RBCC Red Blood Cell Collection

HSPA1A (HSPA1, HSX70) [Confidence: high (present in two of the MS resources)]
Heat shock 70 kDa protein 1A/1B (Heat shock 70 kDa protein 1/2; HSP70-1/HSP70-2; HSP70.1/HSP70.2)
Note: presumably soluble (membrane word is not in UniProt keywords or features)

hRBCD IPI00304925
IPI00304925 Heat shock 70 kDa protein 1 folding of newly translated polypeptides, binding to hydrophobic moieties soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight

Comments
Isoform P08107-2 was detected.

UniProt P08107
ID HSP71_HUMAN Reviewed; 641 AA.
AC P08107; B4E3B6; P19790; Q5JQI4; Q5SP17; Q9UQL9; Q9UQM0;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
read moreDT 15-MAY-2007, sequence version 5.
DT 22-JAN-2014, entry version 176.
DE RecName: Full=Heat shock 70 kDa protein 1A/1B;
DE AltName: Full=Heat shock 70 kDa protein 1/2;
DE Short=HSP70-1/HSP70-2;
DE Short=HSP70.1/HSP70.2;
GN Name=HSPA1A; Synonyms=HSPA1, HSX70;
GN and
GN Name=HSPA1B;
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=1700760; DOI=10.1007/BF00187095;
RA Milner C.M., Campbell R.D.;
RT "Structure and expression of the three MHC-linked HSP70 genes.";
RL Immunogenetics 32:242-251(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3931075; DOI=10.1073/pnas.82.19.6455;
RA Hunt C., Morimoto R.I.;
RT "Conserved features of eukaryotic hsp70 genes revealed by comparison
RT with the nucleotide sequence of human hsp70.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:6455-6459(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (HSPA1A AND HSPA1B), AND
RP VARIANTS ASP-110 AND SER-499.
RX PubMed=14656967; DOI=10.1101/gr.1736803;
RA Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S.,
RA Campbell R.D., Hood L.;
RT "Analysis of the gene-dense major histocompatibility complex class III
RT region and its comparison to mouse.";
RL Genome Res. 13:2621-2636(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (HSPA1A AND HSPA1B).
RA Shiina S., Tamiya G., Oka A., Inoko H.;
RT "Homo sapiens 2,229,817bp genomic DNA of 6p21.3 HLA class I region.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Uterus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-95; ASP-110;
RP VAL-467 AND SER-499.
RG NIEHS SNPs program;
RL Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ASP-110.
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, Muscle, Pancreas, PNS, and Skin;
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 [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-36 AND 360-424.
RX PubMed=2538825; DOI=10.1073/pnas.86.6.1968;
RA Sargent C.A., Dunham I., Trowsdale J., Campbell R.D.;
RT "Human major histocompatibility complex contains genes for the major
RT heat shock protein HSP70.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:1968-1972(1989).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22 AND 617-641.
RX PubMed=3786141; DOI=10.1093/nar/14.22.8933;
RA Drabent B., Genthe A., Benecke B.-J.;
RT "In vitro transcription of a human hsp 70 heat shock gene by extracts
RT prepared from heat-shocked and non-heat-shocked human cells.";
RL Nucleic Acids Res. 14:8933-8948(1986).
RN [11]
RP PROTEIN SEQUENCE OF 4-49; 57-71; 77-155; 160-187; 221-247; 273-311;
RP 326-342; 349-357; 362-416; 424-447; 459-469; 510-517; 540-550; 574-595
RP AND 598-641, AND MASS SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RA Bienvenut W.V., Waridel P., Quadroni M.;
RL Submitted (MAR-2009) to UniProtKB.
RN [12]
RP PROTEIN SEQUENCE OF 37-49; 57-71; 78-88; 113-126; 160-187; 221-247;
RP 302-311; 329-342; 349-357; 362-384; 540-550 AND 574-589, AND MASS
RP SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [13]
RP PROTEIN SEQUENCE OF 551-567, METHYLATION AT LYS-561, MUTAGENESIS OF
RP LYS-561, AND MASS SPECTROMETRY.
RX PubMed=23349634; DOI=10.1371/journal.pgen.1003210;
RA Cloutier P., Lavallee-Adam M., Faubert D., Blanchette M., Coulombe B.;
RT "A newly uncovered group of distantly related lysine
RT methyltransferases preferentially interact with molecular chaperones
RT to regulate their activity.";
RL PLoS Genet. 9:E1003210-E1003210(2013).
RN [14]
RP INTERACTION WITH TERT.
RX PubMed=11274138; DOI=10.1074/jbc.C100055200;
RA Forsythe H.L., Jarvis J.L., Turner J.W., Elmore L.W., Holt S.E.;
RT "Stable association of hsp90 and p23, but Not hsp70, with active human
RT telomerase.";
RL J. Biol. Chem. 276:15571-15574(2001).
RN [15]
RP INTERACTION WITH DNAJC7.
RX PubMed=12853476; DOI=10.1093/emboj/cdg362;
RA Brychzy A., Rein T., Winklhofer K.F., Hartl F.U., Young J.C.,
RA Obermann W.M.;
RT "Cofactor Tpr2 combines two TPR domains and a J domain to regulate the
RT Hsp70/Hsp90 chaperone system.";
RL EMBO J. 22:3613-3623(2003).
RN [16]
RP INTERACTION WITH TSC2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=15963462; DOI=10.1016/j.bbrc.2005.05.175;
RA Nellist M., Burgers P.C., van den Ouweland A.M.W., Halley D.J.J.,
RA Luider T.M.;
RT "Phosphorylation and binding partner analysis of the TSC1-TSC2
RT complex.";
RL Biochem. Biophys. Res. Commun. 333:818-826(2005).
RN [17]
RP INTERACTION WITH PPP5C, AND MASS SPECTROMETRY.
RX PubMed=15383005; DOI=10.1042/BJ20040690;
RA Zeke T., Morrice N., Vazquez-Martin C., Cohen P.T.;
RT "Human protein phosphatase 5 dissociates from heat-shock proteins and
RT is proteolytically activated in response to arachidonic acid and the
RT microtubule-depolymerizing drug nocodazole.";
RL Biochem. J. 385:45-56(2005).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [19]
RP INTERACTION WITH IRAK1BP1, AND MASS SPECTROMETRY.
RX PubMed=17233114; DOI=10.1089/dna.2006.25.704;
RA Haag Breese E., Uversky V.N., Georgiadis M.M., Harrington M.A.;
RT "The disordered amino-terminus of SIMPL interacts with members of the
RT 70-kDa heat-shock protein family.";
RL DNA Cell Biol. 25:704-714(2006).
RN [20]
RP FUNCTION AS A RECEPTOR FOR ROTAVIRUS A.
RX PubMed=16537599; DOI=10.1128/JVI.80.7.3322-3331.2006;
RA Perez-Vargas J., Romero P., Lopez S., Arias C.F.;
RT "The peptide-binding and ATPase domains of recombinant hsc70 are
RT required to interact with rotavirus and reduce its infectivity.";
RL J. Virol. 80:3322-3331(2006).
RN [21]
RP IDENTIFICATION IN A MRNP GRANULE COMPLEX, IDENTIFICATION BY MASS
RP SPECTROMETRY, AND SUBCELLULAR LOCATION.
RX PubMed=17289661; DOI=10.1074/mcp.M600346-MCP200;
RA Joeson L., Vikesaa J., Krogh A., Nielsen L.K., Hansen T., Borup R.,
RA Johnsen A.H., Christiansen J., Nielsen F.C.;
RT "Molecular composition of IMP1 ribonucleoprotein granules.";
RL Mol. Cell. Proteomics 6:798-811(2007).
RN [22]
RP INTERACTION WITH DNAJC7.
RX PubMed=18620420; DOI=10.1021/bi800770g;
RA Moffatt N.S., Bruinsma E., Uhl C., Obermann W.M., Toft D.;
RT "Role of the cochaperone Tpr2 in Hsp90 chaperoning.";
RL Biochemistry 47:8203-8213(2008).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [24]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [25]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-108; LYS-246 AND LYS-348,
