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-SEP-2018, entry version 101. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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 RT the 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 RP AND 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., RA Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., RA Shu H., Chen X., Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., RA 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA 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., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA 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., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA 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 RT project: 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., RA Xie Y.H., 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 RT proliferation of leukemic progenitor cells through NF-YB and p300 in RT acute myeloid 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 RP PPP2R2D, ASSOCIATION WITH THE PP2A CATALYTIC SUBUNIT, AND SUBCELLULAR RP 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 RT 2A and regulates the phosphorylation of ribosomal protein S6 kinase RT and heat 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., RA Aburatani H., 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 CC negative transcriptional regulation of CDC25B expression CC (PubMed:22132193). Plays a role in the dephosphorylation of the CC heat shock factor HSF1 and ribosomal protein S6 kinase (S6K) by CC the protein phosphatase PP2A (PubMed:25816751, PubMed:26496226). CC Involved in the regulation of cell proliferation and resistance to CC thermal stress (PubMed:22132193, PubMed:25355627, CC PubMed:26496226). Involved in the cell cycle checkpoint and CC survival in response to ionizing radiation (PubMed:19238419, CC PubMed:22132193). Associates with chromatin to the CDC25B promoter CC (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- CC terminal regions) with PPP2R2B (PubMed:25816751, PubMed:26496226). CC Interacts with PPP2R2A, PPP2R2C and PPP2R2D (PubMed:25816751). CC Interacts (via N-terminus) with RPS6KB1 (PubMed:26496226). CC Interacts (via central region) with HSF1; this interaction CC promotes PPP2CA-induced HSF1 dephosphorylation, leading to CC enhanced HSF1 transcriptional activity (PubMed:25816751, CC PubMed:26496226, PubMed:26754925). {ECO:0000269|PubMed:25816751, CC ECO:0000269|PubMed:26496226, ECO:0000269|PubMed:26754925}. CC -!- INTERACTION: CC Self; NbExp=2; IntAct=EBI-1774000, EBI-1774000; CC Q00613:HSF1; NbExp=3; IntAct=EBI-1774000, EBI-719620; CC Q8N4C8-4:MINK1; NbExp=2; IntAct=EBI-1774000, EBI-11475194; CC P23443:RPS6KB1; NbExp=2; IntAct=EBI-1774000, EBI-1775921; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:25816751}. CC Cytoplasm {ECO:0000269|PubMed:25816751}. Note=Predominantly CC cytoplasmic (PubMed:25816751). Translocated in the nucleus during CC heat shock (PubMed:25816751). {ECO:0000269|PubMed:25816751}. CC -!- TISSUE SPECIFICITY: Expressed in acute myeloid leukemia (AML) CC cells. {ECO:0000269|PubMed:22132193}. CC -!- INDUCTION: Up-regulated by heat shock in a heat shock HSF1- CC dependent manner (PubMed:25355627). Up-regulated by ionizing CC radiation (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 UniGene; Hs.15725; -. DR ProteinModelPortal; Q5VY09; -. DR SMR; Q5VY09; -. DR BioGrid; 119430; 5. 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 MaxQB; Q5VY09; -. DR PaxDb; Q5VY09; -. DR PeptideAtlas; Q5VY09; -. DR PRIDE; Q5VY09; -. DR ProteomicsDB; 65619; -. 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; HPA029894; -. DR MIM; 607177; gene. DR neXtProt; NX_Q5VY09; -. DR OpenTargets; ENSG00000162783; -. DR PharmGKB; PA29640; -. DR eggNOG; ENOG410J10V; Eukaryota. DR eggNOG; ENOG4111NZJ; LUCA. DR GeneTree; ENSGT00900000141021; -. DR HOGENOM; HOG000112999; -. DR HOVERGEN; HBG105469; -. DR InParanoid; Q5VY09; -. DR OMA; MNPWSTA; -. DR OrthoDB; EOG091G0HLK; -. DR PhylomeDB; Q5VY09; -. DR TreeFam; TF331376; -. DR ChiTaRS; IER5; human. DR GenomeRNAi; 51278; -. DR PRO; PR:Q5VY09; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; ENSG00000162783; Expressed in 235 organ(s), highest expression level in amniotic fluid. DR CleanEx; HS_IER5; -. DR Genevisible; Q5VY09; HS. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. 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 proliferation; IMP:UniProtKB. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR InterPro; IPR008653; IER. DR PANTHER; PTHR15895; PTHR15895; 1. DR Pfam; PF05760; IER; 2. PE 1: Evidence at protein level; KW Activator; Complete proteome; Cytoplasm; Nucleus; Polymorphism; KW Reference proteome; Repressor; Stress response; Transcription; KW Transcription regulation. FT CHAIN 1 327 Immediate early response gene 5 protein. FT /FTId=PRO_0000190438. FT VARIANT 92 92 R -> H (in dbSNP:rs3747955). FT {ECO:0000269|PubMed:15498874}. FT /FTId=VAR_028404. FT VARIANT 168 168 V -> I (in dbSNP:rs3747954). FT /FTId=VAR_028405. FT VARIANT 194 194 R -> G (in dbSNP:rs1416829). FT {ECO:0000269|PubMed:15498874}. FT /FTId=VAR_028406. FT VARIANT 202 202 Q -> R (in dbSNP:rs1361365). FT {ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:15498874, FT ECO:0000269|Ref.1, ECO:0000269|Ref.2}. FT /FTId=VAR_028407. FT VARIANT 285 285 P -> S (in dbSNP:rs3747951). FT /FTId=VAR_028408. FT CONFLICT 161 161 G -> A (in Ref. 2; CAB91983). FT {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 //