Full text data of HSPA8
HSPA8
(HSC70, HSP73, HSPA10)
[Confidence: high (present in two of the MS resources)]
Heat shock cognate 71 kDa protein (Heat shock 70 kDa protein 8)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Heat shock cognate 71 kDa protein (Heat shock 70 kDa protein 8)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00003865
IPI00003865 Heat shock cognate 71 kDa protein Splice isoform 1 of P11142 Heat shock cognate 71 kDa protein membrane and soluble n/a 2 n/a n/a n/a n/a n/a n/a 34 n/a 2 n/a 4 n/a n/a 1 n/a 3 3 5 from cytoplasmic to nuclear NSLESYAFNMK, ITITNDKGR, SQIHDIVLVGGSTR found at its expected molecular weight found at molecular weight
IPI00003865 Heat shock cognate 71 kDa protein Splice isoform 1 of P11142 Heat shock cognate 71 kDa protein membrane and soluble n/a 2 n/a n/a n/a n/a n/a n/a 34 n/a 2 n/a 4 n/a n/a 1 n/a 3 3 5 from cytoplasmic to nuclear NSLESYAFNMK, ITITNDKGR, SQIHDIVLVGGSTR found at its expected molecular weight found at molecular weight
Comments
Isoform P11142-2 was detected.
Isoform P11142-2 was detected.
UniProt
P11142
ID HSP7C_HUMAN Reviewed; 646 AA.
AC P11142; Q9H3R6;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUL-1989, sequence version 1.
DT 22-JAN-2014, entry version 174.
DE RecName: Full=Heat shock cognate 71 kDa protein;
DE AltName: Full=Heat shock 70 kDa protein 8;
GN Name=HSPA8; Synonyms=HSC70, HSP73, HSPA10;
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] (ISOFORM 1).
RX PubMed=3037489; DOI=10.1093/nar/15.13.5181;
RA Dworniczak B.P., Mirault M.-E.;
RT "Structure and expression of a human gene coding for a 71 kd heat
RT shock 'cognate' protein.";
RL Nucleic Acids Res. 15:5181-5197(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=11093761;
RA Tsukahara F., Yoshioka T., Muraki T.;
RT "Molecular and functional characterization of HSC54, a novel variant
RT of human heat shock cognate protein 70.";
RL Mol. Pharmacol. 58:1257-1263(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Niswonger M.L., Berk L.R., Srivastava P.K.;
RT "Complete coding sequence of human HSC70.";
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta, 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 [5]
RP PROTEIN SEQUENCE OF 2-49; 57-71; 77-102; 103-155; 160-188; 221-247;
RP 273-311; 326-342; 349-416; 424-447; 452-493; 510-517; 540-550; 570-597
RP AND 602-646, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2,
RP AND MASS SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RA Bienvenut W.V., Waridel P., Quadroni M.;
RL Submitted (MAR-2009) to UniProtKB.
RN [6]
RP PROTEIN SEQUENCE OF 2-49; 57-72; 78-88; 113-188; 221-247; 300-319;
RP 326-342; 349-357; 362-384; 424-447; 452-469; 510-517; 540-550 AND
RP 584-609, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, AND
RP MASS SPECTROMETRY.
RC TISSUE=Colon carcinoma, and Ovarian carcinoma;
RA Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Kolch W.,
RA Bilsland A.E., Keith W.N.;
RL Submitted (JAN-2010) to UniProtKB.
RN [7]
RP PROTEIN SEQUENCE OF 4-49; 57-71; 77-88; 113-126; 129-155; 160-187;
RP 221-246; 300-311; 329-342; 362-384; 424-447; 540-550 AND 574-583, AND
RP MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [8]
RP PROTEIN SEQUENCE OF 50-55; 103-107 AND 580-596.
RX PubMed=1286667; DOI=10.1002/elps.11501301199;
RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E.,
RA Vandekerckhove J.;
RT "Microsequences of 145 proteins recorded in the two-dimensional gel
RT protein database of normal human epidermal keratinocytes.";
RL Electrophoresis 13:960-969(1992).
RN [9]
RP PROTEIN SEQUENCE OF 77-86; 221-236 AND 302-311.
RX PubMed=8713105; DOI=10.1006/bbrc.1996.1082;
RA Egerton M., Moritz R.L., Druker B., Kelso A., Simpson R.J.;
RT "Identification of the 70kD heat shock cognate protein (Hsc70) and
RT alpha-actinin-1 as novel phosphotyrosine-containing proteins in T
RT lymphocytes.";
RL Biochem. Biophys. Res. Commun. 224:666-674(1996).
RN [10]
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 [11]
RP SUBCELLULAR LOCATION.
RX PubMed=1586970;
RA Hattori H., Liu Y.-C., Tohnai I., Ueda M., Kaneda T., Kobayashi T.,
RA Tanabe K., Ohtsuka K.;
RT "Intracellular localization and partial amino acid sequence of a
RT stress-inducible 40-kDa protein in HeLa cells.";
RL Cell Struct. Funct. 17:77-86(1992).
RN [12]
RP INTERACTION WITH BAG1, AND DOMAIN.
RX PubMed=9305631; DOI=10.1093/emboj/16.16.4887;
RA Takayama S., Bimston D.N., Matsuzawa S.-I., Freeman B.C.,
RA Aime-Sempe C., Xie Z., Morimoto R.I., Reed J.C.;
RT "BAG-1 modulates the chaperone activity of Hsp70/Hsc70.";
RL EMBO J. 16:4887-4896(1997).
RN [13]
RP INTERACTION WITH BAG1.
RX PubMed=9679980;
RA Takayama S., Krajewski S., Krajewska M., Kitada S., Zapata J.M.,
RA Kochel K., Knee D., Scudiero D., Tudor G., Miller G.J., Miyashita T.,
RA Yamada M., Reed J.C.;
RT "Expression and location of Hsp70/Hsc-binding anti-apoptotic protein
RT BAG-1 and its variants in normal tissues and tumor cell lines.";
RL Cancer Res. 58:3116-3131(1998).
RN [14]
RP INTERACTION WITH SV40 VP1.
RX PubMed=11147964;
RA Sainis L., Angelidis C., Pagoulatos G.N., Lazaridis L.;
RT "HSC70 interactions with SV40 viral proteins differ between permissive
RT and nonpermissive mammalian cells.";
RL Cell Stress Chaperones 5:132-138(2000).
RN [15]
RP FUNCTION, AND INTERACTION WITH CITED1.
RX PubMed=10722728; DOI=10.1074/jbc.275.12.8825;
RA Yahata T., de Caestecker M.P., Lechleider R.J., Andriole S.,
RA Roberts A.B., Isselbacher K.J., Shioda T.;
RT "The MSG1 non-DNA-binding transactivator binds to the p300/CBP
RT coactivators, enhancing their functional link to the Smad
RT transcription factors.";
RL J. Biol. Chem. 275:8825-8834(2000).
RN [16]
RP INTERACTION WITH PACRG.
RX PubMed=14532270; DOI=10.1074/jbc.M309655200;
RA Imai Y., Soda M., Murakami T., Shoji M., Abe K., Takahashi R.;
RT "A product of the human gene adjacent to parkin is a component of Lewy
RT bodies and suppresses Pael receptor-induced cell death.";
RL J. Biol. Chem. 278:51901-51910(2003).
RN [17]
RP ISGYLATION.
RX PubMed=16139798; DOI=10.1016/j.bbrc.2005.08.132;
RA Giannakopoulos N.V., Luo J.K., Papov V., Zou W., Lenschow D.J.,
RA Jacobs B.S., Borden E.C., Li J., Virgin H.W., Zhang D.E.;
RT "Proteomic identification of proteins conjugated to ISG15 in mouse and
RT human cells.";
RL Biochem. Biophys. Res. Commun. 336:496-506(2005).
RN [18]
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 [19]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [20]
RP INTERACTION WITH HERC5, AND ISGYLATION.
RX PubMed=16815975; DOI=10.1073/pnas.0600397103;
RA Wong J.J., Pung Y.F., Sze N.S., Chin K.C.;
RT "HERC5 is an IFN-induced HECT-type E3 protein ligase that mediates
RT type I IFN-induced ISGylation of protein targets.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:10735-10740(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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-153, AND MASS
RP SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [23]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
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 [24]
RP IDENTIFICATION IN A COMPLEX WITH HCFC1; MKI67; C11ORF30; MATR3;
RP ZNF335; TUBB2A; CCAR2; ASCL2; RBBP5 AND WDR5.
RX PubMed=19131338; DOI=10.1074/jbc.M805872200;
RA Garapaty S., Xu C.F., Trojer P., Mahajan M.A., Neubert T.A.,
RA Samuels H.H.;
RT "Identification and characterization of a novel nuclear protein
RT complex involved in nuclear hormone receptor-mediated gene
RT regulation.";
RL J. Biol. Chem. 284:7542-7552(2009).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [26]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-246; LYS-319; LYS-589;
RP LYS-597 AND LYS-601, 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 [27]
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 [28]
RP IDENTIFICATION AS A COMPONENT OF THE PRP19-CDC5L COMPLEX, AND
RP SUBCELLULAR LOCATION.
RX PubMed=20176811; DOI=10.1128/MCB.01505-09;
RA Grote M., Wolf E., Will C.L., Lemm I., Agafonov D.E., Schomburg A.,
RA Fischle W., Urlaub H., Luhrmann R.;
RT "Molecular architecture of the human Prp19/CDC5L complex.";
RL Mol. Cell. Biol. 30:2105-2119(2010).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-362, AND MASS
RP 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 [30]
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 [31]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [32]
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 [33]
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 1-634.
RX PubMed=19586912; DOI=10.1074/jbc.M109.033894;
RA Kajander T., Sachs J.N., Goldman A., Regan L.;
RT "Electrostatic interactions of Hsp-organizing protein
RT tetratricopeptide domains with Hsp70 and Hsp90: computational analysis
RT and protein engineering.";
RL J. Biol. Chem. 284:25364-25374(2009).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 4-381 IN COMPLEXES WITH ATP
RP AND ATP ANALOGS.
RX PubMed=19256508; DOI=10.1021/jm801627a;
RA Williamson D.S., Borgognoni J., Clay A., Daniels Z., Dokurno P.,
RA Drysdale M.J., Foloppe N., Francis G.L., Graham C.J., Howes R.,
RA Macias A.T., Murray J.B., Parsons R., Shaw T., Surgenor A.E.,
RA Terry L., Wang Y., Wood M., Massey A.J.;
RT "Novel adenosine-derived inhibitors of 70 kDa heat shock protein,
RT discovered through structure-based design.";
RL J. Med. Chem. 52:1510-1513(2009).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 4-381 IN COMPLEXES WITH ATP
RP ANALOGS.
RX PubMed=21526763; DOI=10.1021/jm101625x;
RA Macias A.T., Williamson D.S., Allen N., Borgognoni J., Clay A.,
RA Daniels Z., Dokurno P., Drysdale M.J., Francis G.L., Graham C.J.,
RA Howes R., Matassova N., Murray J.B., Parsons R., Shaw T.,
RA Surgenor A.E., Terry L., Wang Y., Wood M., Massey A.J.;
RT "Adenosine-derived inhibitors of 78 kDa glucose regulated protein
RT (Grp78) ATPase: insights into isoform selectivity.";
RL J. Med. Chem. 54:4034-4041(2011).
CC -!- FUNCTION: Acts as a repressor of transcriptional activation.
CC Inhibits the transcriptional coactivator activity of CITED1 on
CC Smad-mediated transcription. Chaperone. Component of the PRP19-
CC CDC5L complex that forms an integral part of the spliceosome and
CC is required for activating pre-mRNA splicing. May have a
CC scaffolding role in the spliceosome assembly as it contacts all
CC other components of the core complex.
CC -!- SUBUNIT: Identified in a IGF2BP1-dependent mRNP granule complex
CC containing untranslated mRNAs. Interacts with PACRG. Interacts
CC with HSPH1/HSP105. Interacts with IRAK1BP1 and BAG1. Interacts
CC with DNAJC7. Interacts with CITED1 (via N-terminus); the
CC interaction suppresses the association of CITED1 to p300/CBP and
CC Smad-mediated transcription transactivation. Component of the
CC PRP19-CDC5L splicing complex composed of a core complex comprising
CC a homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2, and at least
CC three less stably associated proteins CTNNBL1, CWC15 and HSPA8.
CC Interacts with SV40 VP1. Interacts with TRIM5. Part of a complex
CC composed at least of ASCL2, C11orf30/EMSY, HCFC1, HSPA8, CCAR2,
CC MATR3, MKI67, RBBP5, TUBB2A, WDR5 and ZNF335; this complex may
CC have a histone H3-specific methyltransferase activity. Interacts
CC with METTL21A.
CC -!- INTERACTION:
CC Q99IB8:- (xeno); NbExp=3; IntAct=EBI-351896, EBI-6927928;
CC P60709:ACTB; NbExp=2; IntAct=EBI-351896, EBI-353944;
CC Q9GZX7:AICDA; NbExp=2; IntAct=EBI-351896, EBI-3834328;
CC P49407:ARRB1; NbExp=4; IntAct=EBI-351896, EBI-743313;
CC P32121:ARRB2; NbExp=4; IntAct=EBI-351896, EBI-714559;
CC Q9NQ11:ATP13A2; NbExp=2; IntAct=EBI-351896, EBI-6308763;
CC Q99933:BAG1; NbExp=10; IntAct=EBI-351896, EBI-1030678;
CC P00338:LDHA; NbExp=4; IntAct=EBI-351896, EBI-372327;
CC Q5S007:LRRK2; NbExp=3; IntAct=EBI-351896, EBI-5323863;
CC P03485:M (xeno); NbExp=4; IntAct=EBI-351896, EBI-2547543;
CC Q9UNE7:STUB1; NbExp=5; IntAct=EBI-351896, EBI-357085;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Melanosome. Nucleus, nucleolus.
CC Note=Localized in cytoplasmic mRNP granules containing
CC untranslated mRNAs. Translocates rapidly from the cytoplasm to the
CC nuclei, and especially to the nucleoli, upon heat shock.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P11142-1; Sequence=Displayed;
CC Name=2; Synonyms=HSC54;
CC IsoId=P11142-2; Sequence=VSP_002427;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- INDUCTION: Constitutively synthesized.
CC -!- DOMAIN: The N-terminal 1-386 residues constitute the ATPase
CC domain, while residues 387-646 form the peptide-binding domain.
CC -!- PTM: Acetylated.
CC -!- PTM: ISGylated.
CC -!- PTM: Trimethylation at Lys-561 reduces fibrillar SNCA binding.
CC -!- SIMILARITY: Belongs to the heat shock protein 70 family.
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DR EMBL; Y00371; CAA68445.1; -; Genomic_DNA.
DR EMBL; AB034951; BAB18615.1; -; mRNA.
DR EMBL; AF352832; AAK17898.1; -; mRNA.
DR EMBL; BC016179; AAH16179.1; -; mRNA.
DR EMBL; BC016660; AAH16660.1; -; mRNA.
DR EMBL; BC019816; AAH19816.1; -; mRNA.
DR PIR; A27077; A27077.
DR RefSeq; NP_006588.1; NM_006597.5.
DR RefSeq; NP_694881.1; NM_153201.3.
DR RefSeq; XP_005271592.1; XM_005271535.1.
DR UniGene; Hs.180414; -.
DR PDB; 3AGY; X-ray; 1.85 A; C/D/F=639-646.
DR PDB; 3AGZ; X-ray; 2.51 A; C/D/E/F=639-646.
DR PDB; 3ESK; X-ray; 2.05 A; B=635-646.
DR PDB; 3FZF; X-ray; 2.20 A; A=4-381.
DR PDB; 3FZH; X-ray; 2.00 A; A=4-381.
DR PDB; 3FZK; X-ray; 2.10 A; A=4-381.
DR PDB; 3FZL; X-ray; 2.20 A; A=4-381.
DR PDB; 3FZM; X-ray; 2.30 A; A=4-381.
DR PDB; 3LDQ; X-ray; 1.90 A; A=4-381.
DR PDB; 3M3Z; X-ray; 2.10 A; A=4-381.
DR PDB; 4HWI; X-ray; 2.27 A; A=5-381.
DR PDBsum; 3AGY; -.
DR PDBsum; 3AGZ; -.
DR PDBsum; 3ESK; -.
DR PDBsum; 3FZF; -.
DR PDBsum; 3FZH; -.
DR PDBsum; 3FZK; -.
DR PDBsum; 3FZL; -.
DR PDBsum; 3FZM; -.
DR PDBsum; 3LDQ; -.
DR PDBsum; 3M3Z; -.
DR PDBsum; 4HWI; -.
DR ProteinModelPortal; P11142; -.
DR SMR; P11142; 1-621.
DR IntAct; P11142; 82.
DR MINT; MINT-4998609; -.
DR STRING; 9606.ENSP00000227378; -.
DR BindingDB; P11142; -.
DR ChEMBL; CHEMBL1275223; -.
DR PhosphoSite; P11142; -.
DR DMDM; 123648; -.
DR DOSAC-COBS-2DPAGE; P11142; -.
DR OGP; P11142; -.
DR REPRODUCTION-2DPAGE; IPI00003865; -.
DR SWISS-2DPAGE; P11142; -.
DR UCD-2DPAGE; P11142; -.
DR PaxDb; P11142; -.
DR PeptideAtlas; P11142; -.
DR PRIDE; P11142; -.
DR DNASU; 3312; -.
DR Ensembl; ENST00000227378; ENSP00000227378; ENSG00000109971.
DR Ensembl; ENST00000453788; ENSP00000404372; ENSG00000109971.
DR Ensembl; ENST00000532636; ENSP00000437125; ENSG00000109971.
DR Ensembl; ENST00000534624; ENSP00000432083; ENSG00000109971.
DR GeneID; 3312; -.
DR KEGG; hsa:3312; -.
DR UCSC; uc001pyo.3; human.
DR CTD; 3312; -.
DR GeneCards; GC11M122969; -.
DR H-InvDB; HIX0033867; -.
DR HGNC; HGNC:5241; HSPA8.
DR HPA; CAB002056; -.
DR MIM; 600816; gene.
DR neXtProt; NX_P11142; -.
DR PharmGKB; PA29507; -.
DR eggNOG; COG0443; -.
DR HOGENOM; HOG000228135; -.
DR HOVERGEN; HBG051845; -.
DR InParanoid; P11142; -.
DR KO; K03283; -.
DR OMA; PMIVVEY; -.
DR OrthoDB; EOG7PCJGF; -.
DR PhylomeDB; P11142; -.
DR Reactome; REACT_111045; Developmental Biology.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_13685; Neuronal System.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; HSPA8; human.
DR EvolutionaryTrace; P11142; -.
DR GeneWiki; HSPA8; -.
DR GenomeRNAi; 3312; -.
DR NextBio; 13136; -.
DR PMAP-CutDB; P11142; -.
DR PRO; PR:P11142; -.
DR ArrayExpress; P11142; -.
DR Bgee; P11142; -.
DR CleanEx; HS_HSPA8; -.
DR Genevestigator; P11142; -.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0061202; C:clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane; TAS:Reactome.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0000974; C:Prp19 complex; IDA:UniProtKB.
DR GO; GO:0030529; C:ribonucleoprotein complex; IDA:UniProtKB.
DR GO; GO:0005681; C:spliceosomal complex; IEA:UniProtKB-KW.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042623; F:ATPase activity, coupled; NAS:UniProtKB.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0051085; P:chaperone mediated protein folding requiring cofactor; IEA:Ensembl.
