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Protein

Tumor necrosis factor receptor superfamily member 10B

Gene

TNFRSF10B

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. Essential for ER stress-induced apoptosis.1 Publication

GO - Molecular functioni

  • receptor activity Source: UniProtKB
  • TRAIL 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:ENSG00000120889-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.
SignaLinkiO14763.
SIGNORiO14763.

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor necrosis factor receptor superfamily member 10B
Alternative name(s):
Death receptor 5
TNF-related apoptosis-inducing ligand receptor 2
Short name:
TRAIL receptor 2
Short name:
TRAIL-R2
CD_antigen: CD262
Gene namesi
Name:TNFRSF10B
Synonyms:DR5, KILLER, TRAILR2, TRICK2, ZTNFR9
ORF Names:UNQ160/PRO186
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:11905. TNFRSF10B.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini56 – 210ExtracellularSequence analysisAdd BLAST155
Transmembranei211 – 231HelicalSequence analysisAdd BLAST21
Topological domaini232 – 440CytoplasmicSequence analysisAdd BLAST209

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

Involvement in diseasei

Squamous cell carcinoma of the head and neck (HNSCC)
The disease may be caused by mutations affecting the gene represented in this entry.
Disease descriptionA non-melanoma skin cancer affecting the head and neck. The hallmark of cutaneous SCC is malignant transformation of normal epidermal keratinocytes.
See also OMIM:275355

Organism-specific databases

DisGeNETi8795.
MalaCardsiTNFRSF10B.
MIMi275355. phenotype.
OpenTargetsiENSG00000120889.
Orphaneti67037. Squamous cell carcinoma of head and neck.
PharmGKBiPA36598.

Chemistry databases

ChEMBLiCHEMBL1075153.
GuidetoPHARMACOLOGYi1880.

Polymorphism and mutation databases

BioMutaiTNFRSF10B.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 551 PublicationAdd BLAST55
ChainiPRO_000003458056 – 440Tumor necrosis factor receptor superfamily member 10BAdd BLAST385

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi81 ↔ 94
Disulfide bondi97 ↔ 113
Disulfide bondi116 ↔ 129
Disulfide bondi119 ↔ 137
Disulfide bondi139 ↔ 153
Disulfide bondi156 ↔ 170
Disulfide bondi160 ↔ 178

Keywords - PTMi

Disulfide bond

Proteomic databases

MaxQBiO14763.
PaxDbiO14763.
PeptideAtlasiO14763.
PRIDEiO14763.

PTM databases

iPTMnetiO14763.
PhosphoSitePlusiO14763.
SwissPalmiO14763.

Expressioni

Tissue specificityi

Widely expressed in adult and fetal tissues; very highly expressed in tumor cell lines such as HeLaS3, K-562, HL-60, SW480, A-549 and G-361; highly expressed in heart, peripheral blood lymphocytes, liver, pancreas, spleen, thymus, prostate, ovary, uterus, placenta, testis, esophagus, stomach and throughout the intestinal tract; not detectable in brain.

Inductioni

By ER stress. Regulated by p53/TP53.1 Publication

Gene expression databases

BgeeiENSG00000120889.
CleanExiHS_TNFRSF10B.
ExpressionAtlasiO14763. baseline and differential.
GenevisibleiO14763. HS.

Organism-specific databases

HPAiHPA023625.

Interactioni

Subunit structurei

Homotrimer. Can interact with TRADD and RIPK1. Interacts with HCMV protein UL141; this interaction prevents TNFRSF10B cell surface expression. Two TNFRSF10B monomers interact with a UL141 homodimer.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
TNFSF10P5059121EBI-518882,EBI-495373

GO - Molecular functioni

  • TRAIL binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114323. 62 interactors.
DIPiDIP-33566N.
IntActiO14763. 13 interactors.
MINTiMINT-109111.
STRINGi9606.ENSP00000276431.

Chemistry databases

BindingDBiO14763.

Structurei

Secondary structure

1440
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi77 – 79Combined sources3
Beta strandi85 – 87Combined sources3
Beta strandi89 – 91Combined sources3
Beta strandi94 – 96Combined sources3
Turni99 – 101Combined sources3
Beta strandi106 – 108Combined sources3
Beta strandi110 – 112Combined sources3
Beta strandi123 – 127Combined sources5
Beta strandi131 – 133Combined sources3
Beta strandi136 – 142Combined sources7
Beta strandi143 – 145Combined sources3
Beta strandi153 – 155Combined sources3
Beta strandi164 – 166Combined sources3
Beta strandi172 – 174Combined sources3
Beta strandi178 – 180Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1D0GX-ray2.40R/S/T54-183[»]
1D4VX-ray2.20A69-184[»]
1DU3X-ray2.20A/B/C/G/H/I54-183[»]
1ZA3X-ray3.35R/S54-183[»]
2H9GX-ray2.32R/S54-183[»]
3X3FX-ray2.10A54-184[»]
4I9XX-ray2.10C/D58-184[»]
4N90X-ray3.30R/S/T57-182[»]
4OD2X-ray3.20S73-183[»]
ProteinModelPortaliO14763.
SMRiO14763.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO14763.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati57 – 94TNFR-Cys 1Add BLAST38
Repeati97 – 137TNFR-Cys 2Add BLAST41
Repeati138 – 178TNFR-Cys 3Add BLAST41
Repeati192 – 206TAPEAdd BLAST15
Domaini339 – 422DeathPROSITE-ProRule annotationAdd BLAST84

