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O95150 (TNF15_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tumor necrosis factor ligand superfamily member 15
Alternative name(s):
TNF ligand-related molecule 1
Vascular endothelial cell growth inhibitor
Gene names
Name:TNFSF15
Synonyms:TL1, VEGI
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length251 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.2 Ref.3 Ref.9

Subunit structure

Homotrimer. Ref.10

Subcellular location

Membrane; Single-pass type II membrane protein Probable Ref.2 Ref.3.

Tumor necrosis factor ligand superfamily member 15, secreted form: Secreted Ref.2 Ref.3.

Tissue specificity

Specifically expressed in endothelial cells. Detected in monocytes, placenta, lung, liver, kidney, skeletal muscle, pancreas, spleen, prostate, small intestine and colon. Ref.1 Ref.2 Ref.3 Ref.8

Induction

Up-regulated by IL1A/interleukin-1 alpha and TNF. Ref.2 Ref.3

Sequence similarities

Belongs to the tumor necrosis factor family.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O95150-1)

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.
Isoform 2 (identifier: O95150-2)

Also known as: VEGI-192;

The sequence of this isoform differs from the canonical sequence as follows:
     1-85: MAEDLGLSFG...EFAPSHQQVY → MQLTKGRLHFSHPLSHTKHISPFVTD
Isoform 3 (identifier: O95150-3)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 251251Tumor necrosis factor ligand superfamily member 15, membrane form
PRO_0000185505
Chain72 – 251180Tumor necrosis factor ligand superfamily member 15, secreted form
PRO_0000333234

Regions

Topological domain1 – 3535Cytoplasmic Potential
Transmembrane36 – 5621Helical; Signal-anchor for type II membrane protein; Potential
Topological domain57 – 251195Extracellular Potential

Sites

Site71 – 722Cleavage
Site1871Important for binding TNFRSF6B
Site1901Important for binding TNFRSF6B

Amino acid modifications

Glycosylation1331N-linked (GlcNAc...) Potential
Glycosylation2291N-linked (GlcNAc...) Potential
Disulfide bond162 ↔ 202 Ref.10

Natural variations

Alternative sequence1 – 8585MAEDL…HQQVY → MQLTKGRLHFSHPLSHTKHI SPFVTD in isoform 2.
VSP_033492
Alternative sequence1 – 7777Missing in isoform 3.
VSP_033493
Alternative sequence78 – 10023APSHQ…RAHLT → MRRFLSKVYSFPMRKLILFL VFP in isoform 3.
VSP_033494
Natural variant1101F → L.
Corresponds to variant rs16931745 [ dbSNP | Ensembl ].
VAR_043130

Experimental info

Sequence conflict341R → H in AAI04463. Ref.7

Secondary structure

.................................... 251
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (TL1A) (VEGI-251) [UniParc].

Last modified May 20, 2008. Version 2.
Checksum: 65ED70E367E3446D

FASTA25128,087
        10         20         30         40         50         60 
MAEDLGLSFG ETASVEMLPE HGSCRPKARS SSARWALTCC LVLLPFLAGL TTYLLVSQLR 

        70         80         90        100        110        120 
AQGEACVQFQ ALKGQEFAPS HQQVYAPLRA DGDKPRAHLT VVRQTPTQHF KNQFPALHWE 

       130        140        150        160        170        180 
HELGLAFTKN RMNYTNKFLL IPESGDYFIY SQVTFRGMTS ECSEIRQAGR PNKPDSITVV 

       190        200        210        220        230        240 
ITKVTDSYPE PTQLLMGTKS VCEVGSNWFQ PIYLGAMFSL QEGDKLMVNV SDISLVDYTK 

       250 
EDKTFFGAFL L 

« Hide

Isoform 2 (VEGI-192) [UniParc].

Checksum: CC7D2E73CEF5A53A
Show »

FASTA19221,857
Isoform 3 (VEGI-174) [UniParc].

Checksum: CCB83BA7EE673B98
Show »