RP AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [26]
RP INTERACTION WITH TRIM5.
RX PubMed=20053985; DOI=10.1074/jbc.M109.040618;
RA Hwang C.Y., Holl J., Rajan D., Lee Y., Kim S., Um M., Kwon K.S.,
RA Song B.;
RT "Hsp70 interacts with the retroviral restriction factor TRIM5alpha and
RT assists the folding of TRIM5alpha.";
RL J. Biol. Chem. 285:7827-7837(2010).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-631; SER-633 AND
RP THR-636, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [28]
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 [29]
RP INTERACTION WITH CHCHD3.
RX PubMed=21081504; DOI=10.1074/jbc.M110.171975;
RA Darshi M., Mendiola V.L., Mackey M.R., Murphy A.N., Koller A.,
RA Perkins G.A., Ellisman M.H., Taylor S.S.;
RT "ChChd3, an inner mitochondrial membrane protein, is essential for
RT maintaining crista integrity and mitochondrial function.";
RL J. Biol. Chem. 286:2918-2932(2011).
RN [30]
RP METHYLATION AT LYS-561, MUTAGENESIS OF LYS-561, AND INTERACTION WITH
RP METTL21A.
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 [31]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-382 IN COMPLEX WITH ADP,
RP AND ATP-BINDING.
RX PubMed=10216320; DOI=10.1107/S0907444999002103;
RA Osipiuk J., Walsh M.A., Freeman B.C., Morimoto R.I., Joachimiak A.;
RT "Structure of a new crystal form of human hsp70 ATPase domain.";
RL Acta Crystallogr. D 55:1105-1107(1999).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (1.77 ANGSTROMS) OF 389-641 IN COMPLEX WITH ATP
RP ANALOG, AND ATP-BINDING.
RX PubMed=20179333; DOI=10.1107/S0907444909053979;
RA Shida M., Arakawa A., Ishii R., Kishishita S., Takagi T.,
RA Kukimoto-Niino M., Sugano S., Tanaka A., Shirouzu M., Yokoyama S.;
RT "Direct inter-subdomain interactions switch between the closed and
RT open forms of the Hsp70 nucleotide-binding domain in the nucleotide-
RT free state.";
RL Acta Crystallogr. D 66:223-232(2010).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (2.14 ANGSTROMS) OF 1-387 IN COMPLEX WITH ADP,
RP AND ATP-BINDING.
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).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-388 IN COMPLEX WITH BAG5.
RX PubMed=20223214; DOI=10.1016/j.str.2010.01.004;
RA Arakawa A., Handa N., Ohsawa N., Shida M., Kigawa T., Hayashi F.,
RA Shirouzu M., Yokoyama S.;
RT "The C-terminal BAG domain of BAG5 induces conformational changes of
RT the Hsp70 nucleotide-binding domain for ADP-ATP exchange.";
RL Structure 18:309-319(2010).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS) OF 1-388, ATP-BINDING, AND
RP MUTAGENESIS OF ASP-10 AND ASP-199.
RX PubMed=21608060; DOI=10.1002/pro.663;
RA Arakawa A., Handa N., Shirouzu M., Yokoyama S.;
RT "Biochemical and structural studies on the high affinity of Hsp70 for
RT ADP.";
RL Protein Sci. 20:1367-1379(2011).
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. In
CC case of rotavirus A infection, serves as a post-attachment
CC receptor for the virus to facilitate entry into the cell.
CC -!- SUBUNIT: Component of the CatSper complex. Identified in a
CC IGF2BP1-dependent mRNP granule complex containing untranslated
CC mRNAs. Interacts with CHCHD3, DNAJC7, IRAK1BP1, PPP5C and TSC2.
CC Interacts with TERT; the interaction occurs in the absence of the
CC RNA component, TERC, and dissociates once the TERT complex has
CC formed. Interacts with TRIM5 (via B30.2/SPRY domain). Interacts
CC with METTL21A.
CC -!- INTERACTION:
CC Q9HB09-2:BCL2L12; NbExp=2; IntAct=EBI-629985, EBI-6969019;
CC P00533:EGFR; NbExp=4; IntAct=EBI-629985, EBI-297353;
CC P15976:GATA1; NbExp=5; IntAct=EBI-629985, EBI-3909284;
CC P08473:MME; NbExp=3; IntAct=EBI-629985, EBI-353759;
CC Q62392:Phlda1 (xeno); NbExp=2; IntAct=EBI-629985, EBI-309727;
CC P53350:PLK1; NbExp=5; IntAct=EBI-629985, EBI-476768;
CC P35467:S100a1 (xeno); NbExp=4; IntAct=EBI-629985, EBI-6477109;
CC P37840:SNCA; NbExp=7; IntAct=EBI-629985, EBI-985879;
CC P32589:SSE1 (xeno); NbExp=2; IntAct=EBI-629985, EBI-8648;
CC Q9UNE7:STUB1; NbExp=4; IntAct=EBI-629985, EBI-357085;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Note=Localized in cytoplasmic
CC mRNP granules containing untranslated mRNAs.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P08107-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P08107-2; Sequence=VSP_044427;
CC -!- TISSUE SPECIFICITY: HSPA1B is testis-specific.
CC -!- INDUCTION: By heat shock.
CC -!- SIMILARITY: Belongs to the heat shock protein 70 family.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/hspa1a/";
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DR EMBL; M59828; AAA63226.1; -; Genomic_DNA.
DR EMBL; M59830; AAA63227.1; -; Genomic_DNA.
DR EMBL; M11717; AAA52697.1; -; Genomic_DNA.
DR EMBL; AF134726; AAD21815.1; -; Genomic_DNA.
DR EMBL; AF134726; AAD21816.1; -; Genomic_DNA.
DR EMBL; BA000025; BAB63299.1; -; Genomic_DNA.
DR EMBL; BA000025; BAB63300.1; -; Genomic_DNA.
DR EMBL; AK304652; BAG65428.1; -; mRNA.
DR EMBL; DQ388429; ABD48956.1; -; Genomic_DNA.
DR EMBL; DQ451402; ABD96830.1; -; Genomic_DNA.
DR EMBL; AL662834; CAI17737.1; -; Genomic_DNA.
DR EMBL; AL662834; CAI17738.1; -; Genomic_DNA.
DR EMBL; AL671762; CAI18216.1; -; Genomic_DNA.
DR EMBL; AL671762; CAI18217.1; -; Genomic_DNA.
DR EMBL; AL929592; CAI18464.1; -; Genomic_DNA.
DR EMBL; AL929592; CAI18466.1; -; Genomic_DNA.
DR EMBL; BC002453; AAH02453.1; -; mRNA.
DR EMBL; BC009322; AAH09322.1; -; mRNA.
DR EMBL; BC018740; AAH18740.1; -; mRNA.
DR EMBL; BC057397; AAH57397.1; -; mRNA.
DR EMBL; BC063507; AAH63507.1; -; mRNA.
DR EMBL; M24743; AAA59844.1; -; Genomic_DNA.
DR EMBL; M24744; AAA59845.1; -; Genomic_DNA.
DR EMBL; X04676; CAA28381.1; -; Genomic_DNA.
DR EMBL; X04677; CAA28382.1; -; Genomic_DNA.
DR PIR; A29160; A29160.
DR PIR; A45871; A45871.
DR PIR; I59139; I59139.
DR PIR; I79540; I79540.
DR RefSeq; NP_005336.3; NM_005345.5.
DR RefSeq; NP_005337.2; NM_005346.4.
DR RefSeq; XP_005249126.1; XM_005249069.1.
DR RefSeq; XP_005272869.1; XM_005272812.1.
DR RefSeq; XP_005274914.1; XM_005274857.1.
DR RefSeq; XP_005275026.1; XM_005274969.1.
DR RefSeq; XP_005275454.1; XM_005275397.1.
DR UniGene; Hs.274402; -.
DR UniGene; Hs.702139; -.
DR UniGene; Hs.719966; -.
DR PDB; 1HJO; X-ray; 2.30 A; A=3-382.
DR PDB; 1S3X; X-ray; 1.84 A; A=1-382.
DR PDB; 1XQS; X-ray; 2.90 A; C/D=184-371.
DR PDB; 2E88; X-ray; 1.80 A; A=1-388.
DR PDB; 2E8A; X-ray; 1.77 A; A=1-388.
DR PDB; 2LMG; NMR; -; A=537-610.
DR PDB; 3A8Y; X-ray; 2.30 A; A/B=1-388.
DR PDB; 3ATU; X-ray; 1.65 A; A=1-388.
DR PDB; 3ATV; X-ray; 1.58 A; A=1-388.
DR PDB; 3AY9; X-ray; 1.75 A; A=1-388.
DR PDB; 3D2E; X-ray; 2.35 A; B/D=1-382.
DR PDB; 3D2F; X-ray; 2.30 A; B/D=1-382.
DR PDB; 3JXU; X-ray; 2.14 A; A=1-387.
DR PDB; 3LOF; X-ray; 2.40 A; A/B/C/D/E/F=534-641.
DR PDB; 4J8F; X-ray; 2.70 A; A=1-382.
DR PDBsum; 1HJO; -.
DR PDBsum; 1S3X; -.
DR PDBsum; 1XQS; -.
DR PDBsum; 2E88; -.
DR PDBsum; 2E8A; -.
DR PDBsum; 2LMG; -.
DR PDBsum; 3A8Y; -.
DR PDBsum; 3ATU; -.
DR PDBsum; 3ATV; -.
DR PDBsum; 3AY9; -.
DR PDBsum; 3D2E; -.
DR PDBsum; 3D2F; -.
DR PDBsum; 3JXU; -.
DR PDBsum; 3LOF; -.
DR PDBsum; 4J8F; -.
DR ProteinModelPortal; P08107; -.
DR SMR; P08107; 1-613.
DR DIP; DIP-211N; -.
DR IntAct; P08107; 102.
DR MINT; MINT-96699; -.
DR STRING; 9606.ENSP00000364802; -.
DR BindingDB; P08107; -.
DR ChEMBL; CHEMBL5460; -.
DR TCDB; 1.A.33.1.3; the cation channel-forming heat shock protein-70 (hsp70) family.
DR PhosphoSite; P08107; -.
DR DOSAC-COBS-2DPAGE; P08107; -.
DR OGP; P08107; -.
DR REPRODUCTION-2DPAGE; IPI00304925; -.
DR SWISS-2DPAGE; P08107; -.
DR UCD-2DPAGE; P08107; -.
DR PaxDb; P08107; -.
DR PRIDE; P08107; -.
DR DNASU; 3303; -.
DR Ensembl; ENST00000375650; ENSP00000364801; ENSG00000204388.
DR Ensembl; ENST00000375651; ENSP00000364802; ENSG00000204389.
DR Ensembl; ENST00000391548; ENSP00000375391; ENSG00000224501.
DR Ensembl; ENST00000391555; ENSP00000375399; ENSG00000212866.
DR Ensembl; ENST00000400040; ENSP00000382915; ENSG00000215328.
DR Ensembl; ENST00000430065; ENSP00000404524; ENSG00000235941.
DR Ensembl; ENST00000433487; ENSP00000408907; ENSG00000234475.
DR Ensembl; ENST00000441618; ENSP00000406359; ENSG00000237724.
DR Ensembl; ENST00000445736; ENSP00000403530; ENSG00000231555.
DR Ensembl; ENST00000450744; ENSP00000393087; ENSG00000232804.
DR GeneID; 3303; -.
DR GeneID; 3304; -.
DR KEGG; hsa:3303; -.
DR KEGG; hsa:3304; -.
DR UCSC; uc003nxj.3; human.
DR CTD; 3303; -.
DR CTD; 3304; -.
DR GeneCards; GC06P031823; -.
DR GeneCards; GC06P031824; -.
DR GeneCards; GC06Pi31794; -.
DR GeneCards; GC06Pi31806; -.
DR GeneCards; GC06Pj31770; -.
DR GeneCards; GC06Pj31782; -.
DR GeneCards; GC06Pk31765; -.
DR GeneCards; GC06Pk31777; -.
DR GeneCards; GC06Pn31773; -.
DR GeneCards; GC06Pn31785; -.
DR H-InvDB; HIX0058169; -.
DR H-InvDB; HIX0058187; -.
DR H-InvDB; HIX0166160; -.
DR HGNC; HGNC:5232; HSPA1A.
DR HGNC; HGNC:5233; HSPA1B.
DR HPA; CAB008640; -.
DR HPA; CAB032815; -.
DR MIM; 140550; gene.
DR MIM; 603012; gene.
DR neXtProt; NX_P08107; -.
DR PharmGKB; PA29499; -.
DR eggNOG; COG0443; -.
DR HOGENOM; HOG000228135; -.
DR HOVERGEN; HBG051845; -.
DR InParanoid; P08107; -.
DR KO; K03283; -.
DR OMA; CSETISW; -.
DR OrthoDB; EOG7PCJGF; -.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; HSPA1A; human.
DR EvolutionaryTrace; P08107; -.
DR GeneWiki; HSPA1A; -.
DR NextBio; 13103; -.
DR PRO; PR:P08107; -.
DR ArrayExpress; P08107; -.
DR Bgee; P08107; -.
DR CleanEx; HS_HSPA1A; -.
DR Genevestigator; P08107; -.
DR GO; GO:0016235; C:aggresome; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; TAS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; TAS:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0030529; C:ribonucleoprotein complex; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003725; F:double-stranded RNA binding; IDA:MGI.
DR GO; GO:0044183; F:protein binding involved in protein folding; IDA:BHF-UCL.
DR GO; GO:0051082; F:unfolded protein binding; TAS:UniProtKB.
DR GO; GO:0001618; F:virus receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0010467; P:gene expression; TAS:Reactome.
DR GO; GO:0006402; P:mRNA catabolic process; IDA:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0030308; P:negative regulation of cell growth; IMP:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell proliferation; IMP:UniProtKB.
DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IMP:BHF-UCL.
DR GO; GO:0090084; P:negative regulation of inclusion body assembly; IDA:BHF-UCL.
DR GO; GO:0045648; P:positive regulation of erythrocyte differentiation; IMP:UniProtKB.
DR GO; GO:0042026; P:protein refolding; IDA:BHF-UCL.
DR GO; GO:0006986; P:response to unfolded protein; IDA:UniProtKB.
DR GO; GO:0009615; P:response to virus; IEA:GOC.
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; Acetylation; Alternative splicing; ATP-binding;
KW Chaperone; Complete proteome; Cytoplasm; Direct protein sequencing;
KW Host cell receptor for virus entry; Methylation; Nucleotide-binding;
KW Phosphoprotein; Polymorphism; Receptor; Reference proteome;
KW Stress response.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 641 Heat shock 70 kDa protein 1A/1B.
FT /FTId=PRO_0000078249.
FT NP_BIND 12 15 ATP.
FT NP_BIND 202 204 ATP.
FT NP_BIND 268 275 ATP.
FT NP_BIND 339 342 ATP.
FT BINDING 71 71 ATP.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 108 108 N6-acetyllysine.
FT MOD_RES 246 246 N6-acetyllysine.
FT MOD_RES 348 348 N6-acetyllysine.
FT MOD_RES 561 561 N6,N6,N6-trimethyllysine; by METTL21A.
FT MOD_RES 631 631 Phosphoserine.
FT MOD_RES 633 633 Phosphoserine.
FT MOD_RES 636 636 Phosphothreonine.
FT VAR_SEQ 96 150 Missing (in isoform 2).
FT /FTId=VSP_044427.
FT VARIANT 95 95 I -> V.
FT /FTId=VAR_032152.
FT VARIANT 110 110 E -> D (in dbSNP:rs562047).
FT /FTId=VAR_029053.
FT VARIANT 467 467 A -> V.
FT /FTId=VAR_032153.
FT VARIANT 499 499 N -> S (in dbSNP:rs483638).
FT /FTId=VAR_029054.
FT MUTAGEN 10 10 D->A: Reduces affinity for ADP.
FT MUTAGEN 199 199 D->A: Reduces affinity for ADP.
FT MUTAGEN 561 561 K->R: Complete loss of in vitro
FT methylation by METTL21A.
FT CONFLICT 7 7 I -> V (in Ref. 2; AAA52697 and 10;
FT CAA28381).
FT CONFLICT 355 355 N -> D (in Ref. 5; BAG65428).
FT CONFLICT 370 370 A -> G (in Ref. 2; AAA52697).
FT CONFLICT 469 469 Missing (in Ref. 2; AAA52697).
FT CONFLICT 497 497 K -> N (in Ref. 5; BAG65428).
FT STRAND 7 10
FT STRAND 13 22
FT STRAND 25 28
FT STRAND 36 39
FT STRAND 42 44
FT STRAND 49 51
FT HELIX 53 56
FT TURN 57 61
FT HELIX 63 65
FT HELIX 70 73
FT HELIX 81 87
FT STRAND 91 97
FT STRAND 100 107
FT STRAND 110 114
FT HELIX 116 135
FT STRAND 141 146
FT HELIX 152 164
FT STRAND 168 174
FT HELIX 175 182
FT TURN 183 186
FT STRAND 190 200
FT STRAND 205 213
FT STRAND 216 225
FT HELIX 226 228
FT HELIX 230 249
FT HELIX 253 255
FT HELIX 257 273
FT TURN 274 276
FT STRAND 277 288
FT STRAND 291 298
FT HELIX 299 305
FT HELIX 307 311
FT HELIX 314 323
FT HELIX 328 330
FT STRAND 333 338
FT HELIX 339 342
FT HELIX 344 353
FT TURN 354 356
FT TURN 365 367
FT HELIX 368 381
FT HELIX 534 553
FT HELIX 556 558
FT HELIX 564 583
FT HELIX 589 612
SQ SEQUENCE 641 AA; 70052 MW; 78F513118C96DE66 CRC64;
MAKAAAIGID LGTTYSCVGV FQHGKVEIIA NDQGNRTTPS YVAFTDTERL IGDAAKNQVA
LNPQNTVFDA KRLIGRKFGD PVVQSDMKHW PFQVINDGDK PKVQVSYKGE TKAFYPEEIS
SMVLTKMKEI AEAYLGYPVT NAVITVPAYF NDSQRQATKD AGVIAGLNVL RIINEPTAAA
IAYGLDRTGK GERNVLIFDL GGGTFDVSIL TIDDGIFEVK ATAGDTHLGG EDFDNRLVNH
FVEEFKRKHK KDISQNKRAV RRLRTACERA KRTLSSSTQA SLEIDSLFEG IDFYTSITRA
RFEELCSDLF RSTLEPVEKA LRDAKLDKAQ IHDLVLVGGS TRIPKVQKLL QDFFNGRDLN
KSINPDEAVA YGAAVQAAIL MGDKSENVQD LLLLDVAPLS LGLETAGGVM TALIKRNSTI
PTKQTQIFTT YSDNQPGVLI QVYEGERAMT KDNNLLGRFE LSGIPPAPRG VPQIEVTFDI
DANGILNVTA TDKSTGKANK ITITNDKGRL SKEEIERMVQ EAEKYKAEDE VQRERVSAKN
ALESYAFNMK SAVEDEGLKG KISEADKKKV LDKCQEVISW LDANTLAEKD EFEHKRKELE
QVCNPIISGL YQGAGGPGPG GFGAQGPKGG SGSGPTIEEV D
//

