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P46695

- IEX1_HUMAN

UniProt

P46695 - IEX1_HUMAN

Protein

Radiation-inducible immediate-early gene IEX-1

Gene

IER3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 122 (01 Oct 2014)
      Sequence version 4 (11 Jan 2011)
      Previous versions | rss
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    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

    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 1 Publication; Single-pass type II membrane protein 1 Publication

    GO - Cellular componenti

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

    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...)Sequence Analysis

    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.2 Publications
    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.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 8282CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini100 – 15657ExtracellularSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei83 – 9917Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the IER3 family.Curated

    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

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti54 – 541A → G in AAB36278. (PubMed:8603392)Curated
    Sequence conflicti106 – 1061P → R in AAB36278. (PubMed:8603392)Curated

    Natural variant

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

    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

    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: October 1, 2014
    This is version 122 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