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P46695 (IEX1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Radiation-inducible immediate-early gene IEX-1
Alternative name(s):
Differentiation-dependent gene 2 protein
Short name=Protein DIF-2
Immediate early protein GLY96
Immediate early response 3 protein
PACAP-responsive gene 1 protein
Short name=Protein PRG1
Gene names
Name:IER3
Synonyms:DIF2, IEX1, PRG1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length156 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May play a role in the ERK signaling pathway by inhibiting the dephosphorylation of ERK by phosphatase PP2A-PPP2R5C holoenzyme. Acts also as an ERK downstream effector mediating survival. As a member of the NUPR1/RELB/IER3 survival pathway, may provide pancreatic ductal adenocarcinoma with remarkable resistance to cell stress, such as starvation or gemcitabine treatment. Ref.8 Ref.9 Ref.11

Subunit structure

Interacts with the PPP2R5C-PP2A holoenzyme and ERK kinases; regulates ERK dephosphorylation. Ref.8 Ref.9

Subcellular location

Membrane; Single-pass type II membrane protein Ref.8.

Induction

By radiation, 12-O-tetradecanoyl phorbol-13 acetate (TPA), okadaic acid, TNF and NUPR1. Ref.11

Post-translational modification

Phosphorylated at Thr-18, Thr-123 and Ser-126 by MAPK1/ERK2 and probably MAPK3/ERK1. Upon phosphorylation by MAPK1/ERK2 and MAPK3/ERK1, acquires the ability to inhibit cell death induced by various stimuli. Ref.8

Glycosylated.

Sequence similarities

Belongs to the IER3 family.

Ontologies

Keywords
   Cellular componentMembrane
   Coding sequence diversityPolymorphism
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   PTMGlycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processanatomical structure morphogenesis

Traceable author statement Ref.3. Source: ProtInc

apoptotic process

Traceable author statement Ref.3. Source: ProtInc

intrinsic apoptotic signaling pathway in response to DNA damage

Inferred from electronic annotation. Source: Ensembl

mitotic G2 DNA damage checkpoint

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Traceable author statement PubMed 9703517. Source: ProtInc

negative regulation of glycolytic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of inflammatory response

Inferred from electronic annotation. Source: Ensembl

negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of systemic arterial blood pressure

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein catabolic process

Inferred from electronic annotation. Source: Ensembl

regulation of DNA repair

Inferred from electronic annotation. Source: Ensembl

regulation of nucleocytoplasmic transport

Inferred from electronic annotation. Source: Ensembl

regulation of reactive oxygen species metabolic process

Inferred from electronic annotation. Source: Ensembl

regulation of response to DNA damage stimulus

Inferred from mutant phenotype PubMed 20467439. Source: MGI

response to protozoan

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentintegral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

nucleus

Inferred from direct assay PubMed 20467439. Source: MGI

   Molecular_functionprotein binding

Inferred from physical interaction PubMed 15451437Ref.9. Source: IntAct

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 156156Radiation-inducible immediate-early gene IEX-1
PRO_0000084159

Regions

Topological domain1 – 8282Cytoplasmic Potential
Transmembrane83 – 9917Helical; Signal-anchor for type II membrane protein; Potential
Topological domain100 – 15657Extracellular Potential

Amino acid modifications

Modified residue181Phosphothreonine; by MAPK1 Ref.8
Modified residue311Phosphoserine Ref.10
Modified residue1231Phosphothreonine; by MAPK1 Ref.8
Modified residue1261Phosphoserine; by MAPK1 Ref.8
Glycosylation1331N-linked (GlcNAc...) Potential

Natural variations

Natural variant1271A → P. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.7
Corresponds to variant rs3094124 [ dbSNP | Ensembl ].
VAR_058496

Experimental info

Sequence conflict541A → G in AAB36278. Ref.1
Sequence conflict1061P → R in AAB36278. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P46695 [UniParc].

Last modified January 11, 2011. Version 4.
Checksum: 83C06116C81B8341

FASTA15616,903
        10         20         30         40         50         60 
MCHSRSCHPT MTILQAPTPA PSTIPGPRRG SGPEIFTFDP LPEPAAAPAG RPSASRGHRK 

        70         80         90        100        110        120 
RSRRVLYPRV VRRQLPVEEP NPAKRLLFLL LTIVFCQILM AEEGVPAPLP PEDAPNAASL 

