs.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:11847-11852(2010).
RN [7]
RP IDENTIFICATION IN THE CATSPER COMPLEX.
RC STRAIN=C57BL/6J;
RX PubMed=21224844; DOI=10.1038/ncomms1153;
RA Chung J.J., Navarro B., Krapivinsky G., Krapivinsky L., Clapham D.E.;
RT "A novel gene required for male fertility and functional CATSPER channel
RT formation in spermatozoa.";
RL Nat. Commun. 2:153-153(2011).
RN [8]
RP INTERACTION WITH RABL2, AND TISSUE SPECIFICITY.
RX PubMed=23055941; DOI=10.1371/journal.pgen.1002969;
RA Lo J.C., Jamsai D., O'Connor A.E., Borg C., Clark B.J., Whisstock J.C.,
RA Field M.C., Adams V., Ishikawa T., Aitken R.J., Whittle B., Goodnow C.C.,
RA Ormandy C.J., O'Bryan M.K.;
RT "RAB-like 2 has an essential role in male fertility, sperm intra-flagellar
RT transport, and tail assembly.";
RL PLoS Genet. 8:E1002969-E1002969(2012).
RN [9]
RP FUNCTION, INTERACTION WITH SHCBP1L, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=24557841; DOI=10.1093/molehr/gau014;
RA Liu M., Shi X., Bi Y., Qi L., Guo X., Wang L., Zhou Z., Sha J.;
RT "SHCBP1L, a conserved protein in mammals, is predominantly expressed in
RT male germ cells and maintains spindle stability during meiosis in testis.";
RL Mol. Hum. Reprod. 20:463-475(2014).
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. The affinity
CC for polypeptides is regulated by its nucleotide bound state. In the
CC ATP-bound form, it has a low affinity for substrate proteins. However,
CC upon hydrolysis of the ATP to ADP, it undergoes a conformational change
CC that increases its affinity for substrate proteins. It goes through
CC repeated cycles of ATP hydrolysis and nucleotide exchange, which
CC permits cycles of substrate binding and release (By similarity). Plays
CC a role in spermatogenesis (PubMed:24557841). In association with
CC SHCBP1L may participate in the maintenance of spindle integrity during
CC meiosis in male germ cells (PubMed:24557841).
CC {ECO:0000250|UniProtKB:P54652, ECO:0000269|PubMed:24557841}.
CC -!- SUBUNIT: Interacts with FKBP6 (By similarity). Interacts with ZNF541
CC (PubMed:18849567). Component of the CatSper complex (PubMed:21224844).
CC Interacts with RABL2/RABL2A; binds preferentially to GTP-bound RABL2
CC (PubMed:23055941). Interacts with SHCBP1L; this interaction may promote
CC the recruitment of HSPA2 to the spindle (PubMed:24557841). Interacts
CC with MOV10L1 (PubMed:20547853). {ECO:0000250|UniProtKB:P54652,
CC ECO:0000269|PubMed:18849567, ECO:0000269|PubMed:20547853,
CC ECO:0000269|PubMed:21224844, ECO:0000269|PubMed:23055941,
CC ECO:0000269|PubMed:24557841}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, spindle
CC {ECO:0000269|PubMed:24557841}. Note=Colocalizes with SHCBP1L at spindle
CC during the meiosis process (PubMed:24557841).
CC {ECO:0000269|PubMed:24557841}.
CC -!- TISSUE SPECIFICITY: Expressed in male germ cells (at protein level)
CC (PubMed:24557841, PubMed:23055941, PubMed:3405224).
CC {ECO:0000269|PubMed:23055941, ECO:0000269|PubMed:24557841,
CC ECO:0000269|PubMed:3405224}.
CC -!- DEVELOPMENTAL STAGE: Specifically expressed in prophage stage of
CC meiosis (PubMed:3405224). {ECO:0000269|PubMed:3405224}.
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; M20567; AAA37859.1; -; Genomic_DNA.
DR EMBL; CH466526; EDL36460.1; -; Genomic_DNA.
DR EMBL; BC004714; AAH04714.1; -; mRNA.
DR EMBL; BC052350; AAH52350.1; -; mRNA.
DR CCDS; CCDS25993.1; -.
DR PIR; S10859; S10859.
DR RefSeq; NP_001002012.1; NM_001002012.1.
DR RefSeq; NP_032327.2; NM_008301.4.
DR RefSeq; XP_006515547.1; XM_006515484.3.
