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Protein

Tumor necrosis factor ligand superfamily member 15

Gene

TNFSF15

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

Functioni

Receptor for TNFRSF25 and TNFRSF6B. Mediates activation of NF-kappa-B. Inhibits vascular endothelial growth and angiogenesis (in vitro). Promotes activation of caspases and apoptosis.4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei187Important for binding TNFRSF6B1
Sitei190Important for binding TNFRSF6B1

GO - Molecular functioni

  • cytokine activity Source: UniProtKB-KW
  • signaling receptor binding Source: ProtInc
  • tumor necrosis factor receptor binding Source: InterPro

GO - Biological processi

Keywordsi

Molecular functionCytokine

Enzyme and pathway databases

ReactomeiR-HSA-5669034 TNFs bind their physiological receptors
SIGNORiO95150

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor necrosis factor ligand superfamily member 15
Alternative name(s):
TNF ligand-related molecule 1
Vascular endothelial cell growth inhibitor
Cleaved into the following 2 chains:
Gene namesi
Name:TNFSF15
Synonyms:TL1, VEGI
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000181634.7
HGNCiHGNC:11931 TNFSF15
MIMi604052 gene
neXtProtiNX_O95150

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 – 35CytoplasmicSequence analysisAdd BLAST35
Transmembranei36 – 56Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini57 – 251ExtracellularSequence analysisAdd BLAST195

Keywords - Cellular componenti

Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi9966
MalaCardsiTNFSF15
OpenTargetsiENSG00000181634
Orphaneti186 Primary biliary cholangitis
PharmGKBiPA36623

Polymorphism and mutation databases

BioMutaiTNFSF15

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001855051 – 251Tumor necrosis factor ligand superfamily member 15, membrane formAdd BLAST251
ChainiPRO_000033323472 – 251Tumor necrosis factor ligand superfamily member 15, secreted formAdd BLAST180

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi133N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi162 ↔ 2021 Publication
Glycosylationi229N-linked (GlcNAc...) asparagineSequence analysis1

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei71 – 72Cleavage2

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO95150
PeptideAtlasiO95150
PRIDEiO95150
ProteomicsDBi50663
50664 [O95150-2]
50665 [O95150-3]

Expressioni

Tissue specificityi

Specifically expressed in endothelial cells. Detected in monocytes, placenta, lung, liver, kidney, skeletal muscle, pancreas, spleen, prostate, small intestine and colon.4 Publications

Inductioni

Up-regulated by IL1A/interleukin-1 alpha and TNF.2 Publications

Gene expression databases

BgeeiENSG00000181634 Expressed in 112 organ(s), highest expression level in cartilage tissue
CleanExiHS_TNFSF15
ExpressionAtlasiO95150 baseline and differential
GenevisibleiO95150 HS

Organism-specific databases

HPAiHPA012948
HPA046522

Interactioni

Subunit structurei

Homotrimer.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
TNFRSF6BO954073EBI-15910629,EBI-524171

GO - Molecular functioni

Protein-protein interaction databases

BioGridi115291, 2 interactors
DIPiDIP-59562N
IntActiO95150, 2 interactors
STRINGi9606.ENSP00000363157

Structurei

Secondary structure

1251
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO95150
SMRiO95150
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO95150

Family & Domainsi

Sequence similaritiesi

Belongs to the tumor necrosis factor family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IFSK Eukaryota
ENOG4111Y6F LUCA
GeneTreeiENSGT00530000062992
HOGENOMiHOG000060140
HOVERGENiHBG067254
InParanoidiO95150
KOiK05478
OMAiGTTSECG
OrthoDBiEOG091G0MFC
PhylomeDBiO95150
TreeFamiTF332169

Family and domain databases

CDDicd00184 TNF, 1 hit
Gene3Di2.60.120.40, 1 hit
InterProiView protein in InterPro
IPR006053 TNF
IPR006052 TNF_dom
IPR008064 TNFSF15
IPR008983 Tumour_necrosis_fac-like_dom
PANTHERiPTHR11471:SF24 PTHR11471:SF24, 1 hit
PfamiView protein in Pfam
PF00229 TNF, 1 hit
PRINTSiPR01234 TNECROSISFCT
SMARTiView protein in SMART
SM00207 TNF, 1 hit
SUPFAMiSSF49842 SSF49842, 1 hit
PROSITEiView protein in PROSITE
PS50049 TNF_2, 1 hit

