IER5_HUMAN
ID IER5_HUMAN Reviewed; 327 AA.
AC Q5VY09; B2RBV3; Q8WY68; Q9NY49; Q9NZP9;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Immediate early response gene 5 protein;
GN Name=IER5; ORFNames=PP4583, SBBI48;
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 ARG-202.
RC TISSUE=Dendritic cell;
RA Zhang W., Wan T., Yuan Z., He L., Li N., Cao X.;
RT "Transcript profile of dendritic cells: insights into dendritic cell
RT biology and identification of novel genes.";
RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ARG-202.
RA Biederbick A., Lenz H.J., Elsaesser H.P.;
RT "Isolation and characterisation of a 34 kDa protein associated with the
RT lysosomal/autophagic compartment.";
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS HIS-92; GLY-194 AND
RP ARG-202.
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X.,
RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X.,
RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-202.
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-202.
RC TISSUE=Cervix;
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 [7]
RP FUNCTION, AND INDUCTION.
RX PubMed=19238419; DOI=10.1007/s00411-009-0213-4;
RA Ding K.K., Shang Z.F., Hao C., Xu Q.Z., Shen J.J., Yang C.J., Xie Y.H.,
RA Qiao C., Wang Y., Xu L.L., Zhou P.K.;
RT "Induced expression of the IER5 gene by gamma-ray irradiation and its
RT involvement in cell cycle checkpoint control and survival.";
RL Radiat. Environ. Biophys. 48:205-213(2009).
RN [8]
RP FUNCTION, CHROMATIN BINDING, AND TISSUE SPECIFICITY.
RX PubMed=22132193; DOI=10.1371/journal.pone.0028011;
RA Nakamura S., Nagata Y., Tan L., Takemura T., Shibata K., Fujie M.,
RA Fujisawa S., Tanaka Y., Toda M., Makita R., Tsunekawa K., Yamada M.,
RA Yamaoka M., Yamashita J., Ohnishi K., Yamashita M.;
RT "Transcriptional repression of Cdc25B by IER5 inhibits the proliferation of
RT leukemic progenitor cells through NF-YB and p300 in acute myeloid
RT leukemia.";
RL PLoS ONE 6:E28011-E28011(2011).
RN [9]
RP INDUCTION.
RX PubMed=25355627; DOI=10.1111/febs.13134;
RA Ishikawa Y., Sakurai H.;
RT "Heat-induced expression of the immediate-early gene IER5 and its
RT involvement in the proliferation of heat-shocked cells.";
RL FEBS J. 282:332-340(2015).
RN [10]
RP FUNCTION, INTERACTION WITH HSF1; PPP2R2A; PPP2R2B; PPP2R2C AND PPP2R2D,
RP ASSOCIATION WITH THE PP2A CATALYTIC SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=25816751; DOI=10.1016/j.febslet.2015.03.019;
RA Ishikawa Y., Kawabata S., Sakurai H.;
RT "HSF1 transcriptional activity is modulated by IER5 and PP2A/B55.";
RL FEBS Lett. 589:1150-1155(2015).
RN [11]
RP FUNCTION, SUBUNIT, INTERACTION WITH HSF1; PPP2R2B AND RPS6KB1, AND
RP ASSOCIATION WITH THE PP2A CATALYTIC SUBUNIT.
RX PubMed=26496226; DOI=10.1016/j.febslet.2015.10.013;
RA Kawabata S., Ishita Y., Ishikawa Y., Sakurai H.;
RT "Immediate-early response 5 (IER5) interacts with protein phosphatase 2A
RT and regulates the phosphorylation of ribosomal protein S6 kinase and heat
RT shock factor 1.";
RL FEBS Lett. 589:3679-3685(2015).
RN [12]
RP INTERACTION WITH HSF1.
RX PubMed=26754925; DOI=10.1038/srep19174;
RA Asano Y., Kawase T., Okabe A., Tsutsumi S., Ichikawa H., Tatebe S.,
RA Kitabayashi I., Tashiro F., Namiki H., Kondo T., Semba K., Aburatani H.,
RA Taya Y., Nakagama H., Ohki R.;
RT "IER5 generates a novel hypo-phosphorylated active form of HSF1 and
RT contributes to tumorigenesis.";
RL Sci. Rep. 6:19174-19174(2016).
