Full text data of HSPA2
HSPA2
[Confidence: low (only semi-automatic identification from reviews)]
Heat shock-related 70 kDa protein 2; Heat shock 70 kDa protein 2
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Heat shock-related 70 kDa protein 2; Heat shock 70 kDa protein 2
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P54652
ID HSP72_HUMAN Reviewed; 639 AA.
AC P54652; Q15508; Q53XM3; Q9UE78;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-1996, sequence version 1.
DT 22-JAN-2014, entry version 130.
DE RecName: Full=Heat shock-related 70 kDa protein 2;
DE Short=Heat shock 70 kDa protein 2;
GN Name=HSPA2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7829106; DOI=10.1006/geno.1994.1462;
RA Bonnycastle L.L.C., Yu C.-E., Hunt C.R., Trask B.J., Clancy K.P.,
RA Weber J.L., Patterson D., Schellenberg G.D.;
RT "Cloning, sequencing, and mapping of the human chromosome 14 heat
RT shock protein gene (HSPA2).";
RL Genomics 23:85-93(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Goralski T.J., Krensky A.M.;
RL Submitted (APR-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-191 AND GLU-496.
RG NIEHS SNPs program;
RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Eye;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-126.
RX PubMed=7849706; DOI=10.1093/hmg/3.10.1819;
RA Roux A.-F., Nguyen V.T.T., Squire J.A., Cox D.W.;
RT "A heat shock gene at 14q22: mapping and expression.";
RL Hum. Mol. Genet. 3:1819-1822(1994).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP METHYLATION AT LYS-564, AND MUTAGENESIS OF LYS-564.
RX PubMed=23921388; DOI=10.1074/jbc.M113.483248;
RA Jakobsson M.E., Moen A., Bousset L., Egge-Jacobsen W., Kernstock S.,
RA Melki R., Falnes P.O.;
RT "Identification and characterization of a novel human
RT methyltransferase modulating Hsp70 function through lysine
RT methylation.";
RL J. Biol. Chem. 288:27752-27763(2013).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 6-386 IN COMPLEX WITH ADP AND
RP PHOSPHATE.
RX PubMed=20072699; DOI=10.1371/journal.pone.0008625;
RA Wisniewska M., Karlberg T., Lehtio L., Johansson I., Kotenyova T.,
RA Moche M., Schuler H.;
RT "Crystal structures of the ATPase domains of four human Hsp70
RT isoforms: HSPA1L/Hsp70-hom, HSPA2/Hsp70-2, HSPA6/Hsp70B', and
RT HSPA5/BiP/GRP78.";
RL PLoS ONE 5:E8625-E8625(2010).
CC -!- FUNCTION: In cooperation with other chaperones, Hsp70s stabilize
CC preexistent proteins against aggregation and mediate the folding
CC of newly translated polypeptides in the cytosol as well as within
CC organelles. These chaperones participate in all these processes
CC through their ability to recognize nonnative conformations of
CC other proteins. They bind extended peptide segments with a net
CC hydrophobic character exposed by polypeptides during translation
CC and membrane translocation, or following stress-induced damage.
CC -!- SUBUNIT: Interacts with ZNF541. Component of the CatSper complex
CC (By similarity). Interacts with RABL2/RABL2A; binds preferentially
CC to GTP-bound RABL2 (By similarity).
CC -!- INTERACTION:
CC Q9NZL4:HSPBP1; NbExp=3; IntAct=EBI-356991, EBI-356763;
CC -!- SIMILARITY: Belongs to the heat shock protein 70 family.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/hspa2/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; L26336; AAA52698.1; -; Genomic_DNA.
DR EMBL; U56725; AAD11466.1; -; mRNA.
DR EMBL; BT009815; AAP88817.1; -; mRNA.
DR EMBL; DQ489378; ABE96830.1; -; Genomic_DNA.
DR EMBL; BC001752; AAH01752.1; -; mRNA.
DR EMBL; BC036107; AAH36107.1; -; mRNA.
DR EMBL; AH006615; AAC50076.1; -; Genomic_DNA.
DR PIR; A55719; A55719.
DR PIR; I37564; I37564.
DR RefSeq; NP_068814.2; NM_021979.3.
DR UniGene; Hs.432648; -.
DR PDB; 3I33; X-ray; 1.30 A; A=6-386.
DR PDB; 4FSV; X-ray; 1.80 A; A=2-387.
DR PDBsum; 3I33; -.
DR PDBsum; 4FSV; -.
DR ProteinModelPortal; P54652; -.
