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Protein

DNA damage-inducible transcript 4 protein

Gene

DDIT4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 (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.By similarity8 Publications

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Antiviral defense, Apoptosis

Enzyme and pathway databases

ReactomeiR-HSA-5628897. TP53 Regulates Metabolic Genes.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA damage-inducible transcript 4 protein
Alternative name(s):
HIF-1 responsive protein RTP801
Protein regulated in development and DNA damage response 1
Short name:
REDD-1
Gene namesi
Name:DDIT4
Synonyms:REDD1, RTP801
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:24944. DDIT4.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • intracellular Source: LIFEdb
  • mitochondrion Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi19S → A: Strongly inhibits proteasomal degradation. 1 Publication1
Mutagenesisi23T → A: Strongly inhibits proteasomal degradation. Strongly inhibits proteasomal degradation; when associated with A-25. 1 Publication1
Mutagenesisi25T → A: Strongly inhibits proteasomal degradation; when associated with A-23. 1 Publication1
Mutagenesisi103S → L or W: No effect on inhibition of mTORC1. 1 Publication1
Mutagenesisi133R → A: No effect on inhibition of mTORC1. 1 Publication1
Mutagenesisi137S → A or D: No effect on inhibition of mTORC1. 1 Publication1
Mutagenesisi139P → A: Abolishes inhibition of mTORC1. 1 Publication1
Mutagenesisi140C → S: Mildly reduces inhibition of mTORC1. 1 Publication1
Mutagenesisi219K → A: Reduces inhibition of mTORC1. Abolishes inhibition of mTORC1; when associated with A-222. 1 Publication1
Mutagenesisi221L → A: Reduces inhibition of mTORC1. 1 Publication1
Mutagenesisi222Y → A: Reduces inhibition of mTORC1. Abolishes inhibition of mTORC1; when associated with A-219. 1 Publication1

Organism-specific databases

DisGeNETi54541.
OpenTargetsiENSG00000168209.
PharmGKBiPA134977994.

Polymorphism and mutation databases

BioMutaiDDIT4.
DMDMi74753036.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003071971 – 232DNA damage-inducible transcript 4 proteinAdd BLAST232

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei19Phosphoserine1 Publication1
Modified residuei23Phosphothreonine1 Publication1
Modified residuei25Phosphothreonine1 Publication1
Modified residuei121Phosphoserine1 Publication1

Post-translational modificationi

Phosphorylated by GSK3B; this promotes proteasomal degradation.1 Publication
Polyubiquitinated by a DCX (DDB1-CUL4A-RBX1) E3 ubiquitin-protein ligase complex with BTRC as substrate-recognition component, leading to its proteasomal degradation.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ9NX09.
PaxDbiQ9NX09.
PeptideAtlasiQ9NX09.
PRIDEiQ9NX09.

PTM databases

iPTMnetiQ9NX09.
PhosphoSitePlusiQ9NX09.

Expressioni

Tissue specificityi

Broadly expressed, with lowest levels in brain, skeletal muscle and intestine. Up-regulated in substantia nigra neurons from Parkinson disease patients (at protein level).4 Publications

Inductioni

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).7 Publications

Gene expression databases

BgeeiENSG00000168209.
CleanExiHS_DDIT4.
ExpressionAtlasiQ9NX09. baseline and differential.
GenevisibleiQ9NX09. HS.

Organism-specific databases

HPAiHPA034507.
HPA034508.

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 DDIT4.3 Publications

Protein-protein interaction databases

BioGridi120028. 13 interactors.
IntActiQ9NX09. 10 interactors.
MINTiMINT-1405734.
STRINGi9606.ENSP00000307305.

Structurei

Secondary structure

1232
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi90 – 104Combined sources15
Beta strandi107 – 112Combined sources6
Helixi121 – 135Combined sources15
Helixi141 – 144Combined sources4
Beta strandi145 – 153Combined sources9
Beta strandi156 – 165Combined sources10
Beta strandi173 – 180Combined sources8
Beta strandi214 – 220Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3LQ9X-ray2.00A/B89-226[»]
ProteinModelPortaliQ9NX09.
SMRiQ9NX09.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9NX09.

Family & Domainsi

Sequence similaritiesi

Belongs to the DDIT4 family.Curated

Phylogenomic databases

eggNOGiENOG410IIEE. Eukaryota.
ENOG4111N0W. LUCA.
GeneTreeiENSGT00530000063652.
HOGENOMiHOG000082523.
HOVERGENiHBG104439.
InParanoidiQ9NX09.
KOiK08270.
OMAiRLCANLM.
OrthoDBiEOG091G0LVJ.
PhylomeDBiQ9NX09.
TreeFamiTF105007.

