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Q9D3F7

- DDIT4_MOUSE

UniProt

Q9D3F7 - DDIT4_MOUSE

Protein

DNA damage-inducible transcript 4 protein

Gene

Ddit4

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 87 (01 Oct 2014)
      Sequence version 1 (01 Jun 2001)
      Previous versions | rss
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    Functioni

    Regulates cell growth, proliferation and survival via inhibition of the activity of the mammalian target of rapamycin complex 1 (mTORC1). Inhibition of mTORC1 is mediated by a pathway that involves DDIT4/REDD1, AKT1, the TSC1-TSC2 complex and the GTPase RHEB. Plays an important role in responses to cellular energy levels and cellular stress, including responses to hypoxia and DNA damage. Regulates p53/TP53-mediated apoptosis in response to DNA damage via its effect on mTORC1 activity. Its role in the response to hypoxia depends on the cell type; it mediates mTORC1 inhibition in fibroblasts and thymocytes, but not in hepatocytes. Inhibits neuronal differentiation and neurite outgrowth mediated by NGF via its effect on mTORC1 activity. Required for normal neuron migration during embryonic brain development. Plays a role in neuronal cell death. Required for mTORC1-mediated defense against viral protein synthesis and virus replication.6 Publications

    GO - Molecular functioni

    1. 14-3-3 protein binding Source: MGI

    GO - Biological processi

    1. brain development Source: UniProtKB
    2. cell proliferation Source: UniProtKB
    3. defense response to virus Source: UniProtKB-KW
    4. intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: UniProtKB
    5. negative regulation of glycolytic process Source: MGI
    6. negative regulation of intracellular signal transduction Source: UniProtKB
    7. negative regulation of peptidyl-serine phosphorylation Source: UniProtKB
    8. negative regulation of peptidyl-threonine phosphorylation Source: UniProtKB
    9. negative regulation of TOR signaling Source: MGI
    10. neuron differentiation Source: UniProtKB
    11. neuron migration Source: UniProtKB
    12. neurotrophin TRK receptor signaling pathway Source: UniProtKB
    13. positive regulation of neuron death Source: UniProtKB
    14. protein complex disassembly Source: MGI
    15. reactive oxygen species metabolic process Source: MGI
    16. response to hypoxia Source: MGI

    Keywords - Biological processi

    Antiviral defense, Apoptosis

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    DNA damage-inducible transcript 4 protein
    Alternative name(s):
    Dexamethasone-induced gene 2 protein
    HIF-1 responsive protein RTP801
    Protein regulated in development and DNA damage response 1
    Short name:
    REDD-1
    Gene namesi
    Name:Ddit4
    Synonyms:Dig2, Redd1, Rtp801
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 10

    Organism-specific databases

    MGIiMGI:1921997. Ddit4.

    Subcellular locationi

    Mitochondrion 1 Publication. Cytoplasmcytosol 1 Publication

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. cytosol Source: UniProtKB-SubCell
    3. mitochondrion Source: MGI

    Keywords - Cellular componenti

    Cytoplasm, Mitochondrion

    Pathology & Biotechi

    Disruption phenotypei

    No visible phenotype. Mice are normal and less sensitive to oxygen-induced retinopathy. Mitochondria show increased production of reactive oxygen species. Newborn mice show increased radiation-induced apoptosis in brain and thymus, due to increased levels of TP53 and increased TP53 activity. Likewise, cultured embryonic fibroblasts are highly sensitive to DNA damage caused by UV irradiation or doxomycin and display increased levels of TP53 and increased TP53 activity, leading to increased apoptosis. Cultured embryonic fibroblasts are more susceptible to cell death caused by influenza virus infection and produce about 200 times more virus particles than wild-type.5 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 229229DNA damage-inducible transcript 4 proteinPRO_0000307198Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei16 – 161PhosphoserineBy similarity
    Modified residuei20 – 201PhosphothreonineBy similarity
    Modified residuei118 – 1181PhosphoserineBy similarity

    Post-translational modificationi

    Phosphorylated by GSK3B; this promotes proteasomal degradation.By similarity
    Polyubiquitinated by a DCX (DDB1-CUL4A-RBX1) E3 ubiquitin-protein ligase complex with BTRC as substrate-recognition component, leading to its proteasomal degradation.By similarity

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    PRIDEiQ9D3F7.

    PTM databases

    PhosphoSiteiQ9D3F7.

    Expressioni

    Tissue specificityi

    Ubiquitously expressed.2 Publications

    Developmental stagei

    Expressed at E7. At E11, expressed in the apical ectodermal ridge. At E13.5, expressed in the whisker pad, eyelid, breast primordia and developing limb. At E14.5, expressed in supraorbital and suborbital follicles, whisker pad, limbs and patches of developing epidermis.2 Publications

    Inductioni

    By dexamethasone, heat-shock or osmotic stress. Up-regulated by hypoxia, in a HIF1A-dependent but TP53-independent mechanism. Up-regulated upon energy stress. Up-regulated in brain from MPTP-intoxicated mice, a model for Parkinson disease (at protein level). Up-regulated by hypoxia in bowel, liver, spleen, heart, lung, brain and kidney.7 Publications

    Gene expression databases

    ArrayExpressiQ9D3F7.
    BgeeiQ9D3F7.
    CleanExiMM_DDIT4.
    GenevestigatoriQ9D3F7.

    Interactioni

    Subunit structurei

    Monomer. Interacts with BTRC. Identified in a complex with CUL4A, DDB1 and BTRC. Interacts with TXNIP; this inhibits the proteasomal degradation of DDIT4 By similarity.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliQ9D3F7.
    SMRiQ9D3F7. Positions 86-219.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the DDIT4 family.Curated

    Phylogenomic databases

    eggNOGiNOG78982.
    GeneTreeiENSGT00530000063652.
    HOGENOMiHOG000082523.
    HOVERGENiHBG104439.
    InParanoidiQ9D3F7.
    KOiK08270.
    OMAiDEHLCAS.
    OrthoDBiEOG7P2XTF.
    PhylomeDBiQ9D3F7.
    TreeFamiTF105007.

    Family and domain databases

    InterProiIPR012918. RTP801-like.
    [Graphical view]
    PANTHERiPTHR12478. PTHR12478. 1 hit.
    PfamiPF07809. RTP801_C. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q9D3F7-1 [UniParc]FASTAAdd to Basket

    « Hide

    MPSLWDRFSS SSSSSSSSRT PAADRPPRSA WGSAAREEGL DRCASLESSD    50
    CESLDSSNSG FGPEEDSSYL DGVSLPDFEL LSDPEDEHLC ANLMQLLQES 100
    LSQARLGSRR PARLLMPSQL VSQVGKELLR LAYSEPCGLR GALLDVCVEQ 150
    GKSCHSVAQL ALDPSLVPTF QLTLVLRLDS RLWPKIQGLL SSANSSLVPG 200
    YSQSLTLSTG FRVIKKKLYS SEQLLIEEC 229
    Length:229
    Mass (Da):24,871
    Last modified:June 1, 2001 - v1
    Checksum:iFE7EA24D3FF63949
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY260552 mRNA. Translation: AAP13851.1.
    AK017926 mRNA. Translation: BAB31006.1.
    AK081046 mRNA. Translation: BAC38121.1.
    BC131992 mRNA. Translation: AAI31993.1.
    BC132645 mRNA. Translation: AAI32646.1.
    CCDSiCCDS23868.1.
    RefSeqiNP_083359.1. NM_029083.2.
    UniGeneiMm.21697.

    Genome annotation databases

    EnsembliENSMUST00000020308; ENSMUSP00000020308; ENSMUSG00000020108.
    GeneIDi74747.
    KEGGimmu:74747.
    UCSCiuc007fee.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY260552 mRNA. Translation: AAP13851.1 .
    AK017926 mRNA. Translation: BAB31006.1 .
    AK081046 mRNA. Translation: BAC38121.1 .
    BC131992 mRNA. Translation: AAI31993.1 .
    BC132645 mRNA. Translation: AAI32646.1 .
    CCDSi CCDS23868.1.
    RefSeqi NP_083359.1. NM_029083.2.
    UniGenei Mm.21697.

    3D structure databases

    ProteinModelPortali Q9D3F7.
    SMRi Q9D3F7. Positions 86-219.
    ModBasei Search...
    MobiDBi Search...

    PTM databases

    PhosphoSitei Q9D3F7.

    Proteomic databases

    PRIDEi Q9D3F7.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000020308 ; ENSMUSP00000020308 ; ENSMUSG00000020108 .
    GeneIDi 74747.
    KEGGi mmu:74747.
    UCSCi uc007fee.1. mouse.

