HS74L_HUMAN
ID HS74L_HUMAN Reviewed; 839 AA.
AC O95757; A2ICT2; Q4W5M5; Q8IWA2;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2010, sequence version 3.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Heat shock 70 kDa protein 4L;
DE AltName: Full=Heat shock 70-related protein APG-1;
DE AltName: Full=Heat-shock protein family A member 4-like protein;
DE Short=HSPA4-like protein;
DE AltName: Full=Osmotic stress protein 94;
GN Name=HSPA4L; Synonyms=APG1, OSP94;
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], AND VARIANT SER-211.
RC TISSUE=Testis;
RX PubMed=10524232; DOI=10.1016/s0378-1119(99)00325-x;
RA Nonoguchi K., Itoh K., Xue J.H., Tokuchi H., Nishiyama H., Kaneko Y.,
RA Tatsumi K., Okuno H., Tomiwa K., Fujita J.;
RT "Cloning of human cDNAs for Apg-1 and Apg-2, members of the Hsp110 family,
RT and chromosomal assignment of their genes.";
RL Gene 237:21-28(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INDUCTION.
RC TISSUE=Heart;
RX PubMed=19169850; DOI=10.1007/s12033-009-9144-1;
RA Mala J.G., Takeuchi S.;
RT "Molecular cloning of OSP94: A significant biomarker protein of
RT hypertensive human heart and a member of HSP110 family.";
RL Mol. Biotechnol. 42:175-194(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-761, AND IDENTIFICATION BY
RP 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 [7]
RP IDENTIFICATION BY 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 [8]
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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-74; SER-508 AND SER-579, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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).
CC -!- FUNCTION: Possesses chaperone activity in vitro where it inhibits
CC aggregation of citrate synthase. {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Note=May translocate to the nucleus after heat shock. {ECO:0000250}.
CC -!- INDUCTION: By heat shock and osmotic imbalance.
CC {ECO:0000269|PubMed:19169850}.
CC -!- SIMILARITY: Belongs to the heat shock protein 70 family. {ECO:0000305}.
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DR EMBL; AB023421; BAA75063.1; -; mRNA.
DR EMBL; EF197155; ABM69040.1; -; mRNA.
DR EMBL; AC093591; AAY40975.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX05198.1; -; Genomic_DNA.
DR EMBL; BC040560; AAH40560.1; -; mRNA.
DR CCDS; CCDS3734.1; -.
DR RefSeq; NP_001304310.1; NM_001317381.1.
DR RefSeq; NP_001304311.1; NM_001317382.1.
DR RefSeq; NP_001304312.1; NM_001317383.1.
DR RefSeq; NP_055093.2; NM_014278.3.
DR AlphaFoldDB; O95757; -.
DR SMR; O95757; -.
DR BioGRID; 116500; 150.
DR IntAct; O95757; 52.
DR MINT; O95757; -.
DR STRING; 9606.ENSP00000296464; -.
DR GlyGen; O95757; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O95757; -.
DR MetOSite; O95757; -.
DR PhosphoSitePlus; O95757; -.
DR SwissPalm; O95757; -.
DR BioMuta; HSPA4L; -.
DR REPRODUCTION-2DPAGE; IPI00295485; -.
DR EPD; O95757; -.
DR jPOST; O95757; -.
DR MassIVE; O95757; -.
DR MaxQB; O95757; -.
DR PaxDb; O95757; -.
DR PeptideAtlas; O95757; -.
DR PRIDE; O95757; -.
DR ProteomicsDB; 51027; -.
DR Antibodypedia; 26922; 153 antibodies from 28 providers.
DR DNASU; 22824; -.
DR Ensembl; ENST00000296464.9; ENSP00000296464.3; ENSG00000164070.12.
DR Ensembl; ENST00000508776.5; ENSP00000422482.1; ENSG00000164070.12.
DR GeneID; 22824; -.
DR KEGG; hsa:22824; -.
DR MANE-Select; ENST00000296464.9; ENSP00000296464.3; NM_014278.4; NP_055093.2.
DR UCSC; uc003ifm.4; human.
DR CTD; 22824; -.
DR DisGeNET; 22824; -.
DR GeneCards; HSPA4L; -.
DR HGNC; HGNC:17041; HSPA4L.
DR HPA; ENSG00000164070; Tissue enhanced (brain, testis).
DR MIM; 619077; gene.
DR neXtProt; NX_O95757; -.
DR OpenTargets; ENSG00000164070; -.
DR PharmGKB; PA134905749; -.
DR VEuPathDB; HostDB:ENSG00000164070; -.
DR eggNOG; KOG0103; Eukaryota.