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi250 – 253Poly-Gly4

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.
HOVERGENiHBG061626.
InParanoidiO14763.
KOiK04722.
OMAiEMEVQEP.
OrthoDBiEOG091G0MOV.
PhylomeDBiO14763.
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]

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Long (identifier: O14763-1) [UniParc]FASTAAdd to basket
Also known as: TRICK2B

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
MEQRGQNAPA ASGARKRHGP GPREARGARP GPRVPKTLVL VVAAVLLLVS
60 70 80 90 100
AESALITQQD LAPQQRAAPQ QKRSSPSEGL CPPGHHISED GRDCISCKYG
110 120 130 140 150
QDYSTHWNDL LFCLRCTRCD SGEVELSPCT TTRNTVCQCE EGTFREEDSP
160 170 180 190 200
EMCRKCRTGC PRGMVKVGDC TPWSDIECVH KESGTKHSGE VPAVEETVTS
210 220 230 240 250
SPGTPASPCS LSGIIIGVTV AAVVLIVAVF VCKSLLWKKV LPYLKGICSG
260 270 280 290 300
GGGDPERVDR SSQRPGAEDN VLNEIVSILQ PTQVPEQEME VQEPAEPTGV
310 320 330 340 350
NMLSPGESEH LLEPAEAERS QRRRLLVPAN EGDPTETLRQ CFDDFADLVP
360 370 380 390 400
FDSWEPLMRK LGLMDNEIKV AKAEAAGHRD TLYTMLIKWV NKTGRDASVH
410 420 430 440
TLLDALETLG ERLAKQKIED HLLSSGKFMY LEGNADSAMS
Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Length:440
Mass (Da):47,878
Last modified:November 30, 2010 - v2
Checksum:i60358EAF2A835870
GO
Isoform 3 (identifier: O14763-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     119-440: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:118
Mass (Da):12,793
Checksum:i6ED1332A3DF0FD39
GO
Isoform Short (identifier: O14763-2) [UniParc]FASTAAdd to basket
Also known as: TRICK2A

The sequence of this isoform differs from the canonical sequence as follows:
     185-213: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:411
Mass (Da):45,083
Checksum:i57D50020E72CC954
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti439M → L in AAB67103 (PubMed:9242611).Curated1
Sequence conflicti439M → L in AAQ88644 (PubMed:12975309).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01615332P → L.10 PublicationsCorresponds to variant rs1129424dbSNPEnsembl.1
Natural variantiVAR_01615467A → V.6 PublicationsCorresponds to variant rs1047266dbSNPEnsembl.1
Natural variantiVAR_059831191V → A.5 PublicationsCorresponds to variant rs13265018dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_039125119 – 440Missing in isoform 3. 1 PublicationAdd BLAST322
Alternative sequenceiVSP_006490185 – 213Missing in isoform Short. 9 PublicationsAdd BLAST29

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF018657 mRNA. Translation: AAB70577.1.
AF018658 mRNA. Translation: AAB70578.1.
AF016849 mRNA. Translation: AAC51778.1.
AF016266 mRNA. Translation: AAB81180.1.
AF016268 mRNA. Translation: AAC01565.1.
AF020501 mRNA. Translation: AAB71412.1.
AF022386 mRNA. Translation: AAB71949.1.
AF012628 mRNA. Translation: AAB67109.1.
AF012535 mRNA. Translation: AAB67103.1.
AB014718 Genomic DNA. Translation: BAA33723.1.
AF153687 mRNA. Translation: AAF75587.1.
AF192548 mRNA. Translation: AAF07175.1.
AY358277 mRNA. Translation: AAQ88644.1.
BX538104 mRNA. Translation: CAD98017.1.
AC107959 Genomic DNA. No translation available.
BC001281 mRNA. Translation: AAH01281.1.
CCDSiCCDS6035.1. [O14763-1]
CCDS6036.1. [O14763-2]
RefSeqiNP_003833.4. NM_003842.4. [O14763-1]
NP_671716.2. NM_147187.2. [O14763-2]
UniGeneiHs.521456.
Hs.661668.

