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Protein

Radiation-inducible immediate-early gene IEX-1

Gene

IER3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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 - Biological processi

  • anatomical structure morphogenesis Source: ProtInc
  • apoptotic process Source: ProtInc
  • negative regulation of apoptotic process Source: ProtInc
  • regulation of phosphatidylinositol 3-kinase signaling Source: Reactome
  • regulation of response to DNA damage stimulus Source: MGI
Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:ENSG00000137331-MONOMER.
ReactomeiR-HSA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
SIGNORiP46695.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:5392. IER3.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 82CytoplasmicSequence analysisAdd BLAST82
Transmembranei83 – 99Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST17
Topological domaini100 – 156ExtracellularSequence analysisAdd BLAST57

GO - Cellular componenti

  • cytosol Source: Reactome
  • integral component of membrane Source: UniProtKB-KW
  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi8870.
OpenTargetsiENSG00000137331.
PharmGKBiPA29639.

Polymorphism and mutation databases

BioMutaiIER3.
DMDMi317373569.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000841591 – 156Radiation-inducible immediate-early gene IEX-1Add BLAST156

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei18Phosphothreonine; by MAPK11 Publication1
Modified residuei31PhosphoserineCombined sources1
Modified residuei123Phosphothreonine; by MAPK11 Publication1
Modified residuei126Phosphoserine; by MAPK11 Publication1
Glycosylationi133N-linked (GlcNAc...)Sequence analysis1

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.
PeptideAtlasiP46695.
PRIDEiP46695.

PTM databases

iPTMnetiP46695.
PhosphoSitePlusiP46695.

Expressioni

Inductioni

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

Gene expression databases

BgeeiENSG00000137331.
CleanExiHS_IER3.
ExpressionAtlasiP46695. baseline and differential.
GenevisibleiP46695. HS.

Organism-specific databases

HPAiHPA043847.

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
RELAQ042066EBI-1748945,EBI-73886

Protein-protein interaction databases

BioGridi114390. 10 interactors.
IntActiP46695. 11 interactors.
MINTiMINT-2835388.
STRINGi9606.ENSP00000259874.

Structurei

3D structure databases

ProteinModelPortaliP46695.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the IER3 family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IZ8Q. Eukaryota.
ENOG410Z2E4. LUCA.
GeneTreeiENSGT00390000003213.
HOGENOMiHOG000113001.
HOVERGENiHBG000172.
InParanoidiP46695.
OMAiMDISAFF.
OrthoDBiEOG091G0UO1.
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

        10         20         30         40         50
MCHSRSCHPT MTILQAPTPA PSTIPGPRRG SGPEIFTFDP LPEPAAAPAG
60 70 80 90 100
RPSASRGHRK RSRRVLYPRV VRRQLPVEEP NPAKRLLFLL LTIVFCQILM
110 120 130 140 150
AEEGVPAPLP PEDAPNAASL APTPVSAVLE PFNLTSEPSD YALDLSTFLQ

QHPAAF
Length:156
Mass (Da):16,903
Last modified:January 11, 2011 - v4
Checksum:i83C06116C81B8341
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti54A → G in AAB36278 (PubMed:8603392).Curated1
Sequence conflicti106P → R in AAB36278 (PubMed:8603392).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_058496127A → P.6 PublicationsCorresponds to variant rs3094124dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.730861.
Hs.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.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.730861.
Hs.76095.

3D structure databases

ProteinModelPortaliP46695.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114390. 10 interactors.
IntActiP46695. 11 interactors.
MINTiMINT-2835388.
STRINGi9606.ENSP00000259874.

PTM databases

iPTMnetiP46695.
PhosphoSitePlusiP46695.

Polymorphism and mutation databases

BioMutaiIER3.
DMDMi317373569.

Proteomic databases

PaxDbiP46695.
PeptideAtlasiP46695.
PRIDEiP46695.

Protocols and materials databases

DNASUi8870.
Structural Biology KnowledgebaseSearch...

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.4. human.

Organism-specific databases

CTDi8870.
DisGeNETi8870.
GeneCardsiIER3.
HGNCiHGNC:5392. IER3.
HPAiHPA043847.
MIMi602996. gene.
neXtProtiNX_P46695.
OpenTargetsiENSG00000137331.
PharmGKBiPA29639.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IZ8Q. Eukaryota.
ENOG410Z2E4. LUCA.
GeneTreeiENSGT00390000003213.
HOGENOMiHOG000113001.
HOVERGENiHBG000172.
InParanoidiP46695.
OMAiMDISAFF.
OrthoDBiEOG091G0UO1.
PhylomeDBiP46695.
TreeFamiTF338252.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000137331-MONOMER.
ReactomeiR-HSA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
SIGNORiP46695.

Miscellaneous databases

ChiTaRSiIER3. human.
GeneWikiiIER3.
GenomeRNAii8870.
PROiP46695.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000137331.
CleanExiHS_IER3.
ExpressionAtlasiP46695. baseline and differential.
GenevisibleiP46695. HS.

Family and domain databases

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

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: November 30, 2016
This is version 140 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.