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Protein

Tumor necrosis factor ligand superfamily member 15

Gene

TNFSF15

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
  • receptor binding Source: ProtInc
  • tumor necrosis factor receptor binding Source: InterPro

GO - Biological processi

  • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
  • activation of NF-kappaB-inducing kinase activity Source: MGI
  • apoptotic process Source: InterPro
  • cytokine metabolic process Source: MGI
  • immune response Source: InterPro
  • signal transduction Source: ProtInc
  • tumor necrosis factor-mediated signaling pathway Source: Reactome

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.

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 cirrhosis.
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.

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.
CleanExiHS_TNFSF15.
ExpressionAtlasiO95150. baseline and differential.
GenevisibleiO95150. HS.

Organism-specific databases

HPAiHPA012948.
HPA046522.

Interactioni

Subunit structurei

Homotrimer.2 Publications

GO - Molecular functioni

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

Protein-protein interaction databases

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

Structurei

Secondary structure

1251
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi96 – 101Combined sources6
Beta strandi111 – 113Combined sources3
Beta strandi120 – 123Combined sources4
Beta strandi127 – 129Combined sources3
Beta strandi133 – 135Combined sources3
Beta strandi138 – 140Combined sources3
Beta strandi145 – 156Combined sources12
Beta strandi161 – 164Combined sources4
Turni167 – 169Combined sources3
Beta strandi175 – 184Combined sources10
Beta strandi186 – 188Combined sources3
Beta strandi192 – 200Combined sources9
Beta strandi204 – 206Combined sources3
Beta strandi209 – 220Combined sources12
Beta strandi225 – 231Combined sources7
Helixi233 – 235Combined sources3
Turni241 – 243Combined sources3
Beta strandi244 – 250Combined sources7

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...

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

Gene3Di2.60.120.40. 1 hit.
InterProiView protein in InterPro
IPR006053. TNF.
IPR006052. TNF_dom.
IPR008064. TNFSF15.
IPR008983. Tumour_necrosis_fac-like_dom.
PANTHERiPTHR11471:SF41. PTHR11471:SF41. 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

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

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. Translation: CAH73730.1.
AL390240 Genomic DNA. Translation: CAH73731.1.
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

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: September 27, 2017
This is version 147 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. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  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. SIMILARITY comments
    Index of protein domains and families