O95150 (TNF15_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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:

1. Tumor necrosis factor ligand superfamily member 15, membrane form
2. Tumor necrosis factor ligand superfamily member 15, secreted form

Gene names

Name:	TNFSF15
Synonyms:	TL1, VEGI

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	251 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal-anchor Transmembrane Transmembrane helix
Molecular function	Cytokine
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	activation of NF-kappaB-inducing kinase activity Inferred from direct assay Ref.3. Source: MGI activation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from direct assay Ref.3. Source: MGI cytokine metabolic process Inferred from direct assay Ref.3. Source: MGI immune response Inferred from electronic annotation. Source: InterPro positive regulation of cytokine secretion Inferred from electronic annotation. Source: Compara
Cellular_component	extracellular space Inferred from electronic annotation. Source: UniProtKB-KW integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	receptor binding Traceable author statement Ref.8. Source: ProtInc
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 251

251

Tumor necrosis factor ligand superfamily member 15, membrane form

PRO_0000185505

Chain

72 – 251

180

Tumor necrosis factor ligand superfamily member 15, secreted form

PRO_0000333234

Regions

Topological domain

1 – 35

35

Cytoplasmic Potential

Transmembrane

36 – 56

21

Helical; Signal-anchor for type II membrane protein; Potential

Topological domain

57 – 251

195

Extracellular Potential

Sites

Site

71 – 72

2

Cleavage

Site

187

1

Important for binding TNFRSF6B

Site

190

1

Important for binding TNFRSF6B

Amino acid modifications

Glycosylation

133

1

N-linked (GlcNAc...) Potential

Glycosylation

229

1

N-linked (GlcNAc...) Potential

Disulfide bond

162 ↔ 202

Ref.10

Natural variations

Alternative sequence

1 – 85

85

MAEDL…HQQVY → MQLTKGRLHFSHPLSHTKHI SPFVTD in isoform 2.

VSP_033492

Alternative sequence

1 – 77

77

Missing in isoform 3.

VSP_033493

Alternative sequence

78 – 100

23

APSHQ…RAHLT → MRRFLSKVYSFPMRKLILFL VFP in isoform 3.

VSP_033494

Natural variant

110

1

F → L.
Corresponds to variant rs16931745 [ dbSNP | Ensembl ].

VAR_043130

Experimental info

Sequence conflict

34

1

R → H in AAI04463. Ref.7

Secondary structure

1

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251

Helix Strand Turn

Details...

Beta strand

96 – 101

6

Beta strand

111 – 113

3

Beta strand

120 – 123

4

Beta strand

127 – 129

3

Beta strand

133 – 135

3

Beta strand

138 – 140

3

Beta strand

145 – 156

12

Beta strand

161 – 164

4

Turn

167 – 169

3

Beta strand

175 – 184

10

Beta strand

186 – 188

3

Beta strand

192 – 200

9

Beta strand

204 – 206

3

Beta strand

209 – 220

12

Beta strand

225 – 231

7

Helix

233 – 235

3

Turn

241 – 243

3

Beta strand

244 – 250

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (TL1A) (VEGI-251) [UniParc]. Last modified May 20, 2008. Version 2. Checksum: 65ED70E367E3446D	FASTA	251	28,087
	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
	Isoform 2 (VEGI-192) [UniParc]. Checksum: CC7D2E73CEF5A53A	FASTA	192	21,857
	10 20 30 40 50 60 MQLTKGRLHF SHPLSHTKHI SPFVTDAPLR ADGDKPRAHL TVVRQTPTQH FKNQFPALHW 70 80 90 100 110 120 EHELGLAFTK NRMNYTNKFL LIPESGDYFI YSQVTFRGMT SECSEIRQAG RPNKPDSITV 130 140 150 160 170 180 VITKVTDSYP EPTQLLMGTK SVCEVGSNWF QPIYLGAMFS LQEGDKLMVN VSDISLVDYT 190 KEDKTFFGAF LL
	Isoform 3 (VEGI-174) [UniParc]. Checksum: CCB83BA7EE673B98	FASTA	174	20,131
	10 20 30 40 50 60 MRRFLSKVYS FPMRKLILFL VFPVVRQTPT QHFKNQFPAL HWEHELGLAF TKNRMNYTNK 70 80 90 100 110 120 FLLIPESGDY FIYSQVTFRG MTSECSEIRQ AGRPNKPDSI TVVITKVTDS YPEPTQLLMG 130 140 150 160 170 TKSVCEVGSN WFQPIYLGAM FSLQEGDKLM VNVSDISLVD YTKEDKTFFG AFLL

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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. , 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.

IPI

IPI00021380.
IPI00184879.
IPI00478864.

RefSeq

NP_001191273.1. NM_001204344.1.
NP_005109.2. NM_005118.3.

UniGene

Hs.23349.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2O0O	X-ray	3.00	A/B/C	72-251	[»]
2QE3	X-ray	2.50	A	72-251	[»]
2RE9	X-ray	2.10	A/B/C	72-251	[»]
2RJK	X-ray	2.30	A	72-251	[»]
2RJL	X-ray	2.05	A	72-251	[»]
3K51	X-ray	2.45	A	72-251	[»]
3MI8	X-ray	2.95	A	72-251	[»]

ProteinModelPortal

O95150.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-59562N.

STRING

9606.ENSP00000363157.

Proteomic databases

PaxDb

O95150.

PRIDE

O95150.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000374044; ENSP00000363156; ENSG00000181634.
ENST00000374045; ENSP00000363157; ENSG00000181634.

GeneID

9966.

KEGG

hsa:9966.

UCSC

uc004bjg.3. human.
uc004bjh.3. human.

Organism-specific databases

CTD

9966.

GeneCards

GC09M117551.

HGNC

HGNC:11931. TNFSF15.

HPA

HPA012948.

MIM

604052. gene.

neXtProt

NX_O95150.

PharmGKB

PA36623.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG40368.

HOGENOM

HOG000060140.

HOVERGEN

HBG067254.

InParanoid

O95150.

KO

K05478.

OMA

LKNQFPA.

OrthoDB

EOG4P5K9X.

PhylomeDB

O95150.

Gene expression databases

ArrayExpress

O95150.

Bgee

O95150.

CleanEx

HS_TNFSF15.

Genevestigator

O95150.

GermOnline

ENSG00000181634. Homo sapiens.

Family and domain databases

Gene3D

2.60.120.40. 1 hit.

InterPro

IPR006052. TNF.
IPR006053. TNF_a/b/c.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]

Pfam

PF00229. TNF. 1 hit.
[Graphical view]

PRINTS

PR01234. TNECROSISFCT.

SMART

SM00207. TNF. 1 hit.
[Graphical view]

SUPFAM

SSF49842. TNF_like. 1 hit.

PROSITE

PS50049. TNF_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O95150.

GenomeRNAi

9966.

NextBio

37610.

SOURCE

Search...

Entry information

Entry name

TNF15_HUMAN

Accession

Primary (citable) accession number: O95150
Secondary accession number(s): Q3SX69 , Q5VJK8, Q5VWH1, Q8NFE9

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 6, 2002
Last sequence update:	May 20, 2008
Last modified:	May 1, 2013
This is version 113 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.