Human Gene DDIT4 (ENST00000307365.3) from GENCODE V47lift37
Description: 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 (By similarity). Required for mTORC1-mediated defense against viral protein synthesis and virus replication (By similarity). 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. (from UniProt Q9NX09) Gencode Transcript: ENST00000307365.3 Gencode Gene: ENSG00000168209.4 Transcript (Including UTRs) Position: hg19 chr10:74,033,678-74,035,794 Size: 2,117 Total Exon Count: 3 Strand: + Coding Region Position: hg19 chr10:74,033,975-74,034,946 Size: 972 Coding Exon Count: 2
ID:DDIT4_HUMAN DESCRIPTION: RecName: Full=DNA damage-inducible transcript 4 protein; AltName: Full=HIF-1 responsive protein RTP801; AltName: Full=Protein regulated in development and DNA damage response 1; Short=REDD-1; 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 (By similarity).Required for mTORC1-mediated defense against viral protein synthesis and virus replication (By similarity). 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. SUBUNIT: Monomer. Interacts with BTRC. Identified in a complex with CUL4A, DDB1 and BTRC. Interacts with TXNIP; this inhibits the proteasomal degradation of DDIT4. SUBCELLULAR LOCATION: Mitochondrion (By similarity). Cytoplasm, cytosol. TISSUE SPECIFICITY: Broadly expressed, with lowest levels in brain, skeletal muscle and intestine. Up-regulated in substantia nigra neurons from Parkinson disease patients (at protein level). INDUCTION: Up-regulated in fibroblasts upon ionizing radiation, via a TP53-dependent pathway. Up-regulated by TP63 in primary keratinocytes, and down-regulated during keratinocyte differentiation. Up-regulated upon DNA alkylation. Up-regulated by amyloid beta-peptide and retinoic acid. Up-regulated by hypoxia, via a PI3K and HIF1A-dependent but TP53/TP63-independent mechanism (at protein level). PTM: Phosphorylated by GSK3B; this promotes proteasomal degradation. PTM: Polyubiquitinated by a DCX (DDB1-CUL4A-RBX1) E3 ubiquitin- protein ligase complex with BTRC as substrate-recognition component, leading to its proteasomal degradation. SIMILARITY: Belongs to the DDIT4 family.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9NX09
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0071889 14-3-3 protein binding
Biological Process: GO:0001666 response to hypoxia GO:0001764 neuron migration GO:0006915 apoptotic process GO:0007420 brain development GO:0008283 cell proliferation GO:0009968 negative regulation of signal transduction GO:0010801 negative regulation of peptidyl-threonine phosphorylation GO:0030182 neuron differentiation GO:0032007 negative regulation of TOR signaling GO:0032984 macromolecular complex disassembly GO:0033137 negative regulation of peptidyl-serine phosphorylation GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator GO:0045820 negative regulation of glycolytic process GO:0048011 neurotrophin TRK receptor signaling pathway GO:0051607 defense response to virus GO:0071549 cellular response to dexamethasone stimulus GO:0072593 reactive oxygen species metabolic process GO:1901216 positive regulation of neuron death GO:1902532 negative regulation of intracellular signal transduction
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