Family and domain databases

InterProiIPR012918. RTP801-like.
[Graphical view]
PANTHERiPTHR12478. PTHR12478. 1 hit.
PfamiPF07809. RTP801_C. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9NX09-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPSLWDRFSS SSTSSSPSSL PRTPTPDRPP RSAWGSATRE EGFDRSTSLE
60 70 80 90 100
SSDCESLDSS NSGFGPEEDT AYLDGVSLPD FELLSDPEDE HLCANLMQLL
110 120 130 140 150
QESLAQARLG SRRPARLLMP SQLVSQVGKE LLRLAYSEPC GLRGALLDVC
160 170 180 190 200
VEQGKSCHSV GQLALDPSLV PTFQLTLVLR LDSRLWPKIQ GLFSSANSPF
210 220 230
LPGFSQSLTL STGFRVIKKK LYSSEQLLIE EC
Length:232
Mass (Da):25,371
Last modified:October 1, 2000 - v1
Checksum:i774E941EBDD08198
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti228L → P in CAB66603 (PubMed:11230166).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY090097 mRNA. Translation: AAM10442.1.
AF335324 mRNA. Translation: AAL38424.1.
AL136668 mRNA. Translation: CAB66603.1.
AK000507 mRNA. Translation: BAA91214.1.
AL683820 Genomic DNA. Translation: CAH73863.1.
CH471083 Genomic DNA. Translation: EAW54452.1.
BC000708 mRNA. Translation: AAH00708.1.
BC007714 mRNA. Translation: AAH07714.1.
BC015236 mRNA. Translation: AAH15236.1.
CCDSiCCDS7315.1.
RefSeqiNP_061931.1. NM_019058.2.
UniGeneiHs.744875.

Genome annotation databases

EnsembliENST00000307365; ENSP00000307305; ENSG00000168209.
GeneIDi54541.
KEGGihsa:54541.
UCSCiuc001jsx.2. human.

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY090097 mRNA. Translation: AAM10442.1.
AF335324 mRNA. Translation: AAL38424.1.
AL136668 mRNA. Translation: CAB66603.1.
AK000507 mRNA. Translation: BAA91214.1.
AL683820 Genomic DNA. Translation: CAH73863.1.
CH471083 Genomic DNA. Translation: EAW54452.1.
BC000708 mRNA. Translation: AAH00708.1.
BC007714 mRNA. Translation: AAH07714.1.
BC015236 mRNA. Translation: AAH15236.1.
CCDSiCCDS7315.1.
RefSeqiNP_061931.1. NM_019058.2.
UniGeneiHs.744875.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3LQ9X-ray2.00A/B89-226[»]
ProteinModelPortaliQ9NX09.
SMRiQ9NX09.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120028. 13 interactors.
IntActiQ9NX09. 10 interactors.
MINTiMINT-1405734.
STRINGi9606.ENSP00000307305.

PTM databases

iPTMnetiQ9NX09.
PhosphoSitePlusiQ9NX09.

Polymorphism and mutation databases

BioMutaiDDIT4.
DMDMi74753036.

Proteomic databases

MaxQBiQ9NX09.
PaxDbiQ9NX09.
PeptideAtlasiQ9NX09.
PRIDEiQ9NX09.

Protocols and materials databases

DNASUi54541.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000307365; ENSP00000307305; ENSG00000168209.
GeneIDi54541.
KEGGihsa:54541.
UCSCiuc001jsx.2. human.

Organism-specific databases

CTDi54541.
DisGeNETi54541.
GeneCardsiDDIT4.
HGNCiHGNC:24944. DDIT4.
HPAiHPA034507.
HPA034508.
MIMi607729. gene.
neXtProtiNX_Q9NX09.
OpenTargetsiENSG00000168209.
PharmGKBiPA134977994.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IIEE. Eukaryota.
ENOG4111N0W. LUCA.
GeneTreeiENSGT00530000063652.
HOGENOMiHOG000082523.
HOVERGENiHBG104439.
InParanoidiQ9NX09.
KOiK08270.
OMAiRLCANLM.
OrthoDBiEOG091G0LVJ.
PhylomeDBiQ9NX09.
TreeFamiTF105007.

Enzyme and pathway databases

ReactomeiR-HSA-5628897. TP53 Regulates Metabolic Genes.

Miscellaneous databases

ChiTaRSiDDIT4. human.
EvolutionaryTraceiQ9NX09.
GeneWikiiDDIT4.
GenomeRNAii54541.
PROiQ9NX09.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000168209.
CleanExiHS_DDIT4.
ExpressionAtlasiQ9NX09. baseline and differential.
GenevisibleiQ9NX09. HS.

Family and domain databases

InterProiIPR012918. RTP801-like.
[Graphical view]
PANTHERiPTHR12478. PTHR12478. 1 hit.
PfamiPF07809. RTP801_C. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDDIT4_HUMAN
AccessioniPrimary (citable) accession number: Q9NX09
Secondary accession number(s): Q9H0S3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 23, 2007
Last sequence update: October 1, 2000
Last modified: November 30, 2016
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.