DR GO; GO:0010467; P:gene expression; TAS:Reactome.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0016071; P:mRNA metabolic process; TAS:Reactome.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-dependent; IDA:UniProtKB.
DR GO; GO:0007269; P:neurotransmitter secretion; TAS:Reactome.
DR GO; GO:0006892; P:post-Golgi vesicle-mediated transport; TAS:Reactome.
DR GO; GO:0006457; P:protein folding; NAS:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; IEA:Ensembl.
DR GO; GO:0006986; P:response to unfolded protein; NAS:UniProtKB.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
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-virus interaction; Methylation; mRNA processing; mRNA splicing;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism;
KW Reference proteome; Repressor; Spliceosome; Stress response;
KW Transcription; Transcription regulation; Ubl conjugation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 646 Heat shock cognate 71 kDa protein.
FT /FTId=PRO_0000078270.
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 REGION 186 377 Interaction with BAG1.
FT BINDING 71 71 ATP.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 153 153 Phosphoserine.
FT MOD_RES 246 246 N6-acetyllysine.
FT MOD_RES 319 319 N6-acetyllysine.
FT MOD_RES 362 362 Phosphoserine.
FT MOD_RES 561 561 N6,N6,N6-trimethyllysine; by METTL21A.
FT MOD_RES 589 589 N6-acetyllysine.
FT MOD_RES 597 597 N6-acetyllysine.
FT MOD_RES 601 601 N6-acetyllysine.
FT VAR_SEQ 464 616 Missing (in isoform 2).
FT /FTId=VSP_002427.
FT VARIANT 32 32 D -> Y (in dbSNP:rs11551602).
FT /FTId=VAR_049619.
FT VARIANT 459 459 F -> L (in dbSNP:rs11551598).
FT /FTId=VAR_049620.
FT MUTAGEN 561 561 K->R: Complete loss of in vitro
FT methylation by METTL21A.
FT STRAND 6 10
FT STRAND 13 22
FT STRAND 25 28
FT STRAND 36 39
FT STRAND 42 44
FT STRAND 49 51
FT HELIX 53 57
FT TURN 58 61
FT STRAND 65 67
FT HELIX 70 72
FT TURN 73 75
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 HELIX 185 187
FT STRAND 193 200
FT STRAND 205 213
FT STRAND 216 225
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 307 312
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 STRAND 357 360
FT TURN 365 367
FT HELIX 368 380
FT STRAND 641 644
SQ SEQUENCE 646 AA; 70898 MW; 9AA27B210730670C CRC64;
MSKGPAVGID LGTTYSCVGV FQHGKVEIIA NDQGNRTTPS YVAFTDTERL IGDAAKNQVA
MNPTNTVFDA KRLIGRRFDD AVVQSDMKHW PFMVVNDAGR PKVQVEYKGE TKSFYPEEVS
SMVLTKMKEI AEAYLGKTVT NAVVTVPAYF NDSQRQATKD AGTIAGLNVL RIINEPTAAA
IAYGLDKKVG AERNVLIFDL GGGTFDVSIL TIEDGIFEVK STAGDTHLGG EDFDNRMVNH
FIAEFKRKHK KDISENKRAV RRLRTACERA KRTLSSSTQA SIEIDSLYEG IDFYTSITRA
RFEELNADLF RGTLDPVEKA LRDAKLDKSQ IHDIVLVGGS TRIPKIQKLL QDFFNGKELN
KSINPDEAVA YGAAVQAAIL SGDKSENVQD LLLLDVTPLS LGIETAGGVM TVLIKRNTTI
PTKQTQTFTT YSDNQPGVLI QVYEGERAMT KDNNLLGKFE LTGIPPAPRG VPQIEVTFDI
DANGILNVSA VDKSTGKENK ITITNDKGRL SKEDIERMVQ EAEKYKAEDE KQRDKVSSKN
SLESYAFNMK ATVEDEKLQG KINDEDKQKI LDKCNEIINW LDKNQTAEKE EFEHQQKELE
KVCNPIITKL YQSAGGMPGG MPGGFPGGGA PPSGGASSGP TIEEVD
//
ID HSP7C_HUMAN Reviewed; 646 AA.
AC P11142; Q9H3R6;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUL-1989, sequence version 1.
DT 22-JAN-2014, entry version 174.
DE RecName: Full=Heat shock cognate 71 kDa protein;
DE AltName: Full=Heat shock 70 kDa protein 8;
GN Name=HSPA8; Synonyms=HSC70, HSP73, HSPA10;
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] (ISOFORM 1).
RX PubMed=3037489; DOI=10.1093/nar/15.13.5181;
RA Dworniczak B.P., Mirault M.-E.;
RT "Structure and expression of a human gene coding for a 71 kd heat
RT shock 'cognate' protein.";
RL Nucleic Acids Res. 15:5181-5197(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=11093761;
RA Tsukahara F., Yoshioka T., Muraki T.;
RT "Molecular and functional characterization of HSC54, a novel variant
RT of human heat shock cognate protein 70.";
RL Mol. Pharmacol. 58:1257-1263(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Niswonger M.L., Berk L.R., Srivastava P.K.;
RT "Complete coding sequence of human HSC70.";
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta, 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 [5]
RP PROTEIN SEQUENCE OF 2-49; 57-71; 77-102; 103-155; 160-188; 221-247;
RP 273-311; 326-342; 349-416; 424-447; 452-493; 510-517; 540-550; 570-597
RP AND 602-646, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2,
RP AND MASS SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RA Bienvenut W.V., Waridel P., Quadroni M.;
RL Submitted (MAR-2009) to UniProtKB.
RN [6]
RP PROTEIN SEQUENCE OF 2-49; 57-72; 78-88; 113-188; 221-247; 300-319;
RP 326-342; 349-357; 362-384; 424-447; 452-469; 510-517; 540-550 AND
RP 584-609, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, AND
RP MASS SPECTROMETRY.
RC TISSUE=Colon carcinoma, and Ovarian carcinoma;
RA Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Kolch W.,
RA Bilsland A.E., Keith W.N.;
RL Submitted (JAN-2010) to UniProtKB.
RN [7]
RP PROTEIN SEQUENCE OF 4-49; 57-71; 77-88; 113-126; 129-155; 160-187;
RP 221-246; 300-311; 329-342; 362-384; 424-447; 540-550 AND 574-583, AND
RP MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [8]
RP PROTEIN SEQUENCE OF 50-55; 103-107 AND 580-596.
RX PubMed=1286667; DOI=10.1002/elps.11501301199;
RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E.,
RA Vandekerckhove J.;
RT "Microsequences of 145 proteins recorded in the two-dimensional gel
RT protein database of normal human epidermal keratinocytes.";
RL Electrophoresis 13:960-969(1992).
RN [9]
RP PROTEIN SEQUENCE OF 77-86; 221-236 AND 302-311.
RX PubMed=8713105; DOI=10.1006/bbrc.1996.1082;
RA Egerton M., Moritz R.L., Druker B., Kelso A., Simpson R.J.;
RT "Identification of the 70kD heat shock cognate protein (Hsc70) and
RT alpha-actinin-1 as novel phosphotyrosine-containing proteins in T
RT lymphocytes.";
RL Biochem. Biophys. Res. Commun. 224:666-674(1996).
RN [10]
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 [11]
RP SUBCELLULAR LOCATION.
RX PubMed=1586970;
RA Hattori H., Liu Y.-C., Tohnai I., Ueda M., Kaneda T., Kobayashi T.,
RA Tanabe K., Ohtsuka K.;
RT "Intracellular localization and partial amino acid sequence of a
RT stress-inducible 40-kDa protein in HeLa cells.";
RL Cell Struct. Funct. 17:77-86(1992).
RN [12]
RP INTERACTION WITH BAG1, AND DOMAIN.
RX PubMed=9305631; DOI=10.1093/emboj/16.16.4887;
RA Takayama S., Bimston D.N., Matsuzawa S.-I., Freeman B.C.,
RA Aime-Sempe C., Xie Z., Morimoto R.I., Reed J.C.;
RT "BAG-1 modulates the chaperone activity of Hsp70/Hsc70.";
RL EMBO J. 16:4887-4896(1997).
RN [13]
RP INTERACTION WITH BAG1.
RX PubMed=9679980;
RA Takayama S., Krajewski S., Krajewska M., Kitada S., Zapata J.M.,
RA Kochel K., Knee D., Scudiero D., Tudor G., Miller G.J., Miyashita T.,
RA Yamada M., Reed J.C.;
RT "Expression and location of Hsp70/Hsc-binding anti-apoptotic protein
RT BAG-1 and its variants in normal tissues and tumor cell lines.";
RL Cancer Res. 58:3116-3131(1998).
RN [14]
RP INTERACTION WITH SV40 VP1.
RX PubMed=11147964;
RA Sainis L., Angelidis C., Pagoulatos G.N., Lazaridis L.;
RT "HSC70 interactions with SV40 viral proteins differ between permissive
RT and nonpermissive mammalian cells.";
RL Cell Stress Chaperones 5:132-138(2000).
RN [15]
RP FUNCTION, AND INTERACTION WITH CITED1.
RX PubMed=10722728; DOI=10.1074/jbc.275.12.8825;
RA Yahata T., de Caestecker M.P., Lechleider R.J., Andriole S.,
RA Roberts A.B., Isselbacher K.J., Shioda T.;
RT "The MSG1 non-DNA-binding transactivator binds to the p300/CBP
RT coactivators, enhancing their functional link to the Smad
RT transcription factors.";
RL J. Biol. Chem. 275:8825-8834(2000).
RN [16]
RP INTERACTION WITH PACRG.
RX PubMed=14532270; DOI=10.1074/jbc.M309655200;
RA Imai Y., Soda M., Murakami T., Shoji M., Abe K., Takahashi R.;
RT "A product of the human gene adjacent to parkin is a component of Lewy
RT bodies and suppresses Pael receptor-induced cell death.";
RL J. Biol. Chem. 278:51901-51910(2003).