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

This entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: O95150-1) [UniParc]FASTAAdd to basket
Also known as: TL1A, VEGI-251

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
MAEDLGLSFG ETASVEMLPE HGSCRPKARS SSARWALTCC LVLLPFLAGL
60 70 80 90 100
TTYLLVSQLR AQGEACVQFQ ALKGQEFAPS HQQVYAPLRA DGDKPRAHLT
110 120 130 140 150
VVRQTPTQHF KNQFPALHWE HELGLAFTKN RMNYTNKFLL IPESGDYFIY
160 170 180 190 200
SQVTFRGMTS ECSEIRQAGR PNKPDSITVV ITKVTDSYPE PTQLLMGTKS
210 220 230 240 250
VCEVGSNWFQ PIYLGAMFSL QEGDKLMVNV SDISLVDYTK EDKTFFGAFL

L
Length:251
Mass (Da):28,087
Last modified:May 20, 2008 - v2
Checksum:i65ED70E367E3446D
GO
Isoform 2 (identifier: O95150-2) [UniParc]FASTAAdd to basket
Also known as: VEGI-192

The sequence of this isoform differs from the canonical sequence as follows:
     1-85: MAEDLGLSFG...EFAPSHQQVY → MQLTKGRLHFSHPLSHTKHISPFVTD

Show »
Length:192
Mass (Da):21,857
Checksum:iCC7D2E73CEF5A53A
GO
Isoform 3 (identifier: O95150-3) [UniParc]FASTAAdd to basket
Also known as: VEGI-174

The sequence of this isoform differs from the canonical sequence as follows:
     1-77: Missing.
     78-100: APSHQQVYAPLRADGDKPRAHLT → MRRFLSKVYSFPMRKLILFLVFP

Note: No experimental confirmation available.
Show »
Length:174
Mass (Da):20,131
Checksum:iCCB83BA7EE673B98
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
X6R8I9X6R8I9_HUMAN
Tumor necrosis factor ligand superf...
TNFSF15
174Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti34R → H in AAI04463 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_043130110F → L. Corresponds to variant dbSNP:rs16931745Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0334921 – 85MAEDL…HQQVY → MQLTKGRLHFSHPLSHTKHI SPFVTD in isoform 2. 1 PublicationAdd BLAST85
Alternative sequenceiVSP_0334931 – 77Missing in isoform 3. 1 PublicationAdd BLAST77
Alternative sequenceiVSP_03349478 – 100APSHQ…RAHLT → MRRFLSKVYSFPMRKLILFL VFP in isoform 3. 1 PublicationAdd BLAST23

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF039390 mRNA Translation: AAD08783.1
AY434464 mRNA Translation: AAR98573.1
AF520785 mRNA Translation: AAM77366.1
AK291642 mRNA Translation: BAF84331.1
AL390240 Genomic DNA No translation available.
CH471090 Genomic DNA Translation: EAW87431.1
BC069435 mRNA Translation: AAH69435.1
BC074940 mRNA Translation: AAH74940.1
BC074941 mRNA Translation: AAH74941.1
BC104462 mRNA Translation: AAI04463.1
BC104463 mRNA Translation: AAI04464.1
CCDSiCCDS6809.1 [O95150-1]
RefSeqiNP_001191273.1, NM_001204344.1 [O95150-2]
NP_005109.2, NM_005118.3 [O95150-1]
UniGeneiHs.23349

Genome annotation databases

EnsembliENST00000374045; ENSP00000363157; ENSG00000181634 [O95150-1]
GeneIDi9966
KEGGihsa:9966
UCSCiuc004bjh.4 human [O95150-1]

