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Q9D3F7

- DDIT4_MOUSE

UniProt

Q9D3F7 - DDIT4_MOUSE

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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

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
Complete GO annotation...

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. mitochondrion Source: MGI
Complete GO annotation...

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

BgeeiQ9D3F7.
CleanExiMM_DDIT4.
ExpressionAtlasiQ9D3F7. baseline and differential.
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

        10         20         30         40         50
MPSLWDRFSS SSSSSSSSRT PAADRPPRSA WGSAAREEGL DRCASLESSD
60 70 80 90 100
CESLDSSNSG FGPEEDSSYL DGVSLPDFEL LSDPEDEHLC ANLMQLLQES
110 120 130 140 150
LSQARLGSRR PARLLMPSQL VSQVGKELLR LAYSEPCGLR GALLDVCVEQ
160 170 180 190 200
GKSCHSVAQL ALDPSLVPTF QLTLVLRLDS RLWPKIQGLL SSANSSLVPG
210 220
YSQSLTLSTG FRVIKKKLYS SEQLLIEEC
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

Bgeei Q9D3F7.
CleanExi MM_DDIT4.
ExpressionAtlasi Q9D3F7. baseline and differential.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 88 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