       130        140        150 
APTPVSAVLE PFNLTSEPSD YALDLSTFLQ QHPAAF 

« Hide

References

« Hide 'large scale' references
[1]"Identification and characterization of a radiation-inducible glycosylated human early-response gene."
Kondratyev A.D., Chung K.-N., Jung M.O.
Cancer Res. 56:1498-1502(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PRO-127.
Tissue: Placenta.
[2]"PRG1: a novel early-response gene transcriptionally induced by pituitary adenylate cyclase activating polypeptide in a pancreatic carcinoma cell line."
Schaefer H., Trauzold A., Siegel E.G., Folsch U.R., Schmidt W.E.
Cancer Res. 56:2641-2648(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT PRO-127.
[3]"Identification and characterization of a novel monocyte/macrophage differentiation-dependent gene that is responsive to lipopolysaccharide, ceramide, and lysophosphatidylcholine."
Pietzsch A., Buechler C., Aslanidis C., Schmitz G.
Biochem. Biophys. Res. Commun. 235:4-9(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PRO-127.
[4]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT PRO-127.
[5]"Homo sapiens 2,229,817bp genomic DNA of 6p21.3 HLA class I region."
Shiina S., Tamiya G., Oka A., Inoko H.
Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT PRO-127.
[6]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT PRO-127.
Tissue: Cervix and Skin.
[8]"IEX-1: a new ERK substrate involved in both ERK survival activity and ERK activation."
Garcia J., Ye Y., Arranz V., Letourneux C., Pezeron G., Porteu F.
EMBO J. 21:5151-5163(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-18; THR-123 AND SER-126, INTERACTION WITH MAPK1/ERK2, SUBCELLULAR LOCATION, FUNCTION.
[9]"B56-containing PP2A dephosphorylate ERK and their activity is controlled by the early gene IEX-1 and ERK."
Letourneux C., Rocher G., Porteu F.
EMBO J. 25:727-738(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PPP2R5C AND PPP2CA.
[10]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-31, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"Nuclear protein 1 promotes pancreatic cancer development and protects cells from stress by inhibiting apoptosis."
Hamidi T., Algul H., Cano C.E., Sandi M.J., Molejon M.I., Riemann M., Calvo E.L., Lomberk G., Dagorn J.C., Weih F., Urrutia R., Schmid R.M., Iovanna J.L.
J. Clin. Invest. 122:2092-2103(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION BY NUPR1.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
S81914 mRNA. Translation: AAB36278.1.
X96438 Genomic DNA. Translation: CAA65304.1.
Y14551 mRNA. Translation: CAA74886.1.
BT006703 mRNA. Translation: AAP35349.1.
BA000025 Genomic DNA. Translation: BAB63319.1.
AL662797 Genomic DNA. Translation: CAI18210.1.
BC000844 mRNA. Translation: AAH00844.1.
BC005080 mRNA. Translation: AAH05080.1.
CCDSCCDS4689.1.
PIRJC5537.
RefSeqNP_003888.2. NM_003897.3.
UniGeneHs.76095.

3D structure databases

ProteinModelPortalP46695.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114390. 9 interactions.
IntActP46695. 9 interactions.
MINTMINT-2835388.

PTM databases

PhosphoSiteP46695.

Polymorphism databases

DMDM317373569.

Proteomic databases

PaxDbP46695.
PRIDEP46695.

Protocols and materials databases

DNASU8870.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000259874; ENSP00000259874; ENSG00000137331.
ENST00000383560; ENSP00000373054; ENSG00000206478.
ENST00000416884; ENSP00000406245; ENSG00000227231.
ENST00000435856; ENSP00000412283; ENSG00000235030.
ENST00000439190; ENSP00000397956; ENSG00000237155.
ENST00000450236; ENSP00000398139; ENSG00000230128.
GeneID8870.
KEGGhsa:8870.
UCSCuc003nrn.3. human.

Organism-specific databases

CTD8870.
GeneCardsGC06M030766.
GC06Mj30700.
GC06Mk30701.
GC06Ml30755.
GC06Mn30700.
GC06Mo30702.
HGNCHGNC:5392. IER3.
HPACAB019300.
HPA043847.
MIM602996. gene.
neXtProtNX_P46695.
PharmGKBPA29639.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG46208.
HOGENOMHOG000113001.
HOVERGENHBG000172.
InParanoidP46695.
OMAMDISAFF.
PhylomeDBP46695.
TreeFamTF338252.

Gene expression databases

ArrayExpressP46695.
BgeeP46695.
CleanExHS_IER3.
GenevestigatorP46695.

Family and domain databases

InterProIPR024829. IEX-1.
[Graphical view]
PANTHERPTHR16915. PTHR16915. 1 hit.
PRINTSPR02100. GENEIEX1.
ProtoNetSearch...

Other

ChiTaRSIER3. human.
GeneWikiIER3.
GenomeRNAi8870.
NextBio33301.
PROP46695.
SOURCESearch...

Entry information

Entry nameIEX1_HUMAN
AccessionPrimary (citable) accession number: P46695
Secondary accession number(s): Q5SU30, Q92691, Q93044
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: January 11, 2011
Last modified: July 9, 2014
This is version 121 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM