ID   HSP74_HUMAN             Reviewed;         840 AA.
AC   P34932; O95756; Q2TAL4;
DT   01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT   23-SEP-2008, sequence version 4.
DT   25-JAN-2012, entry version 118.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
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 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.,
RA   Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
RA   Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
RA   Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
RA   Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
RA   Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
RA   Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
RA   Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
RA   Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
RA   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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain, 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   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-749.
RC   TISSUE=Lymphocyte;
RX   MEDLINE=93329076; 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   [5]
RP   PROTEIN SEQUENCE OF 20-33; 111-124; 170-185; 222-234; 333-346; 361-374
RP   AND 391-422, AND 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   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-89 AND TYR-336, AND MASS
RP   SPECTROMETRY.
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
RT   cells.";
RL   Nat. Biotechnol. 23:94-101(2005).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-552, 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   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-76 AND THR-538, AND MASS
RP   SPECTROMETRY.
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   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-415, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Embryonic kidney;
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   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-76 AND TYR-336, AND MASS
RP   SPECTROMETRY.
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 MASS
RP   SPECTROMETRY.
RX   PubMed=19608861; DOI=10.1126/science.1175371;
RA   Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.,
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.,
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).
CC   -!- SUBUNIT: Interacts with TJP1/ZO-1 (By similarity).
CC   -!- SUBCELLULAR LOCATION: Cytoplasm (Probable).
CC   -!- PTM: Phosphorylated upon DNA damage, probably by ATM or ATR.
CC   -!- SIMILARITY: Belongs to the heat shock protein 70 family.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA02807.1; Type=Frameshift; Positions=567, 586, 697, 715, 722;
CC   -----------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution-NoDerivs License
CC   -----------------------------------------------------------------------
DR   EMBL; AB023420; BAA75062.1; -; mRNA.
DR   EMBL; AC113410; -; NOT_ANNOTATED_CDS; Genomic_DNA.
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   IPI; IPI00002966; -.
DR   PIR; I56208; I56208.
DR   RefSeq; NP_002145.3; NM_002154.3.
DR   UniGene; Hs.90093; -.
DR   ProteinModelPortal; P34932; -.
DR   SMR; P34932; 1-689.
DR   DIP; DIP-460N; -.
DR   IntAct; P34932; 12.
DR   MINT; MINT-1159519; -.
DR   STRING; P34932; -.
DR   PhosphoSite; P34932; -.
DR   DMDM; 206729934; -.
DR   DOSAC-COBS-2DPAGE; P34932; -.
DR   REPRODUCTION-2DPAGE; IPI00002966; -.
DR   REPRODUCTION-2DPAGE; P34932; -.
DR   PRIDE; P34932; -.
DR   Ensembl; ENST00000304858; ENSP00000302961; ENSG00000170606.
DR   GeneID; 3308; -.
DR   KEGG; hsa:3308; -.
DR   CTD; 3308; -.
DR   GeneCards; GC05P132415; -.
DR   HGNC; HGNC:5237; HSPA4.
DR   HPA; CAB025529; -.
DR   HPA; HPA010023; -.
DR   MIM; 601113; gene.
DR   neXtProt; NX_P34932; -.
DR   PharmGKB; PA29503; -.
DR   HOGENOM; HBG315155; -.
DR   HOVERGEN; HBG047955; -.
DR   InParanoid; P34932; -.
DR   OMA; ICSPIIS; -.
DR   OrthoDB; EOG415GCS; -.
DR   PhylomeDB; P34932; -.
DR   NextBio; 13119; -.
DR   ArrayExpress; P34932; -.
DR   Bgee; P34932; -.
DR   CleanEx; HS_HSPA4; -.
DR   Genevestigator; P34932; -.
DR   GermOnline; ENSG00000170606; Homo sapiens.
DR   GO; GO:0005634; C:nucleus; IDA:HPA.
DR   GO; GO:0005524; F:ATP binding; NAS:UniProtKB.
DR   GO; GO:0034619; ?:?; IDA:BHF-UCL.
DR   GO; GO:0045040; P:protein import into mitochondrial outer membrane; IDA:BHF-UCL.
DR   GO; GO:0006986; P:response to unfolded protein; NAS:UniProtKB.
DR   InterPro; IPR018181; Heat_shock_70_CS.
DR   InterPro; IPR001023; Hsp70.
DR   InterPro; IPR013126; Hsp_70.
DR   KO; K09489; -.
DR   PANTHER; PTHR19375; Hsp70; 1.
DR   Pfam; PF00012; HSP70; 1.
DR   PRINTS; PR00301; HEATSHOCK70.
DR   PROSITE; PS00297; HSP70_1; FALSE_NEG.
DR   PROSITE; PS00329; HSP70_2; 1.
DR   PROSITE; PS01036; HSP70_3; 1.
PE   1: Evidence at protein level;
KW   Acetylation; ATP-binding; Complete proteome; Cytoplasm;
KW   Direct protein sequencing; Nucleotide-binding; Phosphoprotein;
KW   Reference proteome; Stress response.
FT   CHAIN         1    840       Heat shock 70 kDa protein 4.
FT                                /FTId=PRO_0000078262.
FT   MOD_RES      76     76       Phosphoserine.
FT   MOD_RES      89     89       Phosphotyrosine.
FT   MOD_RES     336    336       Phosphotyrosine.
FT   MOD_RES     415    415       Phosphoserine.
FT   MOD_RES     430    430       N6-acetyllysine.
FT   MOD_RES     538    538       Phosphothreonine.
FT   MOD_RES     552    552       Phosphoserine.
FT   MOD_RES     660    660       Phosphotyrosine (By similarity).
FT   MOD_RES     679    679       N6-acetyllysine.
FT   CONFLICT     94     94       L -> W (in Ref. 4; AAA02807).
FT   CONFLICT    190    190       A -> R (in Ref. 4; AAA02807).
FT   CONFLICT    583    586       NQLL -> ESAI (in Ref. 4; AAA02807).
FT   CONFLICT    622    622       E -> R (in Ref. 1; BAA75062).
FT   CONFLICT    644    644       D -> G (in Ref. 1; BAA75062).
FT   CONFLICT    746    749       NNKL -> EVTP (in Ref. 4; AAA02807).
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
//