    Organism-specific databases

    CTDi 54541.
    MGIi MGI:1921997. Ddit4.

    Phylogenomic databases

    eggNOGi NOG78982.
    GeneTreei ENSGT00530000063652.
    HOGENOMi HOG000082523.
    HOVERGENi HBG104439.
    InParanoidi Q9D3F7.
    KOi K08270.
    OMAi DEHLCAS.
    OrthoDBi EOG7P2XTF.
    PhylomeDBi Q9D3F7.
    TreeFami TF105007.

    Miscellaneous databases

    ChiTaRSi DDIT4. mouse.
    NextBioi 341548.
    PROi Q9D3F7.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9D3F7.
    Bgeei Q9D3F7.
    CleanExi MM_DDIT4.
    Genevestigatori Q9D3F7.

    Family and domain databases

    InterProi IPR012918. RTP801-like.
    [Graphical view ]
    PANTHERi PTHR12478. PTHR12478. 1 hit.
    Pfami PF07809. RTP801_C. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Dexamethasone-induced gene 2 (dig2) is a novel pro-survival stress gene induced rapidly by diverse apoptotic signals."
      Wang Z., Malone M.H., Thomenius M.J., Zhong F., Xu F., Distelhorst C.W.
      J. Biol. Chem. 278:27053-27058(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
      Strain: C57BL/6.
      Tissue: Thymus.
    2. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J.
      Tissue: Cerebellum and Thymus.
    3. "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].
      Tissue: Brain.
    4. "REDD1, a developmentally regulated transcriptional target of p63 and p53, links p63 to regulation of reactive oxygen species."
      Ellisen L.W., Ramsayer K.D., Johannessen C.M., Yang A., Beppu H., Minda K., Oliner J.D., McKeon F., Haber D.A.
      Mol. Cell 10:995-1005(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION, DEVELOPMENTAL STAGE, INDUCTION.
    5. Cited for: INDUCTION.
    6. "Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex."
      Brugarolas J., Lei K., Hurley R.L., Manning B.D., Reiling J.H., Hafen E., Witters L.A., Ellisen L.W., Kaelin W.G. Jr.
      Genes Dev. 18:2893-2904(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION, FUNCTION.
    7. Cited for: INDUCTION, DISRUPTION PHENOTYPE.
    8. "Regulation of mTOR and cell growth in response to energy stress by REDD1."
      Sofer A., Lei K., Johannessen C.M., Ellisen L.W.
      Mol. Cell. Biol. 25:5834-5845(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION, INDUCTION.
    9. "RTP801 is elevated in Parkinson brain substantia nigral neurons and mediates death in cellular models of Parkinson's disease by a mechanism involving mammalian target of rapamycin inactivation."
      Malagelada C., Ryu E.J., Biswas S.C., Jackson-Lewis V., Greene L.A.
      J. Neurosci. 26:9996-10005(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION.
    10. "Negative feedback control of HIF-1 through REDD1-regulated ROS suppresses tumorigenesis."
      Horak P., Crawford A.R., Vadysirisack D.D., Nash Z.M., DeYoung M.P., Sgroi D., Ellisen L.W.
      Proc. Natl. Acad. Sci. U.S.A. 107:4675-4680(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION.
    11. "Cell-type-dependent regulation of mTORC1 by REDD1 and the tumor suppressors TSC1/TSC2 and LKB1 in response to hypoxia."
      Wolff N.C., Vega-Rubin-de-Celis S., Xie X.J., Castrillon D.H., Kabbani W., Brugarolas J.
      Mol. Cell. Biol. 31:1870-1884(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INDUCTION, TISSUE SPECIFICITY.
    12. "Feedback control of p53 translation by REDD1 and mTORC1 limits the p53-dependent DNA damage response."
      Vadysirisack D.D., Baenke F., Ory B., Lei K., Ellisen L.W.
      Mol. Cell. Biol. 31:4356-4365(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DISRUPTION PHENOTYPE.
    13. Cited for: FUNCTION, DISRUPTION PHENOTYPE.

    Entry informationi

    Entry nameiDDIT4_MOUSE
    AccessioniPrimary (citable) accession number: Q9D3F7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 23, 2007
    Last sequence update: June 1, 2001
    Last modified: October 1, 2014
    This is version 87 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3