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 12-AUG-2020, entry version 114. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 SMR; Q5VY09; -. DR BioGRID; 119430; 7. 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; 136 antibodies. DR Ensembl; ENST00000367577; ENSP00000356549; ENSG00000162783. DR GeneID; 51278; -. DR KEGG; hsa:51278; -. DR UCSC; uc001got.5; human. DR CTD; 51278; -. DR DisGeNET; 51278; -. DR EuPathDB; HostDB:ENSG00000162783.10; -. 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 eggNOG; ENOG502S0NB; Eukaryota. DR GeneTree; ENSGT00900000141021; -. DR HOGENOM; CLU_057338_0_0_1; -. DR InParanoid; Q5VY09; -. DR OMA; RPCGCPL; -. DR OrthoDB; 1503216at2759; -. DR PhylomeDB; Q5VY09; -. DR TreeFam; TF331376; -. DR PathwayCommons; Q5VY09; -. DR BioGRID-ORCS; 51278; 10 hits in 869 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 247 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; Polymorphism; 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 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 //