MIM 140550
*RECORD*
*FIELD* NO
140550
*FIELD* TI
*140550 HEAT-SHOCK 70-KD PROTEIN 1A; HSPA1A
;;HEAT-SHOCK 70-KD PROTEIN 1; HSPA1;;
HEAT-SHOCK PROTEIN, 70-KD, 1;;
read moreHSP70-1;;
HSP70-1A;;
HSP72;;
HEAT-SHOCK 70-KD PROTEIN, INDUCIBLE; HSP70I
*FIELD* TX

CLONING

A number of organisms, such as Drosophila, respond to elevated
temperature by synthesizing a small number of specific proteins. This
phenomenon occurs also in yeast and in cultured HeLa cells. Exposure of
HeLa cells to a temperature of 45 degrees C for 10 minutes leads to an
increased synthesis of at least 3 sets of proteins with molecular masses
of about 100,000, 72,000-74,000, and 37,000 daltons (Slater et al.,
1981). The phenomenon is blocked by actinomycin D, suggesting
transcriptional control. In vitro translation of cytoplasmic RNA from
heat-shocked cells, followed by 2-D gel analysis of the translation
products, shows that the major 72,000- to 74,000-dalton band consists of
7 polypeptides, designated alpha, alpha-prime, beta, gamma, delta,
epsilon, and zeta. The increase in synthesis of the heat-shock proteins
begins soon after heat treatment but does not reach a maximum until 2
hours later. The pattern of induction suggests coordinate regulation. To
study this, Cato et al. (1981) cloned the cDNA sequences encoding the
beta, gamma, delta, and epsilon heat-shock polypeptides. Hickey et al.
(1986) isolated cDNA clones representing at least 5 distinct
heat-inducible mRNAs in human cells.

Milner and Campbell (1990) determined that the HSPA1A gene encodes a
predicted 641-amino acid protein. By Northern blot analysis of HeLa cell
RNA, they detected an approximately 2.4-kb HSPA1A transcript that was
constitutively expressed at low levels and was induced following heat
shock.

GENE FUNCTION

While the function of the ubiquitous, highly conserved heat-shock
proteins was unknown, an intriguing relationship between expression of
heat-shock proteins and transformation had been observed. Pelham (1986)
speculated on the function of heat-shock proteins.