CC -!- FUNCTION: Plays a role as a transcription factor (PubMed:22132193,
CC PubMed:25355627). Mediates positive transcriptional regulation of
CC several chaperone genes during the heat shock response in a HSF1-
CC dependent manner (PubMed:25355627, PubMed:25816751). Mediates negative
CC transcriptional regulation of CDC25B expression (PubMed:22132193).
CC Plays a role in the dephosphorylation of the heat shock factor HSF1 and
CC ribosomal protein S6 kinase (S6K) by the protein phosphatase PP2A
CC (PubMed:25816751, PubMed:26496226). Involved in the regulation of cell
CC proliferation and resistance to thermal stress (PubMed:22132193,
CC PubMed:25355627, PubMed:26496226). Involved in the cell cycle
CC checkpoint and survival in response to ionizing radiation
CC (PubMed:19238419, PubMed:22132193). Associates with chromatin to the
CC CDC25B promoter (PubMed:22132193). {ECO:0000269|PubMed:19238419,
CC ECO:0000269|PubMed:22132193, ECO:0000269|PubMed:25355627,
CC ECO:0000269|PubMed:25816751, ECO:0000269|PubMed:26496226}.
CC -!- SUBUNIT: Monomer (PubMed:26496226). Homodimer (PubMed:26496226).
CC Associates with the catalytic subunit of protein phosphatase PP2A
CC (PubMed:25816751, PubMed:26496226). Interacts (via N- and C-terminal
CC regions) with PPP2R2B (PubMed:25816751, PubMed:26496226). Interacts
CC with PPP2R2A, PPP2R2C and PPP2R2D (PubMed:25816751). Interacts (via N-
CC terminus) with RPS6KB1 (PubMed:26496226). Interacts (via central
CC region) with HSF1; this interaction promotes PPP2CA-induced HSF1
CC dephosphorylation, leading to enhanced HSF1 transcriptional activity
CC (PubMed:25816751, PubMed:26496226, PubMed:26754925).
CC {ECO:0000269|PubMed:25816751, ECO:0000269|PubMed:26496226,
CC ECO:0000269|PubMed:26754925}.
CC -!- INTERACTION:
CC Q5VY09; Q00613: HSF1; NbExp=3; IntAct=EBI-1774000, EBI-719620;
CC Q5VY09; Q5VY09: IER5; NbExp=2; IntAct=EBI-1774000, EBI-1774000;
CC Q5VY09; Q8N4C8-4: MINK1; NbExp=2; IntAct=EBI-1774000, EBI-11475194;
CC Q5VY09; P23443: RPS6KB1; NbExp=2; IntAct=EBI-1774000, EBI-1775921;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:25816751}. Cytoplasm
CC {ECO:0000269|PubMed:25816751}. Note=Predominantly cytoplasmic
CC (PubMed:25816751). Translocated in the nucleus during heat shock
CC (PubMed:25816751). {ECO:0000269|PubMed:25816751}.
CC -!- TISSUE SPECIFICITY: Expressed in acute myeloid leukemia (AML) cells.
CC {ECO:0000269|PubMed:22132193}.
CC -!- INDUCTION: Up-regulated by heat shock in a heat shock HSF1-dependent
CC manner (PubMed:25355627). Up-regulated by ionizing radiation
CC (PubMed:19238419). {ECO:0000269|PubMed:19238419,
CC ECO:0000269|PubMed:25355627}.
CC -!- SIMILARITY: Belongs to the IER family. {ECO:0000305}.
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DR EMBL; AF178984; AAF44348.1; -; mRNA.
DR EMBL; AJ251089; CAB91983.1; -; mRNA.
DR EMBL; AF258581; AAG23784.1; -; mRNA.
DR EMBL; AK314830; BAG37350.1; -; mRNA.
DR EMBL; AL356267; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000128; AAH00128.1; -; mRNA.
DR CCDS; CCDS1343.1; -.
DR RefSeq; NP_057629.2; NM_016545.4.
DR AlphaFoldDB; Q5VY09; -.
DR SMR; Q5VY09; -.
DR BioGRID; 119430; 9.
DR IntAct; Q5VY09; 10.
DR MINT; Q5VY09; -.
DR STRING; 9606.ENSP00000356549; -.
DR iPTMnet; Q5VY09; -.
DR PhosphoSitePlus; Q5VY09; -.
DR BioMuta; IER5; -.
DR DMDM; 116242521; -.
DR EPD; Q5VY09; -.
DR MassIVE; Q5VY09; -.
DR MaxQB; Q5VY09; -.
DR PaxDb; Q5VY09; -.
