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Protein

Tumor necrosis factor receptor superfamily member 10A

Gene

TNFRSF10A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for the cytotoxic ligand TNFSF10/TRAIL. 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. Promotes the activation of NF-kappa-B.1 Publication

GO - Molecular functioni

  • death receptor activity Source: ProtInc
  • protease binding Source: UniProtKB
  • receptor activity Source: UniProtKB
  • TRAIL binding Source: UniProtKB
  • transcription factor binding Source: UniProtKB
  • tumor necrosis factor-activated receptor activity Source: GO_Central

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

BioCyciZFISH:ENSG00000104689-MONOMER.
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-6803211. TP53 Regulates Transcription of Death Receptors and Ligands.
R-HSA-69416. Dimerization of procaspase-8.
R-HSA-75158. TRAIL signaling.
SignaLinkiO00220.
SIGNORiO00220.

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor necrosis factor receptor superfamily member 10A
Alternative name(s):
Death receptor 4
TNF-related apoptosis-inducing ligand receptor 1
Short name:
TRAIL receptor 1
Short name:
TRAIL-R1
CD_antigen: CD261
Gene namesi
Name:TNFRSF10A
Synonyms:APO2, DR4, TRAILR1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:11904. TNFRSF10A.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini24 – 239ExtracellularSequence analysisAdd BLAST216
Transmembranei240 – 262HelicalSequence analysisAdd BLAST23
Topological domaini263 – 468CytoplasmicSequence analysisAdd BLAST206

GO - Cellular componenti

  • cell surface Source: UniProtKB
  • integral component of membrane Source: UniProtKB
  • integral component of plasma membrane Source: GO_Central
  • intracellular Source: GOC
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi8797.
OpenTargetsiENSG00000104689.
PharmGKBiPA36597.

Chemistry databases

ChEMBLiCHEMBL3551.
GuidetoPHARMACOLOGYi1879.

Polymorphism and mutation databases

BioMutaiTNFRSF10A.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Sequence analysisAdd BLAST23
ChainiPRO_000003457924 – 468Tumor necrosis factor receptor superfamily member 10AAdd BLAST445

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei52Omega-N-methylarginineCombined sources1
Disulfide bondi132 ↔ 145PROSITE-ProRule annotation
Disulfide bondi148 ↔ 164PROSITE-ProRule annotation
Glycosylationi156N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi167 ↔ 180PROSITE-ProRule annotation
Disulfide bondi170 ↔ 188PROSITE-ProRule annotation
Disulfide bondi190 ↔ 204PROSITE-ProRule annotation
Disulfide bondi207 ↔ 221PROSITE-ProRule annotation
Disulfide bondi211 ↔ 229PROSITE-ProRule annotation
Modified residuei424PhosphoserineCombined sources1
Modified residuei463PhosphoserineCombined sources1
Modified residuei466PhosphoserineCombined sources1

Keywords - PTMi

Disulfide bond, Glycoprotein, Methylation, Phosphoprotein

Proteomic databases

EPDiO00220.
MaxQBiO00220.
PaxDbiO00220.
PeptideAtlasiO00220.
PRIDEiO00220.

PTM databases

iPTMnetiO00220.
PhosphoSitePlusiO00220.
SwissPalmiO00220.

Expressioni

Tissue specificityi

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

BgeeiENSG00000104689.
CleanExiHS_TNFRSF10A.
ExpressionAtlasiO00220. baseline and differential.
GenevisibleiO00220. HS.

Organism-specific databases

HPAiHPA054475.

Interactioni

Subunit structurei

Can interact with TRADD and RIPK1. Interacts with ARAP1. Interacts with HCMV protein UL141; this interaction prevents TNFRSF10A cell surface expression.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ARAP1Q96P484EBI-518861,EBI-710003
CASP8Q147909EBI-518861,EBI-78060
TNFSF10P505914EBI-518861,EBI-495373

GO - Molecular functioni

  • protease binding Source: UniProtKB
  • TRAIL binding Source: UniProtKB
  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114325. 47 interactors.
IntActiO00220. 11 interactors.
MINTiMINT-99073.
STRINGi9606.ENSP00000221132.

