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UniProtKB - Q15628 (TRADD_HUMAN)

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Protein

Tumor necrosis factor receptor type 1-associated DEATH domain protein

Gene

TRADD

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 similarity). 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

GO - Molecular functioni

  • death domain binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • kinase binding Source: BHF-UCL
  • molecular adaptor activity Source: BHF-UCL
  • protein-containing complex binding Source: Ensembl
  • tumor necrosis factor receptor binding Source: Ensembl
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Biological processApoptosis

Enzyme and pathway databases

ReactomeiR-HSA-140534 Ligand-dependent caspase activation
R-HSA-3371378 Regulation by c-FLIP
R-HSA-5213460 RIPK1-mediated regulated necrosis
R-HSA-5218900 CASP8 activity is inhibited
R-HSA-5357786 TNFR1-induced proapoptotic signaling
R-HSA-5357905 Regulation of TNFR1 signaling
R-HSA-5357956 TNFR1-induced NFkappaB signaling pathway
R-HSA-5675482 Regulation of necroptotic cell death
R-HSA-69416 Dimerization of procaspase-8
R-HSA-75893 TNF signaling
SignaLinkiQ15628
SIGNORiQ15628

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:TRADD
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000102871.15
HGNCiHGNC:12030 TRADD
MIMi603500 gene
neXtProtiNX_Q15628

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

Organism-specific databases

DisGeNETi8717
OpenTargetsiENSG00000102871
PharmGKBiPA36707

Polymorphism and mutation databases

BioMutaiTRADD
DMDMi6094511

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000656021 – 312Tumor necrosis factor receptor type 1-associated DEATH domain proteinAdd BLAST312

Proteomic databases

EPDiQ15628
MaxQBiQ15628
PaxDbiQ15628
PeptideAtlasiQ15628
PRIDEiQ15628
ProteomicsDBi60663

PTM databases

iPTMnetiQ15628
PhosphoSitePlusiQ15628

Expressioni

Tissue specificityi

Found in all examined tissues.

Gene expression databases

BgeeiENSG00000102871
CleanExiHS_TRADD
GenevisibleiQ15628 HS

Organism-specific databases

HPAiCAB004602
HPA071341

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:7758105, PubMed:8612133, PubMed:14585990, PubMed:21307340). Subsequently, TRADD, RIPK1 and TRAF2 dissociate from TNFRSF1A and form cytoplasmic complex II with FADD and caspase CASP8 promoting cell apoptosis (PubMed:21307340). Within complex I, interacts with TNFRSF1A/TNFR1, TRAF2 and kinase RIPK1 (PubMed:7758105, PubMed:10892748, PubMed:8612133). 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 (PubMed:21307340). Within complex I Interacts with scaffold protein DAB2IP (PubMed:15310755). Interacts with autophagy receptor SQSTM1 (PubMed:10356400). Interacts with E3 ligase TRIP12 (By similarity). Interacts with kinase HIPK2 (PubMed:11032752). Interacts with keratin KRT14 (PubMed:11684708). Interacts with keratin KRT18 (PubMed:11684708). Interacts with keratins KRT16 and KRT17 (By similarity).By similarity9 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • death domain binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • kinase binding Source: BHF-UCL
  • tumor necrosis factor receptor binding Source: Ensembl
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi114257, 44 interactors
CORUMiQ15628
DIPiDIP-285N
IntActiQ15628, 20 interactors
MINTiQ15628
STRINGi9606.ENSP00000341268

Structurei

Secondary structure

1312
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi12 – 25Combined sources14
Helixi28 – 33Combined sources6
Turni35 – 37Combined sources3
Helixi38 – 52Combined sources15
Turni56 – 58Combined sources3
Beta strandi59 – 66Combined sources8
Beta strandi68 – 79Combined sources12
Helixi80 – 91Combined sources12
Helixi94 – 106Combined sources13
Beta strandi114 – 120Combined sources7
Helixi125 – 128Combined sources4
Helixi132 – 141Combined sources10
Helixi150 – 162Combined sources13
Beta strandi201 – 204Combined sources4
Beta strandi207 – 210Combined sources4
Helixi216 – 226Combined sources11
Helixi227 – 229Combined sources3
Helixi230 – 240Combined sources11
Helixi242 – 244Combined sources3
Helixi248 – 255Combined sources8
Turni257 – 259Combined sources3
Helixi261 – 275Combined sources15
Beta strandi277 – 279Combined sources3
Helixi282 – 292Combined sources11
Helixi295 – 301Combined sources7
Beta strandi306 – 308Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1F2HNMR-A1-169[»]
1F3VX-ray2.00A1-179[»]
5XMENMR-A199-312[»]
ProteinModelPortaliQ15628
SMRiQ15628
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ15628

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini179 – 289DeathPROSITE-ProRule annotationAdd BLAST111

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni222 – 289Interaction with KRT14 and KRT181 PublicationAdd BLAST68

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi147 – 163Nuclear export signalBy similarityAdd BLAST17
Motifi231 – 244Nuclear localization signalBy similarityAdd BLAST14

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi192 – 198Poly-Pro7

Domaini

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

Phylogenomic databases

eggNOGiENOG410IF81 Eukaryota
ENOG4111IRA LUCA
GeneTreeiENSGT00390000002016
HOGENOMiHOG000059664
HOVERGENiHBG054083
InParanoidiQ15628
KOiK03171
OMAiFCGRQPC
OrthoDBiEOG091G0DXR
PhylomeDBiQ15628
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

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q15628-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAAGQNGHEE WVGSAYLFVE SSLDKVVLSD AYAHPQQKVA VYRALQAALA 
        60         70         80         90        100
ESGGSPDVLQ MLKIHRSDPQ LIVQLRFCGR QPCGRFLRAY REGALRAALQ 
       110        120        130        140        150
RSLAAALAQH SVPLQLELRA GAERLDALLA DEERCLSCIL AQQPDRLRDE 
       160        170        180        190        200
ELAELEDALR NLKCGSGARG GDGEVASAPL QPPVPSLSEV KPPPPPPPAQ 
       210        220        230        240        250
TFLFQGQPVV NRPLSLKDQQ TFARSVGLKW RKVGRSLQRG CRALRDPALD 
       260        270        280        290        300
SLAYEYEREG LYEQAFQLLR RFVQAEGRRA TLQRLVEALE ENELTSLAED 
       310 
LLGLTDPNGG LA
Length:312
Mass (Da):34,247
Last modified:July 15, 1999 - v2
Checksum:i5645D7E63E5FF05A
GO
Isoform 2 (identifier: Q15628-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-60: Missing.

Note: No experimental confirmation available.
Show »
Length:252
Mass (Da):27,904
Checksum:i669B381D012B108A
GO

Sequence cautioni

The sequence AAA98482 differs from that shown. Reason: Erroneous initiation.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0565261 – 60Missing in isoform 2. 1 PublicationAdd BLAST60

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L41690 mRNA Translation: AAA98482.1 Different initiation.
AJ311614, AJ311615, AJ311616 Genomic DNA Translation: CAC38018.2
AY995114 Genomic DNA Translation: AAX89407.1
BT006934 mRNA Translation: AAP35580.1
AY575851 Genomic DNA Translation: AAS68637.1
AK090673 mRNA Translation: BAG52211.1
AK315654 mRNA Translation: BAG38020.1
AC074143 Genomic DNA No translation available.
CH471092 Genomic DNA Translation: EAW83081.1
BC004491 mRNA Translation: AAH04491.1
CCDSiCCDS10829.1 [Q15628-1]
PIRiA56911
RefSeqiNP_001310481.1, NM_001323552.1 [Q15628-1]
NP_003780.1, NM_003789.3 [Q15628-1]
XP_005256270.1, XM_005256213.3 [Q15628-2]
XP_016879304.1, XM_017023815.1 [Q15628-1]
UniGeneiHs.460996

Genome annotation databases

EnsembliENST00000345057; ENSP00000341268; ENSG00000102871 [Q15628-1]
ENST00000486556; ENSP00000462591; ENSG00000102871 [Q15628-2]
GeneIDi8717
KEGGihsa:8717
UCSCiuc002erh.2 human [Q15628-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiTRADD_HUMAN
AccessioniPrimary (citable) accession number: Q15628
Secondary accession number(s): B2RDS3, B3KQZ9, Q52NZ1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 15, 1999
Last modified: June 20, 2018
This is version 180 of the entry and version 2 of the sequence. See 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, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: 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

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