P46695 (IEX1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	IER3
Synonyms:	DIF2, IEX1, PRG1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	156 AA.
Sequence status	Complete.
Protein existence	Evidence 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 component	Membrane
Coding sequence diversity	Polymorphism
Domain	Signal-anchor Transmembrane Transmembrane helix
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	anatomical structure morphogenesis Traceable author statement Ref.3. Source: ProtInc apoptotic process Traceable author statement Ref.3. Source: ProtInc negative regulation of apoptotic process Traceable author statement PubMed 9703517. Source: ProtInc negative regulation of glycolysis Inferred from electronic annotation. Source: Compara negative regulation of inflammatory response Inferred from electronic annotation. Source: Compara negative regulation of systemic arterial blood pressure Inferred from electronic annotation. Source: Compara positive regulation of apoptotic process Inferred from electronic annotation. Source: Compara positive regulation of protein catabolic process Inferred from electronic annotation. Source: Compara regulation of reactive oxygen species metabolic process Inferred from electronic annotation. Source: Compara regulation of response to DNA damage stimulus Inferred from mutant phenotype PubMed 20467439. Source: MGI response to protozoan Inferred from electronic annotation. Source: Compara
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW nucleus Inferred from direct assay PubMed 20467439. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CAMLG	P49069	2	EBI-1748945,EBI-1748958

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 156	156	Radiation-inducible immediate-early gene IEX-1		PRO_0000084159
Regions
	Topological domain	1 – 82	82	Cytoplasmic Potential
	Transmembrane	83 – 99	17	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	100 – 156	57	Extracellular Potential
Amino acid modifications
	Modified residue	18	1	Phosphothreonine; by MAPK1 Ref.8
	Modified residue	31	1	Phosphoserine Ref.10
	Modified residue	123	1	Phosphothreonine; by MAPK1 Ref.8
	Modified residue	126	1	Phosphoserine; by MAPK1 Ref.8
	Glycosylation	133	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	127	1	A → P. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.7 Corresponds to variant rs3094124 [ dbSNP | Ensembl ].		VAR_058496
Experimental info
	Sequence conflict	54	1	A → G in AAB36278. Ref.1
	Sequence conflict	106	1	P → R in AAB36278. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P46695 [UniParc]. Last modified January 11, 2011. Version 4. Checksum: 83C06116C81B8341	FASTA	156	16,903
	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

References

	« Hide 'large scale' referencesShow '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. , 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, MASS SPECTROMETRY. 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.
IPI	IPI00007831.
PIR	JC5537.
RefSeq	NP_003888.2. NM_003897.3.
UniGene	Hs.76095.
3D structure databases
ProteinModelPortal	P46695.
ModBase	Search...
Protein-protein interaction databases
IntAct	P46695. 5 interactions.
MINT	MINT-2835388.
PTM databases
PhosphoSite	P46695.
Polymorphism databases
DMDM	3123229.
Proteomic databases
PaxDb	P46695.
PRIDE	P46695.
Protocols and materials databases
DNASU	8870.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000259874; ENSP00000259874; ENSG00000137331. ENST00000383560; ENSP00000373054; ENSG00000206478. ENST00000416884; ENSP00000406245; ENSG00000227231. ENST00000435856; ENSP00000412283; ENSG00000235030. ENST00000439190; ENSP00000397956; ENSG00000237155. ENST00000450236; ENSP00000398139; ENSG00000230128.
GeneID	8870.
KEGG	hsa:8870.
UCSC	uc003nrn.3. human.
Organism-specific databases
CTD	8870.
GeneCards	GC06M030766.
HGNC	HGNC:5392. IER3.
HPA	CAB019300.
MIM	602996. gene.
neXtProt	NX_P46695.
PharmGKB	PA29639.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG46208.
HOGENOM	HOG000113001.
HOVERGEN	HBG000172.
InParanoid	P46695.
OrthoDB	EOG4BK553.
PhylomeDB	P46695.
Gene expression databases
ArrayExpress	P46695.
Bgee	P46695.
CleanEx	HS_IER3.
Genevestigator	P46695.
GermOnline	ENSG00000137331. Homo sapiens.
Family and domain databases
InterPro	IPR024829. IEX-1. [Graphical view]
PANTHER	PTHR16915. PTHR16915. 1 hit.
PRINTS	PR02100. GENEIEX1.
ProtoNet	Search...
Other
ChiTaRS	IER3. human.
GenomeRNAi	8870.
NextBio	33301.
SOURCE	Search...

Entry information

Entry name

IEX1_HUMAN

Accession

Primary (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:	April 3, 2013
This is version 110 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.