Chemistry databases

BindingDBiO00220.

Structurei

3D structure databases

ProteinModelPortaliO00220.
SMRiO00220.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati107 – 145TNFR-Cys 1Add BLAST39
Repeati147 – 188TNFR-Cys 2Add BLAST42
Repeati189 – 229TNFR-Cys 3Add BLAST41
Domaini365 – 448DeathPROSITE-ProRule annotationAdd BLAST84

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi29 – 32Poly-Ala4

Sequence similaritiesi

Contains 1 death domain.PROSITE-ProRule annotation
Contains 3 TNFR-Cys repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IZX0. Eukaryota.
ENOG4111ZZM. LUCA.
GeneTreeiENSGT00730000110985.
HOGENOMiHOG000142423.
HOVERGENiHBG061626.
InParanoidiO00220.
KOiK04722.
OMAiGTQQWEH.
OrthoDBiEOG091G0MOV.
PhylomeDBiO00220.
TreeFamiTF333916.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
InterProiIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR001368. TNFR/NGFR_Cys_rich_reg.
IPR020465. TNFR_10.
[Graphical view]
PfamiPF00531. Death. 1 hit.
PF00020. TNFR_c6. 2 hits.
[Graphical view]
PIRSFiPIRSF037867. CD261_antigen. 1 hit.
PRINTSiPR01956. TNFACTORR10.
SMARTiSM00005. DEATH. 1 hit.
SM00208. TNFR. 2 hits.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
PROSITEiPS50017. DEATH_DOMAIN. 1 hit.
PS00652. TNFR_NGFR_1. 2 hits.
PS50050. TNFR_NGFR_2. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O00220-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAPPPARVHL GAFLAVTPNP GSAASGTEAA AATPSKVWGS SAGRIEPRGG
60 70 80 90 100
GRGALPTSMG QHGPSARARA GRAPGPRPAR EASPRLRVHK TFKFVVVGVL
110 120 130 140 150
LQVVPSSAAT IKLHDQSIGT QQWEHSPLGE LCPPGSHRSE HPGACNRCTE
160 170 180 190 200
GVGYTNASNN LFACLPCTAC KSDEEERSPC TTTRNTACQC KPGTFRNDNS
210 220 230 240 250
AEMCRKCSRG CPRGMVKVKD CTPWSDIECV HKESGNGHNI WVILVVTLVV
260 270 280 290 300
PLLLVAVLIV CCCIGSGCGG DPKCMDRVCF WRLGLLRGPG AEDNAHNEIL
310 320 330 340 350
SNADSLSTFV SEQQMESQEP ADLTGVTVQS PGEAQCLLGP AEAEGSQRRR
360 370 380 390 400
LLVPANGADP TETLMLFFDK FANIVPFDSW DQLMRQLDLT KNEIDVVRAG
410 420 430 440 450
TAGPGDALYA MLMKWVNKTG RNASIHTLLD ALERMEERHA REKIQDLLVD
460
SGKFIYLEDG TGSAVSLE
Length:468
Mass (Da):50,089
Last modified:November 30, 2010 - v3
Checksum:i7E96619D0BDC0CD4
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti281W → C in BAF83988 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05234911G → V.Corresponds to variant rs34737614dbSNPEnsembl.1
Natural variantiVAR_01614933T → I.Corresponds to variant rs20577dbSNPEnsembl.1
Natural variantiVAR_052350105P → R.Corresponds to variant rs11986840dbSNPEnsembl.1
Natural variantiVAR_016150141H → R.2 PublicationsCorresponds to variant rs6557634dbSNPEnsembl.1
Natural variantiVAR_016151209R → T.2 PublicationsCorresponds to variant rs20575dbSNPEnsembl.1
Natural variantiVAR_016152228E → A.Corresponds to variant rs20576dbSNPEnsembl.1
Natural variantiVAR_052351297N → H.Corresponds to variant rs17088980dbSNPEnsembl.1
Natural variantiVAR_052352441R → K.5 PublicationsCorresponds to variant rs2230229dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U90875 mRNA. Translation: AAC51226.1.
BT006906 mRNA. Translation: AAP35552.1.
AK291299 mRNA. Translation: BAF83988.1.
EF064713 Genomic DNA. Translation: ABK41896.1.
AC100861 Genomic DNA. No translation available.
BC012866 mRNA. Translation: AAH12866.1.
CCDSiCCDS6039.1.
RefSeqiNP_003835.3. NM_003844.3.
UniGeneiHs.213467.
Hs.591834.