FASTA17420,131

References

« Hide 'large scale' references
[1]"VEGI, a novel cytokine of the tumor necrosis factor family, is an angiogenesis inhibitor that suppresses the growth of colon carcinomas in vivo."
Zhai Y., Ni J., Jiang G.-W., Lu J., Xing L., Lincoln C., Carter K.C., Janat F., Kozak D., Xu S., Rojas L., Aggarwal B.B., Ruben S., Li L.-Y., Gentz R., Yu G.-L.
FASEB J. 13:181-189(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, TISSUE SPECIFICITY.
Tissue: Umbilical vein.
[2]"A novel secreted splice variant of vascular endothelial cell growth inhibitor."
Chew L.-J., Pan H., Yu J., Tian S., Huang W.-Q., Zhang J.Y., Pang S., Li L.-Y.
FASEB J. 16:742-744(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INDUCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[3]"TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator."
Migone T.-S., Zhang J., Luo X., Zhuang L., Chen C., Hu B., Hong J.S., Perry J.W., Chen S.-F., Zhou J.X.H., Cho Y.H., Ullrich S., Kanakaraj P., Carrell J., Boyd E., Olsen H.S., Hu G., Pukac L. expand/collapse author list , Liu D., Ni J., Kim S., Gentz R., Feng P., Moore P.A., Ruben S.M., Wei P.
Immunity 16:479-492(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF N-TERMINUS, FUNCTION, INTERACTION WITH TNFRSF25 AND TNFRSF6B, SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, INDUCTION, TISSUE SPECIFICITY.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Placenta.
[5]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[8]"Characterization of a novel TNF-like ligand and recently described TNF ligand and TNF receptor superfamily genes and their constitutive and inducible expression in hematopoietic and non-hematopoietic cells."
Tan K.B., Harrop J., Reddy M., Young P., Terrett J., Emery J., Moore G., Truneh A.
Gene 204:35-46(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION (ISOFORM 3), TISSUE SPECIFICITY.
[9]"VEGI, a new member of the TNF family activates nuclear factor-kappa B and c-Jun N-terminal kinase and modulates cell growth."
Haridas V., Shrivastava A., Su J., Yu G.-L., Ni J., Liu D., Chen S.-F., Ni Y., Ruben S.M., Gentz R., Aggarwal B.B.
Oncogene 18:6496-6504(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"X-ray crystal structure of TNF ligand family member TL1A at 2.1A."
Jin T., Guo F., Kim S., Howard A., Zhang Y.-Z.
Biochem. Biophys. Res. Commun. 364:1-6(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 71-251, DISULFIDE BOND, SUBUNIT.
[11]"Decoy strategies: the structure of TL1A:DcR3 complex."
Zhan C., Patskovsky Y., Yan Q., Li Z., Ramagopal U., Cheng H., Brenowitz M., Hui X., Nathenson S.G., Almo S.C.
Structure 19:162-171(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 72-251 IN COMPLEX WITH TNFRSF6B.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001191273.1. NM_001204344.1.
NP_005109.2. NM_005118.3.
UniGeneHs.23349.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalO95150.
SMRO95150. Positions 88-251.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115291. 2 interactions.
DIPDIP-59562N.
STRING9606.ENSP00000363157.

Proteomic databases

PaxDbO95150.
PRIDEO95150.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000374045; ENSP00000363157; ENSG00000181634. [O95150-1]
GeneID9966.
KEGGhsa:9966.
UCSCuc004bjg.3. human. [O95150-2]
uc004bjh.3. human. [O95150-1]

Organism-specific databases

CTD9966.
GeneCardsGC09M117551.
HGNCHGNC:11931. TNFSF15.
HPAHPA012948.
MIM604052. gene.
neXtProtNX_O95150.
Orphanet186. Primary biliary cirrhosis.
PharmGKBPA36623.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG40368.
HOGENOMHOG000060140.
HOVERGENHBG067254.
InParanoidO95150.
KOK05478.
OMATSECGEI.
OrthoDBEOG7V4B0Q.
PhylomeDBO95150.
TreeFamTF332169.

Gene expression databases

ArrayExpressO95150.
BgeeO95150.
CleanExHS_TNFSF15.
GenevestigatorO95150.

Family and domain databases

Gene3D2.60.120.40. 1 hit.
InterProIPR006053. TNF.
IPR006052. TNF_dom.
IPR008064. TNFalpha/TNFSF15.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
PANTHERPTHR11471:SF7. PTHR11471:SF7. 1 hit.
PfamPF00229. TNF. 1 hit.
[Graphical view]
PRINTSPR01234. TNECROSISFCT.
SMARTSM00207. TNF. 1 hit.
[Graphical view]
SUPFAMSSF49842. SSF49842. 1 hit.
PROSITEPS50049. TNF_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO95150.
GeneWikiVascular_endothelial_growth_inhibitor.
GenomeRNAi9966.
NextBio37610.
PROO95150.
SOURCESearch...

Entry information

Entry nameTNF15_HUMAN
AccessionPrimary (citable) accession number: O95150
Secondary accession number(s): Q3SX69 expand/collapse secondary AC list , Q5VJK8, Q5VWH1, Q8NFE9
Entry history
Integrated into UniProtKB/Swiss-Prot: June 6, 2002
Last sequence update: May 20, 2008
Last modified: April 16, 2014
This is version 122 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM