IEX1_HUMAN
ID IEX1_HUMAN Reviewed; 156 AA.
AC P46695; Q5SU30; Q92691; Q93044;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 4.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Radiation-inducible immediate-early gene IEX-1;
DE AltName: Full=Differentiation-dependent gene 2 protein;
DE Short=Protein DIF-2;
DE AltName: Full=Immediate early protein GLY96;
DE AltName: Full=Immediate early response 3 protein;
DE AltName: Full=PACAP-responsive gene 1 protein;
DE Short=Protein PRG1;
GN Name=IER3; Synonyms=DIF2, IEX1, PRG1;
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 PRO-127.
RC TISSUE=Placenta;
RX PubMed=8603392;
RA Kondratyev A.D., Chung K.-N., Jung M.O.;
RT "Identification and characterization of a radiation-inducible glycosylated
RT human early-response gene.";
RL Cancer Res. 56:1498-1502(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT PRO-127.
RX PubMed=8653710;
RA Schaefer H., Trauzold A., Siegel E.G., Folsch U.R., Schmidt W.E.;
RT "PRG1: a novel early-response gene transcriptionally induced by pituitary
RT adenylate cyclase activating polypeptide in a pancreatic carcinoma cell
RT line.";
RL Cancer Res. 56:2641-2648(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT PRO-127.
RX PubMed=9196025; DOI=10.1006/bbrc.1997.6715;
RA Pietzsch A., Buechler C., Aslanidis C., Schmitz G.;
RT "Identification and characterization of a novel monocyte/macrophage
RT differentiation-dependent gene that is responsive to lipopolysaccharide,
RT ceramide, and lysophosphatidylcholine.";
RL Biochem. Biophys. Res. Commun. 235:4-9(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PRO-127.
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT PRO-127.
RA Shiina S., Tamiya G., Oka A., Inoko H.;
RT "Homo sapiens 2,229,817bp genomic DNA of 6p21.3 HLA class I region.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PRO-127.
RC TISSUE=Cervix, 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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PHOSPHORYLATION AT THR-18; THR-123 AND SER-126, INTERACTION WITH
RP MAPK1/ERK2, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=12356731; DOI=10.1093/emboj/cdf488;
RA Garcia J., Ye Y., Arranz V., Letourneux C., Pezeron G., Porteu F.;
RT "IEX-1: a new ERK substrate involved in both ERK survival activity and ERK
RT activation.";
RL EMBO J. 21:5151-5163(2002).
RN [9]
RP FUNCTION, AND INTERACTION WITH PPP2R5C AND PPP2CA.
RX PubMed=16456541; DOI=10.1038/sj.emboj.7600980;
RA Letourneux C., Rocher G., Porteu F.;
RT "B56-containing PP2A dephosphorylate ERK and their activity is controlled
RT by the early gene IEX-1 and ERK.";
RL EMBO J. 25:727-738(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-31, AND IDENTIFICATION BY
RP 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 [11]
RP FUNCTION, AND INDUCTION BY NUPR1.
RX PubMed=22565310; DOI=10.1172/jci60144;
RA Hamidi T., Algul H., Cano C.E., Sandi M.J., Molejon M.I., Riemann M.,
RA Calvo E.L., Lomberk G., Dagorn J.C., Weih F., Urrutia R., Schmid R.M.,
RA Iovanna J.L.;
RT "Nuclear protein 1 promotes pancreatic cancer development and protects
RT cells from stress by inhibiting apoptosis.";
RL J. Clin. Invest. 122:2092-2103(2012).
CC -!- FUNCTION: May play a role in the ERK signaling pathway by inhibiting
CC the dephosphorylation of ERK by phosphatase PP2A-PPP2R5C holoenzyme.
CC Acts also as an ERK downstream effector mediating survival. As a member
CC of the NUPR1/RELB/IER3 survival pathway, may provide pancreatic ductal
CC adenocarcinoma with remarkable resistance to cell stress, such as
CC starvation or gemcitabine treatment. {ECO:0000269|PubMed:12356731,
CC ECO:0000269|PubMed:16456541, ECO:0000269|PubMed:22565310}.