DR AlphaFoldDB; P17156; -.
DR SMR; P17156; -.
DR BioGRID; 200453; 39.
DR CORUM; P17156; -.
DR DIP; DIP-42071N; -.
DR ELM; P17156; -.
DR IntAct; P17156; 10.
DR MINT; P17156; -.
DR STRING; 10090.ENSMUSP00000079306; -.
DR iPTMnet; P17156; -.
DR PhosphoSitePlus; P17156; -.
DR SwissPalm; P17156; -.
DR REPRODUCTION-2DPAGE; IPI00331546; -.
DR REPRODUCTION-2DPAGE; P17156; -.
DR UCD-2DPAGE; P17156; -.
DR EPD; P17156; -.
DR jPOST; P17156; -.
DR MaxQB; P17156; -.
DR PaxDb; P17156; -.
DR PeptideAtlas; P17156; -.
DR PRIDE; P17156; -.
DR ProteomicsDB; 273194; -.
DR Antibodypedia; 6; 280 antibodies from 35 providers.
DR DNASU; 15512; -.
DR Ensembl; ENSMUST00000080449; ENSMUSP00000079306; ENSMUSG00000059970.
DR Ensembl; ENSMUST00000219555; ENSMUSP00000151408; ENSMUSG00000059970.
DR GeneID; 15512; -.
DR KEGG; mmu:15512; -.
DR UCSC; uc007nyf.1; mouse.
DR CTD; 3306; -.
DR MGI; MGI:96243; Hspa2.
DR VEuPathDB; HostDB:ENSMUSG00000059970; -.
DR eggNOG; KOG0101; Eukaryota.
DR GeneTree; ENSGT00940000154813; -.
DR HOGENOM; CLU_005965_3_0_1; -.
DR InParanoid; P17156; -.
DR OMA; GCKVQNA; -.
DR OrthoDB; 288077at2759; -.
DR PhylomeDB; P17156; -.
DR TreeFam; TF105042; -.
DR Reactome; R-MMU-3371453; Regulation of HSF1-mediated heat shock response.
DR Reactome; R-MMU-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand.
DR Reactome; R-MMU-3371568; Attenuation phase.
DR BioGRID-ORCS; 15512; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Hspa2; mouse.
DR PRO; PR:P17156; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; P17156; protein.
DR Bgee; ENSMUSG00000059970; Expressed in seminiferous tubule of testis and 221 other tissues.
DR Genevisible; P17156; MM.
DR GO; GO:0036128; C:CatSper complex; IDA:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0001673; C:male germ cell nucleus; IDA:MGI.
DR GO; GO:0072687; C:meiotic spindle; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0043209; C:myelin sheath; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
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; IDA:MGI.
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; ISO:MGI.
DR GO; GO:0097718; F:disordered domain specific binding; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0051861; F:glycolipid binding; IDA:MGI.
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; ISO:MGI.
DR GO; GO:0051082; F:unfolded protein binding; ISO:MGI.
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; IMP:MGI.
DR GO; GO:0007140; P:male meiotic nuclear division; IMP:MGI.
DR GO; GO:0090084; P:negative regulation of inclusion body assembly; ISO:MGI.
DR GO; GO:0032781; P:positive regulation of ATP-dependent activity; IMP:CACAO.
DR GO; GO:1901896; P:positive regulation of ATPase-coupled calcium transmembrane transporter activity; IMP:CACAO.
DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; IMP:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:MGI.
DR GO; GO:0042026; P:protein refolding; ISO:MGI.
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; IMP:MGI.
DR GO; GO:0007283; P:spermatogenesis; IMP:UniProtKB.
DR GO; GO:0070194; P:synaptonemal complex disassembly; IMP:MGI.
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; Differentiation;
KW Methylation; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Spermatogenesis; Stress response.
FT CHAIN 1..633
FT /note="Heat shock-related 70 kDa protein 2"
FT /id="PRO_0000078259"
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:0000250|UniProtKB:P14659"
FT MOD_RES 408
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P14659"
FT MOD_RES 414
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P14659"
FT MOD_RES 564
FT /note="N6,N6,N6-trimethyllysine; by METTL21A; in vitro"
FT /evidence="ECO:0000250|UniProtKB:P54652"
FT CONFLICT 71
FT /note="A -> R (in Ref. 1; AAA37859)"
FT /evidence="ECO:0000305"
FT CONFLICT 222
FT /note="V -> L (in Ref. 1; AAA37859)"
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