DR SMR; P54652; 3-613.
DR IntAct; P54652; 12.
DR MINT; MINT-1146083; -.
DR STRING; 9606.ENSP00000247207; -.
DR ChEMBL; CHEMBL2062348; -.
DR PhosphoSite; P54652; -.
DR DMDM; 1708307; -.
DR REPRODUCTION-2DPAGE; IPI00007702; -.
DR PaxDb; P54652; -.
DR PeptideAtlas; P54652; -.
DR PRIDE; P54652; -.
DR DNASU; 3306; -.
DR Ensembl; ENST00000247207; ENSP00000247207; ENSG00000126803.
DR Ensembl; ENST00000394709; ENSP00000378199; ENSG00000126803.
DR GeneID; 3306; -.
DR KEGG; hsa:3306; -.
DR UCSC; uc001xhj.3; human.
DR CTD; 3306; -.
DR GeneCards; GC14P065002; -.
DR HGNC; HGNC:5235; HSPA2.
DR HPA; HPA000798; -.
DR MIM; 140560; gene.
DR neXtProt; NX_P54652; -.
DR PharmGKB; PA29501; -.
DR eggNOG; COG0443; -.
DR HOGENOM; HOG000228135; -.
DR HOVERGEN; HBG051845; -.
DR InParanoid; P54652; -.
DR KO; K03283; -.
DR OMA; RDIAGNK; -.
DR OrthoDB; EOG7PCJGF; -.
DR PhylomeDB; P54652; -.
DR Reactome; REACT_111183; Meiosis.
DR Reactome; REACT_115566; Cell Cycle.
DR ChiTaRS; HSPA2; human.
DR EvolutionaryTrace; P54652; -.
DR GeneWiki; HSPA2; -.
DR GenomeRNAi; 3306; -.
DR NextBio; 13115; -.
DR PRO; PR:P54652; -.
DR Bgee; P54652; -.
DR CleanEx; HS_HSPA2; -.
DR Genevestigator; P54652; -.
DR GO; GO:0036128; C:CatSper complex; ISS:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0001673; C:male germ cell nucleus; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0000795; C:synaptonemal complex; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0051861; F:glycolipid binding; IEA:Ensembl.
DR GO; GO:0051082; F:unfolded protein binding; TAS:ProtInc.
DR GO; GO:0007140; P:male meiosis; TAS:ProtInc.
DR GO; GO:0007141; P:male meiosis I; IEA:Ensembl.
DR GO; GO:0031662; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G2/M transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0006986; P:response to unfolded protein; TAS:ProtInc.
DR GO; GO:0007286; P:spermatid development; TAS:ProtInc.
DR GO; GO:0070194; P:synaptonemal complex disassembly; IEA:Ensembl.
DR InterPro; IPR018181; Heat_shock_70_CS.
DR InterPro; IPR013126; Hsp_70_fam.
DR Pfam; PF00012; HSP70; 1.
DR PRINTS; PR00301; HEATSHOCK70.
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 3D-structure; ATP-binding; Chaperone; Complete proteome; Methylation;
KW Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome;
KW Stress response.
FT CHAIN 1 639 Heat shock-related 70 kDa protein 2.
FT /FTId=PRO_0000078258.
FT NP_BIND 13 16 ATP.
FT NP_BIND 205 207 ATP.
FT NP_BIND 271 278 ATP.
FT NP_BIND 342 345 ATP.
FT BINDING 72 72 ATP.
FT MOD_RES 403 403 Phosphoserine (By similarity).
FT MOD_RES 408 408 Phosphothreonine (By similarity).
FT MOD_RES 414 414 Phosphothreonine (By similarity).
FT MOD_RES 564 564 N6,N6,N6-trimethyllysine; by METTL21A; in
FT vitro.
FT VARIANT 191 191 C -> S (in dbSNP:rs45456191).
FT /FTId=VAR_032706.
FT VARIANT 496 496 K -> E.
FT /FTId=VAR_032707.
FT MUTAGEN 564 564 K->A: Abolishes methylation by METTL21A.
FT CONFLICT 14 14 T -> P (in Ref. 5; AAH36107).
FT CONFLICT 54 54 Missing (in Ref. 6; AAC50076).
FT CONFLICT 80 80 E -> G (in Ref. 5; AAH36107).
FT CONFLICT 266 266 L -> S (in Ref. 2; AAD11466).