RN [17]
RP ISGYLATION.
RX PubMed=16139798; DOI=10.1016/j.bbrc.2005.08.132;
RA Giannakopoulos N.V., Luo J.K., Papov V., Zou W., Lenschow D.J.,
RA Jacobs B.S., Borden E.C., Li J., Virgin H.W., Zhang D.E.;
RT "Proteomic identification of proteins conjugated to ISG15 in mouse and
RT human cells.";
RL Biochem. Biophys. Res. Commun. 336:496-506(2005).
RN [18]
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 [19]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [20]
RP INTERACTION WITH HERC5, AND ISGYLATION.
RX PubMed=16815975; DOI=10.1073/pnas.0600397103;
RA Wong J.J., Pung Y.F., Sze N.S., Chin K.C.;
RT "HERC5 is an IFN-induced HECT-type E3 protein ligase that mediates
RT type I IFN-induced ISGylation of protein targets.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:10735-10740(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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-153, AND MASS
RP SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [23]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
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 [24]
RP IDENTIFICATION IN A COMPLEX WITH HCFC1; MKI67; C11ORF30; MATR3;
RP ZNF335; TUBB2A; CCAR2; ASCL2; RBBP5 AND WDR5.
RX PubMed=19131338; DOI=10.1074/jbc.M805872200;
RA Garapaty S., Xu C.F., Trojer P., Mahajan M.A., Neubert T.A.,
RA Samuels H.H.;
RT "Identification and characterization of a novel nuclear protein
RT complex involved in nuclear hormone receptor-mediated gene
RT regulation.";
RL J. Biol. Chem. 284:7542-7552(2009).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [26]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-246; LYS-319; LYS-589;
RP LYS-597 AND LYS-601, 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 [27]
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 [28]
RP IDENTIFICATION AS A COMPONENT OF THE PRP19-CDC5L COMPLEX, AND
RP SUBCELLULAR LOCATION.
RX PubMed=20176811; DOI=10.1128/MCB.01505-09;
RA Grote M., Wolf E., Will C.L., Lemm I., Agafonov D.E., Schomburg A.,
RA Fischle W., Urlaub H., Luhrmann R.;
RT "Molecular architecture of the human Prp19/CDC5L complex.";
RL Mol. Cell. Biol. 30:2105-2119(2010).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-362, AND MASS
RP 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 [30]
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 [31]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [32]
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 [33]
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 1-634.
RX PubMed=19586912; DOI=10.1074/jbc.M109.033894;
RA Kajander T., Sachs J.N., Goldman A., Regan L.;
RT "Electrostatic interactions of Hsp-organizing protein
RT tetratricopeptide domains with Hsp70 and Hsp90: computational analysis
RT and protein engineering.";
RL J. Biol. Chem. 284:25364-25374(2009).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 4-381 IN COMPLEXES WITH ATP
RP AND ATP ANALOGS.
RX PubMed=19256508; DOI=10.1021/jm801627a;
RA Williamson D.S., Borgognoni J., Clay A., Daniels Z., Dokurno P.,
RA Drysdale M.J., Foloppe N., Francis G.L., Graham C.J., Howes R.,
RA Macias A.T., Murray J.B., Parsons R., Shaw T., Surgenor A.E.,
RA Terry L., Wang Y., Wood M., Massey A.J.;
RT "Novel adenosine-derived inhibitors of 70 kDa heat shock protein,
RT discovered through structure-based design.";
RL J. Med. Chem. 52:1510-1513(2009).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 4-381 IN COMPLEXES WITH ATP
RP ANALOGS.
RX PubMed=21526763; DOI=10.1021/jm101625x;
RA Macias A.T., Williamson D.S., Allen N., Borgognoni J., Clay A.,
RA Daniels Z., Dokurno P., Drysdale M.J., Francis G.L., Graham C.J.,
RA Howes R., Matassova N., Murray J.B., Parsons R., Shaw T.,
RA Surgenor A.E., Terry L., Wang Y., Wood M., Massey A.J.;
RT "Adenosine-derived inhibitors of 78 kDa glucose regulated protein
RT (Grp78) ATPase: insights into isoform selectivity.";
RL J. Med. Chem. 54:4034-4041(2011).
CC -!- FUNCTION: Acts as a repressor of transcriptional activation.
CC Inhibits the transcriptional coactivator activity of CITED1 on
CC Smad-mediated transcription. Chaperone. Component of the PRP19-
CC CDC5L complex that forms an integral part of the spliceosome and
CC is required for activating pre-mRNA splicing. May have a
CC scaffolding role in the spliceosome assembly as it contacts all
CC other components of the core complex.
CC -!- SUBUNIT: Identified in a IGF2BP1-dependent mRNP granule complex
CC containing untranslated mRNAs. Interacts with PACRG. Interacts
CC with HSPH1/HSP105. Interacts with IRAK1BP1 and BAG1. Interacts
CC with DNAJC7. Interacts with CITED1 (via N-terminus); the
CC interaction suppresses the association of CITED1 to p300/CBP and
CC Smad-mediated transcription transactivation. Component of the
CC PRP19-CDC5L splicing complex composed of a core complex comprising
CC a homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2, and at least
CC three less stably associated proteins CTNNBL1, CWC15 and HSPA8.
CC Interacts with SV40 VP1. Interacts with TRIM5. Part of a complex
CC composed at least of ASCL2, C11orf30/EMSY, HCFC1, HSPA8, CCAR2,
CC MATR3, MKI67, RBBP5, TUBB2A, WDR5 and ZNF335; this complex may
CC have a histone H3-specific methyltransferase activity. Interacts
CC with METTL21A.
CC -!- INTERACTION:
CC Q99IB8:- (xeno); NbExp=3; IntAct=EBI-351896, EBI-6927928;
CC P60709:ACTB; NbExp=2; IntAct=EBI-351896, EBI-353944;
CC Q9GZX7:AICDA; NbExp=2; IntAct=EBI-351896, EBI-3834328;
CC P49407:ARRB1; NbExp=4; IntAct=EBI-351896, EBI-743313;
CC P32121:ARRB2; NbExp=4; IntAct=EBI-351896, EBI-714559;
CC Q9NQ11:ATP13A2; NbExp=2; IntAct=EBI-351896, EBI-6308763;
CC Q99933:BAG1; NbExp=10; IntAct=EBI-351896, EBI-1030678;
CC P00338:LDHA; NbExp=4; IntAct=EBI-351896, EBI-372327;
CC Q5S007:LRRK2; NbExp=3; IntAct=EBI-351896, EBI-5323863;
CC P03485:M (xeno); NbExp=4; IntAct=EBI-351896, EBI-2547543;
CC Q9UNE7:STUB1; NbExp=5; IntAct=EBI-351896, EBI-357085;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Melanosome. Nucleus, nucleolus.
CC Note=Localized in cytoplasmic mRNP granules containing
CC untranslated mRNAs. Translocates rapidly from the cytoplasm to the
CC nuclei, and especially to the nucleoli, upon heat shock.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P11142-1; Sequence=Displayed;
CC Name=2; Synonyms=HSC54;
CC IsoId=P11142-2; Sequence=VSP_002427;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- INDUCTION: Constitutively synthesized.
CC -!- DOMAIN: The N-terminal 1-386 residues constitute the ATPase
CC domain, while residues 387-646 form the peptide-binding domain.
CC -!- PTM: Acetylated.
CC -!- PTM: ISGylated.
CC -!- PTM: Trimethylation at Lys-561 reduces fibrillar SNCA binding.
CC -!- SIMILARITY: Belongs to the heat shock protein 70 family.
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DR EMBL; Y00371; CAA68445.1; -; Genomic_DNA.
DR EMBL; AB034951; BAB18615.1; -; mRNA.
DR EMBL; AF352832; AAK17898.1; -; mRNA.
DR EMBL; BC016179; AAH16179.1; -; mRNA.
DR EMBL; BC016660; AAH16660.1; -; mRNA.
DR EMBL; BC019816; AAH19816.1; -; mRNA.
DR PIR; A27077; A27077.
DR RefSeq; NP_006588.1; NM_006597.5.
DR RefSeq; NP_694881.1; NM_153201.3.
DR RefSeq; XP_005271592.1; XM_005271535.1.
DR UniGene; Hs.180414; -.
DR PDB; 3AGY; X-ray; 1.85 A; C/D/F=639-646.
DR PDB; 3AGZ; X-ray; 2.51 A; C/D/E/F=639-646.
DR PDB; 3ESK; X-ray; 2.05 A; B=635-646.
DR PDB; 3FZF; X-ray; 2.20 A; A=4-381.
DR PDB; 3FZH; X-ray; 2.00 A; A=4-381.
DR PDB; 3FZK; X-ray; 2.10 A; A=4-381.
DR PDB; 3FZL; X-ray; 2.20 A; A=4-381.
DR PDB; 3FZM; X-ray; 2.30 A; A=4-381.
DR PDB; 3LDQ; X-ray; 1.90 A; A=4-381.
DR PDB; 3M3Z; X-ray; 2.10 A; A=4-381.
DR PDB; 4HWI; X-ray; 2.27 A; A=5-381.
DR PDBsum; 3AGY; -.
DR PDBsum; 3AGZ; -.
DR PDBsum; 3ESK; -.
DR PDBsum; 3FZF; -.
DR PDBsum; 3FZH; -.
DR PDBsum; 3FZK; -.
DR PDBsum; 3FZL; -.
DR PDBsum; 3FZM; -.
DR PDBsum; 3LDQ; -.
DR PDBsum; 3M3Z; -.
DR PDBsum; 4HWI; -.
DR ProteinModelPortal; P11142; -.
DR SMR; P11142; 1-621.
DR IntAct; P11142; 82.
DR MINT; MINT-4998609; -.