Cytokine and protooncogene mRNAs are rapidly degraded through AU-rich
elements in the 3-prime untranslated region. Rapid decay involves
AU-rich binding protein AUF1 (601324), which complexes with heat-shock
proteins HSC70 (600816) and HSP70, translation initiation factor EIF4G
(600495), and poly(A)-binding protein (604679). AU-rich mRNA decay is
associated with displacement of EIF4G from AUF1, ubiquitination of AUF1,
and degradation of AUF1 by proteasomes. Laroia et al. (1999) found that
induction of HSP70 by heat shock, downregulation of the
ubiquitin-proteasome network, or inactivation of ubiquitinating enzyme
E1 (314370), all result in HSP70 sequestration of AUF1 in the
perinucleus-nucleus, and all 3 processes block decay of AU-rich mRNAs
and AUF1 protein. These results link the rapid degradation of cytokine
mRNAs to the ubiquitin-proteasome pathway.

During adenovirus late infection, or heat shock of cells, translation of
most capped cellular mRNAs is inhibited and adenovirus late mRNAs are
translated by a mechanism called ribosome shunting. In shunting,
ribosomes are loaded onto mRNA by a cap-dependent process, but then
shunt or bypass large segments of the mRNA before initiating translation
at a downstream AUG. Ribosome shunting is mediated by the 5-prime
noncoding region of adenovirus mRNAs, called the tripartite leader,
which shares striking complementarity to 18S rRNAs. Yueh and Schneider
(2000) found that the 5-prime noncoding region of human HSP70 mRNA
contains an element related to the adenovirus tripartite leader
sequence. This element promoted ribosome shunting for HSP70 expression
during heat shock when cap-dependent protein synthesis was blocked.

Unfolded PAELR (602583) is a substrate of the E3 ubiquitin ligase parkin
(602544). Accumulation of PAELR in the endoplasmic reticulum (ER) of
dopaminergic neurons induces ER stress leading to neurodegeneration.
Imai et al. (2002) showed that CHIP (607207), HSP70, parkin, and PAELR
formed a complex in vitro and in vivo. The amount of CHIP in the complex
increased during ER stress. CHIP promoted the dissociation of HSP70 from
parkin and PAELR, thus facilitating parkin-mediated PAELR
ubiquitination. Moreover, CHIP enhanced parkin-mediated in vitro
ubiquitination of PAELR in the absence of HSP70. CHIP also enhanced the
ability of parkin to inhibit cell death induced by PAELR. The authors
concluded that CHIP is therefore a mammalian E4-like molecule that
positively regulates parkin E3 activity.

HSPs are molecular chaperones that control protein folding and prevent
aggregation of proteins. They complex with peptides and bind to
dendritic cells (DCs) and macrophages before being internalized in a
receptor-dependent manner. HSPs then colocalize with MHC class I
molecules to initiate protective and tumor-specific cytotoxic
T-lymphocyte (CTL) responses. Using flow cytometric and Western blot
analyses with binding inhibition assays, Delneste et al. (2002) found
that HSP70 bound LOX1 (OLR1; 602601), but not other scavenger receptors
tested, on both DCs and macrophages to gain access to the MHC class I
pathway to initiate CTL responses.

Young et al. (2003) showed that the cytosolic chaperones HSP90 (140571)
and HSP70 dock onto a specialized tetratricopeptide (TPR) domain in the
import receptor TOMM70 (606081) at the outer mitochondrial membrane.
This interaction served to deliver a set of preproteins to the receptor
for subsequent membrane translocation dependent on the HSP90 ATPase.
Disruption of the chaperone/TOMM70 recognition inhibited the import of
these preproteins into mitochondria. Young et al. (2003) proposed a
mechanism in which chaperones are recruited for a specific targeting
event by a membrane-bound receptor.

TIM44 (605058), a peripheral inner membrane protein, tethers
mitochondrial HSP70 to the import channel. Liu et al. (2003) showed that
regulated interactions maximized occupancy of the active, ATP-bound
mitochondrial HSP70 at the channel through its intrinsic high affinity
for TIM44, as well as through release of ADP-bound mitochondrial HSP70
from TIM44 by the cofactor MGE1. A model peptide substrate rapidly
released mitochondrial HSP70 from TIM44, even in the absence of ATP
hydrolysis. In vivo, the analogous interaction of translocating
polypeptide would release mitochondrial HSP70 from the channel.
Consistent with the ratchet model of translocation, subsequent
hydrolysis of ATP would trap the polypeptide, driving import by
preventing its movement back toward the cytosol.

Shimizu et al. (1999) found that peripheral blood mononuclear cells of
18 major depression patients expressed a short HSPA1A transcript that
utilized exon 1 rather than exon 2, which is found in the more common
HSPA1A transcript. No protein was associated with expression of this
short HSPA1A mRNA, possibly due to lack of a TATA box or loss of
internal ribosome binding sites.

Becker et al. (2002) found that mouse macrophages expressing Cd40
(109535) specifically bound and internalized human HSP70 with its bound
peptide. Binding of HSP70-peptide complex to the exoplasmic domain of
Cd40 was mediated by the N-terminal nucleotide-binding domain of HSP70
in its ADP state. Binding between HSP70 and Cd40 increased in the
presence of the peptide substrate, and binding induced signaling via p38
(600289). Becker et al. (2002) concluded that CD40 is a cochaperone-like
receptor that mediates the uptake of exogenous HSP70-peptide complexes
by macrophages and dendritic cells.

Ficker et al. (2003) demonstrated that the cytosolic chaperones HSP70
and HSP90 interact directly with the core-glycosylated form of the
wildtype HERG (152427) gene product (the alpha subunit of the I(Kr)
cardiac potassium channel) present in the ER, but not the fully
glycosylated, cell surface form. Trafficking-deficient mutants remained
tightly associated with HSP70 and HSP90 in the ER, whereas a
nonfunctional but trafficking HERG was released from the chaperones
during maturation, comparable to the wildtype. Ficker et al. (2003)
concluded that HSP90 and HSP70 are crucial for the maturation of
wildtype HERG as well as the retention of trafficking-deficient HERG
mutants.

Kalia et al. (2004) demonstrated that rat Bag5 (603885) directly
interacts with Hsp70 and parkin (602544). Bag5 inhibited both
Hsp70-mediated refolding of misfolded proteins and parkin E3 ubiquitin
ligase activity, and enhanced the sequestration of parkin in protein
aggregates. In rats, overexpression of Bag5 resulted in increased death
of dopaminergic neurons compared to controls, whereas overexpression of
an inhibitory mutant Bag5 resulted in increased dopaminergic survival.
Kalia et al. (2004) concluded that Bag5 is a negative regulator of both
Hsp70 and parkin function that sensitizes dopaminergic neurons to
injury-induced death and thus promotes neurodegeneration.

Using recombinant human and bovine proteins for pull-down assays, Okada
et al. (2004) showed that the Ca(2+)-binding protein S100A1 (176940),
but not calmodulin (see 114180), interacted with heat-shock chaperone
components HSP90, HSP70, FKBP52 (FKBP4; 600611), and CYP40 (PPID;
601753). Coimmunoprecipitation studies confirmed the interactions.
S100A1 contributed to protein refolding in the HSP70/HSP90
multichaperone complex.

Rohde et al. (2005) found that cancer cells depleted of HSP70 and
HSP70-2 (HSPA2; 140560) 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.

