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P46695

- IEX1_HUMAN

UniProt

P46695 - IEX1_HUMAN

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Protein

Radiation-inducible immediate-early gene IEX-1

Gene
IER3, DIF2, IEX1, PRG1
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.3 Publications

GO - Molecular functioni

  1. protein binding Source: IntAct

GO - Biological processi

  1. anatomical structure morphogenesis Source: ProtInc
  2. apoptotic process Source: ProtInc
  3. intrinsic apoptotic signaling pathway in response to DNA damage Source: Ensembl
  4. mitotic G2 DNA damage checkpoint Source: Ensembl
  5. negative regulation of apoptotic process Source: ProtInc
  6. negative regulation of glycolytic process Source: Ensembl
  7. negative regulation of inflammatory response Source: Ensembl
  8. negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway Source: Ensembl
  9. negative regulation of systemic arterial blood pressure Source: Ensembl
  10. positive regulation of protein catabolic process Source: Ensembl
  11. regulation of DNA repair Source: Ensembl
  12. regulation of nucleocytoplasmic transport Source: Ensembl
  13. regulation of reactive oxygen species metabolic process Source: Ensembl
  14. regulation of response to DNA damage stimulus Source: MGI
  15. response to protozoan Source: Ensembl
Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:IER3
Synonyms:DIF2, IEX1, PRG1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 6

Organism-specific databases

HGNCiHGNC:5392. IER3.

Subcellular locationi

Membrane; Single-pass type II membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 8282Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei83 – 9917Helical; Signal-anchor for type II membrane protein; Reviewed predictionAdd
BLAST
Topological domaini100 – 15657Extracellular Reviewed predictionAdd
BLAST

GO - Cellular componenti

  1. integral component of membrane Source: UniProtKB-KW
  2. nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA29639.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 156156Radiation-inducible immediate-early gene IEX-1PRO_0000084159Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei18 – 181Phosphothreonine; by MAPK11 Publication
Modified residuei31 – 311Phosphoserine1 Publication
Modified residuei123 – 1231Phosphothreonine; by MAPK11 Publication
Modified residuei126 – 1261Phosphoserine; by MAPK11 Publication
Glycosylationi133 – 1331N-linked (GlcNAc...) Reviewed prediction

Post-translational modificationi

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.1 Publication
Glycosylated.

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP46695.
PRIDEiP46695.

PTM databases

PhosphoSiteiP46695.

Expressioni

Inductioni

By radiation, 12-O-tetradecanoyl phorbol-13 acetate (TPA), okadaic acid, TNF and NUPR1.1 Publication

Gene expression databases

ArrayExpressiP46695.
BgeeiP46695.
CleanExiHS_IER3.
GenevestigatoriP46695.

Organism-specific databases

HPAiCAB019300.
HPA043847.

Interactioni

Subunit structurei

Interacts with the PPP2R5C-PP2A holoenzyme and ERK kinases; regulates ERK dephosphorylation.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CAMLGP490692EBI-1748945,EBI-1748958
PPP2CAP677752EBI-1748945,EBI-712311
PPP2R5BQ151734EBI-1748945,EBI-1369497
PPP2R5CQ133622EBI-1748945,EBI-1266156

Protein-protein interaction databases

BioGridi114390. 9 interactions.
IntActiP46695. 9 interactions.
MINTiMINT-2835388.

Structurei

3D structure databases

ProteinModelPortaliP46695.

Family & Domainsi

Sequence similaritiesi

Belongs to the IER3 family.

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG46208.
HOGENOMiHOG000113001.
HOVERGENiHBG000172.
InParanoidiP46695.
OMAiMDISAFF.
PhylomeDBiP46695.
TreeFamiTF338252.

Family and domain databases

InterProiIPR024829. IEX-1.
[Graphical view]
PANTHERiPTHR16915. PTHR16915. 1 hit.
PRINTSiPR02100. GENEIEX1.

Sequencei

Sequence statusi: Complete.

