O00220 · TR10A_HUMAN
- ProteinTumor necrosis factor receptor superfamily member 10A
- GeneTNFRSF10A
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids468 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Receptor for the cytotoxic ligand TNFSF10/TRAIL (PubMed:26457518, PubMed:38532423).
The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis (PubMed:19090789).
Promotes the activation of NF-kappa-B (PubMed:9430227).
The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis (PubMed:19090789).
Promotes the activation of NF-kappa-B (PubMed:9430227).
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Aspect | Term | |
---|---|---|
Cellular Component | cell surface | |
Cellular Component | cytosol | |
Cellular Component | Golgi apparatus | |
Cellular Component | membrane raft | |
Cellular Component | plasma membrane | |
Cellular Component | plasma membrane raft | |
Molecular Function | death receptor activity | |
Molecular Function | identical protein binding | |
Molecular Function | protease binding | |
Molecular Function | signaling receptor activity | |
Molecular Function | TRAIL binding | |
Biological Process | activation of NF-kappaB-inducing kinase activity | |
Biological Process | apoptotic process | |
Biological Process | cellular response to mechanical stimulus | |
Biological Process | extrinsic apoptotic signaling pathway | |
Biological Process | extrinsic apoptotic signaling pathway via death domain receptors | |
Biological Process | positive regulation of apoptotic process | |
Biological Process | signal transduction | |
Biological Process | TRAIL-activated apoptotic signaling pathway |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTumor necrosis factor receptor superfamily member 10A
- Alternative names
- CD Antigen Name
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO00220
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Single-pass type I membrane protein
Note: Palmitoylation is required for association with membranes.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 24-239 | Extracellular | ||||
Sequence: ASGTEAAAATPSKVWGSSAGRIEPRGGGRGALPTSMGQHGPSARARAGRAPGPRPAREASPRLRVHKTFKFVVVGVLLQVVPSSAATIKLHDQSIGTQQWEHSPLGELCPPGSHRSEHPGACNRCTEGVGYTNASNNLFACLPCTACKSDEEERSPCTTTRNTACQCKPGTFRNDNSAEMCRKCSRGCPRGMVKVKDCTPWSDIECVHKESGNGHN | ||||||
Transmembrane | 240-262 | Helical | ||||
Sequence: IWVILVVTLVVPLLLVAVLIVCC | ||||||
Topological domain | 263-468 | Cytoplasmic | ||||
Sequence: CIGSGCGGDPKCMDRVCFWRLGLLRGPGAEDNAHNEILSNADSLSTFVSEQQMESQEPADLTGVTVQSPGEAQCLLGPAEAEGSQRRRLLVPANGADPTETLMLFFDKFANIVPFDSWDQLMRQLDLTKNEIDVVRAGTAGPGDALYAMLMKWVNKTGRNASIHTLLDALERMEERHAREKIQDLLVDSGKFIYLEDGTGSAVSLE |
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_052349 | 11 | in dbSNP:rs34737614 | |||
Sequence: G → V | ||||||
Natural variant | VAR_016149 | 33 | in dbSNP:rs20577 | |||
Sequence: T → I | ||||||
Natural variant | VAR_052350 | 105 | in dbSNP:rs11986840 | |||
Sequence: P → R | ||||||
Natural variant | VAR_016150 | 141 | in dbSNP:rs17620 | |||
Sequence: H → R | ||||||
Natural variant | VAR_016151 | 209 | in dbSNP:rs20575 | |||
Sequence: R → T | ||||||
Natural variant | VAR_016152 | 228 | in dbSNP:rs20576 | |||
Sequence: E → A | ||||||
Mutagenesis | 261 | No effect on palmitoylation. Loss of palmitoylation, decreased association with membranes, decreased oligomerization, decreased death-induced signaling complex assembly associated with decreased function in TRAIL-induced cell death; when associated with S-262 and S-263. | ||||
