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Protein

Tumor necrosis factor ligand superfamily member 10

Gene

TNFSF10

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

Functioni

Cytokine that binds to TNFRSF10A/TRAILR1, TNFRSF10B/TRAILR2, TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4 and possibly also to TNFRSF11B/OPG. Induces apoptosis. Its activity may be modulated by binding to the decoy receptors TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4 and TNFRSF11B/OPG that cannot induce apoptosis.

Cofactori

Zn2+Note: Binds 1 zinc ion per trimer.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi230Zinc1

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • receptor binding Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Keywords - Biological processi

Apoptosis

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000121858-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-69416. Dimerization of procaspase-8.
R-HSA-75158. TRAIL signaling.
SIGNORiP50591.

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor necrosis factor ligand superfamily member 10
Alternative name(s):
Apo-2 ligand
Short name:
Apo-2L
TNF-related apoptosis-inducing ligand
Short name:
Protein TRAIL
CD_antigen: CD253
Gene namesi
Name:TNFSF10
Synonyms:APO2L, TRAIL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:11925. TNFSF10.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 17CytoplasmicSequence analysisAdd BLAST17
Transmembranei18 – 38Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini39 – 281ExtracellularSequence analysisAdd BLAST243

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • extracellular region Source: Reactome
  • extracellular space Source: UniProtKB-KW
  • integral component of plasma membrane Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi8743.
OpenTargetsiENSG00000121858.
PharmGKBiPA36618.

Chemistry databases

ChEMBLiCHEMBL5813.

Polymorphism and mutation databases

BioMutaiTNFSF10.
DMDMi1730015.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001855031 – 281Tumor necrosis factor ligand superfamily member 10Add BLAST281

Post-translational modificationi

Tyrosine phosphorylated by PKDCC/VLK.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP50591.
PaxDbiP50591.
PeptideAtlasiP50591.
PRIDEiP50591.

PTM databases

iPTMnetiP50591.
PhosphoSitePlusiP50591.

Expressioni

Tissue specificityi

Widespread; most predominant in spleen, lung and prostate.

Gene expression databases

BgeeiENSG00000121858.
CleanExiHS_TNFSF10.
ExpressionAtlasiP50591. baseline and differential.
GenevisibleiP50591. HS.

Organism-specific databases

HPAiHPA054938.

Interactioni

Subunit structurei

Homotrimer.

Binary interactionsi

WithEntry#Exp.IntActNotes
CUL3Q136182EBI-495373,EBI-456129
TNFRSF10AO002204EBI-495373,EBI-518861
TNFRSF10BO1476321EBI-495373,EBI-518882

GO - Molecular functioni

  • receptor binding Source: ProtInc

Protein-protein interaction databases

BioGridi114280. 15 interactors.
DIPiDIP-6230N.
IntActiP50591. 18 interactors.
MINTiMINT-109168.
STRINGi9606.ENSP00000241261.

Chemistry databases

BindingDBiP50591.

Structurei

Secondary structure

1281
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi123 – 127Combined sources5
Turni137 – 139Combined sources3
Beta strandi144 – 146Combined sources3
Beta strandi148 – 150Combined sources3
Turni158 – 161Combined sources4
Beta strandi163 – 170Combined sources8
Beta strandi173 – 178Combined sources6
Beta strandi180 – 193Combined sources14
Beta strandi205 – 213Combined sources9
Beta strandi215 – 218Combined sources4
Beta strandi220 – 228Combined sources9
Beta strandi237 – 250Combined sources14
Beta strandi255 – 262Combined sources8
Helixi263 – 265Combined sources3
Turni270 – 272Combined sources3
Beta strandi273 – 279Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1D0GX-ray2.40A/B/D114-281[»]
1D2QX-ray2.80A/B114-281[»]
1D4VX-ray2.20B119-281[»]
1DG6X-ray1.30A91-281[»]
1DU3X-ray2.20D/E/F/J/K/L114-281[»]
4N90X-ray3.30A/B/C114-281[»]
ProteinModelPortaliP50591.
SMRiP50591.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP50591.

Family & Domainsi

Sequence similaritiesi

Belongs to the tumor necrosis factor family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IIX7. Eukaryota.
ENOG410YS4F. LUCA.
GeneTreeiENSGT00530000063443.
HOGENOMiHOG000230484.
HOVERGENiHBG059007.
InParanoidiP50591.
KOiK04721.
OMAiQTCVLIL.
OrthoDBiEOG091G0F3S.
PhylomeDBiP50591.
TreeFamiTF332169.

Family and domain databases

Gene3Di2.60.120.40. 1 hit.
InterProiIPR021184. TNF_CS.
IPR006052. TNF_dom.
IPR017355. TNF_ligand_10/11.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
PfamiPF00229. TNF. 1 hit.
[Graphical view]
PIRSFiPIRSF038013. TNF10_TNF11. 1 hit.
SMARTiSM00207. TNF. 1 hit.
[Graphical view]
SUPFAMiSSF49842. SSF49842. 1 hit.
PROSITEiPS00251. TNF_1. 1 hit.
PS50049. TNF_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P50591-1) [UniParc]FASTAAdd to basket

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
MAMMEVQGGP SLGQTCVLIV IFTVLLQSLC VAVTYVYFTN ELKQMQDKYS
60 70 80 90 100
KSGIACFLKE DDSYWDPNDE ESMNSPCWQV KWQLRQLVRK MILRTSEETI
110 120 130 140 150
STVQEKQQNI SPLVRERGPQ RVAAHITGTR GRSNTLSSPN SKNEKALGRK
160 170 180 190 200
INSWESSRSG HSFLSNLHLR NGELVIHEKG FYYIYSQTYF RFQEEIKENT
210 220 230 240 250
KNDKQMVQYI YKYTSYPDPI LLMKSARNSC WSKDAEYGLY SIYQGGIFEL
260 270 280
KENDRIFVSV TNEHLIDMDH EASFFGAFLV G
Length:281
Mass (Da):32,509
Last modified:October 1, 1996 - v1
Checksum:iDDAAAF78DAAB2F6D
GO
Isoform 2 (identifier: P50591-2) [UniParc]FASTAAdd to basket
Also known as: TRAIL-short, TRAIL-s

The sequence of this isoform differs from the canonical sequence as follows:
     91-101: MILRTSEETIS → TPRMKRLWAAK
     102-281: Missing.

Note: Induced upon HIV infection, antagonizes signaling via TRAIL receptor R2 (TNFRSF10B).
Show »
Length:101
Mass (Da):11,746
Checksum:i205B6BA004A7C104
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05258433V → I.Corresponds to variant rs6763816dbSNPEnsembl.1
Natural variantiVAR_05258547D → E.Corresponds to variant rs16845759dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04350791 – 101MILRTSEETIS → TPRMKRLWAAK in isoform 2. 3 PublicationsAdd BLAST11
Alternative sequenceiVSP_043508102 – 281Missing in isoform 2. 3 PublicationsAdd BLAST180

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U37518 mRNA. Translation: AAC50332.1.
U57059 mRNA. Translation: AAB01233.1.
DQ848564 mRNA. Translation: ABI24016.1.
EU183231 mRNA. Translation: ABW24658.1.
AK296085 mRNA. Translation: BAG58840.1.
AC007919 Genomic DNA. No translation available.
AC016938 Genomic DNA. No translation available.
BC032722 mRNA. Translation: AAH32722.1.
CCDSiCCDS3219.1. [P50591-1]
CCDS54680.1. [P50591-2]
RefSeqiNP_001177871.1. NM_001190942.1. [P50591-2]
NP_003801.1. NM_003810.3. [P50591-1]
UniGeneiHs.478275.

Genome annotation databases

EnsembliENST00000241261; ENSP00000241261; ENSG00000121858. [P50591-1]
ENST00000420541; ENSP00000389931; ENSG00000121858. [P50591-2]
GeneIDi8743.
KEGGihsa:8743.
UCSCiuc003fie.4. human. [P50591-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U37518 mRNA. Translation: AAC50332.1.
U57059 mRNA. Translation: AAB01233.1.
DQ848564 mRNA. Translation: ABI24016.1.
EU183231 mRNA. Translation: ABW24658.1.
AK296085 mRNA. Translation: BAG58840.1.
AC007919 Genomic DNA. No translation available.
AC016938 Genomic DNA. No translation available.
BC032722 mRNA. Translation: AAH32722.1.
CCDSiCCDS3219.1. [P50591-1]
CCDS54680.1. [P50591-2]
RefSeqiNP_001177871.1. NM_001190942.1. [P50591-2]
NP_003801.1. NM_003810.3. [P50591-1]
UniGeneiHs.478275.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1D0GX-ray2.40A/B/D114-281[»]
1D2QX-ray2.80A/B114-281[»]
1D4VX-ray2.20B119-281[»]
1DG6X-ray1.30A91-281[»]
1DU3X-ray2.20D/E/F/J/K/L114-281[»]
4N90X-ray3.30A/B/C114-281[»]
ProteinModelPortaliP50591.
SMRiP50591.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114280. 15 interactors.
DIPiDIP-6230N.
IntActiP50591. 18 interactors.
MINTiMINT-109168.
STRINGi9606.ENSP00000241261.

Chemistry databases

BindingDBiP50591.
ChEMBLiCHEMBL5813.

PTM databases

iPTMnetiP50591.
PhosphoSitePlusiP50591.

Polymorphism and mutation databases

BioMutaiTNFSF10.
DMDMi1730015.

Proteomic databases

EPDiP50591.
PaxDbiP50591.
PeptideAtlasiP50591.
PRIDEiP50591.

Protocols and materials databases

DNASUi8743.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000241261; ENSP00000241261; ENSG00000121858. [P50591-1]
ENST00000420541; ENSP00000389931; ENSG00000121858. [P50591-2]
GeneIDi8743.
KEGGihsa:8743.
UCSCiuc003fie.4. human. [P50591-1]

Organism-specific databases

CTDi8743.
DisGeNETi8743.
GeneCardsiTNFSF10.
HGNCiHGNC:11925. TNFSF10.
HPAiHPA054938.
MIMi603598. gene.
neXtProtiNX_P50591.
OpenTargetsiENSG00000121858.
PharmGKBiPA36618.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IIX7. Eukaryota.
ENOG410YS4F. LUCA.
GeneTreeiENSGT00530000063443.
HOGENOMiHOG000230484.
HOVERGENiHBG059007.
InParanoidiP50591.
KOiK04721.
OMAiQTCVLIL.
OrthoDBiEOG091G0F3S.
PhylomeDBiP50591.
TreeFamiTF332169.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000121858-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-69416. Dimerization of procaspase-8.
R-HSA-75158. TRAIL signaling.
SIGNORiP50591.

Miscellaneous databases

ChiTaRSiTNFSF10. human.
EvolutionaryTraceiP50591.
GeneWikiiTRAIL.
GenomeRNAii8743.
PROiP50591.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000121858.
CleanExiHS_TNFSF10.
ExpressionAtlasiP50591. baseline and differential.
GenevisibleiP50591. HS.

Family and domain databases

Gene3Di2.60.120.40. 1 hit.
InterProiIPR021184. TNF_CS.
IPR006052. TNF_dom.
IPR017355. TNF_ligand_10/11.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
PfamiPF00229. TNF. 1 hit.
[Graphical view]
PIRSFiPIRSF038013. TNF10_TNF11. 1 hit.
SMARTiSM00207. TNF. 1 hit.
[Graphical view]
SUPFAMiSSF49842. SSF49842. 1 hit.
PROSITEiPS00251. TNF_1. 1 hit.
PS50049. TNF_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTNF10_HUMAN
AccessioniPrimary (citable) accession number: P50591
Secondary accession number(s): A1Y9B3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 2, 2016
This is version 167 of the entry and version 1 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, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 3
    Human chromosome 3: 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.