FT STRAND 8 12
FT STRAND 14 23
FT STRAND 26 29
FT STRAND 37 40
FT STRAND 43 45
FT STRAND 50 52
FT HELIX 54 58
FT TURN 59 62
FT HELIX 64 66
FT HELIX 71 73
FT TURN 74 76
FT HELIX 82 88
FT STRAND 92 98
FT STRAND 101 108
FT STRAND 111 115
FT HELIX 117 136
FT STRAND 142 147
FT HELIX 153 166
FT STRAND 169 175
FT HELIX 176 183
FT TURN 184 187
FT STRAND 191 194
FT STRAND 197 203
FT STRAND 208 216
FT STRAND 219 228
FT HELIX 233 252
FT HELIX 260 276
FT TURN 277 279
FT STRAND 280 291
FT STRAND 294 301
FT HELIX 302 308
FT HELIX 310 315
FT HELIX 317 327
FT HELIX 331 333
FT STRAND 336 341
FT HELIX 342 345
FT HELIX 347 356
FT TURN 357 359
FT TURN 368 370
FT HELIX 371 383
SQ SEQUENCE 639 AA; 70021 MW; 3851755494E7B729 CRC64;
MSARGPAIGI DLGTTYSCVG VFQHGKVEII ANDQGNRTTP SYVAFTDTER LIGDAAKNQV
AMNPTNTIFD AKRLIGRKFE DATVQSDMKH WPFRVVSEGG KPKVQVEYKG ETKTFFPEEI
SSMVLTKMKE IAEAYLGGKV HSAVITVPAY 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
AKNALESYTY NIKQTVEDEK LRGKISEQDK NKILDKCQEV INWLDRNQMA EKDEYEHKQK
ELERVCNPII SKLYQGGPGG GSGGGGSGAS GGPTIEEVD
//
ID HSP72_HUMAN Reviewed; 639 AA.
AC P54652; Q15508; Q53XM3; Q9UE78;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-1996, sequence version 1.
DT 22-JAN-2014, entry version 130.
DE RecName: Full=Heat shock-related 70 kDa protein 2;
DE Short=Heat shock 70 kDa protein 2;
GN Name=HSPA2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7829106; DOI=10.1006/geno.1994.1462;
RA Bonnycastle L.L.C., Yu C.-E., Hunt C.R., Trask B.J., Clancy K.P.,
RA Weber J.L., Patterson D., Schellenberg G.D.;
RT "Cloning, sequencing, and mapping of the human chromosome 14 heat
RT shock protein gene (HSPA2).";
RL Genomics 23:85-93(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Goralski T.J., Krensky A.M.;
RL Submitted (APR-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-191 AND GLU-496.
RG NIEHS SNPs program;
RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Eye;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-126.
RX PubMed=7849706; DOI=10.1093/hmg/3.10.1819;
RA Roux A.-F., Nguyen V.T.T., Squire J.A., Cox D.W.;
RT "A heat shock gene at 14q22: mapping and expression.";
RL Hum. Mol. Genet. 3:1819-1822(1994).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP METHYLATION AT LYS-564, AND MUTAGENESIS OF LYS-564.
RX PubMed=23921388; DOI=10.1074/jbc.M113.483248;
RA Jakobsson M.E., Moen A., Bousset L., Egge-Jacobsen W., Kernstock S.,
RA Melki R., Falnes P.O.;
RT "Identification and characterization of a novel human
RT methyltransferase modulating Hsp70 function through lysine
RT methylation.";
RL J. Biol. Chem. 288:27752-27763(2013).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 6-386 IN COMPLEX WITH ADP AND
RP PHOSPHATE.
RX PubMed=20072699; DOI=10.1371/journal.pone.0008625;
RA Wisniewska M., Karlberg T., Lehtio L., Johansson I., Kotenyova T.,
RA Moche M., Schuler H.;
RT "Crystal structures of the ATPase domains of four human Hsp70
RT isoforms: HSPA1L/Hsp70-hom, HSPA2/Hsp70-2, HSPA6/Hsp70B', and
RT HSPA5/BiP/GRP78.";
RL PLoS ONE 5:E8625-E8625(2010).
CC -!- FUNCTION: In cooperation with other chaperones, Hsp70s stabilize
CC preexistent proteins against aggregation and mediate the folding
CC of newly translated polypeptides in the cytosol as well as within
CC organelles. These chaperones participate in all these processes
CC through their ability to recognize nonnative conformations of
CC other proteins. They bind extended peptide segments with a net
CC hydrophobic character exposed by polypeptides during translation
CC and membrane translocation, or following stress-induced damage.
CC -!- SUBUNIT: Interacts with ZNF541. Component of the CatSper complex
CC (By similarity). Interacts with RABL2/RABL2A; binds preferentially
CC to GTP-bound RABL2 (By similarity).
CC -!- INTERACTION:
CC Q9NZL4:HSPBP1; NbExp=3; IntAct=EBI-356991, EBI-356763;
CC -!- SIMILARITY: Belongs to the heat shock protein 70 family.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/hspa2/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; L26336; AAA52698.1; -; Genomic_DNA.
DR EMBL; U56725; AAD11466.1; -; mRNA.
DR EMBL; BT009815; AAP88817.1; -; mRNA.
DR EMBL; DQ489378; ABE96830.1; -; Genomic_DNA.
DR EMBL; BC001752; AAH01752.1; -; mRNA.
DR EMBL; BC036107; AAH36107.1; -; mRNA.
DR EMBL; AH006615; AAC50076.1; -; Genomic_DNA.
DR PIR; A55719; A55719.
DR PIR; I37564; I37564.
DR RefSeq; NP_068814.2; NM_021979.3.
DR UniGene; Hs.432648; -.
DR PDB; 3I33; X-ray; 1.30 A; A=6-386.
DR PDB; 4FSV; X-ray; 1.80 A; A=2-387.
DR PDBsum; 3I33; -.
DR PDBsum; 4FSV; -.
DR ProteinModelPortal; P54652; -.
DR SMR; P54652; 3-613.
DR IntAct; P54652; 12.
DR MINT; MINT-1146083; -.
DR STRING; 9606.ENSP00000247207; -.
DR ChEMBL; CHEMBL2062348; -.
DR PhosphoSite; P54652; -.
DR DMDM; 1708307; -.
DR REPRODUCTION-2DPAGE; IPI00007702; -.
DR PaxDb; P54652; -.
DR PeptideAtlas; P54652; -.
DR PRIDE; P54652; -.
DR DNASU; 3306; -.
DR Ensembl; ENST00000247207; ENSP00000247207; ENSG00000126803.
DR Ensembl; ENST00000394709; ENSP00000378199; ENSG00000126803.
DR GeneID; 3306; -.
DR KEGG; hsa:3306; -.
DR UCSC; uc001xhj.3; human.
DR CTD; 3306; -.
DR GeneCards; GC14P065002; -.
DR HGNC; HGNC:5235; HSPA2.
DR HPA; HPA000798; -.
DR MIM; 140560; gene.
DR neXtProt; NX_P54652; -.
DR PharmGKB; PA29501; -.
DR eggNOG; COG0443; -.
DR HOGENOM; HOG000228135; -.
DR HOVERGEN; HBG051845; -.
DR InParanoid; P54652; -.
DR KO; K03283; -.
DR OMA; RDIAGNK; -.
DR OrthoDB; EOG7PCJGF; -.
DR PhylomeDB; P54652; -.
DR Reactome; REACT_111183; Meiosis.
DR Reactome; REACT_115566; Cell Cycle.
DR ChiTaRS; HSPA2; human.
DR EvolutionaryTrace; P54652; -.
DR GeneWiki; HSPA2; -.
DR GenomeRNAi; 3306; -.
DR NextBio; 13115; -.
DR PRO; PR:P54652; -.
DR Bgee; P54652; -.
DR CleanEx; HS_HSPA2; -.
DR Genevestigator; P54652; -.
DR GO; GO:0036128; C:CatSper complex; ISS:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0001673; C:male germ cell nucleus; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0000795; C:synaptonemal complex; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0051861; F:glycolipid binding; IEA:Ensembl.
DR GO; GO:0051082; F:unfolded protein binding; TAS:ProtInc.
DR GO; GO:0007140; P:male meiosis; TAS:ProtInc.
DR GO; GO:0007141; P:male meiosis I; IEA:Ensembl.
DR GO; GO:0031662; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G2/M transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0006986; P:response to unfolded protein; TAS:ProtInc.
DR GO; GO:0007286; P:spermatid development; TAS:ProtInc.
DR GO; GO:0070194; P:synaptonemal complex disassembly; IEA:Ensembl.
DR InterPro; IPR018181; Heat_shock_70_CS.
DR InterPro; IPR013126; Hsp_70_fam.
DR Pfam; PF00012; HSP70; 1.
DR PRINTS; PR00301; HEATSHOCK70.
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 3D-structure; ATP-binding; Chaperone; Complete proteome; Methylation;
KW Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome;
KW Stress response.
FT CHAIN 1 639 Heat shock-related 70 kDa protein 2.
FT /FTId=PRO_0000078258.