DR STRING; 9606.ENSP00000227378; -.
DR BindingDB; P11142; -.
DR ChEMBL; CHEMBL1275223; -.
DR PhosphoSite; P11142; -.
DR DMDM; 123648; -.
DR DOSAC-COBS-2DPAGE; P11142; -.
DR OGP; P11142; -.
DR REPRODUCTION-2DPAGE; IPI00003865; -.
DR SWISS-2DPAGE; P11142; -.
DR UCD-2DPAGE; P11142; -.
DR PaxDb; P11142; -.
DR PeptideAtlas; P11142; -.
DR PRIDE; P11142; -.
DR DNASU; 3312; -.
DR Ensembl; ENST00000227378; ENSP00000227378; ENSG00000109971.
DR Ensembl; ENST00000453788; ENSP00000404372; ENSG00000109971.
DR Ensembl; ENST00000532636; ENSP00000437125; ENSG00000109971.
DR Ensembl; ENST00000534624; ENSP00000432083; ENSG00000109971.
DR GeneID; 3312; -.
DR KEGG; hsa:3312; -.
DR UCSC; uc001pyo.3; human.
DR CTD; 3312; -.
DR GeneCards; GC11M122969; -.
DR H-InvDB; HIX0033867; -.
DR HGNC; HGNC:5241; HSPA8.
DR HPA; CAB002056; -.
DR MIM; 600816; gene.
DR neXtProt; NX_P11142; -.
DR PharmGKB; PA29507; -.
DR eggNOG; COG0443; -.
DR HOGENOM; HOG000228135; -.
DR HOVERGEN; HBG051845; -.
DR InParanoid; P11142; -.
DR KO; K03283; -.
DR OMA; PMIVVEY; -.
DR OrthoDB; EOG7PCJGF; -.
DR PhylomeDB; P11142; -.
DR Reactome; REACT_111045; Developmental Biology.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_13685; Neuronal System.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; HSPA8; human.
DR EvolutionaryTrace; P11142; -.
DR GeneWiki; HSPA8; -.
DR GenomeRNAi; 3312; -.
DR NextBio; 13136; -.
DR PMAP-CutDB; P11142; -.
DR PRO; PR:P11142; -.
DR ArrayExpress; P11142; -.
DR Bgee; P11142; -.
DR CleanEx; HS_HSPA8; -.
DR Genevestigator; P11142; -.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0061202; C:clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane; TAS:Reactome.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0000974; C:Prp19 complex; IDA:UniProtKB.
DR GO; GO:0030529; C:ribonucleoprotein complex; IDA:UniProtKB.
DR GO; GO:0005681; C:spliceosomal complex; IEA:UniProtKB-KW.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042623; F:ATPase activity, coupled; NAS:UniProtKB.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0051085; P:chaperone mediated protein folding requiring cofactor; IEA:Ensembl.
DR GO; GO:0010467; P:gene expression; TAS:Reactome.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0016071; P:mRNA metabolic process; TAS:Reactome.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-dependent; IDA:UniProtKB.
DR GO; GO:0007269; P:neurotransmitter secretion; TAS:Reactome.
DR GO; GO:0006892; P:post-Golgi vesicle-mediated transport; TAS:Reactome.
DR GO; GO:0006457; P:protein folding; NAS:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; IEA:Ensembl.
DR GO; GO:0006986; P:response to unfolded protein; NAS:UniProtKB.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
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-virus interaction; Methylation; mRNA processing; mRNA splicing;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism;
KW Reference proteome; Repressor; Spliceosome; Stress response;
KW Transcription; Transcription regulation; Ubl conjugation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 646 Heat shock cognate 71 kDa protein.
FT /FTId=PRO_0000078270.
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 REGION 186 377 Interaction with BAG1.
FT BINDING 71 71 ATP.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 153 153 Phosphoserine.
FT MOD_RES 246 246 N6-acetyllysine.
FT MOD_RES 319 319 N6-acetyllysine.
FT MOD_RES 362 362 Phosphoserine.
FT MOD_RES 561 561 N6,N6,N6-trimethyllysine; by METTL21A.
FT MOD_RES 589 589 N6-acetyllysine.
FT MOD_RES 597 597 N6-acetyllysine.
FT MOD_RES 601 601 N6-acetyllysine.
FT VAR_SEQ 464 616 Missing (in isoform 2).
FT /FTId=VSP_002427.
FT VARIANT 32 32 D -> Y (in dbSNP:rs11551602).
FT /FTId=VAR_049619.
FT VARIANT 459 459 F -> L (in dbSNP:rs11551598).
FT /FTId=VAR_049620.
FT MUTAGEN 561 561 K->R: Complete loss of in vitro
FT methylation by METTL21A.
FT STRAND 6 10
FT STRAND 13 22
FT STRAND 25 28
FT STRAND 36 39
FT STRAND 42 44
FT STRAND 49 51
FT HELIX 53 57
FT TURN 58 61
FT STRAND 65 67
FT HELIX 70 72
FT TURN 73 75
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 HELIX 185 187
FT STRAND 193 200
FT STRAND 205 213
FT STRAND 216 225
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 307 312
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 STRAND 357 360
FT TURN 365 367
FT HELIX 368 380
FT STRAND 641 644
SQ SEQUENCE 646 AA; 70898 MW; 9AA27B210730670C CRC64;
MSKGPAVGID LGTTYSCVGV FQHGKVEIIA NDQGNRTTPS YVAFTDTERL IGDAAKNQVA
MNPTNTVFDA KRLIGRRFDD AVVQSDMKHW PFMVVNDAGR PKVQVEYKGE TKSFYPEEVS
SMVLTKMKEI AEAYLGKTVT NAVVTVPAYF NDSQRQATKD AGTIAGLNVL RIINEPTAAA
IAYGLDKKVG AERNVLIFDL GGGTFDVSIL TIEDGIFEVK STAGDTHLGG EDFDNRMVNH
FIAEFKRKHK KDISENKRAV RRLRTACERA KRTLSSSTQA SIEIDSLYEG IDFYTSITRA
RFEELNADLF RGTLDPVEKA LRDAKLDKSQ IHDIVLVGGS TRIPKIQKLL QDFFNGKELN
KSINPDEAVA YGAAVQAAIL SGDKSENVQD LLLLDVTPLS LGIETAGGVM TVLIKRNTTI
PTKQTQTFTT YSDNQPGVLI QVYEGERAMT KDNNLLGKFE LTGIPPAPRG VPQIEVTFDI
DANGILNVSA VDKSTGKENK ITITNDKGRL SKEDIERMVQ EAEKYKAEDE KQRDKVSSKN
SLESYAFNMK ATVEDEKLQG KINDEDKQKI LDKCNEIINW LDKNQTAEKE EFEHQQKELE
KVCNPIITKL YQSAGGMPGG MPGGFPGGGA PPSGGASSGP TIEEVD
//
MIM
600816
*RECORD*
*FIELD* NO
600816
*FIELD* TI
*600816 HEAT-SHOCK 70-KD PROTEIN 8; HSPA8
;;HEAT-SHOCK COGNATE PROTEIN, 71-KD; HSC71;;
read moreHSP73;;
HSC70;;
HEAT-SHOCK 70-KD PROTEIN 10, FORMERLY; HSPA10, FORMERLY;;
LIPOPOLYSACCHARIDE-ASSOCIATED PROTEIN 1; LAP1;;
LPS-ASSOCIATED PROTEIN 1
*FIELD* TX
CLONING
The family of approximately 70-kD heat-shock proteins, HSP70 (see
140550), contains both heat-inducible and constitutively expressed
members, the latter of which are sometimes called heat-shock cognate
proteins (HSCs). By screening a human genomic library with Drosophila
hsp70 and hsc70 cDNAs, Dworniczak and Mirault (1987) isolated the HSPA8
gene, which they called HSC70. Using HSPA8 genomic sequence to screen a
human cDNA library derived from a hepatic metastasis that originated
from a pancreatic gastrinoma, the authors cloned HSPA8 cDNAs. The HSPA8
gene contains 9 exons and spans 5 kb. The deduced HSPA8 protein has 646
amino acids and a predicted molecular mass of 70,899 Da. In vitro
translation of HSPA8 RNA produced a polypeptide that migrated as a 71-kD
protein in SDS-polyacrylamide gels. HSPA8 RNA and protein were
moderately abundant in unstressed HeLa cells and were only minimally
induced by heat. Dworniczak and Mirault (1987) noted that HSPA8 is
likely the constitutively expressed 71-kD heat-shock protein that is
identical to uncoating ATPase (Ungewickell, 1985; Chappell et al.,
1986), an enzyme that releases clathrin from coated vesicles. They
identified 2 distinct HSPA8-related processed pseudogenes.
GENE FUNCTION
Tavaria et al. (1995) stated that HSPA8 (also known as HSP73) plays an
important role in cells by transiently associating with nascent
polypeptides to facilitate correct folding. The protein folding process
involves other constitutively expressed heat-shock proteins, such as
HSP60 (HSPD1; 118190), HSP90 (HSPCA; 140571), and GRP78 (138120), which
have collectively been termed chaperones. Chaperones are also involved
in maintaining proteins in a semifolded state that enables translocation
through the mitochondrial and endoplasmic reticulum membranes. HSP73
also functions as an ATPase in the disassembly of clathrin-coated
vesicles during transport of membrane components through the cell.
Using a yeast 2-hybrid assay, Hohfeld et al. (1995) showed that rat Hip
(ST13; 606796) bound Hsc70. One Hip oligomer bound the ATPase domains of
at least 2 Hsc70 molecules, and binding was dependent on activation of
the Hsc70 ATPase by Hsp40 (DNAJB1; 604572). Hip stabilized the ADP-bound
form of Hsc70, which had a high affinity for a test protein substrate.
Hohfeld et al. (1995) concluded that HIP contributes to interactions of
HSC70 with target proteins through its own chaperone activity.