Qian et al. (2006) demonstrated that CHIP (607207) not only enhances
HSP70 induction during acute stress, but also mediates its turnover
during the stress recovery process. Central to this dual phase
regulation is its substrate dependence: CHIP preferentially
ubiquitinates chaperone-bound substrates, whereas degradation of HSP70
by CHIP-dependent targeting to the ubiquitin-proteasome system occurs
when misfolded substrates have been depleted. Qian et al. (2006)
concluded that the sequential analysis of the CHIP-associated chaperone
adaptor and its bound substrate provides an elegant mechanism for
maintaining homeostasis by tuning chaperone levels appropriately to
reflect the status of protein building within the cytoplasm.

Ribeil et al. (2007) demonstrated that during erythroid differentiation
but not apoptosis, the chaperone protein Hsp70 protects GATA1 (305371)
from caspase-mediated proteolysis. At the onset of caspase activation,
Hsp70 colocalizes and interacts with GATA1 in the nucleus of erythroid
precursors undergoing terminal differentiation. In contrast,
erythropoietin starvation induces the nuclear export of Hsp70 and the
cleavage of GATA1. In an in vitro assay, Hsp70 protected GATA1 from
caspase-3 (CASP3; 600636)-mediated proteolysis through its
peptide-binding domain. Ribeil et al. (2007) used RNA-mediated
interference to decrease the Hsp70 content of erythroid precursors
cultured in the presence of erythropoietin. This led to GATA1 cleavage,
a decrease in hemoglobin content, downregulation of the expression of
the antiapoptotic protein Bcl-XL (see 600039), and cell death by
apoptosis. These effects were abrogated by the transduction of a
caspase-resistant GATA1 mutant. Thus, Ribeil et al. (2007) concluded
that in erythroid precursors undergoing terminal differentiation, Hsp70
prevents active CASP3 from cleaving GATA1 and inducing apoptosis.

Chung et al. (2008) found that obese insulin-resistant patients had
reduced HSP72 protein expression and increased JNK (see JNK1, 601158)
phosphorylation in skeletal muscle. Overexpression of HSP72 in skeletal
muscle and globally in mice using heat shock therapy, transgenic
overexpression, or pharmacologic means resulted in protection against
diet- or obesity-induced hyperglycemia, hyperinsulinemia, glucose
intolerance, and insulin resistance. The protection was tightly
associated with the prevention of JNK phosphorylation. Chung et al.
(2008) concluded that HSP72 plays an essential role in blocking
inflammation and preventing insulin resistance in the context of genetic
obesity or high-fat feeding.

Kirkegaard et al. (2010) showed that Hsp70 stabilizes lysosomes by
binding to an endolysosomal anionic phospholipid
bis(monoacylglycero)phosphate (BMP), an essential cofactor for lysosomal
sphingomyelin metabolism. In acidic environments Hsp70 binds with high
affinity and specificity to BMP, thereby facilitating the BMP binding
and activity of acid sphingomyelinase (ASM). The inhibition of the
Hsp70-BMP interaction by BMP antibodies or a point mutation in Hsp70
(trp90 to phe), as well as the pharmacologic and genetic inhibition of
ASM, effectively revert the Hsp70-mediated stabilization of lysosomes.
Notably, the reduced ASM activity in cells from patients with
Niemann-Pick disease A (257200) and B (607616), severe lysosomal storage
disorders caused by mutations in the sphingomyelin phosphodiesterase-1
gene (SMPD1; 607616) encoding ASM, is also associated with a marked
decrease in lysosomal stability, and this phenotype can be effectively
corrected by treatment with recombinant Hsp70. Kirkegaard et al. (2010)
concluded that, taken together, their data opened exciting possibilities
for the development of new treatments for lysosomal storage disorders
and cancer with compounds that enter the lysosomal lumen by the
endocytic delivery pathway.

GENE STRUCTURE

Milner and Campbell (1990) reported that the HSPA1A gene, which they
called HSP70-1, lacks introns.

Shimizu et al. (1999) determined that the HSPA1A gene contains 3 exons.
Exons 1 and 2 are alternatively spliced onto exon 3, which is the
protein-coding exon. TATA, CCAAT, and GC boxes are present only in exon
2, while E boxes are present only in exon 1. The exons also differ in
many of the available transcription factor binding sites.

MAPPING

Using a cloned genomic HSP70 DNA sequence, Goate et al. (1987)
demonstrated by somatic cell hybrid and RFLP analyses that there are at
least 3 distinct HSP70 loci in the human genome, one of which is located
on chromosome 6. By Southern analysis, protein gels of Chinese
hamster-human somatic cell hybrids, and in situ hybridization, Harrison
et al. (1986, 1987) demonstrated that functional genes encoding HSP70
map to human chromosomes 6, 14 (HSPA2; 140560), 21, and at least one
other chromosome. The majority of the grains on chromosome 6 were
localized on the short arm with a peak in the region 6p22-p21.3. On
chromosome 14, the localization was 14q22-q24. Both of these regions
contain fragile sites. Two heat-shock genes (140555, 140556) are located
on 1q (Leung et al., 1992), possibly in the area of other components of
the complement system, the regulators of complement activation (RCA;
120830, etc.), clustered on 1q32. Thus, gene duplication events may have
played a role in the evolution of heat-shock genes.

Sargent et al. (1989) demonstrated a duplicated HSP70 locus between the
complement and tumor necrosis factor genes within the human major
histocompatibility complex (MHC) on 6p21.3, 12 kb apart from each other
and 92 kb telomeric to the C2 gene. Gaskins et al. (1990) demonstrated
that an Hsp70 gene is located in the MHC of the mouse also. Milner and
Campbell (1990) found within the human MHC not only 2 copies of the
HSP70 gene (HSPA1A and HSPA1B; 603012) but also a third homolog,
HSP70-HOM (HSPA1L; 140559).

Grosz et al. (1992) concluded that the bovine HSP70-1 and HSP70-2 genes
are homologous to human HSPA1A and HSPA1L because they are located on
bovine chromosome 23 and show synteny with loci on 6p in the human.

MOLECULAR GENETICS

Milner and Campbell (1992) investigated the presence of sequence
variation in the HSPA1A gene among different HLA haplotypes. They found
only very limited sequence variation, which did not result in amino acid
substitutions.

For a discussion of a possible association between variation in the
HSPA1A gene and noise-induced hearing loss, see 613035.

ANIMAL MODEL

Spinocerebellar ataxia type 1 (SCA1; 164400) is a triplet repeat
disease, characterized by loss of motor coordination due to the
degeneration of cerebellar Purkinje cells and brainstem neurons. In SCA1
and other polyglutamine diseases, the expanded protein aggregates into
nuclear inclusions. Because these nuclear inclusions accumulate
molecular chaperones, ubiquitin, and proteasomal subunits (all
components of the cellular protein refolding and degradation machinery),
the authors hypothesized that protein misfolding and impaired protein
clearance may underlie the pathogenesis of polyglutamine diseases. To
determine whether enhancing chaperone activity could mitigate the
phenotype in a mammalian model by reducing protein aggregation, Cummings
et al. (2001) crossbred SCA1 mice with mice overexpressing inducible
HSP70. Although the amount of nuclear inclusions in Purkinje cells
persisted, physiologic and histopathologic analysis revealed that high
levels of HSP70 appeared to afford protection against neurodegeneration
and preserved dendritic arborization in the cerebellum.

Gehrig et al. (2012) showed that increasing the expression of
intramuscular Hsp72 preserves muscle strength and ameliorates the
dystrophic pathology in 2 mouse models of muscular dystrophy. Treatment
with BGP-15, a pharmacologic inducer of Hsp72 that can protect against
obesity-induced insulin resistance, improved muscular architecture,
strength, and contractile function in severely affected diaphragm
muscles in mdx dystrophic mice. In dko mice, a phenocopy of DMD that
results in severe kyphosis, muscle weakness, and premature death, BGP-15
decreased kyphosis, improved the dystrophic pathophysiology in limb and
diaphragm muscles, and extended life span. Gehrig et al. (2012) found
that the sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA;
108730) is dysfunctional in severely affected muscles of mdx and dko
mice, and that Hsp72 interacts with Serca to preserve its function under
conditions of stress, ultimately contributing to the decreased muscle
degeneration seen with Hsp72 upregulation. Treatment with BGP-15
similarly increased Serca activity in dystrophic skeletal muscles.
Gehrig et al. (2012) concluded that their results provided evidence that
increasing the expression of Hsp72 in muscle (through the administration
of BGP-15) has significant therapeutic potential for DMD and related
conditions, either as a self-contained therapy or as an adjuvant with
other potential treatments, including gene, cell, and pharmacologic
therapies.

HISTORY

Gabriele et al. (1996) reported that the hybrid cell line used by
Harrison et al. (1987) for the mapping of a heat-shock 70-kD protein
(HSPA3) to chromosome 21 was found to contain other human chromosome
fragments, calling the validity of the mapping into question. They
presented data indicating that hybrid cell lines containing human
chromosome 21 do not express a human Hsp70.

*FIELD* RF
1. Becker, T.; Hartl, F.-U.; Wieland, F.: CD40, an extracellular
receptor for binding and uptake of Hsp70-peptide complexes. J. Cell
Biol. 158: 1277-1285, 2002.

2. Cato, A. C. B.; Sillar, G. M.; Kioussis, J.; Burdon, R. H.: Molecular
cloning of cDNA sequences coding for the major (beta-, gamma-, delta-,
and epsilon) heat-shock polypeptides of HeLa cells. Gene 16: 27-34,
1981.

3. Chung, J.; Nguyen, A.-K.; Henstridge, D. C.; Holmes, A. G.; Chan,
M. H. S.; Mesa, J. L.; Lancaster, G. I.; Southgate, R. J.; Bruce,
C. R.; Duffy, S. J.; Horvath, I.; Mestril, R.; Watt, M. J.; Hooper,
P. L.; Kingwell, B. A.; Vigh, L.; Hevener, A.; Febbraio, M. A.: HSP72
protects against obesity-induced insulin resistance. Proc. Nat. Acad.
Sci. 105: 1739-1744, 2008.

4. Cummings, C. J.; Sun, Y.; Opal, P.; Antalffy, B.; Mestril, R.;
Orr, H. T.; Dillmann, W. H.; Zoghbi, H. Y.: Over-expression of inducible
HSP70 chaperone suppresses neuropathology and improves motor function
in SCA1 mice. Hum. Molec. Genet. 10: 1511-1518, 2001.

5. Delneste, Y.; Magistrelli, G.; Gauchat, J.-F.; Haeuw, J.-F.; Aubry,
J.-P.; Nakamura, K.; Kawakami-Honda, N.; Goetsch, L.; Sawamura, T.;
Bonnefoy, J.-Y.; Jeannin, P.: Involvement of LOX-1 in dendritic cell-mediated
antigen cross-presentation. Immunity 17: 353-362, 2002.

6. Ficker, E.; Dennis, A. T.; Wang, L.; Brown, A. M.: Role of the
cytosolic chaperones Hsp70 and Hsp90 in maturation of the cardiac
potassium channel hERG. Circ. Res. 92: e87-e100, 2003.

7. Gabriele, T.; Tavaria, M.; Kola, I.; Anderson, R. L.: Analysis
of heat shock protein 70 in human chromosome 21 containing hybrids. Int.
J. Biochem. Cell Biol. 28: 905-910, 1996.

8. Gaskins, H. R.; Prochazka, M.; Nadeau, J. H.; Henson, V. W.; Leiter,
E. H.: Localization of a mouse heat shock Hsp70 gene within the H-2
complex. Immunogenetics 32: 286-289, 1990.

9. Gehrig, S. M.; van der Poel, C.; Sayer, T. A.; Schertzer, J. D.;
Henstridge, D. C.; Church, J. E.; Lamon, S.; Russell, A. P.; Davies,
K. E.; Febbraio, M. A.; Lynch, G. S.: Hsp72 preserves muscle function
and slows progression of severe muscular dystrophy. Nature 484:
394-398, 2012.

10. Goate, A. M.; Cooper, D. N.; Hall, C.; Leung, T. K. C.; Solomon,
E.; Lim, L.: Localization of a human heat-shock HSP70 gene sequence
to chromosome 6 and detection of two other loci by somatic-cell hybrid
and restriction fragment length polymorphism analysis. Hum. Genet. 75:
123-128, 1987.

11. Grosz, M. D.; Womack, J. E.; Skow, L. C.: Syntenic conservation
of HSP70 genes in cattle and humans. Genomics 14: 863-868, 1992.

12. 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.

13. Harrison, G. S.; Morimoto, R.; Kao, F.-T.; Chu, E. H. Y.; Wu,
B. J.; Drabkin, H.: Chromosomal location of human genes encoding
the major heat shock protein HSP70. (Abstract) Am. J. Hum. Genet. 39:
A157 only, 1986.

14. Hickey, E.; Brandon, S. E.; Sadis, S.; Smale, G.; Weber, L. A.
: Molecular cloning of sequences encoding the human heat-shock proteins
and their expression during hyperthermia. Gene 43: 147-154, 1986.

15. Imai, Y.; Soda, M.; Hatakeyama, S.; Akagi, T.; Hashikawa, T.;
Nakayama, K.; Takahashi, R.: CHIP is associated with Parkin, a gene
responsible for familial Parkinson's disease, and enhances its ubiquitin
ligase activity. Molec. Cell 10: 55-67, 2002.

16. Kalia, S. K.; Lee, S.; Smith, P. D.; Liu, L.; Crocker, S. J.;
Thorarinsdottir, T. E.; Glover, J. R.; Fon, E. A.; Park, D. S.; Lozano,
A. M.: BAG5 inhibits parkin and enhances dopaminergic neuron degeneration. Neuron 44:
931-945, 2004.

17. Kirkegaard, T.; Roth, A. G.; Petersen, N. H. T.; Mahalka, A. K.;
Olsen, O. D.; Moilanen, I.; Zylicz, A.; Knudsen, J.; Sandhoff, K.;
Arenz, C.; Kinnunen, P. K. J.; Nylandsted, J.; Jaattela, M.: Hsp70
stabilizes lysosomes and reverts Niemann-Pick disease-associated lysosomal
pathology. Nature 463: 549-553, 2010.

18. Laroia, G.; Cuesta, R.; Brewer, G.; Schneider, R. J.: Control
of mRNA decay by heat shock-ubiquitin-proteasome pathway. Science 284:
499-502, 1999.

19. Leung, T. K. C.; Hall, C.; Rajendran, M.; Spurr, N. K.; Lim, L.
: The human heat-shock genes HSPA6 and HSPA7 are both expressed and
localize to chromosome 1. Genomics 12: 74-79, 1992.

20. Liu, Q.; D'Silva, P.; Walter, W.; Marszalek, J.; Craig, E. A.
: Regulated cycling of mitochondrial Hsp70 at the protein import channel. Science 300:
139-141, 2003.

21. Milner, C. M.; Campbell, R. D.: Polymorphic analysis of the three
MHC-linked HSP70 genes. Immunogenetics 36: 357-362, 1992.