FT NP_BIND 13 16 ATP.
FT NP_BIND 205 207 ATP.
FT NP_BIND 271 278 ATP.
FT NP_BIND 342 345 ATP.
FT BINDING 72 72 ATP.
FT MOD_RES 403 403 Phosphoserine (By similarity).
FT MOD_RES 408 408 Phosphothreonine (By similarity).
FT MOD_RES 414 414 Phosphothreonine (By similarity).
FT MOD_RES 564 564 N6,N6,N6-trimethyllysine; by METTL21A; in
FT vitro.
FT VARIANT 191 191 C -> S (in dbSNP:rs45456191).
FT /FTId=VAR_032706.
FT VARIANT 496 496 K -> E.
FT /FTId=VAR_032707.
FT MUTAGEN 564 564 K->A: Abolishes methylation by METTL21A.
FT CONFLICT 14 14 T -> P (in Ref. 5; AAH36107).
FT CONFLICT 54 54 Missing (in Ref. 6; AAC50076).
FT CONFLICT 80 80 E -> G (in Ref. 5; AAH36107).
FT CONFLICT 266 266 L -> S (in Ref. 2; AAD11466).
FT STRAND 8 12
FT STRAND 14 23
FT STRAND 26 29
FT STRAND 37 40
FT STRAND 43 45
FT STRAND 50 52
FT HELIX 54 58
FT TURN 59 62
FT HELIX 64 66
FT HELIX 71 73
FT TURN 74 76
FT HELIX 82 88
FT STRAND 92 98
FT STRAND 101 108
FT STRAND 111 115
FT HELIX 117 136
FT STRAND 142 147
FT HELIX 153 166
FT STRAND 169 175
FT HELIX 176 183
FT TURN 184 187
FT STRAND 191 194
FT STRAND 197 203
FT STRAND 208 216
FT STRAND 219 228
FT HELIX 233 252
FT HELIX 260 276
FT TURN 277 279
FT STRAND 280 291
FT STRAND 294 301
FT HELIX 302 308
FT HELIX 310 315
FT HELIX 317 327
FT HELIX 331 333
FT STRAND 336 341
FT HELIX 342 345
FT HELIX 347 356
FT TURN 357 359
FT TURN 368 370
FT HELIX 371 383
SQ SEQUENCE 639 AA; 70021 MW; 3851755494E7B729 CRC64;
MSARGPAIGI DLGTTYSCVG VFQHGKVEII ANDQGNRTTP SYVAFTDTER LIGDAAKNQV
AMNPTNTIFD AKRLIGRKFE DATVQSDMKH WPFRVVSEGG KPKVQVEYKG ETKTFFPEEI
SSMVLTKMKE IAEAYLGGKV HSAVITVPAY 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
AKNALESYTY NIKQTVEDEK LRGKISEQDK NKILDKCQEV INWLDRNQMA EKDEYEHKQK
ELERVCNPII SKLYQGGPGG GSGGGGSGAS GGPTIEEVD
//
MIM
140560
*RECORD*
*FIELD* NO
140560
*FIELD* TI
*140560 HEAT-SHOCK 70-KD PROTEIN 2; HSPA2
;;HEAT-SHOCK PROTEIN, 70-KD, 2;;
HSP70-2;;
read moreHEAT-SHOCK PROTEIN, 70-KD, 3;;
HSP70-3
*FIELD* TX
CLONING
Bonnycastle et al. (1994) isolated a genomic clone for HSPA2 and found
that it has a single open reading frame of 1,917 basepairs that encodes
a 639-amino acid protein with a predicted molecular mass of 70,030 Da.
Analysis of the sequence indicated that HSPA2 is the human homolog of
the murine Hsp70-2 gene, with 91.7% identity in the nucleotide coding
sequence and 98.2% in the corresponding amino acid sequence. HSPA2 has
less amino acid homology to the other members of the human HSP70 gene
family. HSPA2 is constitutively expressed in most tissues, with very
high levels in testis and skeletal muscle.
Roux et al. (1994) also cloned the HSPA2 gene, using a genomic probe
derived from one of the HSP genes in the major histocompatibility
complex (MHC) on chromosome 6, which had previously been shown to detect
sequences on chromosome 14 as well. HSPA2 is expressed abundantly in
muscle, heart, esophagus, and brain, and to a lesser extent in testis.