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
AF039390 mRNA Translation: AAD08783.1
AY434464 mRNA Translation: AAR98573.1
AF520785 mRNA Translation: AAM77366.1
AK291642 mRNA Translation: BAF84331.1
AL390240 Genomic DNA No translation available.
CH471090 Genomic DNA Translation: EAW87431.1
BC069435 mRNA Translation: AAH69435.1
BC074940 mRNA Translation: AAH74940.1
BC074941 mRNA Translation: AAH74941.1
BC104462 mRNA Translation: AAI04463.1
BC104463 mRNA Translation: AAI04464.1
CCDSiCCDS6809.1 [O95150-1]
RefSeqiNP_001191273.1, NM_001204344.1 [O95150-2]
NP_005109.2, NM_005118.3 [O95150-1]
UniGeneiHs.23349

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2O0OX-ray3.00A/B/C72-251[»]
2QE3X-ray2.50A72-251[»]
2RE9X-ray2.10A/B/C72-251[»]
2RJKX-ray2.30A72-251[»]
2RJLX-ray2.05A72-251[»]
3K51X-ray2.45A72-251[»]
3MI8X-ray2.95A72-251[»]
ProteinModelPortaliO95150
SMRiO95150
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115291, 2 interactors
DIPiDIP-59562N
IntActiO95150, 2 interactors
STRINGi9606.ENSP00000363157

Polymorphism and mutation databases

BioMutaiTNFSF15

Proteomic databases

PaxDbiO95150
PeptideAtlasiO95150
PRIDEiO95150
ProteomicsDBi50663
50664 [O95150-2]
50665 [O95150-3]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000374045; ENSP00000363157; ENSG00000181634 [O95150-1]
GeneIDi9966
KEGGihsa:9966
UCSCiuc004bjh.4 human [O95150-1]

Organism-specific databases

CTDi9966
DisGeNETi9966
EuPathDBiHostDB:ENSG00000181634.7
GeneCardsiTNFSF15
HGNCiHGNC:11931 TNFSF15
HPAiHPA012948
HPA046522
MalaCardsiTNFSF15
MIMi604052 gene
neXtProtiNX_O95150
OpenTargetsiENSG00000181634
Orphaneti186 Primary biliary cholangitis
PharmGKBiPA36623
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFSK Eukaryota
ENOG4111Y6F LUCA
GeneTreeiENSGT00530000062992
HOGENOMiHOG000060140
HOVERGENiHBG067254
InParanoidiO95150
KOiK05478
OMAiGTTSECG
OrthoDBiEOG091G0MFC
PhylomeDBiO95150
TreeFamiTF332169

Enzyme and pathway databases

ReactomeiR-HSA-5669034 TNFs bind their physiological receptors
SIGNORiO95150

Miscellaneous databases

EvolutionaryTraceiO95150
GeneWikiiVascular_endothelial_growth_inhibitor
GenomeRNAii9966
PROiPR:O95150
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000181634 Expressed in 112 organ(s), highest expression level in cartilage tissue
CleanExiHS_TNFSF15
ExpressionAtlasiO95150 baseline and differential
GenevisibleiO95150 HS

Family and domain databases

CDDicd00184 TNF, 1 hit
Gene3Di2.60.120.40, 1 hit
InterProiView protein in InterPro
IPR006053 TNF
IPR006052 TNF_dom
IPR008064 TNFSF15
IPR008983 Tumour_necrosis_fac-like_dom
PANTHERiPTHR11471:SF24 PTHR11471:SF24, 1 hit
PfamiView protein in Pfam
PF00229 TNF, 1 hit
PRINTSiPR01234 TNECROSISFCT
SMARTiView protein in SMART
SM00207 TNF, 1 hit
SUPFAMiSSF49842 SSF49842, 1 hit
PROSITEiView protein in PROSITE
PS50049 TNF_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTNF15_HUMAN
AccessioniPrimary (citable) accession number: O95150
Secondary accession number(s): Q3SX69
, Q5VJK8, Q5VWH1, Q8NFE9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 6, 2002
Last sequence update: May 20, 2008
Last modified: November 7, 2018
This is version 153 of the entry and version 2 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, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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