UniProtKB - Q15628 (TRADD_HUMAN)
Tumor necrosis factor receptor type 1-associated DEATH domain protein
TRADD
Functioni
Adapter molecule for TNFRSF1A/TNFR1 that specifically associates with the cytoplasmic domain of activated TNFRSF1A/TNFR1 mediating its interaction with FADD (PubMed:7758105, PubMed:8612133, PubMed:23955153).
Overexpression of TRADD leads to two major TNF-induced responses, apoptosis and activation of NF-kappa-B (PubMed:7758105, PubMed:8612133).
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).
By similarity3 PublicationsGO - Molecular functioni
- death domain binding Source: BHF-UCL
- identical protein binding Source: IntAct
- kinase binding Source: BHF-UCL
- protein-containing complex binding Source: Ensembl
- transmembrane receptor protein tyrosine kinase adaptor activity Source: BHF-UCL
- tumor necrosis factor receptor binding Source: Ensembl
GO - Biological processi
- apoptotic process Source: ProtInc
- cellular response to tumor necrosis factor Source: ARUK-UCL
- extrinsic apoptotic signaling pathway Source: UniProtKB
- extrinsic apoptotic signaling pathway via death domain receptors Source: BHF-UCL
- positive regulation of apoptotic process Source: UniProtKB
- positive regulation of cell migration Source: ARUK-UCL
- positive regulation of hair follicle development Source: Ensembl
- positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
- positive regulation of inflammatory response Source: ARUK-UCL
- positive regulation of NF-kappaB transcription factor activity Source: ARUK-UCL
- positive regulation of NIK/NF-kappaB signaling Source: ARUK-UCL
- signal transduction Source: ProtInc
- tumor necrosis factor-mediated signaling pathway Source: BHF-UCL
Keywordsi
Biological process | Apoptosis |
Enzyme and pathway databases
PathwayCommonsi | Q15628 |
Reactomei | R-HSA-140534, Caspase activation via Death Receptors in the presence of ligand 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 R-HSA-9693928, Defective RIPK1-mediated regulated necrosis |
SignaLinki | Q15628 |
SIGNORi | Q15628 |
Names & Taxonomyi
Protein namesi | Recommended name: Tumor necrosis factor receptor type 1-associated DEATH domain proteinCuratedShort name: TNFR1-associated DEATH domain protein1 Publication Alternative name(s): TNFRSF1A-associated via death domain1 Publication |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:12030, TRADD |
MIMi | 603500, gene |
neXtProti | NX_Q15628 |
VEuPathDBi | HostDB:ENSG00000102871 |
Subcellular locationi
Nucleus
- Nucleus By similarity
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Cytoskeleton
- cytoskeleton 1 Publication
Note: Shuttles between the cytoplasm and the nucleus.By similarity
Cytoskeleton
- cytoskeleton Source: UniProtKB-SubCell
Cytosol
- cytosol Source: Reactome
Nucleus
- nucleus Source: UniProtKB-SubCell
Plasma Membrane
- death-inducing signaling complex Source: UniProtKB
- plasma membrane Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
- membrane raft Source: Ensembl
- receptor complex Source: BHF-UCL
- tumor necrosis factor receptor superfamily complex Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, Cytoskeleton, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 235 | R → A or K: Abolished GlcNAcylation by E.coli NleB1. Abolished ability to self-oligomerize. Strongly reduced GlcNAcylation by S.typhimurium Ssek1; when associated with A-245. 2 Publications | 1 | |
Mutagenesisi | 245 | R → A: Strongly reduced GlcNAcylation by S.typhimurium Ssek1; when associated with A-235. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 8717 |
OpenTargetsi | ENSG00000102871 |
PharmGKBi | PA36707 |
Miscellaneous databases
Pharosi | Q15628, Tbio |
Genetic variation databases
BioMutai | TRADD |
DMDMi | 6094511 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000065602 | 1 – 312 | Tumor necrosis factor receptor type 1-associated DEATH domain proteinAdd BLAST | 312 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 235 | (Microbial infection) N-beta-linked (GlcNAc) arginineCombined sources3 Publications | 1 | |
Glycosylationi | 245 | (Microbial infection) N-beta-linked (GlcNAc) arginine1 Publication | 1 |
Post-translational modificationi
Keywords - PTMi
GlycoproteinProteomic databases
EPDi | Q15628 |
jPOSTi | Q15628 |
MassIVEi | Q15628 |
MaxQBi | Q15628 |
PaxDbi | Q15628 |
PeptideAtlasi | Q15628 |
PRIDEi | Q15628 |
ProteomicsDBi | 60663 [Q15628-1] |
PTM databases
iPTMneti | Q15628 |
PhosphoSitePlusi | Q15628 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000102871, Expressed in granulocyte and 230 other tissues |
Genevisiblei | Q15628, HS |
Organism-specific databases
HPAi | ENSG00000102871, Low tissue specificity |
Interactioni
Subunit structurei
Stimulation of TNF-alpha receptor TNFRSF1A leads to the formation of two distinct signaling complexes (PubMed:7758105, PubMed:8612133, PubMed:14585990, PubMed:21307340). 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).
Interacts with FADD (By similarity).
Interacts with TOMM70 (PubMed:20628368).
By similarity11 PublicationsBinary interactionsi
Q15628
GO - Molecular functioni
- death domain binding Source: BHF-UCL
- identical protein binding Source: IntAct
- kinase binding Source: BHF-UCL
- transmembrane receptor protein tyrosine kinase adaptor activity Source: BHF-UCL
- tumor necrosis factor receptor binding Source: Ensembl
Protein-protein interaction databases
BioGRIDi | 114257, 101 interactors |
CORUMi | Q15628 |
DIPi | DIP-285N |
IntActi | Q15628, 71 interactors |
MINTi | Q15628 |
STRINGi | 9606.ENSP00000341268 |
Miscellaneous databases
RNActi | Q15628, protein |
Structurei
Secondary structure
3D structure databases
BMRBi | Q15628 |
SMRi | Q15628 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q15628 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 179 – 289 | DeathPROSITE-ProRule annotationAdd BLAST | 111 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 170 – 195 | DisorderedSequence analysisAdd BLAST | 26 | |
Regioni | 222 – 289 | Interaction with KRT14 and KRT181 PublicationAdd BLAST | 68 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 147 – 163 | Nuclear export signalBy similarityAdd BLAST | 17 | |
Motifi | 231 – 244 | Nuclear localization signalBy similarityAdd BLAST | 14 |
Domaini
Phylogenomic databases
eggNOGi | ENOG502RXWE, Eukaryota |
GeneTreei | ENSGT00390000002016 |
HOGENOMi | CLU_052183_0_0_1 |
InParanoidi | Q15628 |
OMAi | QPCSRFL |
OrthoDBi | 1024816at2759 |
PhylomeDBi | Q15628 |
TreeFami | TF331882 |
Family and domain databases
Gene3Di | 1.10.533.10, 1 hit 3.30.70.680, 1 hit |
InterProi | View protein in InterPro IPR011029, DEATH-like_dom_sf IPR000488, Death_domain IPR035712, TRADD IPR009095, TRADD_N IPR036729, TRADD_N_sf |
PANTHERi | PTHR14913, PTHR14913, 1 hit |
Pfami | View protein in Pfam PF00531, Death, 1 hit PF09034, TRADD_N, 1 hit |
SMARTi | View protein in SMART SM00005, DEATH, 1 hit |
SUPFAMi | SSF47986, SSF47986, 1 hit SSF55044, SSF55044, 1 hit |
PROSITEi | View protein in PROSITE PS50017, DEATH_DOMAIN, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Sequence cautioni
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_056526 | 1 – 60 | Missing in isoform 2. 1 PublicationAdd BLAST | 60 |
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 |
CCDSi | CCDS10829.1 [Q15628-1] |
PIRi | A56911 |
RefSeqi | NP_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] |
Genome annotation databases
Ensembli | ENST00000345057; ENSP00000341268; ENSG00000102871 ENST00000486556; ENSP00000462591; ENSG00000102871 [Q15628-2] |
GeneIDi | 8717 |
KEGGi | hsa:8717 |
MANE-Selecti | ENST00000345057.9; ENSP00000341268.4; NM_003789.4; NP_003780.1 |
UCSCi | uc002erh.2, human [Q15628-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
SeattleSNPs |
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 |
CCDSi | CCDS10829.1 [Q15628-1] |
PIRi | A56911 |
RefSeqi | NP_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] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1F2H | NMR | - | A | 1-169 | [»] | |
1F3V | X-ray | 2.00 | A | 1-179 | [»] | |
5XME | NMR | - | A | 199-312 | [»] | |
6AC0 | X-ray | 1.45 | A | 195-312 | [»] | |