Sequence: C → S | ||||||
Mutagenesis | 262 | No effect on palmitoylation. Loss of palmitoylation, decreased association with membranes, decreased oligomerization, decreased death-induced signaling complex assembly associated with decreased function in TRAIL-induced cell death; when associated with S-261 and S-263. | ||||
Sequence: C → S | ||||||
Mutagenesis | 263 | No effect on palmitoylation. Loss of palmitoylation, decreased association with membranes, decreased oligomerization, decreased death-induced signaling complex assembly associated with decreased function in TRAIL-induced cell death; when associated with S-261 and S-262. | ||||
Sequence: C → S | ||||||
Mutagenesis | 268 | No effect on palmitoylation. | ||||
Sequence: C → S | ||||||
Mutagenesis | 274 | No effect on palmitoylation. | ||||
Sequence: C → S | ||||||
Mutagenesis | 279 | No effect on palmitoylation. | ||||
Sequence: C → S | ||||||
Natural variant | VAR_052351 | 297 | in dbSNP:rs17088980 | |||
Sequence: N → H | ||||||
Natural variant | VAR_052352 | 441 | in dbSNP:rs2230229 | |||
Sequence: R → K |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 683 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for signal, chain, modified residue, disulfide bond, glycosylation, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Signal | 1-23 | UniProt | |||||
Sequence: MAPPPARVHLGAFLAVTPNPGSA | |||||||
Chain | PRO_0000034579 | 24-468 | UniProt | Tumor necrosis factor receptor superfamily member 10A | |||
Sequence: ASGTEAAAATPSKVWGSSAGRIEPRGGGRGALPTSMGQHGPSARARAGRAPGPRPAREASPRLRVHKTFKFVVVGVLLQVVPSSAATIKLHDQSIGTQQWEHSPLGELCPPGSHRSEHPGACNRCTEGVGYTNASNNLFACLPCTACKSDEEERSPCTTTRNTACQCKPGTFRNDNSAEMCRKCSRGCPRGMVKVKDCTPWSDIECVHKESGNGHNIWVILVVTLVVPLLLVAVLIVCCCIGSGCGGDPKCMDRVCFWRLGLLRGPGAEDNAHNEILSNADSLSTFVSEQQMESQEPADLTGVTVQSPGEAQCLLGPAEAEGSQRRRLLVPANGADPTETLMLFFDKFANIVPFDSWDQLMRQLDLTKNEIDVVRAGTAGPGDALYAMLMKWVNKTGRNASIHTLLDALERMEERHAREKIQDLLVDSGKFIYLEDGTGSAVSLE | |||||||
Modified residue | 52 | UniProt | Omega-N-methylarginine | ||||
Sequence: R | |||||||
Disulfide bond | 132↔145 | UniProt | |||||
Sequence: CPPGSHRSEHPGAC | |||||||
Disulfide bond | 148↔164 | UniProt | |||||
Sequence: CTEGVGYTNASNNLFAC | |||||||
Glycosylation | 156 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Disulfide bond | 167↔180 | UniProt | |||||
Sequence: CTACKSDEEERSPC | |||||||
Disulfide bond | 170↔188 | UniProt | |||||
Sequence: CKSDEEERSPCTTTRNTAC | |||||||
Modified residue (large scale data) | 178 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Disulfide bond | 190↔204 | UniProt | |||||
Sequence: CKPGTFRNDNSAEMC | |||||||
Disulfide bond | 207↔221 | UniProt | |||||
Sequence: CSRGCPRGMVKVKDC | |||||||
Disulfide bond | 211↔229 | UniProt | |||||
Sequence: CPRGMVKVKDCTPWSDIEC | |||||||
Modified residue | 424 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 424 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 463 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 463 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 466 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 466 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Palmitoylated (PubMed:19090789).
Palmitoylation of TNFRSF10A is required for its association with lipid rafts, oligomerization and function in TRAIL-induced cell death (PubMed:19090789).
Palmitoylated by ZDHHC3 (Probable)
Palmitoylation of TNFRSF10A is required for its association with lipid rafts, oligomerization and function in TRAIL-induced cell death (PubMed:19090789).
