Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Tumor necrosis factor receptor superfamily member 10A

Gene

TNFRSF10A

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

Functioni

Receptor for the cytotoxic ligand TNFSF10/TRAIL (PubMed:26457518). 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.2 Publications

GO - Molecular functioni

  • death receptor activity Source: ProtInc
  • protease binding Source: UniProtKB
  • signaling 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

Keywordsi

Molecular functionReceptor
Biological processApoptosis

Enzyme and pathway databases

ReactomeiR-HSA-140534 Ligand-dependent caspase activation
R-HSA-202733 Cell surface interactions at the vascular wall
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

EuPathDBiHostDB:ENSG00000104689.9
HGNCiHGNC:11904 TNFRSF10A
MIMi603611 gene
neXtProtiNX_O00220

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

Topology

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

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 annotationCombined sources1 Publication
Disulfide bondi148 ↔ 164PROSITE-ProRule annotationCombined sources1 Publication
Glycosylationi156N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi167 ↔ 180PROSITE-ProRule annotationCombined sources1 Publication
Disulfide bondi170 ↔ 188PROSITE-ProRule annotationCombined sources1 Publication
Disulfide bondi190 ↔ 204PROSITE-ProRule annotationCombined sources1 Publication
Disulfide bondi207 ↔ 221PROSITE-ProRule annotationCombined sources1 Publication
Disulfide bondi211 ↔ 229PROSITE-ProRule annotationCombined sources1 Publication
Modified residuei424PhosphoserineCombined sources1
Modified residuei463PhosphoserineCombined sources1
Modified residuei466PhosphoserineCombined sources1

Keywords - PTMi

Disulfide bond, Glycoprotein, Methylation, Phosphoprotein

Proteomic databases

EPDiO00220
MaxQBiO00220
PaxDbiO00220
PeptideAtlasiO00220
PRIDEiO00220
ProteomicsDBi47790

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

HPAiHPA050958
HPA054475

Interactioni

Subunit structurei

Monomer (PubMed:26457518). Three TNFRSF10A molecules interact with the TNFSF10 homotrimer (PubMed:26457518). Can interact with TRADD and RIPK1. Interacts with ARAP1. Interacts with HCMV protein UL141; this interaction prevents TNFRSF10A cell surface expression.3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi114325, 50 interactors
IntActiO00220, 11 interactors
MINTiO00220
STRINGi9606.ENSP00000221132

Chemistry databases

BindingDBiO00220

Structurei

Secondary structure

1468
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi136 – 138Combined sources3
Beta strandi145 – 147Combined sources3
Turni150 – 152Combined sources3
Beta strandi157 – 159Combined sources3
Beta strandi174 – 178Combined sources5
Beta strandi187 – 190Combined sources4
Beta strandi216 – 219Combined sources4
Beta strandi228 – 230Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5CIRX-ray3.00E/F/G125-232[»]
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

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

CDDicd08315 Death_TRAILR_DR4_DR5, 1 hit
cd10580 TNFRSF10, 1 hit
InterProiView protein in InterPro
IPR011029 DEATH-like_dom_sf
IPR000488 Death_domain
IPR001368 TNFR/NGFR_Cys_rich_reg
IPR020465 TNFR_10
IPR034024 TNFRSF10_N
IPR034029 TNFRSF10A/B_death
PfamiView protein in Pfam
PF00531 Death, 1 hit
PF00020 TNFR_c6, 2 hits
PIRSFiPIRSF037867 CD261_antigen, 1 hit
PRINTSiPR01956 TNFACTORR10
SMARTiView protein in SMART
SM00005 DEATH, 1 hit
SM00208 TNFR, 2 hits
SUPFAMiSSF47986 SSF47986, 1 hit
PROSITEiView protein in PROSITE
PS50017 DEATH_DOMAIN, 1 hit
PS00652 TNFR_NGFR_1, 2 hits
PS50050 TNFR_NGFR_2, 2 hits

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 dbSNP:rs34737614Ensembl.1
Natural variantiVAR_01614933T → I. Corresponds to variant dbSNP:rs20577Ensembl.1
Natural variantiVAR_052350105P → R. Corresponds to variant dbSNP:rs11986840Ensembl.1
Natural variantiVAR_016150141H → R2 PublicationsCorresponds to variant dbSNP:rs17620Ensembl.1
Natural variantiVAR_016151209R → T2 PublicationsCorresponds to variant dbSNP:rs20575Ensembl.1
Natural variantiVAR_016152228E → A. Corresponds to variant dbSNP:rs20576Ensembl.1
Natural variantiVAR_052351297N → H. Corresponds to variant dbSNP:rs17088980Ensembl.1
Natural variantiVAR_052352441R → K5 PublicationsCorresponds to variant dbSNP:rs2230229Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiTR10A_HUMAN
AccessioniPrimary (citable) accession number: O00220
Secondary accession number(s): A8K5I4, Q53Y72, Q96E62
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: November 30, 2010
Last modified: June 20, 2018
This is version 179 of the entry and version 3 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 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health