7CSQ | NMR | - | B | 199-312 | [»] | |
BMRBi | Q15628 | |||||
SMRi | Q15628 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 114257, 101 interactors |
CORUMi | Q15628 |
DIPi | DIP-285N |
IntActi | Q15628, 71 interactors |
MINTi | Q15628 |
STRINGi | 9606.ENSP00000341268 |
PTM databases
iPTMneti | Q15628 |
PhosphoSitePlusi | Q15628 |
Genetic variation databases
BioMutai | TRADD |
DMDMi | 6094511 |
Proteomic databases
EPDi | Q15628 |
jPOSTi | Q15628 |
MassIVEi | Q15628 |
MaxQBi | Q15628 |
PaxDbi | Q15628 |
PeptideAtlasi | Q15628 |
PRIDEi | Q15628 |
ProteomicsDBi | 60663 [Q15628-1] |
Protocols and materials databases
Antibodypediai | 3894, 535 antibodies from 43 providers |
DNASUi | 8717 |
Genome annotation databases
Ensembli | ENST00000345057; ENSP00000341268; ENSG00000102871 ENST00000486556; ENSP00000462591; ENSG00000102871 [Q15628-2] |
GeneIDi | 8717 |
KEGGi | hsa:8717 |
MANE-Selecti | ENST00000345057.9; ENSP00000341268.4; NM_003789.4; NP_003780.1 |
UCSCi | uc002erh.2, human [Q15628-1] |
Organism-specific databases
CTDi | 8717 |
DisGeNETi | 8717 |
GeneCardsi | TRADD |
HGNCi | HGNC:12030, TRADD |
HPAi | ENSG00000102871, Low tissue specificity |
MIMi | 603500, gene |
neXtProti | NX_Q15628 |
OpenTargetsi | ENSG00000102871 |
PharmGKBi | PA36707 |
VEuPathDBi | HostDB:ENSG00000102871 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502RXWE, Eukaryota |
GeneTreei | ENSGT00390000002016 |
HOGENOMi | CLU_052183_0_0_1 |
InParanoidi | Q15628 |
OMAi | QPCSRFL |
OrthoDBi | 1024816at2759 |
PhylomeDBi | Q15628 |
TreeFami | TF331882 |
Enzyme and pathway databases
PathwayCommonsi | Q15628 |
Reactomei | R-HSA-140534, Caspase activation via Death Receptors in the presence of ligand 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 R-HSA-9693928, Defective RIPK1-mediated regulated necrosis |
SignaLinki | Q15628 |
SIGNORi | Q15628 |
Miscellaneous databases
BioGRID-ORCSi | 8717, 10 hits in 1051 CRISPR screens |
EvolutionaryTracei | Q15628 |
GeneWikii | TRADD |
GenomeRNAii | 8717 |
Pharosi | Q15628, Tbio |
PROi | PR:Q15628 |
RNActi | Q15628, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000102871, Expressed in granulocyte and 230 other tissues |
Genevisiblei | Q15628, HS |
Family and domain databases
Gene3Di | 1.10.533.10, 1 hit 3.30.70.680, 1 hit |
InterProi | View protein in InterPro IPR011029, DEATH-like_dom_sf IPR000488, Death_domain IPR035712, TRADD IPR009095, TRADD_N IPR036729, TRADD_N_sf |
PANTHERi | PTHR14913, PTHR14913, 1 hit |
Pfami | View protein in Pfam PF00531, Death, 1 hit PF09034, TRADD_N, 1 hit |
SMARTi | View protein in SMART SM00005, DEATH, 1 hit |
SUPFAMi | SSF47986, SSF47986, 1 hit SSF55044, SSF55044, 1 hit |
PROSITEi | View protein in PROSITE PS50017, DEATH_DOMAIN, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | TRADD_HUMAN | |
Accessioni | Q15628Primary (citable) accession number: Q15628 Secondary accession number(s): B2RDS3, B3KQZ9, Q52NZ1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | July 15, 1999 | |
Last modified: | February 23, 2022 | |
This is version 205 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human chromosome 16
Human chromosome 16: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references