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, which complexes with heat-shock proteins
HSC70 and HSP70, translation initiation factor EIF4G (600495), and
poly(A)-binding protein (PABP, or PABPC1; 604679). AU-rich mRNA decay is
associated with displacement of EIF4G from AUF1, ubiquitination of AUF1,
and degradation of AUF1 by proteasomes. 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
(Larola et al., 1999).
BIM (BCL2L11; 603827) is an apoptotic factor that regulates total blood
cell number. Matsui et al. (2007) uncovered a molecular mechanism for
cytokine-mediated posttranscriptional regulation of Bim mRNA by Hsc70 in
mouse pro-B cell lines. In the absence of Il3 (147740), Hsc70 formed a
complex with Hsp40 and Hip, and this complex, in association with Eif4g
and Pabp, formed a high-stability complex with Bim mRNA that protected
it from ribonucleases. Il3 destabilized Bim mRNA and promoted cell
survival by reducing binding of Hsc70 to Bim mRNA by promoting
interaction of Hsp70 with Bag4 (603884) and Chip (STUB1; 607207) via the
Ras (HRAS; 190020) signaling pathway.
CD14 (158120) and lipopolysaccharide (LPS)-binding protein (LBP; 151990)
are major receptors for LPS; however, binding analyses and TNF
production assays have suggested the presence of additional cell surface
receptors, designated LPS-associated proteins (LAPs), that are distinct
from CD14, LBP, and the Toll-like receptors (see TLR4; 603030). Using
affinity chromatography, peptide mass fingerprinting, and fluorescence
resonance energy transfer, Triantafilou et al. (2001) identified 4
diverse proteins, heat shock cognate protein (HSPA8), HSP90A, chemokine
receptor CXCR4 (162643), and growth/differentiation factor-5 (GDF5;
601146), on monocytes that form an activation cluster after LPS ligation
and are involved in LPS signal transduction. Antibody inhibition
analysis suggested that disruption of cluster formation abrogates TNF
release. Triantafilou et al. (2001) proposed that heat shock proteins,
which are highly conserved from bacteria to eukaryotic cells, are
remnants of an ancient system of antigen presentation and defense
against microbial pathogens.
Tobaben et al. (2001) showed that rat Csp (DNAJC5; 611203) interacted
with Sgt (SGTA; 603419) and Hsc70 in a complex located on the synaptic
vesicle surface. The complex functioned as an ATP-dependent chaperone
that reactivated a denatured substrate. Sgt overexpression in cultured
rat hippocampal neurons inhibited neurotransmitte r release, suggesting
that the Csp/Sgt/Hsc70 complex is important for maintenance of a normal
synapse.
Hundley et al. (2005) reported that ribosome-associated molecular
chaperones have been maintained throughout eukaryotic evolution, as
illustrated by MPP11 (605502), the human ortholog of the yeast
ribosome-associated J protein Zuo. When expressed in yeast, MPP11
partially substituted for Zuo by partnering with the multipurpose Hsp70
Ssa, the homolog of mammalian Hsc70. Hundley et al. (2005) proposed that
in metazoans, ribosome-associated MPP11 recruits the multifunctional
soluble Hsc70 to nascent polypeptide chains as they exit the ribosome.
Cystic fibrosis (219700) arises from misfolding and premature
degradation of CFTR (602421) containing a deletion of phe508 (delF508;
602421.0001). Younger et al. (2006) identified an endoplasmic reticulum
(ER) membrane-associated ubiquitin ligase complex containing the E3 RMA1
(RNF5; 602677), the E2 UBC6E (UBE2J1), and derlin-1 (DERL1; 608813) that
cooperated with the cytosolic HSC70/CHIP E3 complex to triage CFTR and
delFl508. Derlin-1 retained CFTR in the ER membrane and interacted with
RMA1 and UBC6E to promote proteasomal degradation of CFTR. RMA1 could
recognize folding defects in delF508 coincident with translation,
whereas CHIP appeared to act posttranslationally. A folding defect in
delF508 detected by RMA1 involved the inability of the second
membrane-spanning domain of CFTR to productively interact with
N-terminal domains. Younger et al. (2006) concluded that the RMA1 and
CHIP E3 ubiquitin ligases act sequentially in ER membrane and cytosol to
monitor the folding status of CFTR and delF508.
Using mass spectrometry and adult mouse brain proteins immobilized on
nitrocellulose, Leshchyns'ka et al. (2006) found that the intracellular
domain of the cell adhesion molecule Chl1 (607416) bound Hsc70. Mutation
analysis revealed that an HPD motif conserved in mouse and human CHL1
was required for the interaction. ADP potentiated interaction between
Chl1 and Hsc70. Chl1 accumulated in the presynaptic plasma membrane and
recruited Hsc70 in an ADP-dependent manner. In response to synapse
activation, Chl1 was targeted to synaptic vesicles by endocytosis. Chl1
deficiency in Chl1 -/- neurons or disruption of the Chl1-Hsc70
interaction by the isolated HPD peptide caused reduced levels of Hsc70
on synaptic vesicles, reduced clathrin release from clathrin-coated
synaptic vesicles, and reduced marker dye uptake and release in synaptic
boutons.
In a neuronal cell line, Yang et al. (2009) found that
chaperone-mediated autophagy regulated the activity of myocyte enhancer
factor 2D (MEF2D; 600663), a transcription factor required for neuronal
survival. MEF2D was observed to continuously shuttle to the cytoplasm,
interact with the chaperone Hsc70, and undergo degradation. Inhibition
of chaperone-mediated autophagy caused accumulation of inactive MEF2D in
the cytoplasm. MEF2D levels were increased in the brains of
alpha-synuclein transgenic mice and patients with Parkinson disease.
Wildtype alpha-synuclein and a Parkinson disease-associated mutant
(A53T, 163890.0001) disrupted the MEF2D-Hsc70 binding and led to
neuronal death. Thus, Yang et al. (2009) concluded that
chaperone-mediated autophagy modulates the neuronal survival machinery,
and dysregulation of this pathway is associated with Parkinson disease.
Okiyoneda et al. (2010) identified the components of the peripheral
protein quality control network that removes unfolded CFTR containing
the F508del mutation (602421.0001) from the plasma membrane. Based on
their results and proteostatic mechanisms at different subcellular
locations, Okiyoneda et al. (2010) proposed a model in which the
recognition of unfolded cytoplasmic regions of CFTR is mediated by HSC70
in concert with DNAJA1 (602837) and possibly by the HSP90 machinery
(140571). Prolonged interaction with the chaperone-cochaperone complex
recruits CHIP-UBCH5C and leads to ubiquitination of conformationally
damaged CFTR. This ubiquitination is probably influenced by other E3
ligases and deubiquitinating enzyme activities, culminating in
accelerated endocytosis and lysosomal delivery mediated by Ub-binding
clathrin adaptors and the endosomal sorting complex required for
transport (ESCRT) machinery, respectively. In an accompanying
perspective, Hutt and Balch (2010) commented that the yin-yang' balance
maintained by the proteostasis network is critical for normal cellular,
tissue, and organismal physiology.
Scott et al. (2012) found that the 3-prime UTR of rat and human HSC70
contains recognition sequences predicted to bind mature microRNAs
(miRNAs) arising from both the 5-prime and 3-prime ends of the MIR3120
(614722) precursor stem-loop sequence. Overexpression of rat Mir3120 or
a vector containing repeats of the MIR3120 recognition sequence reduced
expression of rat Hsc70 and a human HSC70 reporter gene in rat neuronal
cells. Mir3120 also reduced expression of the HSC70 cochaperone auxilin
(DNAJC6; 608375), and it reduced surface content of clathrin-coated
particles in hippocampal and cortical neurons.
MAPPING
By Southern blot analysis, Tavaria et al. (1995) demonstrated that the
HSP73 gene is located on human chromosome 11. Fluorescence in situ
hybridization further localized HSP73 to 11q23.3-q25.
*FIELD* RF
1. Chappell, T. G.; Welch, W. J.; Schlossman, D. M.; Palter, K. B.;
Schlesinger, M. J.; Rothman, J. E.: Uncoating ATPase is a member
of the 70 kilodalton family of stress proteins. Cell 45: 3-13, 1986.
2. Dworniczak, B.; Mirault, M.-E.: Structure and expression of a
human gene coding for a 71 kd heat shock 'cognate' protein. Nucleic
Acids Res. 15: 5181-5197, 1987.
3. Hohfeld, J.; Minami, Y.; Hartl, F.-U.: Hip, a novel cochaperone
involved in the eukaryotic Hsc70/Hsp40 reaction cycle. Cell 83:
589-598, 1995.
4. Hundley, H. A.; Walter, W.; Bairstow, S.; Craig, E. A.: Human
Mpp11 J protein: ribosome-tethered molecular chaperones are ubiquitous. Science 308:
1032-1034, 2005.
5. Hutt, D.; Balch, W. E.: The proteome in balance. Science 329:
766-767, 2010.
6. Larola, G.; Cuesta, R.; Brewer, G.; Schneider, R. J.: Control
of mRNA decay by heat shock-ubiquitin-proteasome pathway. Science 284:
499-502, 1999.
7. Leshchyns'ka, I.; Sytnyk, V.; Richter, M.; Andreyeva, A.; Puchkov,
D.; Schachner, M.: The adhesion molecular CHL1 regulates uncoating
of clathrin-coated synaptic vesicles. Neuron 52: 1011-1025, 2006.
8. Matsui, H.; Asou, H.; Inaba, T.: Cytokines direct the regulation
of Bim mRNA stability by heat-shock cognate protein 70. Molec. Cell 25:
99-112, 2007.
9. Okiyoneda, T.; Barriere, H.; Bagdany, M.; Rabeh, W. M.; Du, K.;
Hohfeld, J.; Young, J. C.; Lukacs, G. L.: Peripheral protein quality
control removes unfolded CFTR from the plasma membrane. Science 329:
805-810, 2010.
