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Protein

DNA damage-inducible transcript 4 protein

Gene

Ddit4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.6 Publications

GO - Molecular functioni

  • 14-3-3 protein binding Source: MGI

GO - Biological processi

  • brain development Source: UniProtKB
  • cell proliferation Source: UniProtKB
  • cellular response to dexamethasone stimulus Source: MGI
  • defense response to virus Source: MGI
  • intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: UniProtKB
  • negative regulation of glycolytic process Source: MGI
  • negative regulation of intracellular signal transduction Source: UniProtKB
  • negative regulation of peptidyl-serine phosphorylation Source: UniProtKB
  • negative regulation of peptidyl-threonine phosphorylation Source: UniProtKB
  • negative regulation of TOR signaling Source: MGI
  • neuron differentiation Source: UniProtKB
  • neuron migration Source: UniProtKB
  • neurotrophin TRK receptor signaling pathway Source: UniProtKB
  • positive regulation of neuron death Source: UniProtKB
  • protein-containing complex disassembly Source: MGI
  • reactive oxygen species metabolic process Source: MGI
  • response to hypoxia Source: MGI

Keywordsi

Biological processAntiviral defense, Apoptosis

Enzyme and pathway databases

ReactomeiR-MMU-5628897 TP53 Regulates Metabolic Genes

Names & Taxonomyi

Protein namesi
Recommended name:
DNA damage-inducible transcript 4 protein
Alternative name(s):
Dexamethasone-induced gene 2 protein
HIF-1 responsive protein RTP801
Protein regulated in development and DNA damage response 1
Short name:
REDD-1
Gene namesi
Name:Ddit4
Synonyms:Dig2, Redd1, Rtp801
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1921997 Ddit4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Mitochondrion

Pathology & Biotechi

Disruption phenotypei

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.5 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003071981 – 229DNA damage-inducible transcript 4 proteinAdd BLAST229

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei16PhosphoserineBy similarity1
Modified residuei20PhosphothreonineBy similarity1
Modified residuei118PhosphoserineBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9D3F7
PRIDEiQ9D3F7

PTM databases

iPTMnetiQ9D3F7
PhosphoSitePlusiQ9D3F7

Expressioni

Tissue specificityi

Ubiquitously expressed.2 Publications

Developmental stagei

Expressed at E7. At E11, expressed in the apical ectodermal ridge. At E13.5, expressed in the whisker pad, eyelid, breast primordia and developing limb. At E14.5, expressed in supraorbital and suborbital follicles, whisker pad, limbs and patches of developing epidermis.2 Publications

Inductioni

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.7 Publications

Gene expression databases

BgeeiENSMUSG00000020108
CleanExiMM_DDIT4
ExpressionAtlasiQ9D3F7 baseline and differential
GenevisibleiQ9D3F7 MM

Interactioni

Subunit structurei

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).By similarity

GO - Molecular functioni

  • 14-3-3 protein binding Source: MGI

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000020308

Structurei

3D structure databases

ProteinModelPortaliQ9D3F7
SMRiQ9D3F7
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the DDIT4 family.Curated

Phylogenomic databases

eggNOGiENOG410IIEE Eukaryota
ENOG4111N0W LUCA
GeneTreeiENSGT00530000063652
HOGENOMiHOG000082523
HOVERGENiHBG104439
InParanoidiQ9D3F7
KOiK08270
OMAiDEHLCAS
OrthoDBiEOG091G0LVJ
PhylomeDBiQ9D3F7
TreeFamiTF105007

Family and domain databases

Gene3Di1.10.490.100, 1 hit
InterProiView protein in InterPro
IPR012918 RTP801-like
IPR038281 RTP801-like_C_sf
PANTHERiPTHR12478 PTHR12478, 1 hit
PfamiView protein in Pfam
PF07809 RTP801_C, 1 hit

Sequencei

Sequence statusi: Complete.

Q9D3F7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPSLWDRFSS SSSSSSSSRT PAADRPPRSA WGSAAREEGL DRCASLESSD
60 70 80 90 100
CESLDSSNSG FGPEEDSSYL DGVSLPDFEL LSDPEDEHLC ANLMQLLQES
110 120 130 140 150
LSQARLGSRR PARLLMPSQL VSQVGKELLR LAYSEPCGLR GALLDVCVEQ
160 170 180 190 200
GKSCHSVAQL ALDPSLVPTF QLTLVLRLDS RLWPKIQGLL SSANSSLVPG
210 220
YSQSLTLSTG FRVIKKKLYS SEQLLIEEC
Length:229
Mass (Da):24,871
Last modified:June 1, 2001 - v1
Checksum:iFE7EA24D3FF63949
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY260552 mRNA Translation: AAP13851.1
AK017926 mRNA Translation: BAB31006.1
AK081046 mRNA Translation: BAC38121.1
BC131992 mRNA Translation: AAI31993.1
BC132645 mRNA Translation: AAI32646.1
CCDSiCCDS23868.1
RefSeqiNP_083359.1, NM_029083.2
UniGeneiMm.21697

Genome annotation databases

EnsembliENSMUST00000020308; ENSMUSP00000020308; ENSMUSG00000020108
GeneIDi74747
KEGGimmu:74747
UCSCiuc007fee.1 mouse

Similar proteinsi

Entry informationi

Entry nameiDDIT4_MOUSE
AccessioniPrimary (citable) accession number: Q9D3F7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 23, 2007
Last sequence update: June 1, 2001
Last modified: May 23, 2018
This is version 113 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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