CC -!- SUBUNIT: Interacts with the PPP2R5C-PP2A holoenzyme and ERK kinases;
CC regulates ERK dephosphorylation. {ECO:0000269|PubMed:12356731,
CC ECO:0000269|PubMed:16456541}.
CC -!- INTERACTION:
CC P46695; P49069: CAMLG; NbExp=2; IntAct=EBI-1748945, EBI-1748958;
CC P46695; P11912: CD79A; NbExp=3; IntAct=EBI-1748945, EBI-7797864;
CC P46695; Q8N5K1: CISD2; NbExp=3; IntAct=EBI-1748945, EBI-1045797;
CC P46695; Q9Y680: FKBP7; NbExp=3; IntAct=EBI-1748945, EBI-3918971;
CC P46695; P67775: PPP2CA; NbExp=2; IntAct=EBI-1748945, EBI-712311;
CC P46695; Q15173: PPP2R5B; NbExp=4; IntAct=EBI-1748945, EBI-1369497;
CC P46695; Q13362: PPP2R5C; NbExp=2; IntAct=EBI-1748945, EBI-1266156;
CC P46695; Q04206: RELA; NbExp=6; IntAct=EBI-1748945, EBI-73886;
CC P46695; O43765: SGTA; NbExp=6; IntAct=EBI-1748945, EBI-347996;
CC P46695; Q9UKG4: SLC13A4; NbExp=3; IntAct=EBI-1748945, EBI-12808018;
CC P46695; P55061: TMBIM6; NbExp=3; IntAct=EBI-1748945, EBI-1045825;
CC P46695; Q9Y320: TMX2; NbExp=3; IntAct=EBI-1748945, EBI-6447886;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:12356731}; Single-
CC pass type II membrane protein {ECO:0000269|PubMed:12356731}.
CC -!- INDUCTION: By radiation, 12-O-tetradecanoyl phorbol-13 acetate (TPA),
CC okadaic acid, TNF and NUPR1. {ECO:0000269|PubMed:22565310}.
CC -!- PTM: Phosphorylated at Thr-18, Thr-123 and Ser-126 by MAPK1/ERK2 and
CC probably MAPK3/ERK1. Upon phosphorylation by MAPK1/ERK2 and MAPK3/ERK1,
CC acquires the ability to inhibit cell death induced by various stimuli.
CC {ECO:0000269|PubMed:12356731}.
CC -!- PTM: Glycosylated.
CC -!- SIMILARITY: Belongs to the IER3 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/IER3ID40919ch6p21.html";
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DR EMBL; S81914; AAB36278.1; -; mRNA.
DR EMBL; X96438; CAA65304.1; -; Genomic_DNA.
DR EMBL; Y14551; CAA74886.1; -; mRNA.
DR EMBL; BT006703; AAP35349.1; -; mRNA.
DR EMBL; BA000025; BAB63319.1; -; Genomic_DNA.
DR EMBL; AL662797; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000844; AAH00844.1; -; mRNA.
DR EMBL; BC005080; AAH05080.1; -; mRNA.
DR CCDS; CCDS4689.1; -.
DR PIR; JC5537; JC5537.
DR RefSeq; NP_003888.2; NM_003897.3.
DR AlphaFoldDB; P46695; -.
DR BioGRID; 114390; 22.
DR IntAct; P46695; 17.
DR MINT; P46695; -.
DR STRING; 9606.ENSP00000259874; -.
DR GlyGen; P46695; 1 site.
DR iPTMnet; P46695; -.
DR PhosphoSitePlus; P46695; -.
DR BioMuta; IER3; -.
DR DMDM; 317373569; -.
DR jPOST; P46695; -.
DR MassIVE; P46695; -.
DR PaxDb; P46695; -.
DR PeptideAtlas; P46695; -.
DR PRIDE; P46695; -.
DR ProteomicsDB; 55747; -.
DR Antibodypedia; 26624; 180 antibodies from 27 providers.
DR DNASU; 8870; -.
DR Ensembl; ENST00000259874.6; ENSP00000259874.5; ENSG00000137331.12.
DR Ensembl; ENST00000383560.4; ENSP00000373054.4; ENSG00000206478.5.
DR Ensembl; ENST00000416884.2; ENSP00000406245.2; ENSG00000227231.3.
