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Protein

Tumor necrosis factor receptor type 1-associated DEATH domain protein

Gene

Tradd

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Adapter molecule for TNFRSF1A/TNFR1 that specifically associates with the cytoplasmic domain of activated TNFRSF1A/TNFR1 mediating its interaction with FADD. Overexpression of TRADD leads to two major TNF-induced responses, apoptosis and activation of NF-kappa-B (By similarity). The nuclear form acts as a tumor suppressor by preventing ubiquitination and degradation of isoform p19ARF/ARF of CDKN2A by TRIP12: acts by interacting with TRIP12, leading to disrupt interaction between TRIP12 and isoform p19ARF/ARF of CDKN2A.By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

  • extrinsic apoptotic signaling pathway Source: MGI
  • positive regulation of hair follicle development Source: UniProtKB
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
  • protein heterooligomerization Source: Ensembl

Keywordsi

Biological processApoptosis

Enzyme and pathway databases

ReactomeiR-MMU-3371378. Regulation by c-FLIP.
R-MMU-5213460. RIPK1-mediated regulated necrosis.
R-MMU-5218900. CASP8 activity is inhibited.
R-MMU-5357786. TNFR1-induced proapoptotic signaling.
R-MMU-5357905. Regulation of TNFR1 signaling.
R-MMU-5357956. TNFR1-induced NFkappaB signaling pathway.
R-MMU-69416. Dimerization of procaspase-8.
R-MMU-75893. TNF signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor necrosis factor receptor type 1-associated DEATH domain protein
Short name:
TNFR1-associated DEATH domain protein
Alternative name(s):
TNFRSF1A-associated via death domain
Gene namesi
Name:TraddImported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:109200. Tradd.

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, Cytoskeleton, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice develop tumors. In a C57BL/6 genetic background, mice exhibit a shorter lifespan than wild-type, but exhibit low incidences of observable tumor formation. In the FVB/N background, which is more tumor-prone, mice show a significant increas in the spontaneous development of a broad range of tumor types.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi297 – 299EDL → AAA: Dominant-negative mutant, leading to enhanced ubiquitination and degradation of isoform p19ARF/ARF of CDKN2A. 1 Publication3

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002916601 – 310Tumor necrosis factor receptor type 1-associated DEATH domain proteinAdd BLAST310

Proteomic databases

EPDiQ3U0V2.
MaxQBiQ3U0V2.
PaxDbiQ3U0V2.
PRIDEiQ3U0V2.

PTM databases

iPTMnetiQ3U0V2.
PhosphoSitePlusiQ3U0V2.

Expressioni

Gene expression databases

BgeeiENSMUSG00000031887.
CleanExiMM_TRADD.
ExpressionAtlasiQ3U0V2. baseline and differential.
GenevisibleiQ3U0V2. MM.

Interactioni

Subunit structurei

Stimulation of TNF-alpha receptor TNFRSF1A leads to the formation of two distinct signaling complexes. Plasma membrane-bound complex I is composed of TNFRSF1A, TRADD, RIPK1, TRAF2 and BIRC2/c-IAP1 or BIRC3 which interacts with CHUCK/IKK-alpha, IKBKB/IKK-beta and IKBKG/IKK-gamma promoting cell survival (PubMed:14585990). Subsequently, TRADD, RIPK1 and TRAF2 dissociate from TNFRSF1A and form cytoplasmic complex II with FADD and caspase CASP8 promoting cell apoptosis (By similarity). Within complex I, interacts with TNFRSF1A/TNFR1, TRAF2 and kinase RIPK1 (By similarity). Within complex I, interacts with TRPC4AP; the interaction promotes NF-kappa B activation (PubMed:14585990). UXT1 associates with complex I; the interaction prevents the formation of complex II (By similarity). Within complex I Interacts with scaffold protein DAB2IP (By similarity). Interacts with autophagy receptor SQSTM1 (By similarity). Interacts with E3 ligase TRIP12 (PubMed:22561347). Interacts with kinase HIPK2 (By similarity). Interacts with keratin KRT14 (PubMed:16702408). Interacts with keratin KRT18 (By similarity). Interacts with KRT16 and KRT17 (PubMed:16702408).By similarity3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi214812. 1 interactor.
CORUMiQ3U0V2.
DIPiDIP-38039N.
IntActiQ3U0V2. 9 interactors.
STRINGi10090.ENSMUSP00000034359.