P46695-1 [UniParc]FASTAAdd to Basket

« Hide

MCHSRSCHPT MTILQAPTPA PSTIPGPRRG SGPEIFTFDP LPEPAAAPAG    50
RPSASRGHRK RSRRVLYPRV VRRQLPVEEP NPAKRLLFLL LTIVFCQILM 100
AEEGVPAPLP PEDAPNAASL APTPVSAVLE PFNLTSEPSD YALDLSTFLQ 150
QHPAAF 156
Length:156
Mass (Da):16,903
Last modified:January 11, 2011 - v4
Checksum:i83C06116C81B8341
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti127 – 1271A → P.6 Publications
Corresponds to variant rs3094124 [ dbSNP | Ensembl ].
VAR_058496

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti54 – 541A → G in AAB36278. 1 Publication
Sequence conflicti106 – 1061P → R in AAB36278. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS4689.1.
PIRiJC5537.
RefSeqiNP_003888.2. NM_003897.3.
UniGeneiHs.76095.

Genome annotation databases

EnsembliENST00000259874; ENSP00000259874; ENSG00000137331.
ENST00000383560; ENSP00000373054; ENSG00000206478.
ENST00000416884; ENSP00000406245; ENSG00000227231.
ENST00000435856; ENSP00000412283; ENSG00000235030.
ENST00000439190; ENSP00000397956; ENSG00000237155.
ENST00000450236; ENSP00000398139; ENSG00000230128.
GeneIDi8870.
KEGGihsa:8870.
UCSCiuc003nrn.3. human.

Polymorphism databases

DMDMi317373569.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS4689.1.
PIRi JC5537.
RefSeqi NP_003888.2. NM_003897.3.
UniGenei Hs.76095.

3D structure databases

ProteinModelPortali P46695.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 114390. 9 interactions.
IntActi P46695. 9 interactions.
MINTi MINT-2835388.

PTM databases

PhosphoSitei P46695.

Polymorphism databases

DMDMi 317373569.

Proteomic databases

PaxDbi P46695.
PRIDEi P46695.

Protocols and materials databases

DNASUi 8870.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000259874 ; ENSP00000259874 ; ENSG00000137331 .
ENST00000383560 ; ENSP00000373054 ; ENSG00000206478 .
ENST00000416884 ; ENSP00000406245 ; ENSG00000227231 .
ENST00000435856 ; ENSP00000412283 ; ENSG00000235030 .
ENST00000439190 ; ENSP00000397956 ; ENSG00000237155 .
ENST00000450236 ; ENSP00000398139 ; ENSG00000230128 .
GeneIDi 8870.
KEGGi hsa:8870.
UCSCi uc003nrn.3. human.

Organism-specific databases

CTDi 8870.
GeneCardsi GC06M030766.
GC06Mj30700.
GC06Mk30701.
GC06Ml30755.
GC06Mn30700.
GC06Mo30702.
HGNCi HGNC:5392. IER3.
HPAi CAB019300.
HPA043847.
MIMi 602996. gene.
neXtProti NX_P46695.
PharmGKBi PA29639.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG46208.
HOGENOMi HOG000113001.
HOVERGENi HBG000172.
InParanoidi P46695.
OMAi MDISAFF.
PhylomeDBi P46695.
TreeFami TF338252.

Miscellaneous databases

ChiTaRSi IER3. human.
GeneWikii IER3.
GenomeRNAii 8870.
NextBioi 33301.
PROi P46695.
SOURCEi Search...

Gene expression databases

ArrayExpressi P46695.
Bgeei P46695.
CleanExi HS_IER3.
Genevestigatori P46695.

Family and domain databases

InterProi IPR024829. IEX-1.
[Graphical view ]
PANTHERi PTHR16915. PTHR16915. 1 hit.
PRINTSi PR02100. GENEIEX1.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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.

Entry informationi

Entry nameiIEX1_HUMAN
AccessioniPrimary (citable) accession number: P46695
Secondary accession number(s): Q5SU30, Q92691, Q93044
Entry historyi
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 statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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