DR Ensembl; ENST00000435856.2; ENSP00000412283.2; ENSG00000235030.3.
DR Ensembl; ENST00000439190.2; ENSP00000397956.2; ENSG00000237155.3.
DR Ensembl; ENST00000450236.2; ENSP00000398139.2; ENSG00000230128.3.
DR GeneID; 8870; -.
DR KEGG; hsa:8870; -.
DR MANE-Select; ENST00000259874.6; ENSP00000259874.5; NM_003897.4; NP_003888.2.
DR UCSC; uc003nrn.4; human.
DR CTD; 8870; -.
DR DisGeNET; 8870; -.
DR GeneCards; IER3; -.
DR HGNC; HGNC:5392; IER3.
DR HPA; ENSG00000137331; Tissue enhanced (esophagus).
DR MIM; 602996; gene.
DR neXtProt; NX_P46695; -.
DR OpenTargets; ENSG00000137331; -.
DR PharmGKB; PA29639; -.
DR VEuPathDB; HostDB:ENSG00000137331; -.
DR eggNOG; ENOG502S3QE; Eukaryota.
DR GeneTree; ENSGT00390000003213; -.
DR HOGENOM; CLU_138897_0_0_1; -.
DR InParanoid; P46695; -.
DR OMA; VIFCQIL; -.
DR OrthoDB; 1582002at2759; -.
DR PhylomeDB; P46695; -.
DR TreeFam; TF338252; -.
DR PathwayCommons; P46695; -.
DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR SignaLink; P46695; -.
DR SIGNOR; P46695; -.
DR BioGRID-ORCS; 8870; 16 hits in 1072 CRISPR screens.
DR ChiTaRS; IER3; human.
DR GeneWiki; IER3; -.
DR GenomeRNAi; 8870; -.
DR Pharos; P46695; Tbio.
DR PRO; PR:P46695; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P46695; protein.
DR Bgee; ENSG00000137331; Expressed in olfactory segment of nasal mucosa and 95 other tissues.
DR ExpressionAtlas; P46695; baseline and differential.
DR Genevisible; P46695; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0009653; P:anatomical structure morphogenesis; TAS:ProtInc.
DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:ProtInc.
DR GO; GO:2001020; P:regulation of response to DNA damage stimulus; IMP:MGI.
DR InterPro; IPR024829; IEX-1.
DR PANTHER; PTHR16915; PTHR16915; 1.
DR PRINTS; PR02100; GENEIEX1.
PE 1: Evidence at protein level;
KW Glycoprotein; Membrane; Phosphoprotein; Reference proteome; Signal-anchor;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..156
FT /note="Radiation-inducible immediate-early gene IEX-1"
FT /id="PRO_0000084159"
FT TOPO_DOM 1..82
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 83..99
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 100..156
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 1..62
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..19
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 18
FT /note="Phosphothreonine; by MAPK1"
FT /evidence="ECO:0000269|PubMed:12356731"
FT MOD_RES 31
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 123
FT /note="Phosphothreonine; by MAPK1"
FT /evidence="ECO:0000269|PubMed:12356731"
FT MOD_RES 126
FT /note="Phosphoserine; by MAPK1"
FT /evidence="ECO:0000269|PubMed:12356731"
FT CARBOHYD 133
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 127
FT /note="A -> P (in dbSNP:rs3094124)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:8603392, ECO:0000269|PubMed:8653710,
FT ECO:0000269|PubMed:9196025, ECO:0000269|Ref.4,
FT ECO:0000269|Ref.5"
FT /id="VAR_058496"
FT CONFLICT 54
FT /note="A -> G (in Ref. 1; AAB36278)"
FT /evidence="ECO:0000305"
FT CONFLICT 106
FT /note="P -> R (in Ref. 1; AAB36278)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 156 AA; 16903 MW; 83C06116C81B8341 CRC64;
MCHSRSCHPT MTILQAPTPA PSTIPGPRRG SGPEIFTFDP LPEPAAAPAG RPSASRGHRK
RSRRVLYPRV VRRQLPVEEP NPAKRLLFLL LTIVFCQILM AEEGVPAPLP PEDAPNAASL
APTPVSAVLE PFNLTSEPSD YALDLSTFLQ QHPAAF
