InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: DDIT4

Summary

InnateDB Protein

IDBP-77886.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

DDIT4

Protein Name

DNA-damage-inducible transcript 4

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000307305

InnateDB Gene

IDBG-77884 (DDIT4)

Protein Structure

UniProt Annotation

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:0000269PubMed:15545625, ECO:0000269PubMed:15632201, ECO:0000269PubMed:15988001, ECO:0000269PubMed:17005863, ECO:0000269PubMed:17379067, ECO:0000269PubMed:19557001, ECO:0000269PubMed:20166753, ECO:0000269PubMed:21460850}.

Subcellular Localization

Mitochondrion {ECO:0000250}. Cytoplasm, cytosol {ECO:0000269PubMed:12453409}.

Disease Associations

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:0000269PubMed:11884613, ECO:0000269PubMed:12453409, ECO:0000269PubMed:17005863, ECO:0000269PubMed:17379067}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 25 experimentally validated interaction(s) in this database.

Experimentally validated
Total	25 [view]
Protein-Protein	24 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0071889	14-3-3 protein binding

Biological Process

GO:0001666	response to hypoxia
GO:0001764	neuron migration
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:0033137	negative regulation of peptidyl-serine phosphorylation
GO:0042771	intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:0043241	protein complex disassembly
GO:0045820	negative regulation of glycolytic process
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0051607	defense response to virus
GO:0072593	reactive oxygen species metabolic process
GO:1901216	positive regulation of neuron death
GO:1902532	negative regulation of intracellular signal transduction