Genome annotation databases

EnsembliENST00000276431; ENSP00000276431; ENSG00000120889. [O14763-1]
ENST00000347739; ENSP00000317859; ENSG00000120889. [O14763-2]
GeneIDi8795.
KEGGihsa:8795.
UCSCiuc003xct.4. human. [O14763-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF018657 mRNA. Translation: AAB70577.1.
AF018658 mRNA. Translation: AAB70578.1.
AF016849 mRNA. Translation: AAC51778.1.
AF016266 mRNA. Translation: AAB81180.1.
AF016268 mRNA. Translation: AAC01565.1.
AF020501 mRNA. Translation: AAB71412.1.
AF022386 mRNA. Translation: AAB71949.1.
AF012628 mRNA. Translation: AAB67109.1.
AF012535 mRNA. Translation: AAB67103.1.
AB014718 Genomic DNA. Translation: BAA33723.1.
AF153687 mRNA. Translation: AAF75587.1.
AF192548 mRNA. Translation: AAF07175.1.
AY358277 mRNA. Translation: AAQ88644.1.
BX538104 mRNA. Translation: CAD98017.1.
AC107959 Genomic DNA. No translation available.
BC001281 mRNA. Translation: AAH01281.1.
CCDSiCCDS6035.1. [O14763-1]
CCDS6036.1. [O14763-2]
RefSeqiNP_003833.4. NM_003842.4. [O14763-1]
NP_671716.2. NM_147187.2. [O14763-2]
UniGeneiHs.521456.
Hs.661668.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1D0GX-ray2.40R/S/T54-183[»]
1D4VX-ray2.20A69-184[»]
1DU3X-ray2.20A/B/C/G/H/I54-183[»]
1ZA3X-ray3.35R/S54-183[»]
2H9GX-ray2.32R/S54-183[»]
3X3FX-ray2.10A54-184[»]
4I9XX-ray2.10C/D58-184[»]
4N90X-ray3.30R/S/T57-182[»]
4OD2X-ray3.20S73-183[»]
ProteinModelPortaliO14763.
SMRiO14763.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114323. 62 interactors.
DIPiDIP-33566N.
IntActiO14763. 13 interactors.
MINTiMINT-109111.
STRINGi9606.ENSP00000276431.

Chemistry databases

BindingDBiO14763.
ChEMBLiCHEMBL1075153.
GuidetoPHARMACOLOGYi1880.

PTM databases

iPTMnetiO14763.
PhosphoSitePlusiO14763.
SwissPalmiO14763.

Polymorphism and mutation databases

BioMutaiTNFRSF10B.

Proteomic databases

MaxQBiO14763.
PaxDbiO14763.
PeptideAtlasiO14763.
PRIDEiO14763.

Protocols and materials databases

DNASUi8795.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000276431; ENSP00000276431; ENSG00000120889. [O14763-1]
ENST00000347739; ENSP00000317859; ENSG00000120889. [O14763-2]
GeneIDi8795.
KEGGihsa:8795.
UCSCiuc003xct.4. human. [O14763-1]

Organism-specific databases

CTDi8795.
DisGeNETi8795.
GeneCardsiTNFRSF10B.
HGNCiHGNC:11905. TNFRSF10B.
HPAiHPA023625.
MalaCardsiTNFRSF10B.
MIMi275355. phenotype.
603612. gene.
neXtProtiNX_O14763.
OpenTargetsiENSG00000120889.
Orphaneti67037. Squamous cell carcinoma of head and neck.
PharmGKBiPA36598.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IZX0. Eukaryota.
ENOG4111ZZM. LUCA.
GeneTreeiENSGT00730000110985.
HOVERGENiHBG061626.
InParanoidiO14763.
KOiK04722.
OMAiEMEVQEP.
OrthoDBiEOG091G0MOV.
PhylomeDBiO14763.
TreeFamiTF333916.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000120889-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.
SignaLinkiO14763.
SIGNORiO14763.

Miscellaneous databases

EvolutionaryTraceiO14763.
GeneWikiiTNFRSF10B.
GenomeRNAii8795.
PROiO14763.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000120889.
CleanExiHS_TNFRSF10B.
ExpressionAtlasiO14763. baseline and differential.
GenevisibleiO14763. 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 nameiTR10B_HUMAN
AccessioniPrimary (citable) accession number: O14763
Secondary accession number(s): O14720
, O15508, O15517, O15531, Q6UXM8, Q7Z360, Q9BVE0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: November 30, 2010
Last modified: November 30, 2016
This is version 186 of the entry and version 2 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

3D-structure, Complete proteome, Direct protein sequencing, 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
  7. 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.