HSP74_HUMAN
ID HSP74_HUMAN Reviewed; 840 AA.
AC P34932; O95756; Q2TAL4; Q9BUK9;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 4.
DT 03-AUG-2022, entry version 211.
DE RecName: Full=Heat shock 70 kDa protein 4;
DE AltName: Full=HSP70RY;
DE AltName: Full=Heat shock 70-related protein APG-2;
GN Name=HSPA4; Synonyms=APG2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Nonoguchi K., Fujita J.;
RT "Cloning and characterization of human apg-1 and apg-2, members of the
RT hsp110 family, cDNAs and chromosomal assignment of the genes.";
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, 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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-749 (ISOFORM 1).
RC TISSUE=Lymphocyte;
RX PubMed=8335910;
RA Fathallah D.M., Cherif D., Dellagi K., Arnaout M.A.;
RT "Molecular cloning of a novel human hsp70 from a B cell line and its
RT assignment to chromosome 5.";
RL J. Immunol. 151:810-813(1993).
RN [6]
RP PROTEIN SEQUENCE OF 20-33; 111-124; 170-185; 222-234; 333-346; 361-374 AND
RP 391-422, AND IDENTIFICATION BY MASS 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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-89 AND TYR-336, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA 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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-538, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-76 AND TYR-336, AND
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 [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-430 AND LYS-679, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA 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 [12]
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., Buerckstuemmer T.,
RA 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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-76 AND SER-546, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-76; SER-393; THR-538; SER-647
RP AND SER-756, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [16]
RP METHYLATION [LARGE SCALE ANALYSIS] AT LYS-773, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
CC -!- SUBUNIT: Interacts with TJP1/ZO-1. {ECO:0000250}.
CC -!- INTERACTION:
CC P34932; Q6RW13: AGTRAP; NbExp=3; IntAct=EBI-356933, EBI-741181;
CC P34932; Q92624: APPBP2; NbExp=6; IntAct=EBI-356933, EBI-743771;
CC P34932; P00533: EGFR; NbExp=3; IntAct=EBI-356933, EBI-297353;
CC P34932; P11142: HSPA8; NbExp=6; IntAct=EBI-356933, EBI-351896;
CC P34932; P78424: POU6F2; NbExp=3; IntAct=EBI-356933, EBI-12029004;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P34932-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P34932-2; Sequence=VSP_056885;
CC -!- SIMILARITY: Belongs to the heat shock protein 70 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA02807.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AB023420; BAA75062.1; -; mRNA.
DR EMBL; BT007375; AAP36039.1; -; mRNA.
DR EMBL; AC113410; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002526; AAH02526.1; -; mRNA.
DR EMBL; BC110861; AAI10862.1; -; mRNA.
DR EMBL; BC126122; AAI26123.1; -; mRNA.
DR EMBL; BC126124; AAI26125.1; -; mRNA.
DR EMBL; L12723; AAA02807.1; ALT_FRAME; mRNA.
DR CCDS; CCDS4166.1; -. [P34932-1]
DR PIR; I56208; I56208.
DR RefSeq; NP_002145.3; NM_002154.3. [P34932-1]
DR AlphaFoldDB; P34932; -.
DR SMR; P34932; -.
DR BioGRID; 109540; 562.
DR CORUM; P34932; -.
DR DIP; DIP-460N; -.
DR IntAct; P34932; 97.
DR MINT; P34932; -.
DR STRING; 9606.ENSP00000302961; -.
DR DrugBank; DB12695; Phenethyl Isothiocyanate.
DR GlyGen; P34932; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P34932; -.
DR MetOSite; P34932; -.
DR PhosphoSitePlus; P34932; -.
DR SwissPalm; P34932; -.
DR BioMuta; HSPA4; -.
DR DMDM; 206729934; -.
DR DOSAC-COBS-2DPAGE; P34932; -.
DR REPRODUCTION-2DPAGE; IPI00002966; -.
DR REPRODUCTION-2DPAGE; P34932; -.
DR EPD; P34932; -.
DR jPOST; P34932; -.
DR MassIVE; P34932; -.
DR MaxQB; P34932; -.
DR PaxDb; P34932; -.
DR PeptideAtlas; P34932; -.
DR PRIDE; P34932; -.
DR ProteomicsDB; 54957; -. [P34932-1]
DR ProteomicsDB; 79105; -.
DR Antibodypedia; 2204; 514 antibodies from 35 providers.
DR DNASU; 3308; -.
DR Ensembl; ENST00000304858.7; ENSP00000302961.2; ENSG00000170606.16. [P34932-1]
DR GeneID; 3308; -.
DR KEGG; hsa:3308; -.
DR MANE-Select; ENST00000304858.7; ENSP00000302961.2; NM_002154.4; NP_002145.3.
DR UCSC; uc003kyj.4; human. [P34932-1]
DR CTD; 3308; -.
DR DisGeNET; 3308; -.
DR GeneCards; HSPA4; -.
DR HGNC; HGNC:5237; HSPA4.
DR HPA; ENSG00000170606; Low tissue specificity.
DR MIM; 601113; gene.
DR neXtProt; NX_P34932; -.
DR OpenTargets; ENSG00000170606; -.
DR PharmGKB; PA29503; -.
DR VEuPathDB; HostDB:ENSG00000170606; -.
DR eggNOG; KOG0103; Eukaryota.
DR GeneTree; ENSGT00940000156067; -.
DR HOGENOM; CLU_005965_11_2_1; -.
DR InParanoid; P34932; -.
DR OMA; AHFLVQK; -.
DR OrthoDB; 406172at2759; -.
DR PhylomeDB; P34932; -.
DR TreeFam; TF105043; -.
DR PathwayCommons; P34932; -.
DR Reactome; R-HSA-3371453; Regulation of HSF1-mediated heat shock response.
DR SignaLink; P34932; -.
DR BioGRID-ORCS; 3308; 31 hits in 1084 CRISPR screens.
DR ChiTaRS; HSPA4; human.
DR GeneWiki; HSPA4; -.
DR GenomeRNAi; 3308; -.
DR Pharos; P34932; Tbio.
DR PRO; PR:P34932; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P34932; protein.
DR Bgee; ENSG00000170606; Expressed in cervix squamous epithelium and 208 other tissues.
DR ExpressionAtlas; P34932; baseline and differential.
DR Genevisible; P34932; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IEA:GOC.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; NAS:UniProtKB.
DR GO; GO:0140662; F:ATP-dependent protein folding chaperone; IEA:InterPro.
DR GO; GO:0051131; P:chaperone-mediated protein complex assembly; IDA:BHF-UCL.
DR GO; GO:0006457; P:protein folding; IBA:GO_Central.
DR GO; GO:0045040; P:protein insertion into mitochondrial outer membrane; IDA:BHF-UCL.
DR GO; GO:0006986; P:response to unfolded protein; NAS:UniProtKB.
DR CDD; cd11737; HSPA4_NBD; 1.
DR Gene3D; 1.20.1270.10; -; 2.
DR Gene3D; 2.60.34.10; -; 1.
DR InterPro; IPR043129; ATPase_NBD.
DR InterPro; IPR018181; Heat_shock_70_CS.
DR InterPro; IPR029048; HSP70_C_sf.
DR InterPro; IPR029047; HSP70_peptide-bd_sf.
DR InterPro; IPR013126; Hsp_70_fam.
DR InterPro; IPR042052; HSPA4_NBD.
DR Pfam; PF00012; HSP70; 1.
DR SUPFAM; SSF100920; SSF100920; 1.
DR SUPFAM; SSF100934; SSF100934; 2.
DR SUPFAM; SSF53067; SSF53067; 2.
DR PROSITE; PS00329; HSP70_2; 1.
DR PROSITE; PS01036; HSP70_3; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; ATP-binding; Cytoplasm;
KW Direct protein sequencing; Methylation; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Stress response.
FT CHAIN 1..840
FT /note="Heat shock 70 kDa protein 4"
FT /id="PRO_0000078262"
FT REGION 500..575
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 779..840
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 500..534
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 543..567
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 53
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q61316"
FT MOD_RES 76
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 89
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455"
FT MOD_RES 336
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 393
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 415
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61316"
FT MOD_RES 430
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 538
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 546
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 647
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 660
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q61316"
FT MOD_RES 679
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 756
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 773
FT /note="N6-methyllysine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT VAR_SEQ 109..800
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.2"
FT /id="VSP_056885"
FT CONFLICT 94
FT /note="L -> W (in Ref. 5; AAA02807)"
FT /evidence="ECO:0000305"
FT CONFLICT 190
FT /note="A -> R (in Ref. 5; AAA02807)"
FT /evidence="ECO:0000305"
FT CONFLICT 583..586
FT /note="NQLL -> ESAI (in Ref. 5; AAA02807)"
FT /evidence="ECO:0000305"
FT CONFLICT 622
FT /note="E -> R (in Ref. 1; BAA75062)"
FT /evidence="ECO:0000305"
FT CONFLICT 644
FT /note="D -> G (in Ref. 1; BAA75062)"
FT /evidence="ECO:0000305"
FT CONFLICT 746..749
FT /note="NNKL -> EVTP (in Ref. 5; AAA02807)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 840 AA; 94331 MW; 8B690A52A0729C2A CRC64;
MSVVGIDLGF QSCYVAVARA GGIETIANEY SDRCTPACIS FGPKNRSIGA AAKSQVISNA
KNTVQGFKRF HGRAFSDPFV EAEKSNLAYD IVQLPTGLTG IKVTYMEEER NFTTEQVTAM
LLSKLKETAE SVLKKPVVDC VVSVPCFYTD AERRSVMDAT QIAGLNCLRL MNETTAVALA
YGIYKQDLPA LEEKPRNVVF VDMGHSAYQV SVCAFNRGKL KVLATAFDTT LGGRKFDEVL
VNHFCEEFGK KYKLDIKSKI RALLRLSQEC EKLKKLMSAN ASDLPLSIEC FMNDVDVSGT
MNRGKFLEMC NDLLARVEPP LRSVLEQTKL KKEDIYAVEI VGGATRIPAV KEKISKFFGK
ELSTTLNADE AVTRGCALQC AILSPAFKVR EFSITDVVPY PISLRWNSPA EEGSSDCEVF
SKNHAAPFSK VLTFYRKEPF TLEAYYSSPQ DLPYPDPAIA QFSVQKVTPQ SDGSSSKVKV
KVRVNVHGIF SVSSASLVEV HKSEENEEPM ETDQNAKEEE KMQVDQEEPH VEEQQQQTPA
ENKAESEEME TSQAGSKDKK MDQPPQAKKA KVKTSTVDLP IENQLLWQID REMLNLYIEN
EGKMIMQDKL EKERNDAKNA VEEYVYEMRD KLSGEYEKFV SEDDRNSFTL KLEDTENWLY
EDGEDQPKQV YVDKLAELKN LGQPIKIRFQ ESEERPKLFE ELGKQIQQYM KIISSFKNKE
DQYDHLDAAD MTKVEKSTNE AMEWMNNKLN LQNKQSLTMD PVVKSKEIEA KIKELTSTCS
PIISKPKPKV EPPKEEQKNA EQNGPVDGQG DNPGPQAAEQ GTDTAVPSDS DKKLPEMDID