Using Western blot analysis, Son et al. (1999) found significant
expression of a 70-kD HSPA2 protein in testis, but only low expression
in testis with Sertoli cell-only syndrome (see 305700). A small amount
of HSPA2 was detected in breast, stomach, prostate, colon, liver, ovary,
and epididymis. Immunohistochemical analysis of normal testis detected
HSPA2 in spermatocytes and spermatids with normal spermatogenesis,
whereas little to no immunoreactivity was detected in testis with
Sertoli cell-only syndrome.
Huszar et al. (2000) determined that HSPA2 is identical to sperm CKM, a
marker of sperm maturity and function. Immunohistochemical analysis
detected weak expression of HSPA2 in spermatocytes and stronger
expression in spermatids and in the tail of mature sperm.
GENE FUNCTION
During spermiogenesis, both cytoplasmic extrusion and plasma membrane
remodeling, which facilitate the formation of the zona pellucida-binding
site, involve major intrasperm protein transport. Huszar et al. (2000)
noted that immature human sperm, which fail to express HSPA2, show
cytoplasmic retention and lack zona pellucida binding. They suggested
that HSPA2 may be critical to sperm maturation through its role as a
protein chaperone.
Rohde et al. (2005) found elevated expression of HSP70-2 in 5 of 16
(31%) and 4 of 9 (44%) samples from primary and metastatic breast cancer
tissue, respectively, compared with 13 samples from adjacent normal
breast tissue. Cancer cells depleted of HSP70 (HSPA1A; 140550) and
HSP70-2 by small interfering RNA displayed strikingly different
morphologies (detached and round vs flat senescent-like), cell cycle
distribution (G2/M vs G1 arrest), and gene expression profiles.
Concomitant depletion of HSP70 and HSP70-2 had a synergistic
antiproliferative effect on cancer cells.
MAPPING
Several heat-shock protein genes, such as HSPA1, are located in the MHC
on chromosome 6. However, the HSPA2 gene is located on chromosome
14q22-q24 (Harrison et al., 1987). By fluorescence in situ
hybridization, Bonnycastle et al. (1994) mapped a 670-kb YAC containing
HSPA2 to chromosome 14q24.1. Roux et al. (1994) localized HSPA2 to
chromosome 14q22 by study of a somatic cell hybrid panel and by FISH
analysis. Hunt et al. (1993) found that the corresponding gene in the
mouse is located in a region of chromosome 12 homologous to human
chromosome 14.
MOLECULAR GENETICS
For a discussion of a possible association between variation in the
HSPA2 gene and noise-induced hearing loss, see 613035.
ANIMAL MODEL
Dix et al. (1996) showed that female homozygous knockout mice for
Hsp70-2 undergo normal meiosis and are fertile. In contrast, homozygous
male knockout mice lacked postmeiotic spermatids and mature sperm and
were infertile. Hsp70-2 is normally associated with synaptonemal
complexes in the nuclei of meiotic spermatocytes. In the male knockouts,
these structures were abnormal by late prophase. Dix et al. (1996)
observed also a large increase in spermatocyte apoptosis.
*FIELD* RF
1. Bonnycastle, L. L. C.; Yu, C.-E.; Hunt, C. R.; Trask, B. J.; Clancy,
K. P.; Weber, J. L.; Patterson, D.; Schellenberg, G. D.: Cloning,
sequencing, and mapping of the human chromosome 14 heat shock protein
gene (HSPA2). Genomics 23: 85-93, 1994.
2. Dix, D. J.; Allen, J. W.; Collins, B. W.; Mori, C.; Nakamura, N.;
Poorman-Allen, P.; Goulding, E. H.; Eddy, E. M.: Targeted gene disruption
of Hsp70-2 results in failed meiosis, germ cell apoptosis, and male
infertility. Proc. Nat. Acad. Sci. 93: 3264-3268, 1996.
3. Harrison, G. S.; Drabkin, H. A.; Kao, F.-T.; Hartz, J.; Hart, I.
M.; Chu, E. H. Y.; Wu, B. J.; Morimoto, R. I.: Chromosomal location
of human genes encoding major heat-shock protein HSP70. Somat. Cell
Molec. Genet. 13: 119-130, 1987.
4. Hunt, C. R.; Gasser, D. L.; Chaplin, D. D.; Pierce, J. C.; Kozak,
C. A.: Chromosomal localization of five murine HSP70 gene family
members: Hsp70-1, Hsp70-2, Hsp70-3, Hsc70t and Grp78. Genomics 16:
193-198, 1993.
5. Huszar, G.; Stone, K.; Dix, D.; Vigue, L.: Putative creatine kinase
M-isoform in human sperm is identified as the 70-kilodalton heat shock
protein HspA2. Biol. Reprod. 63: 925-932, 2000.