DR GeneTree; ENSGT00940000158736; -.
DR HOGENOM; CLU_005965_5_1_1; -.
DR InParanoid; O95757; -.
DR OMA; AYDRHFG; -.
DR OrthoDB; 406172at2759; -.
DR PhylomeDB; O95757; -.
DR TreeFam; TF105043; -.
DR PathwayCommons; O95757; -.
DR Reactome; R-HSA-3371453; Regulation of HSF1-mediated heat shock response.
DR SignaLink; O95757; -.
DR BioGRID-ORCS; 22824; 7 hits in 1081 CRISPR screens.
DR ChiTaRS; HSPA4L; human.
DR GeneWiki; HSPA4L; -.
DR GenomeRNAi; 22824; -.
DR Pharos; O95757; Tbio.
DR PRO; PR:O95757; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; O95757; protein.
DR Bgee; ENSG00000164070; Expressed in sperm and 166 other tissues.
DR ExpressionAtlas; O95757; baseline and differential.
DR Genevisible; O95757; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0140662; F:ATP-dependent protein folding chaperone; IEA:InterPro.
DR GO; GO:0006457; P:protein folding; ISS:UniProtKB.
DR GO; GO:0006986; P:response to unfolded protein; ISS:UniProtKB.
DR CDD; cd11738; HSPA4L_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; IPR042708; HSPA4L_NBD.
DR Pfam; PF00012; HSP70; 2.
DR SUPFAM; SSF100920; SSF100920; 1.
DR SUPFAM; SSF100934; SSF100934; 2.
DR SUPFAM; SSF53067; SSF53067; 2.
DR PROSITE; PS01036; HSP70_3; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Chaperone; Cytoplasm; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Stress response.
FT CHAIN 1..839
FT /note="Heat shock 70 kDa protein 4L"
FT /id="PRO_0000078280"
FT REGION 503..567
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 786..839
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 791..805
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 807..821
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 822..839
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 74
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 508
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 545
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P48722"
FT MOD_RES 579
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 761
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17525332"
FT VARIANT 211
FT /note="L -> S (in dbSNP:rs1380154)"
FT /evidence="ECO:0000269|PubMed:10524232"
FT /id="VAR_025405"
FT VARIANT 216
FT /note="N -> T (in dbSNP:rs12507229)"
FT /id="VAR_031214"
FT VARIANT 601
FT /note="I -> T (in dbSNP:rs35518193)"
FT /id="VAR_055966"
FT CONFLICT 806
FT /note="H -> R (in Ref. 1; BAA75063)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 839 AA; 94512 MW; 549933AECFF4369A CRC64;
MSVVGIDLGF LNCYIAVARS GGIETIANEY SDRCTPACIS LGSRTRAIGN AAKSQIVTNV
RNTIHGFKKL HGRSFDDPIV QTERIRLPYE LQKMPNGSAG VKVRYLEEER PFAIEQVTGM
LLAKLKETSE NALKKPVADC VISIPSFFTD AERRSVMAAA QVAGLNCLRL MNETTAVALA
YGIYKQDLPP LDEKPRNVVF IDMGHSAYQV LVCAFNKGKL KVLATTFDPY LGGRNFDEAL
VDYFCDEFKT KYKINVKENS RALLRLYQEC EKLKKLMSAN ASDLPLNIEC FMNDLDVSSK
MNRAQFEQLC ASLLARVEPP LKAVMEQANL QREDISSIEI VGGATRIPAV KEQITKFFLK
DISTTLNADE AVARGCALQC AILSPAFKVR EFSITDLVPY SITLRWKTSF EDGSGECEVF
CKNHPAPFSK VITFHKKEPF ELEAFYTNLH EVPYPDARIG SFTIQNVFPQ SDGDSSKVKV
KVRVNIHGIF SVASASVIEK QNLEGDHSDA PMETETSFKN ENKDNMDKMQ VDQEEGHQKC
HAEHTPEEEI DHTGAKTKSA VSDKQDRLNQ TLKKGKVKSI DLPIQSSLCR QLGQDLLNSY
IENEGKMIMQ DKLEKERNDA KNAVEEYVYD FRDRLGTVYE KFITPEDLSK LSAVLEDTEN
WLYEDGEDQP KQVYVDKLQE LKKYGQPIQM KYMEHEERPK ALNDLGKKIQ LVMKVIEAYR
NKDERYDHLD PTEMEKVEKC ISDAMSWLNS KMNAQNKLSL TQDPVVKVSE IVAKSKELDN
FCNPIIYKPK PKAEVPEDKP KANSEHNGPM DGQSGTETKS DSTKDSSQHT KSSGEMEVD