22. Milner, C. M.; Campbell, R. D.: Structure and expression of the
three MHC-linked HSP70 genes. Immunogenetics 32: 242-251, 1990.

23. Okada, M.; Hatakeyama, T.; Itoh, H.; Tokuta, N.; Tokumitsu, H.;
Kobayashi, R.: S100A1 is a novel molecular chaperone and a member
of the Hsp70/Hsp90 multichaperone complex. J. Biol. Chem. 279: 4221-4233,
2004.

24. Pelham, H. R. B.: Speculations on the functions of the major
heat shock and glucose-regulated proteins. Cell 46: 959-961, 1986.

25. Qian, S.-B.; McDonough, H.; Boellmann, F.; Cyr, D. M.; Patterson,
C.: CHIP-mediated stress recovery by sequential ubiquitination of
substrates and Hsp70. Nature 440: 551-555, 2006.

26. Ribeil, J.-A.; Zermati, Y.; Vandekerckhove, J.; Cathelin, S.;
Kersual, J.; Dussiot, M.; Coulon, S.; Moura, I. C.; Zeuner, A.; Kirkegaard-Sorensen,
T.; Varet, B.; Solary, E.; Garrido, C.; Hermine, O.: Hsp70 regulates
erythropoiesis by preventing caspase-3-mediated cleavage of GATA-1. Nature 445:
102-105, 2007.

27. 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.

28. Sargent, C. A.; Dunham, I.; Trowsdale, J.; Campbell, R. D.: Human
major histocompatibility complex contains genes for the major heat
shock protein HSP70. Proc. Nat. Acad. Sci. 86: 1968-1972, 1989.

29. Shimizu, S.; Nomura, K.; Ujihara, M.; Demura, H.: An additional
exon of stress-inducible heat shock protein 70 gene (HSP70-1). Biochem.
Biophys. Res. Commun. 257: 193-198, 1999.

30. Slater, A.; Cato, A. C. B.; Sillar, G. M.; Kioussis, J.; Burdon,
R. H.: The pattern of protein synthesis induced by heat shock of
HeLa cells. Europ. J. Biochem. 117: 341-346, 1981.

31. Young, J. C.; Hoogenraad, N. J.; Hartl, F. U.: Molecular chaperones
Hsp90 and Hsp70 deliver preproteins to the mitochondrial import receptor
Tom70. Cell 112: 41-50, 2003.

32. Yueh, A.; Schneider, R. J.: Translation by ribosome shunting
on adenovirus and hsp70 mRNAs facilitated by complementarity to 18S
rRNA. Genes Dev. 14: 414-421, 2000.

*FIELD* CN
Ada Hamosh - updated: 5/8/2012
Ada Hamosh - updated: 3/9/2010
Patricia A. Hartz - updated: 7/17/2009
Marla J. F. O'Neill - updated: 3/20/2008
Ada Hamosh - updated: 2/20/2007
Ada Hamosh - updated: 5/26/2006
Paul J. Converse - updated: 1/6/2006
Patricia A. Hartz - updated: 10/6/2005
Cassandra L. Kniffin - updated: 4/5/2005
Marla J. F. O'Neill - updated: 3/3/2004
Patricia A. Hartz - updated: 2/27/2004
Ada Hamosh - updated: 4/15/2003
Stylianos E. Antonarakis - updated: 1/15/2003
Stylianos E. Antonarakis - updated: 9/11/2002
George E. Tiller - updated: 12/12/2001
Ada Hamosh - updated: 4/16/1999
Patti M. Sherman - updated: 9/1/1998

*FIELD* CD
Victor A. McKusick: 6/4/1986

*FIELD* ED
alopez: 10/03/2012
alopez: 5/8/2012
terry: 5/8/2012
carol: 12/22/2010
alopez: 9/3/2010
terry: 8/31/2010
alopez: 3/9/2010
terry: 3/9/2010
wwang: 10/14/2009
ckniffin: 9/25/2009
mgross: 8/19/2009
terry: 7/17/2009
mgross: 9/12/2008
wwang: 3/25/2008
terry: 3/20/2008
alopez: 2/22/2007
terry: 2/20/2007
alopez: 6/2/2006
terry: 5/26/2006
mgross: 1/6/2006
mgross: 10/6/2005
carol: 4/20/2005
wwang: 4/18/2005
ckniffin: 4/5/2005
terry: 2/22/2005
carol: 3/3/2004
alopez: 3/2/2004
terry: 2/27/2004
alopez: 4/17/2003
terry: 4/15/2003
mgross: 1/15/2003
mgross: 9/11/2002
carol: 1/8/2002
cwells: 12/18/2001
cwells: 12/12/2001
carol: 2/2/2001
carol: 11/3/2000
mgross: 3/14/2000
alopez: 4/16/1999
psherman: 10/12/1998
alopez: 9/21/1998
terry: 7/29/1998
terry: 7/24/1998
dkim: 7/21/1998
carol: 1/14/1993
supermim: 3/16/1992
carol: 12/19/1991
carol: 11/13/1991
carol: 11/6/1991
carol: 1/10/1991

MIM 603012
*RECORD*
*FIELD* NO
603012
*FIELD* TI
*603012 HEAT-SHOCK 70-KD PROTEIN 1B; HSPA1B
;;HEAT-SHOCK PROTEIN, 70-KD, 1B;;
HSP70-1B;;
read moreHEAT-SHOCK PROTEIN, 70-KD, 2;;
HSP70-2
*FIELD* TX
Heat-shock proteins, or stress proteins, are expressed in response to
heat shock and a variety of other stress stimuli including oxidative
free radicals and toxic metal ions. The human HSP70, or HSPA, multigene
family encodes several highly conserved 70-kD proteins with structural
and functional properties in common, but which vary in their
inducibility in response to metabolic stress. Sargent et al. (1989)
identified a duplicated HSP70 locus in the class III region of the major
histocompatibility complex on 6p21.3. These loci, HSP70-1 (HSPA1A;
140550) and HSP70-2 (HSPA1B), are 12 kb apart and lie 92 kb telomeric to
the C2 gene (613927). Milner and Campbell (1990) determined that the
HSP70-2 gene, like HSP70-1, lacks introns. The HSP70-1 and -2 coding
sequences, which differ by 8 bp that do not alter the derived amino acid
sequence, encode identical 641-amino acid proteins; the 3-prime
untranslated regions of these genes are completely divergent. Northern
blot analysis of HeLa cell RNA detected an approximately 2.4-kb HSP70-2
transcript that was expressed at elevated levels following heat shock.

Milner and Campbell (1992) investigated the presence of sequence
variation in the HSP70-2 gene among different HLA haplotypes. They found
only very limited sequence variation, which did not result in amino acid
substitutions.

*FIELD* RF
1. Milner, C. M.; Campbell, R. D.: Structure and expression of the
three MHC-linked HSP70 genes. Immunogenetics 32: 242-251, 1990.

2. Milner, C. M.; Campbell, R. D.: Polymorphic analysis of the three
MHC-linked HSP70 genes. Immunogenetics 36: 357-362, 1992.

3. Sargent, C. A.; Dunham, I.; Trowsdale, J.; Campbell, R. D.: Human
major histocompatibility complex contains genes for the major heat
shock protein HSP70. Proc. Nat. Acad. Sci. 86: 1968-1972, 1989.

*FIELD* CD
Patti M. Sherman: 8/28/1998

*FIELD* ED
carol: 04/25/2011
mgross: 10/6/2005
carol: 10/26/1999
alopez: 10/9/1998
alopez: 9/21/1998