10. Scott, H.; Howarth, J.; Lee, Y. B.; Wong, L.-F.; Bantounas, I.;
Phylactou, L.; Verkade, P.; Uney, J. B.: MiR-3120 is a mirror microRNA
that targets heat shock cognate protein 70 and auxilin messenger RNAs
and regulates clathrin vesicle uncoating. J. Biol. Chem. 287: 14726-14733,
2012.
11. Tavaria, M.; Gabriele, T.; Anderson, R. L.; Mirault, M.-E.; Baker,
E.; Sutherland, G.; Kola, I.: Localization of the gene encoding the
human heat shock cognate protein, HSP73, to chromosome 11. Genomics 29:
266-268, 1995.
12. Tobaben, S.; Thakur, P.; Fernandez-Chacon, R.; Sudhof, T. C.;
Rettig, J.; Stahl, B.: A trimeric protein complex functions as a
synaptic chaperone machine. Neuron 31: 987-999, 2001.
13. Triantafilou, K.; Triantafilou, M.; Dedrick, R. L.: A CD14-independent
LPS receptor cluster. Nature Immun. 2: 338-345, 2001. Note: Erratum:
Nature Immun. 2: 658 only, 2001.
14. Ungewickell, E.: The 70-kd mammalian heat shock proteins are
structurally and functionally related to the uncoating protein that
releases clathrin triskelia from coated vesicles. EMBO J. 4: 3385-3391,
1985.
15. Yang, Q.; She, H.; Gearing, M.; Colla, E.; Lee, M.; Shacka, J.
J.; Mao, Z.: Regulation of neuronal survival factor MEF2D by chaperone-mediated
autophagy. Science 323: 124-127, 2009.
16. Younger, J. M.; Chen, L.; Ren, H.-Y.; Rosser, M. F. N.; Turnbull,
E. L.; Fan, C.-Y.; Patterson, C.; Cyr, D. M.: Sequential quality-control
checkpoints triage misfolded cystic fibrosis transmembrane conductance
regulator. Cell 126: 571-582, 2006.
*FIELD* CN
Patricia A. Hartz - updated: 7/2/2012
Patricia A. Hartz - updated: 2/4/2011
Ada Hamosh - updated: 9/3/2010
Patricia A. Hartz - updated: 7/17/2009
Ada Hamosh - updated: 1/27/2009
Patricia A. Hartz - updated: 7/16/2007
Patricia A. Hartz - updated: 2/12/2007
Patricia A. Hartz - updated: 2/8/2007
Ada Hamosh - updated: 6/2/2005
Paul J. Converse - updated: 6/28/2001
Ada Hamosh - updated: 4/16/1999
*FIELD* CD
Victor A. McKusick: 10/2/1995
*FIELD* ED
terry: 08/06/2012
mgross: 7/16/2012
terry: 7/2/2012
mgross: 2/10/2011
terry: 2/4/2011
alopez: 9/3/2010
mgross: 7/20/2009
terry: 7/17/2009
alopez: 2/6/2009
terry: 1/27/2009
alopez: 11/13/2008
mgross: 7/16/2007
mgross: 2/12/2007
mgross: 2/8/2007
joanna: 11/1/2005
alopez: 6/3/2005
terry: 6/2/2005
mgross: 6/28/2001
carol: 11/6/2000
mgross: 3/14/2000
alopez: 9/7/1999
alopez: 4/16/1999
terry: 7/24/1998
mark: 10/2/1995
*RECORD*
*FIELD* NO
600816
*FIELD* TI
*600816 HEAT-SHOCK 70-KD PROTEIN 8; HSPA8
;;HEAT-SHOCK COGNATE PROTEIN, 71-KD; HSC71;;
read moreHSP73;;
HSC70;;
HEAT-SHOCK 70-KD PROTEIN 10, FORMERLY; HSPA10, FORMERLY;;
LIPOPOLYSACCHARIDE-ASSOCIATED PROTEIN 1; LAP1;;
LPS-ASSOCIATED PROTEIN 1
*FIELD* TX
CLONING
The family of approximately 70-kD heat-shock proteins, HSP70 (see
140550), contains both heat-inducible and constitutively expressed
members, the latter of which are sometimes called heat-shock cognate
proteins (HSCs). By screening a human genomic library with Drosophila
hsp70 and hsc70 cDNAs, Dworniczak and Mirault (1987) isolated the HSPA8
gene, which they called HSC70. Using HSPA8 genomic sequence to screen a
human cDNA library derived from a hepatic metastasis that originated
from a pancreatic gastrinoma, the authors cloned HSPA8 cDNAs. The HSPA8
gene contains 9 exons and spans 5 kb. The deduced HSPA8 protein has 646
amino acids and a predicted molecular mass of 70,899 Da. In vitro
translation of HSPA8 RNA produced a polypeptide that migrated as a 71-kD
protein in SDS-polyacrylamide gels. HSPA8 RNA and protein were
moderately abundant in unstressed HeLa cells and were only minimally
induced by heat. Dworniczak and Mirault (1987) noted that HSPA8 is
likely the constitutively expressed 71-kD heat-shock protein that is
identical to uncoating ATPase (Ungewickell, 1985; Chappell et al.,
1986), an enzyme that releases clathrin from coated vesicles. They
identified 2 distinct HSPA8-related processed pseudogenes.
GENE FUNCTION
Tavaria et al. (1995) stated that HSPA8 (also known as HSP73) plays an
important role in cells by transiently associating with nascent
polypeptides to facilitate correct folding. The protein folding process
involves other constitutively expressed heat-shock proteins, such as
HSP60 (HSPD1; 118190), HSP90 (HSPCA; 140571), and GRP78 (138120), which
have collectively been termed chaperones. Chaperones are also involved
in maintaining proteins in a semifolded state that enables translocation
through the mitochondrial and endoplasmic reticulum membranes. HSP73
also functions as an ATPase in the disassembly of clathrin-coated
vesicles during transport of membrane components through the cell.
Using a yeast 2-hybrid assay, Hohfeld et al. (1995) showed that rat Hip
(ST13; 606796) bound Hsc70. One Hip oligomer bound the ATPase domains of
at least 2 Hsc70 molecules, and binding was dependent on activation of
the Hsc70 ATPase by Hsp40 (DNAJB1; 604572). Hip stabilized the ADP-bound
form of Hsc70, which had a high affinity for a test protein substrate.
Hohfeld et al. (1995) concluded that HIP contributes to interactions of
HSC70 with target proteins through its own chaperone activity.
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, which complexes with heat-shock proteins
HSC70 and HSP70, translation initiation factor EIF4G (600495), and
poly(A)-binding protein (PABP, or PABPC1; 604679). AU-rich mRNA decay is
associated with displacement of EIF4G from AUF1, ubiquitination of AUF1,
and degradation of AUF1 by proteasomes. 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
(Larola et al., 1999).
BIM (BCL2L11; 603827) is an apoptotic factor that regulates total blood
cell number. Matsui et al. (2007) uncovered a molecular mechanism for
cytokine-mediated posttranscriptional regulation of Bim mRNA by Hsc70 in
mouse pro-B cell lines. In the absence of Il3 (147740), Hsc70 formed a
complex with Hsp40 and Hip, and this complex, in association with Eif4g
and Pabp, formed a high-stability complex with Bim mRNA that protected
it from ribonucleases. Il3 destabilized Bim mRNA and promoted cell
survival by reducing binding of Hsc70 to Bim mRNA by promoting
interaction of Hsp70 with Bag4 (603884) and Chip (STUB1; 607207) via the
Ras (HRAS; 190020) signaling pathway.
CD14 (158120) and lipopolysaccharide (LPS)-binding protein (LBP; 151990)
are major receptors for LPS; however, binding analyses and TNF
production assays have suggested the presence of additional cell surface
receptors, designated LPS-associated proteins (LAPs), that are distinct
from CD14, LBP, and the Toll-like receptors (see TLR4; 603030). Using
affinity chromatography, peptide mass fingerprinting, and fluorescence
resonance energy transfer, Triantafilou et al. (2001) identified 4
diverse proteins, heat shock cognate protein (HSPA8), HSP90A, chemokine
receptor CXCR4 (162643), and growth/differentiation factor-5 (GDF5;
601146), on monocytes that form an activation cluster after LPS ligation
and are involved in LPS signal transduction. Antibody inhibition
analysis suggested that disruption of cluster formation abrogates TNF
release. Triantafilou et al. (2001) proposed that heat shock proteins,
which are highly conserved from bacteria to eukaryotic cells, are
remnants of an ancient system of antigen presentation and defense
against microbial pathogens.
Tobaben et al. (2001) showed that rat Csp (DNAJC5; 611203) interacted
with Sgt (SGTA; 603419) and Hsc70 in a complex located on the synaptic
vesicle surface. The complex functioned as an ATP-dependent chaperone
that reactivated a denatured substrate. Sgt overexpression in cultured
rat hippocampal neurons inhibited neurotransmitte r release, suggesting
that the Csp/Sgt/Hsc70 complex is important for maintenance of a normal
synapse.
Hundley et al. (2005) reported that ribosome-associated molecular
chaperones have been maintained throughout eukaryotic evolution, as
illustrated by MPP11 (605502), the human ortholog of the yeast
ribosome-associated J protein Zuo. When expressed in yeast, MPP11
partially substituted for Zuo by partnering with the multipurpose Hsp70
Ssa, the homolog of mammalian Hsc70. Hundley et al. (2005) proposed that
in metazoans, ribosome-associated MPP11 recruits the multifunctional
soluble Hsc70 to nascent polypeptide chains as they exit the ribosome.
