Q9D3F7 · DDIT4_MOUSE
- ProteinDNA damage-inducible transcript 4 protein
- GeneDdit4
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids229 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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 annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | mitochondrion | |
Molecular Function | 14-3-3 protein binding | |
Biological Process | apoptotic process | |
Biological Process | brain development | |
Biological Process | cellular response to dexamethasone stimulus | |
Biological Process | defense response to virus | |
Biological Process | intracellular signal transduction | |
Biological Process | intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator | |
Biological Process | negative regulation of glycolytic process | |
Biological Process | negative regulation of TOR signaling | |
Biological Process | neuron differentiation | |
Biological Process | neuron migration | |
Biological Process | neurotrophin TRK receptor signaling pathway | |
Biological Process | protein-containing complex disassembly | |
Biological Process | reactive oxygen species metabolic process | |
Biological Process | response to hypoxia |
Keywords
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDNA damage-inducible transcript 4 protein
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ9D3F7
Proteomes
Organism-specific databases
Subcellular Location
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
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 4 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000307198 | 1-229 | DNA damage-inducible transcript 4 protein | |||
Sequence: MPSLWDRFSSSSSSSSSSRTPAADRPPRSAWGSAAREEGLDRCASLESSDCESLDSSNSGFGPEEDSSYLDGVSLPDFELLSDPEDEHLCANLMQLLQESLSQARLGSRRPARLLMPSQLVSQVGKELLRLAYSEPCGLRGALLDVCVEQGKSCHSVAQLALDPSLVPTFQLTLVLRLDSRLWPKIQGLLSSANSSLVPGYSQSLTLSTGFRVIKKKLYSSEQLLIEEC | ||||||
Modified residue | 16 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 20 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 118 | Phosphoserine | ||||
Sequence: S |
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
- PTM
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
Structure
Family & Domains
Features
Showing features for compositional bias, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-23 | Polar residues | ||||
Sequence: MPSLWDRFSSSSSSSSSSRTPAA | ||||||
Region | 1-68 | Disordered | ||||
Sequence: MPSLWDRFSSSSSSSSSSRTPAADRPPRSAWGSAAREEGLDRCASLESSDCESLDSSNSGFGPEEDSS | ||||||
Compositional bias | 49-64 | Polar residues | ||||
Sequence: SDCESLDSSNSGFGPE |
Sequence similarities
Belongs to the DDIT4 family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length229
- Mass (Da)24,871
- Last updated2001-06-01 v1
- ChecksumFE7EA24D3FF63949
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-23 | Polar residues | ||||
Sequence: MPSLWDRFSSSSSSSSSSRTPAA | ||||||
Compositional bias | 49-64 | Polar residues | ||||
Sequence: SDCESLDSSNSGFGPE |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |