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Protein

Tumor necrosis factor ligand superfamily member 10

Gene

TNFSF10

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

Functioni

Cytokine that binds to TNFRSF10A/TRAILR1, TNFRSF10B/TRAILR2, TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4 and possibly also to TNFRSF11B/OPG (PubMed:26457518, PubMed:10549288). Induces apoptosis. Its activity may be modulated by binding to the decoy receptors TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4 and TNFRSF11B/OPG that cannot induce apoptosis.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi230Zinc; shared with trimeric partnerCombined sources2 Publications1

GO - Molecular functioni

  • cytokine activity Source: UniProtKB-KW
  • identical protein binding Source: UniProtKB
  • signaling receptor binding Source: ProtInc
  • TRAIL binding Source: Ensembl
  • tumor necrosis factor receptor binding Source: InterPro
  • zinc ion binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionCytokine
Biological processApoptosis
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-140534 via Death Receptors in the presence of ligand
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

EuPathDBiHostDB:ENSG00000121858.10
HGNCiHGNC:11925 TNFSF10
MIMi603598 gene
neXtProtiNX_P50591

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 domaini1 – 17CytoplasmicSequence analysisAdd BLAST17
Transmembranei18 – 38Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini39 – 281ExtracellularSequence analysisAdd BLAST243

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

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
ProteomicsDBi56254
56255 [P50591-2]

PTM databases

iPTMnetiP50591
PhosphoSitePlusiP50591

Expressioni

Tissue specificityi

Widespread; most predominant in spleen, lung and prostate.

Gene expression databases

BgeeiENSG00000121858 Expressed in 224 organ(s), highest expression level in epithelium of bronchus
CleanExiHS_TNFSF10
ExpressionAtlasiP50591 baseline and differential
GenevisibleiP50591 HS

Organism-specific databases

HPAiHPA054938

Interactioni

Subunit structurei

Homotrimer (PubMed:26457518). One TNFSF10 homotrimer interacts with three TNFSF10A mononers (PubMed:26457518). One TNFSF10 homotrimer interacts with three TNFSF10B mononers (PubMed:10549288).2 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114280, 20 interactors
CORUMiP50591
DIPiDIP-6230N
IntActiP50591, 18 interactors
MINTiP50591
STRINGi9606.ENSP00000241261

Chemistry databases

BindingDBiP50591

Structurei

Secondary structure

1281
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
OMAiNKQMVQY
OrthoDBiEOG091G0F3S
PhylomeDBiP50591
TreeFamiTF332169

Family and domain databases

CDDicd00184 TNF, 1 hit
Gene3Di2.60.120.40, 1 hit
InterProiView protein in InterPro
IPR021184 TNF_CS
IPR006052 TNF_dom
IPR017355 TNF_ligand_10/11
IPR008983 Tumour_necrosis_fac-like_dom
PfamiView protein in Pfam
PF00229 TNF, 1 hit
PIRSFiPIRSF038013 TNF10_TNF11, 1 hit
SMARTiView protein in SMART
SM00207 TNF, 1 hit
SUPFAMiSSF49842 SSF49842, 1 hit
PROSITEiView protein in PROSITE
PS00251 TNF_1, 1 hit
PS50049 TNF_2, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.iShow all

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H7C246H7C246_HUMAN
Tumor necrosis factor ligand superf...
TNFSF10
74Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05258433V → I. Corresponds to variant dbSNP:rs6763816Ensembl.1
Natural variantiVAR_05258547D → E. Corresponds to variant dbSNP:rs16845759Ensembl.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

Similar proteinsi

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[»]
5CIRX-ray3.00A/B/D114-281[»]
ProteinModelPortaliP50591
SMRiP50591
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114280, 20 interactors
CORUMiP50591
DIPiDIP-6230N
IntActiP50591, 18 interactors
MINTiP50591
STRINGi9606.ENSP00000241261

Chemistry databases

BindingDBiP50591
ChEMBLiCHEMBL5813

PTM databases

iPTMnetiP50591
PhosphoSitePlusiP50591

Polymorphism and mutation databases

BioMutaiTNFSF10
DMDMi1730015

Proteomic databases

EPDiP50591
PaxDbiP50591
PeptideAtlasiP50591
PRIDEiP50591
ProteomicsDBi56254
56255 [P50591-2]

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
EuPathDBiHostDB:ENSG00000121858.10
GeneCardsiTNFSF10
HGNCiHGNC:11925 TNFSF10
HPAiHPA054938
MIMi603598 gene
neXtProtiNX_P50591
OpenTargetsiENSG00000121858
PharmGKBiPA36618
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiR-HSA-140534 via Death Receptors in the presence of ligand
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
PROiPR:P50591
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000121858 Expressed in 224 organ(s), highest expression level in epithelium of bronchus
CleanExiHS_TNFSF10
ExpressionAtlasiP50591 baseline and differential
GenevisibleiP50591 HS

Family and domain databases

CDDicd00184 TNF, 1 hit
Gene3Di2.60.120.40, 1 hit
InterProiView protein in InterPro
IPR021184 TNF_CS
IPR006052 TNF_dom
IPR017355 TNF_ligand_10/11
IPR008983 Tumour_necrosis_fac-like_dom
PfamiView protein in Pfam
PF00229 TNF, 1 hit
PIRSFiPIRSF038013 TNF10_TNF11, 1 hit
SMARTiView protein in SMART
SM00207 TNF, 1 hit
SUPFAMiSSF49842 SSF49842, 1 hit
PROSITEiView protein in PROSITE
PS00251 TNF_1, 1 hit
PS50049 TNF_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTNF10_HUMAN
AccessioniPrimary (citable) accession number: P50591
Secondary accession number(s): A1Y9B3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: September 12, 2018
This is version 181 of the entry and version 1 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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