Cystic fibrosis (219700) arises from misfolding and premature
degradation of CFTR (602421) containing a deletion of phe508 (delF508;
602421.0001). Younger et al. (2006) identified an endoplasmic reticulum
(ER) membrane-associated ubiquitin ligase complex containing the E3 RMA1
(RNF5; 602677), the E2 UBC6E (UBE2J1), and derlin-1 (DERL1; 608813) that
cooperated with the cytosolic HSC70/CHIP E3 complex to triage CFTR and
delFl508. Derlin-1 retained CFTR in the ER membrane and interacted with
RMA1 and UBC6E to promote proteasomal degradation of CFTR. RMA1 could
recognize folding defects in delF508 coincident with translation,
whereas CHIP appeared to act posttranslationally. A folding defect in
delF508 detected by RMA1 involved the inability of the second
membrane-spanning domain of CFTR to productively interact with
N-terminal domains. Younger et al. (2006) concluded that the RMA1 and
CHIP E3 ubiquitin ligases act sequentially in ER membrane and cytosol to
monitor the folding status of CFTR and delF508.
Using mass spectrometry and adult mouse brain proteins immobilized on
nitrocellulose, Leshchyns'ka et al. (2006) found that the intracellular
domain of the cell adhesion molecule Chl1 (607416) bound Hsc70. Mutation
analysis revealed that an HPD motif conserved in mouse and human CHL1
was required for the interaction. ADP potentiated interaction between
Chl1 and Hsc70. Chl1 accumulated in the presynaptic plasma membrane and
recruited Hsc70 in an ADP-dependent manner. In response to synapse
activation, Chl1 was targeted to synaptic vesicles by endocytosis. Chl1
deficiency in Chl1 -/- neurons or disruption of the Chl1-Hsc70
interaction by the isolated HPD peptide caused reduced levels of Hsc70
on synaptic vesicles, reduced clathrin release from clathrin-coated
synaptic vesicles, and reduced marker dye uptake and release in synaptic
boutons.
In a neuronal cell line, Yang et al. (2009) found that
chaperone-mediated autophagy regulated the activity of myocyte enhancer
factor 2D (MEF2D; 600663), a transcription factor required for neuronal
survival. MEF2D was observed to continuously shuttle to the cytoplasm,
interact with the chaperone Hsc70, and undergo degradation. Inhibition
of chaperone-mediated autophagy caused accumulation of inactive MEF2D in
the cytoplasm. MEF2D levels were increased in the brains of
alpha-synuclein transgenic mice and patients with Parkinson disease.
Wildtype alpha-synuclein and a Parkinson disease-associated mutant
(A53T, 163890.0001) disrupted the MEF2D-Hsc70 binding and led to
neuronal death. Thus, Yang et al. (2009) concluded that
chaperone-mediated autophagy modulates the neuronal survival machinery,
and dysregulation of this pathway is associated with Parkinson disease.
Okiyoneda et al. (2010) identified the components of the peripheral
protein quality control network that removes unfolded CFTR containing
the F508del mutation (602421.0001) from the plasma membrane. Based on
their results and proteostatic mechanisms at different subcellular
locations, Okiyoneda et al. (2010) proposed a model in which the
recognition of unfolded cytoplasmic regions of CFTR is mediated by HSC70
in concert with DNAJA1 (602837) and possibly by the HSP90 machinery
(140571). Prolonged interaction with the chaperone-cochaperone complex
recruits CHIP-UBCH5C and leads to ubiquitination of conformationally
damaged CFTR. This ubiquitination is probably influenced by other E3
ligases and deubiquitinating enzyme activities, culminating in
accelerated endocytosis and lysosomal delivery mediated by Ub-binding
clathrin adaptors and the endosomal sorting complex required for
transport (ESCRT) machinery, respectively. In an accompanying
perspective, Hutt and Balch (2010) commented that the yin-yang' balance
maintained by the proteostasis network is critical for normal cellular,
tissue, and organismal physiology.
Scott et al. (2012) found that the 3-prime UTR of rat and human HSC70
contains recognition sequences predicted to bind mature microRNAs
(miRNAs) arising from both the 5-prime and 3-prime ends of the MIR3120
(614722) precursor stem-loop sequence. Overexpression of rat Mir3120 or
a vector containing repeats of the MIR3120 recognition sequence reduced
expression of rat Hsc70 and a human HSC70 reporter gene in rat neuronal
cells. Mir3120 also reduced expression of the HSC70 cochaperone auxilin
(DNAJC6; 608375), and it reduced surface content of clathrin-coated
particles in hippocampal and cortical neurons.
MAPPING
By Southern blot analysis, Tavaria et al. (1995) demonstrated that the
HSP73 gene is located on human chromosome 11. Fluorescence in situ
hybridization further localized HSP73 to 11q23.3-q25.
*FIELD* RF
1. Chappell, T. G.; Welch, W. J.; Schlossman, D. M.; Palter, K. B.;
Schlesinger, M. J.; Rothman, J. E.: Uncoating ATPase is a member
of the 70 kilodalton family of stress proteins. Cell 45: 3-13, 1986.
2. Dworniczak, B.; Mirault, M.-E.: Structure and expression of a
human gene coding for a 71 kd heat shock 'cognate' protein. Nucleic
Acids Res. 15: 5181-5197, 1987.
3. Hohfeld, J.; Minami, Y.; Hartl, F.-U.: Hip, a novel cochaperone
involved in the eukaryotic Hsc70/Hsp40 reaction cycle. Cell 83:
589-598, 1995.
4. Hundley, H. A.; Walter, W.; Bairstow, S.; Craig, E. A.: Human
Mpp11 J protein: ribosome-tethered molecular chaperones are ubiquitous. Science 308:
1032-1034, 2005.
5. Hutt, D.; Balch, W. E.: The proteome in balance. Science 329:
766-767, 2010.
6. Larola, G.; Cuesta, R.; Brewer, G.; Schneider, R. J.: Control
of mRNA decay by heat shock-ubiquitin-proteasome pathway. Science 284:
499-502, 1999.
7. Leshchyns'ka, I.; Sytnyk, V.; Richter, M.; Andreyeva, A.; Puchkov,
D.; Schachner, M.: The adhesion molecular CHL1 regulates uncoating
of clathrin-coated synaptic vesicles. Neuron 52: 1011-1025, 2006.
8. Matsui, H.; Asou, H.; Inaba, T.: Cytokines direct the regulation
of Bim mRNA stability by heat-shock cognate protein 70. Molec. Cell 25:
99-112, 2007.
9. Okiyoneda, T.; Barriere, H.; Bagdany, M.; Rabeh, W. M.; Du, K.;
Hohfeld, J.; Young, J. C.; Lukacs, G. L.: Peripheral protein quality
control removes unfolded CFTR from the plasma membrane. Science 329:
805-810, 2010.
10. Scott, H.; Howarth, J.; Lee, Y. B.; Wong, L.-F.; Bantounas, I.;
Phylactou, L.; Verkade, P.; Uney, J. B.: MiR-3120 is a mirror microRNA
that targets heat shock cognate protein 70 and auxilin messenger RNAs
and regulates clathrin vesicle uncoating. J. Biol. Chem. 287: 14726-14733,
2012.
11. Tavaria, M.; Gabriele, T.; Anderson, R. L.; Mirault, M.-E.; Baker,
E.; Sutherland, G.; Kola, I.: Localization of the gene encoding the
human heat shock cognate protein, HSP73, to chromosome 11. Genomics 29:
266-268, 1995.
12. Tobaben, S.; Thakur, P.; Fernandez-Chacon, R.; Sudhof, T. C.;
Rettig, J.; Stahl, B.: A trimeric protein complex functions as a
synaptic chaperone machine. Neuron 31: 987-999, 2001.
13. Triantafilou, K.; Triantafilou, M.; Dedrick, R. L.: A CD14-independent
LPS receptor cluster. Nature Immun. 2: 338-345, 2001. Note: Erratum:
Nature Immun. 2: 658 only, 2001.
14. Ungewickell, E.: The 70-kd mammalian heat shock proteins are
structurally and functionally related to the uncoating protein that
releases clathrin triskelia from coated vesicles. EMBO J. 4: 3385-3391,
1985.
15. Yang, Q.; She, H.; Gearing, M.; Colla, E.; Lee, M.; Shacka, J.
J.; Mao, Z.: Regulation of neuronal survival factor MEF2D by chaperone-mediated
autophagy. Science 323: 124-127, 2009.
16. Younger, J. M.; Chen, L.; Ren, H.-Y.; Rosser, M. F. N.; Turnbull,
E. L.; Fan, C.-Y.; Patterson, C.; Cyr, D. M.: Sequential quality-control
checkpoints triage misfolded cystic fibrosis transmembrane conductance
regulator. Cell 126: 571-582, 2006.
*FIELD* CN
Patricia A. Hartz - updated: 7/2/2012
Patricia A. Hartz - updated: 2/4/2011
Ada Hamosh - updated: 9/3/2010
Patricia A. Hartz - updated: 7/17/2009
Ada Hamosh - updated: 1/27/2009
Patricia A. Hartz - updated: 7/16/2007
Patricia A. Hartz - updated: 2/12/2007
Patricia A. Hartz - updated: 2/8/2007
Ada Hamosh - updated: 6/2/2005
Paul J. Converse - updated: 6/28/2001
Ada Hamosh - updated: 4/16/1999
*FIELD* CD
Victor A. McKusick: 10/2/1995
*FIELD* ED
terry: 08/06/2012
mgross: 7/16/2012
terry: 7/2/2012
mgross: 2/10/2011
terry: 2/4/2011
alopez: 9/3/2010
mgross: 7/20/2009
terry: 7/17/2009
alopez: 2/6/2009
terry: 1/27/2009
alopez: 11/13/2008
mgross: 7/16/2007
mgross: 2/12/2007
mgross: 2/8/2007
joanna: 11/1/2005
alopez: 6/3/2005
terry: 6/2/2005
mgross: 6/28/2001
carol: 11/6/2000
mgross: 3/14/2000
alopez: 9/7/1999
alopez: 4/16/1999
terry: 7/24/1998
mark: 10/2/1995