Genome annotation databases

EnsembliENST00000221132; ENSP00000221132; ENSG00000104689.
GeneIDi8797.
KEGGihsa:8797.
UCSCiuc003xda.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U90875 mRNA. Translation: AAC51226.1.
BT006906 mRNA. Translation: AAP35552.1.
AK291299 mRNA. Translation: BAF83988.1.
EF064713 Genomic DNA. Translation: ABK41896.1.
AC100861 Genomic DNA. No translation available.
BC012866 mRNA. Translation: AAH12866.1.
CCDSiCCDS6039.1.
RefSeqiNP_003835.3. NM_003844.3.
UniGeneiHs.213467.
Hs.591834.

3D structure databases

ProteinModelPortaliO00220.
SMRiO00220.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114325. 47 interactors.
IntActiO00220. 11 interactors.
MINTiMINT-99073.
STRINGi9606.ENSP00000221132.

Chemistry databases

BindingDBiO00220.
ChEMBLiCHEMBL3551.
GuidetoPHARMACOLOGYi1879.

PTM databases

iPTMnetiO00220.
PhosphoSitePlusiO00220.
SwissPalmiO00220.

Polymorphism and mutation databases

BioMutaiTNFRSF10A.

Proteomic databases

EPDiO00220.
MaxQBiO00220.
PaxDbiO00220.
PeptideAtlasiO00220.
PRIDEiO00220.

Protocols and materials databases

DNASUi8797.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000221132; ENSP00000221132; ENSG00000104689.
GeneIDi8797.
KEGGihsa:8797.
UCSCiuc003xda.4. human.

Organism-specific databases

CTDi8797.
DisGeNETi8797.
GeneCardsiTNFRSF10A.
H-InvDBHIX0022944.
HGNCiHGNC:11904. TNFRSF10A.
HPAiHPA054475.
MIMi603611. gene.
neXtProtiNX_O00220.
OpenTargetsiENSG00000104689.
PharmGKBiPA36597.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IZX0. Eukaryota.
ENOG4111ZZM. LUCA.
GeneTreeiENSGT00730000110985.
HOGENOMiHOG000142423.
HOVERGENiHBG061626.
InParanoidiO00220.
KOiK04722.
OMAiGTQQWEH.
OrthoDBiEOG091G0MOV.
PhylomeDBiO00220.
TreeFamiTF333916.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000104689-MONOMER.
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-6803211. TP53 Regulates Transcription of Death Receptors and Ligands.
R-HSA-69416. Dimerization of procaspase-8.
R-HSA-75158. TRAIL signaling.
SignaLinkiO00220.
SIGNORiO00220.

Miscellaneous databases

GeneWikiiTNFRSF10A.
GenomeRNAii8797.
PROiO00220.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000104689.
CleanExiHS_TNFRSF10A.
ExpressionAtlasiO00220. baseline and differential.
GenevisibleiO00220. HS.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
InterProiIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR001368. TNFR/NGFR_Cys_rich_reg.
IPR020465. TNFR_10.
[Graphical view]
PfamiPF00531. Death. 1 hit.
PF00020. TNFR_c6. 2 hits.
[Graphical view]
PIRSFiPIRSF037867. CD261_antigen. 1 hit.
PRINTSiPR01956. TNFACTORR10.
SMARTiSM00005. DEATH. 1 hit.
SM00208. TNFR. 2 hits.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
PROSITEiPS50017. DEATH_DOMAIN. 1 hit.
PS00652. TNFR_NGFR_1. 2 hits.
PS50050. TNFR_NGFR_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTR10A_HUMAN
AccessioniPrimary (citable) accession number: O00220
Secondary accession number(s): A8K5I4, Q53Y72, Q96E62
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: November 30, 2010
Last modified: November 2, 2016
This is version 163 of the entry and version 3 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

Complete proteome, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. 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.