DR PeptideAtlas; Q5VY09; -.
DR PRIDE; Q5VY09; -.
DR ProteomicsDB; 65619; -.
DR Antibodypedia; 34432; 160 antibodies from 22 providers.
DR DNASU; 51278; -.
DR Ensembl; ENST00000367577.7; ENSP00000356549.4; ENSG00000162783.11.
DR GeneID; 51278; -.
DR KEGG; hsa:51278; -.
DR MANE-Select; ENST00000367577.7; ENSP00000356549.4; NM_016545.5; NP_057629.2.
DR UCSC; uc001got.5; human.
DR CTD; 51278; -.
DR DisGeNET; 51278; -.
DR GeneCards; IER5; -.
DR HGNC; HGNC:5393; IER5.
DR HPA; ENSG00000162783; Low tissue specificity.
DR MIM; 607177; gene.
DR neXtProt; NX_Q5VY09; -.
DR OpenTargets; ENSG00000162783; -.
DR PharmGKB; PA29640; -.
DR VEuPathDB; HostDB:ENSG00000162783; -.
DR eggNOG; ENOG502S0NB; Eukaryota.
DR GeneTree; ENSGT00900000141021; -.
DR HOGENOM; CLU_057338_0_0_1; -.
DR InParanoid; Q5VY09; -.
DR OMA; PCGCPLG; -.
DR OrthoDB; 1503216at2759; -.
DR PhylomeDB; Q5VY09; -.
DR TreeFam; TF331376; -.
DR PathwayCommons; Q5VY09; -.
DR SignaLink; Q5VY09; -.
DR BioGRID-ORCS; 51278; 16 hits in 1076 CRISPR screens.
DR ChiTaRS; IER5; human.
DR GenomeRNAi; 51278; -.
DR Pharos; Q5VY09; Tbio.
DR PRO; PR:Q5VY09; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q5VY09; protein.
DR Bgee; ENSG00000162783; Expressed in amniotic fluid and 205 other tissues.
DR Genevisible; Q5VY09; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0034605; P:cellular response to heat; IDA:UniProtKB.
DR GO; GO:1900036; P:positive regulation of cellular response to heat; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:UniProtKB.
DR InterPro; IPR008653; IER.
DR PANTHER; PTHR15895; PTHR15895; 1.
DR Pfam; PF05760; IER; 2.
PE 1: Evidence at protein level;
KW Activator; Cytoplasm; Nucleus; Reference proteome; Repressor;
KW Stress response; Transcription; Transcription regulation.
FT CHAIN 1..327
FT /note="Immediate early response gene 5 protein"
FT /id="PRO_0000190438"
FT REGION 59..166
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 227..313
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 60..95
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 92
FT /note="R -> H (in dbSNP:rs3747955)"
FT /evidence="ECO:0000269|PubMed:15498874"
FT /id="VAR_028404"
FT VARIANT 168
FT /note="V -> I (in dbSNP:rs3747954)"
FT /id="VAR_028405"
FT VARIANT 194
FT /note="R -> G (in dbSNP:rs1416829)"
FT /evidence="ECO:0000269|PubMed:15498874"
FT /id="VAR_028406"
FT VARIANT 202
FT /note="Q -> R (in dbSNP:rs1361365)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:15498874,
FT ECO:0000269|Ref.1, ECO:0000269|Ref.2"
FT /id="VAR_028407"
FT VARIANT 285
FT /note="P -> S (in dbSNP:rs3747951)"
FT /id="VAR_028408"
FT CONFLICT 161
FT /note="G -> A (in Ref. 2; CAB91983)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 327 AA; 33704 MW; E841C5FAF6520A12 CRC64;
MEFKLEAHRI VSISLGKIYN SRVQRGGIKL HKNLLVSLVL RSARQVYLSD PCPGLYLAGP
AGTPAPPPQQ QPGEPAAGPP AGWGEPPPPA ARASWPETEP QPERSSVSDA PRVGDEVPVA
TVTGVGDVFQ GGEADATEAA WSRVEGPRQA AAREAEGTAG GWGVFPEVSR AARRPCGCPL
GGEDPPGTPA ATPRAACCCA PQPAEDEPPA PPAVCPRKRC AAGVGGGPAG CPAPGSTPLK
KPRRNLEQPP SGGEDDDAEE METGNVANLI SIFGSSFSGL LRKSPGGGRE EEEGEESGPE
AAEPGQICCD KPVLRDMNPW STAIVAF