Structurei

3D structure databases

ProteinModelPortaliQ3U0V2.
SMRiQ3U0V2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini213 – 303DeathPROSITE-ProRule annotationAdd BLAST91

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni220 – 287Interaction with KRT14 and KRT18By similarityAdd BLAST68

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi147 – 163Nuclear export signalAdd BLAST17
Motifi229 – 242Nuclear localization signalAdd BLAST14

Domaini

Requires the intact death domain to associate with TNFRSF1A/TNFR1.By similarity

Phylogenomic databases

eggNOGiENOG410IF81. Eukaryota.
ENOG4111IRA. LUCA.
GeneTreeiENSGT00390000002016.
HOGENOMiHOG000059664.
HOVERGENiHBG054083.
InParanoidiQ3U0V2.
KOiK03171.
OMAiFCGRQPC.
OrthoDBiEOG091G0DXR.
PhylomeDBiQ3U0V2.
TreeFamiTF331882.

Family and domain databases

Gene3Di3.30.70.680. 1 hit.
InterProiView protein in InterPro
IPR011029. DEATH-like_dom_sf.
IPR000488. Death_domain.
IPR035712. TRADD.
IPR009095. TRADD_N.
IPR036729. TRADD_N_sf.
PANTHERiPTHR14913. PTHR14913. 1 hit.
PfamiView protein in Pfam
PF00531. Death. 1 hit.
PF09034. TRADD_N. 1 hit.
ProDomiView protein in ProDom or Entries sharing at least one domain
PD182470. TRADD_N. 1 hit.
SMARTiView protein in SMART
SM00005. DEATH. 1 hit.
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF55044. SSF55044. 1 hit.
PROSITEiView protein in PROSITE
PS50017. DEATH_DOMAIN. 1 hit.

Sequencei

Sequence statusi: Complete.

Q3U0V2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAGQNGHEE WVGSAYLFLE SAVDKVILSE AYTDPKKKVA IYKALQTALS
60 70 80 90 100
ESGDSSDVLQ ILKIHCSDPQ LIVQLRFCGR VLCGRFLQAY REGALRTALQ
110 120 130 140 150
RCMAPALAQE ALRLQLELRA GAEQLDSWLT DEERCLNYIL AQKPDRLRDE
160 170 180 190 200
ELAELEDELC KLTCDCTGQG GAIQVASAGS KFPVSSPTEE KPLPAACQTF
210 220 230 240 250
LFHGQLVVNR PLTLQDQQTF ARSVGLKWRR VGRSLQRNCR ALRDPALDSL
260 270 280 290 300
AYEYERDGLY EQAFQLLRRF MQAEGRRATL QRLVEALEEN ELTSLAEDLL
310
GQAEPDGGLA
Length:310
Mass (Da):34,577
Last modified:October 11, 2005 - v1
Checksum:i225F00D4022691BB
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK156540 mRNA. Translation: BAE33749.1.
BC132607 mRNA. Translation: AAI32608.1.
CCDSiCCDS22594.1.
RefSeqiNP_001028333.1. NM_001033161.2.
UniGeneiMm.264255.

Genome annotation databases

EnsembliENSMUST00000034359; ENSMUSP00000034359; ENSMUSG00000031887.
GeneIDi71609.
KEGGimmu:71609.
UCSCiuc009nby.1. mouse.

Similar proteinsi

Entry informationi

Entry nameiTRADD_MOUSE
AccessioniPrimary (citable) accession number: Q3U0V2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 26, 2007
Last sequence update: October 11, 2005
Last modified: November 22, 2017
This is version 105 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

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot