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MT001089

UniProt Annotations

Entry Information

Gene Name	DNA-damage-inducible transcript 4
Protein Entry	DDIT4_HUMAN
UniProt ID	Q9NX09
Species	Human

Comments

Comment type	Description
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. {ECO:0000250, ECO:0000269\|PubMed:15545625, ECO:0000269\|PubMed:15632201, ECO:0000269\|PubMed:15988001, ECO:0000269\|PubMed:17005863, ECO:0000269\|PubMed:17379067, ECO:0000269\|PubMed:19557001, ECO:0000269\|PubMed:20166753, ECO:0000269\|PubMed:21460850}.
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). {ECO:0000269\|PubMed:11884613, ECO:0000269\|PubMed:12453409, ECO:0000269\|PubMed:14646594, ECO:0000269\|PubMed:15592522, ECO:0000269\|PubMed:15751966, ECO:0000269\|PubMed:17379067, ECO:0000269\|PubMed:20166753}.
Ptm	Phosphorylated by GSK3B; this promotes proteasomal degradation. {ECO:0000269\|PubMed:19557001}.
Ptm	Polyubiquitinated by a DCX (DDB1-CUL4A-RBX1) E3 ubiquitin- protein ligase complex with BTRC as substrate-recognition component, leading to its proteasomal degradation. {ECO:0000269\|PubMed:19557001}.
Similarity	Belongs to the DDIT4 family. {ECO:0000305}.
Subcellular Location	Mitochondrion {ECO:0000250}. Cytoplasm, cytosol {ECO:0000269\|PubMed:12453409}.
Subunit	Monomer. Interacts with BTRC. Identified in a complex with CUL4A, DDB1 and BTRC. Interacts with TXNIP; this inhibits the proteasomal degradation of DDIT4. {ECO:0000269\|PubMed:19557001, ECO:0000269\|PubMed:20166753, ECO:0000269\|PubMed:21460850}.
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). {ECO:0000269\|PubMed:11884613, ECO:0000269\|PubMed:12453409, ECO:0000269\|PubMed:17005863, ECO:0000269\|PubMed:17379067}.
Web Resource	Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/DDIT4ID45802ch10q22.html";