Palmitoylated by ZDHHC3 (Probable)
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Widely expressed. High levels are found in spleen, peripheral blood leukocytes, small intestine and thymus, but also in K-562 erythroleukemia cells, MCF-7 breast carcinoma cells and activated T-cells.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Monomer (PubMed:26457518).
Homooligomers and heterooligomers with TNFRSF10B (PubMed:19090789).
Three TNFRSF10A molecules interact with the TNFSF10 homotrimer (PubMed:26457518).
Can interact with TRADD and RIPK1. Interacts with ARAP1. In the absence of stimulation, interacts with BIRC2, DDX3X and GSK3B. The interaction with BIRC2 and DDX3X is further enhanced upon receptor stimulation and accompanied by DDX3X and BIRC2 cleavage (PubMed:18846110).
Interacts with ZDHHC3 (PubMed:22240897).
Interacts with PTPN6; this interaction enables the inhibition of T-cell receptor signaling via LCK (PubMed:38532423).
Homooligomers and heterooligomers with TNFRSF10B (PubMed:19090789).
Three TNFRSF10A molecules interact with the TNFSF10 homotrimer (PubMed:26457518).
Can interact with TRADD and RIPK1. Interacts with ARAP1. In the absence of stimulation, interacts with BIRC2, DDX3X and GSK3B. The interaction with BIRC2 and DDX3X is further enhanced upon receptor stimulation and accompanied by DDX3X and BIRC2 cleavage (PubMed:18846110).
Interacts with ZDHHC3 (PubMed:22240897).
Interacts with PTPN6; this interaction enables the inhibition of T-cell receptor signaling via LCK (PubMed:38532423).
(Microbial infection) Interacts with HCMV protein UL141; this interaction prevents TNFRSF10A cell surface expression.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | O00220 | ARAP1 Q96P48 | 4 | EBI-518861, EBI-710003 | |
BINARY | O00220 | CASP8 Q14790 | 11 | EBI-518861, EBI-78060 | |
BINARY | O00220 | LGALS3BP Q08380 | 2 | EBI-518861, EBI-354956 | |
BINARY | O00220 | TNFSF10 P50591 | 4 | EBI-518861, EBI-495373 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, repeat, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 17-82 | Disordered | ||||
Sequence: TPNPGSAASGTEAAAATPSKVWGSSAGRIEPRGGGRGALPTSMGQHGPSARARAGRAPGPRPAREA | ||||||
Repeat | 107-145 | TNFR-Cys 1 | ||||
Sequence: SAATIKLHDQSIGTQQWEHSPLGELCPPGSHRSEHPGAC | ||||||
Repeat | 147-188 | TNFR-Cys 2 | ||||
Sequence: RCTEGVGYTNASNNLFACLPCTACKSDEEERSPCTTTRNTAC | ||||||
Repeat | 189-229 | TNFR-Cys 3 | ||||
Sequence: QCKPGTFRNDNSAEMCRKCSRGCPRGMVKVKDCTPWSDIEC | ||||||
Domain | 365-448 | Death | ||||
Sequence: MLFFDKFANIVPFDSWDQLMRQLDLTKNEIDVVRAGTAGPGDALYAMLMKWVNKTGRNASIHTLLDALERMEERHAREKIQDLL |
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length468
- Mass (Da)50,089
- Last updated2010-11-30 v3
- Checksum7E96619D0BDC0CD4
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 281 | in Ref. 3; BAF83988 | ||||
Sequence: W → C |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U90875 EMBL· GenBank· DDBJ | AAC51226.1 EMBL· GenBank· DDBJ | mRNA | ||
BT006906 EMBL· GenBank· DDBJ | AAP35552.1 EMBL· GenBank· DDBJ | mRNA | ||
AK291299 EMBL· GenBank· DDBJ | BAF83988.1 EMBL· GenBank· DDBJ | mRNA | ||
EF064713 EMBL· GenBank· DDBJ | ABK41896.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AC100861 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC012866 EMBL· GenBank· DDBJ | AAH12866.1 EMBL· GenBank· DDBJ | mRNA |