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   25-JAN-2012, entry version 98.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT PRO-127.
RC   TISSUE=Placenta;
RX   MEDLINE=96181295; PubMed=8603392;
RA   Kondratyev A.D., Chung K.-N., Jung M.O.;
RT   "Identification and characterization of a radiation-inducible
RT   glycosylated human early-response gene.";
RL   Cancer Res. 56:1498-1502(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT PRO-127.
RX   MEDLINE=96221139; 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
RT   pituitary adenylate cyclase activating polypeptide in a pancreatic
RT   carcinoma cell line.";
RL   Cancer Res. 56:2641-2648(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT PRO-127.
RX   MEDLINE=97339426; 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
RT   lipopolysaccharide, 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
RT   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   MEDLINE=22935763; 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.,
RA   Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA   Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA   Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA   Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA   Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA   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.,
RA   Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA   Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA   Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA   Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA   Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA   Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA   Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA   Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA   Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA   Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA   Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA   McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA   Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA   Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA   Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA   Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA   Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA   Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA   Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA   Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA   Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA   Durbin R.M., Hubbard T., Sulston J.E., Dunham I., 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
RT   project: 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, SUBCELLLAR LOCATION, AND FUNCTION.
RX   PubMed=12356731;
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
RT   ERK 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
RT   controlled by the early gene IEX-1 and ERK.";
RL   EMBO J. 25:727-738(2006).
CC   -!- FUNCTION: May play a role in the ERK signaling pathway by
CC       inhibiting the dephosphorylation of ERK by phosphatase PP2A-
CC       PPP2R5C holoenzyme. Acts also as an ERK downstream effector
CC       mediating survival.
CC   -!- SUBUNIT: Interacts with the PPP2R5C-PP2A holoenzyme and ERK
CC       kinases; regulates ERK dephosphorylation.
CC   -!- INTERACTION:
CC       P49069:CAMLG; NbExp=2; IntAct=EBI-1748945, EBI-1748958;
CC   -!- SUBCELLULAR LOCATION: Membrane; Single-pass type II membrane
CC       protein.
CC   -!- INDUCTION: By radiation, 12-O-tetradecanoyl phorbol-13 acetate
CC       (TPA), okadaic acid and TNF.
CC   -!- PTM: Phosphorylated at Thr-18, Thr-123 and Ser-126 by MAPK1/ERK2
CC       and probably MAPK3/ERK1. Upon phosphorylation by MAPK1/ERK2 and
CC       MAPK3/ERK1, acquires the ability to inhibit cell death induced by
CC       various stimuli.
CC   -!- PTM: Glycosylated.
CC   -!- SIMILARITY: Belongs to the IER3 family.
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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; CAI18210.1; -; Genomic_DNA.
DR   EMBL; BC000844; AAH00844.1; -; mRNA.
DR   EMBL; BC005080; AAH05080.1; -; mRNA.
DR   IPI; IPI00007831; -.
DR   PIR; JC5537; JC5537.
DR   RefSeq; NP_003888.2; NM_003897.3.
DR   UniGene; Hs.591785; -.
DR   ProteinModelPortal; P46695; -.
DR   IntAct; P46695; 5.
DR   MINT; MINT-2835388; -.
DR   PhosphoSite; P46695; -.
DR   DMDM; 3123229; -.
DR   Ensembl; ENST00000259874; ENSP00000259874; ENSG00000137331.
DR   Ensembl; ENST00000383560; ENSP00000373054; ENSG00000206478.
DR   Ensembl; ENST00000416884; ENSP00000406245; ENSG00000227231.
DR   Ensembl; ENST00000435856; ENSP00000412283; ENSG00000235030.
DR   Ensembl; ENST00000439190; ENSP00000397956; ENSG00000237155.
DR   Ensembl; ENST00000450236; ENSP00000398139; ENSG00000230128.
DR   GeneID; 8870; -.
DR   KEGG; hsa:8870; -.
DR   CTD; 8870; -.
DR   GeneCards; GC06M030766; -.
DR   H-InvDB; HIX0057742; -.
DR   H-InvDB; HIX0058162; -.
DR   HGNC; HGNC:5392; IER3.
DR   HPA; CAB019300; -.
DR   MIM; 602996; gene.
DR   neXtProt; NX_P46695; -.
DR   PharmGKB; PA29639; -.
DR   eggNOG; prNOG20022; -.
DR   GeneTree; ENSGT00390000003213; -.
DR   HOVERGEN; HBG000172; -.
DR   InParanoid; P46695; -.
DR   OMA; IFCQILM; -.
DR   OrthoDB; EOG4BK553; -.
DR   PhylomeDB; P46695; -.
DR   NextBio; 33301; -.
DR   CleanEx; HS_IER3; -.
DR   Genevestigator; P46695; -.
DR   GermOnline; ENSG00000137331; Homo sapiens.
DR   GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005515; F:protein binding; IPI:IntAct.
DR   GO; GO:0009653; P:anatomical structure morphogenesis; TAS:ProtInc.
DR   GO; GO:0006916; P:anti-apoptosis; TAS:ProtInc.
DR   GO; GO:0006915; P:apoptotic process; TAS:ProtInc.
DR   InterPro; IPR024829; IEX-1.
DR   PANTHER; PTHR16915; PTHR16915; 1.
PE   1: Evidence at protein level;
KW   Complete proteome; Glycoprotein; Membrane; Phosphoprotein;
KW   Polymorphism; Reference proteome; Signal-anchor; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN         1    156       Radiation-inducible immediate-early gene
FT                                IEX-1.
FT                                /FTId=PRO_0000084159.
FT   TOPO_DOM      1     82       Cytoplasmic (Potential).
FT   TRANSMEM     83     99       Helical; Signal-anchor for type II
FT                                membrane protein; (Potential).
FT   TOPO_DOM    100    156       Extracellular (Potential).
FT   MOD_RES      18     18       Phosphothreonine; by MAPK1.
FT   MOD_RES     123    123       Phosphothreonine; by MAPK1.
FT   MOD_RES     126    126       Phosphoserine; by MAPK1.
FT   CARBOHYD    133    133       N-linked (GlcNAc...) (Potential).
FT   VARIANT     127    127       A -> P (in dbSNP:rs3094124).
FT                                /FTId=VAR_058496.
FT   CONFLICT     54     54       A -> G (in Ref. 1; AAB36278).
FT   CONFLICT    106    106       P -> R (in Ref. 1; AAB36278).
SQ   SEQUENCE   156 AA;  16903 MW;  83C06116C81B8341 CRC64;
     MCHSRSCHPT MTILQAPTPA PSTIPGPRRG SGPEIFTFDP LPEPAAAPAG RPSASRGHRK
     RSRRVLYPRV VRRQLPVEEP NPAKRLLFLL LTIVFCQILM AEEGVPAPLP PEDAPNAASL
     APTPVSAVLE PFNLTSEPSD YALDLSTFLQ QHPAAF
//