Q9D3F7 · DDIT4_MOUSE

  • Protein
    DNA damage-inducible transcript 4 protein
  • Gene
    Ddit4
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

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.

GO annotations

all annotationsall molecular functionvirus receptor activitydna bindingrna bindingcytoskeletal motor activitycatalytic activitygtpase activitystructural molecule activitytransporter activitycytoskeletal protein bindinglipid bindingcyclase activityantioxidant activityoxidoreductase activitytransferase activityhydrolase activitylyase activityisomerase activityligase activityprotein tag activitycargo receptor activityhistone bindingprotein folding chaperonetranslation regulator activitynutrient reservoir activityreceptor ligand activitymolecular transducer activitymolecular adaptor activitytoxin activitycell adhesion mediator activitymolecular function regulator activityvirus coreceptor activitycatalytic activity, acting on a proteincatalytic activity, acting on dnacatalytic activity, acting on rnamolecular carrier activitytranscription regulator activitygeneral transcription initiation factor activitymolecular sensor activitymolecular sequestering activityatp-dependent activityother molecular functionall biological processmitotic cell cyclecytokinesiscytoplasmic translationimmune system processmuscle system processcirculatory system processrenal system processrespiratory system processcarbohydrate metabolic processgeneration of precursor metabolites and energydna replicationdna repairdna recombinationchromatin organizationdna-templated transcriptionregulation of dna-templated transcriptiontrna metabolic processprotein foldingprotein glycosylationamino acid metabolic processmodified amino acid metabolic processlipid metabolic processvitamin metabolic processsulfur compound metabolic processintracellular protein transportnucleocytoplasmic transportautophagyinflammatory responsemitochondrion organizationcytoskeleton organizationmicrotubule-based movementperoxisome organizationlysosome organizationchromosome segregationcell adhesionestablishment or maintenance of cell polarityprogrammed cell deathphotosynthesismrna metabolic processsnrna metabolic processvesicle-mediated transportreproductive processdigestive system processsignalingcell differentiationprotein catabolic processextracellular matrix organizationregulatory ncrna-mediated gene silencingtelomere organizationcell junction organizationwound healingribosome biogenesiscilium organizationanatomical structure developmentcell motilitynervous system processendocrine processprotein maturationtransmembrane transportnucleobase-containing small molecule metabolic processhepaticobiliary system processmembrane organizationprotein-containing complex assemblycell wall organization or biogenesisnitrogen cycle metabolic processprotein localization to plasma membranedefense response to other organismdetoxificationmeiotic nuclear divisionmitotic nuclear divisionmitochondrial gene expressioncarbohydrate derivative metabolic processother biological processall cellular componentnuclear chromosomeextracellular regionextracellular spacecell wallnucleusnuclear envelopenucleoplasmchromosomenucleolusmitochondrionlysosomeendosomevacuoleperoxisomeendoplasmic reticulumgolgi apparatuslipid dropletmicrotubule organizing centercytosolribosomecytoskeletonplasma membraneciliumplastidthylakoidexternal encapsulating structureextracellular matrixcytoplasmic vesicleorganelleother cellular component
Cell color indicative of number of GO terms
AspectTerm
Cellular Componentcytoplasm
Cellular Componentcytosol
Cellular Componentmitochondrion
Molecular Function14-3-3 protein binding
Biological Processapoptotic process
Biological Processbrain development
Biological Processcellular response to dexamethasone stimulus
Biological Processdefense response to virus
Biological Processintracellular signal transduction
Biological Processintrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
Biological Processnegative regulation of glycolytic process
Biological Processnegative regulation of TOR signaling
Biological Processneuron differentiation
Biological Processneuron migration
Biological Processneurotrophin TRK receptor signaling pathway
Biological Processprotein-containing complex disassembly
Biological Processreactive oxygen species metabolic process
Biological Processresponse to hypoxia

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    DNA damage-inducible transcript 4 protein
  • Alternative names
    • Dexamethasone-induced gene 2 protein
    • HIF-1 responsive protein RTP801
    • Protein regulated in development and DNA damage response 1 (REDD-1)

Gene names

    • Name
      Ddit4
    • Synonyms
      Dig2, Redd1, Rtp801

Organism names

  • Taxonomic identifier
  • Strain
    • C57BL/6J
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q9D3F7

Proteomes

Organism-specific databases

Subcellular Location

Keywords

Phenotypes & Variants

Disruption phenotype

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.

Variants

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The viewer provides 4 variants from UniProt as well as other sources including ClinVar and dbSNP.

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PTM/Processing

Features

Showing features for chain, modified residue.

TypeIDPosition(s)Description
ChainPRO_00003071981-229DNA damage-inducible transcript 4 protein
Modified residue16Phosphoserine
Modified residue20Phosphothreonine
Modified residue118Phosphoserine

Post-translational modification

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

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Ubiquitously expressed.

Induction

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.

Developmental stage

Expressed at 7 dpc. At 11 dpc, expressed in the apical ectodermal ridge. At 13.5 dpc, expressed in the whisker pad, eyelid, breast primordia and developing limb. At 14.5 dpc, expressed in supraorbital and suborbital follicles, whisker pad, limbs and patches of developing epidermis.

Gene expression databases

Interaction

Subunit

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).

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for compositional bias, region.

TypeIDPosition(s)Description
Compositional bias1-23Polar residues
Region1-68Disordered
Compositional bias49-64Polar residues

Sequence similarities

Belongs to the DDIT4 family.

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    229
  • Mass (Da)
    24,871
  • Last updated
    2001-06-01 v1
  • Checksum
    FE7EA24D3FF63949
MPSLWDRFSSSSSSSSSSRTPAADRPPRSAWGSAAREEGLDRCASLESSDCESLDSSNSGFGPEEDSSYLDGVSLPDFELLSDPEDEHLCANLMQLLQESLSQARLGSRRPARLLMPSQLVSQVGKELLRLAYSEPCGLRGALLDVCVEQGKSCHSVAQLALDPSLVPTFQLTLVLRLDSRLWPKIQGLLSSANSSLVPGYSQSLTLSTGFRVIKKKLYSSEQLLIEEC

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias1-23Polar residues
Compositional bias49-64Polar residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AY260552
EMBL· GenBank· DDBJ
AAP13851.1
EMBL· GenBank· DDBJ
mRNA
AK017926
EMBL· GenBank· DDBJ
BAB31006.1
EMBL· GenBank· DDBJ
mRNA
AK081046
EMBL· GenBank· DDBJ
BAC38121.1
EMBL· GenBank· DDBJ
mRNA
BC131992
EMBL· GenBank· DDBJ
AAI31993.1
EMBL· GenBank· DDBJ
mRNA
BC132645
EMBL· GenBank· DDBJ
AAI32646.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

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