6. Rohde, M.; Daugaard, M.; Jensen, M. H.; Helin, K.; Nylandsted,
J.; Jaattela, M.: Members of the heat-shock protein 70 family promote
cancer cell growth by distinct mechanisms. Genes Dev. 19: 570-582,
2005.
7. Roux, A.-F.; Nguyen, V. T. T.; Squire, J. A.; Cox, D. W.: A heat
shock gene at 14q22: mapping and expression. Hum. Molec. Genet. 3:
1819-1822, 1994.
8. Son, W.-Y.; Hwang, S.-H.; Han, C.-T.; Lee, J.-H.; Kim, S.; Kim,
Y. C.: Specific expression of heat shock protein HspA2 in human male
germ cells. Molec. Hum. Reprod. 5: 1122-1126, 1999.
*FIELD* CN
Patricia A. Hartz - updated: 9/21/2005
Patricia A. Hartz - updated: 9/16/2005
Alan F. Scott - updated: 5/20/1996
*FIELD* CD
Victor A. McKusick: 9/23/1987
*FIELD* ED
wwang: 10/14/2009
ckniffin: 9/29/2009
mgross: 10/6/2005
terry: 9/21/2005
mgross: 9/16/2005
terry: 7/24/1998
dkim: 7/21/1998
mark: 5/20/1996
terry: 5/20/1996
mark: 12/7/1995
carol: 12/13/1994
terry: 11/7/1994
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/27/1989
marie: 3/25/1988
*RECORD*
*FIELD* NO
140560
*FIELD* TI
*140560 HEAT-SHOCK 70-KD PROTEIN 2; HSPA2
;;HEAT-SHOCK PROTEIN, 70-KD, 2;;
HSP70-2;;
read moreHEAT-SHOCK PROTEIN, 70-KD, 3;;
HSP70-3
*FIELD* TX
CLONING
Bonnycastle et al. (1994) isolated a genomic clone for HSPA2 and found
that it has a single open reading frame of 1,917 basepairs that encodes
a 639-amino acid protein with a predicted molecular mass of 70,030 Da.
Analysis of the sequence indicated that HSPA2 is the human homolog of
the murine Hsp70-2 gene, with 91.7% identity in the nucleotide coding
sequence and 98.2% in the corresponding amino acid sequence. HSPA2 has
less amino acid homology to the other members of the human HSP70 gene
family. HSPA2 is constitutively expressed in most tissues, with very
high levels in testis and skeletal muscle.
Roux et al. (1994) also cloned the HSPA2 gene, using a genomic probe
derived from one of the HSP genes in the major histocompatibility
complex (MHC) on chromosome 6, which had previously been shown to detect
sequences on chromosome 14 as well. HSPA2 is expressed abundantly in
muscle, heart, esophagus, and brain, and to a lesser extent in testis.
Using Western blot analysis, Son et al. (1999) found significant
expression of a 70-kD HSPA2 protein in testis, but only low expression
in testis with Sertoli cell-only syndrome (see 305700). A small amount
of HSPA2 was detected in breast, stomach, prostate, colon, liver, ovary,
and epididymis. Immunohistochemical analysis of normal testis detected
HSPA2 in spermatocytes and spermatids with normal spermatogenesis,
whereas little to no immunoreactivity was detected in testis with
Sertoli cell-only syndrome.
Huszar et al. (2000) determined that HSPA2 is identical to sperm CKM, a
marker of sperm maturity and function. Immunohistochemical analysis
detected weak expression of HSPA2 in spermatocytes and stronger
expression in spermatids and in the tail of mature sperm.
GENE FUNCTION
During spermiogenesis, both cytoplasmic extrusion and plasma membrane
remodeling, which facilitate the formation of the zona pellucida-binding
site, involve major intrasperm protein transport. Huszar et al. (2000)
noted that immature human sperm, which fail to express HSPA2, show
cytoplasmic retention and lack zona pellucida binding. They suggested
that HSPA2 may be critical to sperm maturation through its role as a
protein chaperone.
Rohde et al. (2005) found elevated expression of HSP70-2 in 5 of 16
(31%) and 4 of 9 (44%) samples from primary and metastatic breast cancer
tissue, respectively, compared with 13 samples from adjacent normal
breast tissue. Cancer cells depleted of HSP70 (HSPA1A; 140550) and
HSP70-2 by small interfering RNA displayed strikingly different
morphologies (detached and round vs flat senescent-like), cell cycle
distribution (G2/M vs G1 arrest), and gene expression profiles.
Concomitant depletion of HSP70 and HSP70-2 had a synergistic
antiproliferative effect on cancer cells.
MAPPING
Several heat-shock protein genes, such as HSPA1, are located in the MHC
on chromosome 6. However, the HSPA2 gene is located on chromosome
14q22-q24 (Harrison et al., 1987). By fluorescence in situ
hybridization, Bonnycastle et al. (1994) mapped a 670-kb YAC containing
HSPA2 to chromosome 14q24.1. Roux et al. (1994) localized HSPA2 to
chromosome 14q22 by study of a somatic cell hybrid panel and by FISH
analysis. Hunt et al. (1993) found that the corresponding gene in the
mouse is located in a region of chromosome 12 homologous to human
chromosome 14.
MOLECULAR GENETICS
For a discussion of a possible association between variation in the
HSPA2 gene and noise-induced hearing loss, see 613035.
ANIMAL MODEL
Dix et al. (1996) showed that female homozygous knockout mice for
Hsp70-2 undergo normal meiosis and are fertile. In contrast, homozygous
male knockout mice lacked postmeiotic spermatids and mature sperm and
were infertile. Hsp70-2 is normally associated with synaptonemal
complexes in the nuclei of meiotic spermatocytes. In the male knockouts,
these structures were abnormal by late prophase. Dix et al. (1996)
observed also a large increase in spermatocyte apoptosis.
*FIELD* RF
1. Bonnycastle, L. L. C.; Yu, C.-E.; Hunt, C. R.; Trask, B. J.; Clancy,
K. P.; Weber, J. L.; Patterson, D.; Schellenberg, G. D.: Cloning,
sequencing, and mapping of the human chromosome 14 heat shock protein
gene (HSPA2). Genomics 23: 85-93, 1994.
2. Dix, D. J.; Allen, J. W.; Collins, B. W.; Mori, C.; Nakamura, N.;
Poorman-Allen, P.; Goulding, E. H.; Eddy, E. M.: Targeted gene disruption
of Hsp70-2 results in failed meiosis, germ cell apoptosis, and male
infertility. Proc. Nat. Acad. Sci. 93: 3264-3268, 1996.
3. Harrison, G. S.; Drabkin, H. A.; Kao, F.-T.; Hartz, J.; Hart, I.
M.; Chu, E. H. Y.; Wu, B. J.; Morimoto, R. I.: Chromosomal location
of human genes encoding major heat-shock protein HSP70. Somat. Cell
Molec. Genet. 13: 119-130, 1987.
4. Hunt, C. R.; Gasser, D. L.; Chaplin, D. D.; Pierce, J. C.; Kozak,
C. A.: Chromosomal localization of five murine HSP70 gene family
members: Hsp70-1, Hsp70-2, Hsp70-3, Hsc70t and Grp78. Genomics 16:
193-198, 1993.
5. Huszar, G.; Stone, K.; Dix, D.; Vigue, L.: Putative creatine kinase
M-isoform in human sperm is identified as the 70-kilodalton heat shock
protein HspA2. Biol. Reprod. 63: 925-932, 2000.
6. Rohde, M.; Daugaard, M.; Jensen, M. H.; Helin, K.; Nylandsted,
J.; Jaattela, M.: Members of the heat-shock protein 70 family promote
cancer cell growth by distinct mechanisms. Genes Dev. 19: 570-582,
2005.
7. Roux, A.-F.; Nguyen, V. T. T.; Squire, J. A.; Cox, D. W.: A heat
shock gene at 14q22: mapping and expression. Hum. Molec. Genet. 3:
1819-1822, 1994.
8. Son, W.-Y.; Hwang, S.-H.; Han, C.-T.; Lee, J.-H.; Kim, S.; Kim,
Y. C.: Specific expression of heat shock protein HspA2 in human male
germ cells. Molec. Hum. Reprod. 5: 1122-1126, 1999.
*FIELD* CN
Patricia A. Hartz - updated: 9/21/2005
Patricia A. Hartz - updated: 9/16/2005
Alan F. Scott - updated: 5/20/1996
*FIELD* CD
Victor A. McKusick: 9/23/1987
*FIELD* ED
wwang: 10/14/2009
ckniffin: 9/29/2009
mgross: 10/6/2005
terry: 9/21/2005
mgross: 9/16/2005
terry: 7/24/1998
dkim: 7/21/1998
mark: 5/20/1996
terry: 5/20/1996
mark: 12/7/1995
carol: 12/13/1994
terry: 11/7/1994
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/27/1989
marie: 3/25/1988