Reviewed, UniProtKB/Swiss-Prot O43557 (TNF14_HUMAN)

Names and origin

Protein names

Recommended name:
    Tumor necrosis factor ligand superfamily member 14
Alternative name(s):
    Herpesvirus entry mediator-ligand
      Short name=HVEM-L
    CD_antigen=CD258
Cleaved into the following 2 chains:
    1- Recommended name:
            Tumor necrosis factor ligand superfamily member 14, membrane form
    2- Recommended name:
            Tumor necrosis factor ligand superfamily member 14, soluble form

Gene names

Name:	TNFSF14
Synonyms:	HVEML, LIGHT
ORF Names:	UNQ391/PRO726

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	240 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	Cytokine that binds to TNFRSF3/LTBR. Binding to the decoy receptor TNFRSF6B modulates its effects. Activates NFKB, stimulates the proliferation of T-cells, and inhibits growth of the adenocarcinoma HT-29. Acts as a receptor for Herpes simplex virus.
Subunit structure	Homotrimer.
Subcellular location	Tumor necrosis factor ligand superfamily member 14, membrane form: Cell membrane; Single-pass type II membrane protein. Tumor necrosis factor ligand superfamily member 14, soluble form: Secreted. Isoform 2: Cytoplasm.
Tissue specificity	Predominantly expressed in the spleen but also found in the brain. Weakly expressed in peripheral lymphoid tissues and in heart, placenta, liver, lung, appendix, and kidney, and no expression seen in fetal tissues, endocrine glands, or nonhematopoietic tumor lines.
Induction	Up-regulated after T-cell activation.
Post-translational modification	N-glycosylated. The soluble form of isoform 1 derives from the membrane form by proteolytic processing.
Sequence similarities	Belongs to the tumor necrosis factor family.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal-anchor Transmembrane
Molecular function	Cytokine
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	T cell homeostasis Non-traceable author statement. Source: UniProtKB T cell proliferation Ref.2 Non-traceable author statement. Source: UniProtKB immune response Inferred from electronic annotation. Source: InterPro induction of apoptosis Traceable author statement. Source: ProtInc release of cytoplasmic sequestered NF-kappaB Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular space Inferred from electronic annotation. Source: UniProtKB-KW integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	caspase inhibitor activity Inferred from direct assay. Source: UniProtKB cytokine activity Inferred from electronic annotation. Source: UniProtKB-KW tumor necrosis factor receptor binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TNFRSF6B	O95407	1	EBI-524131,EBI-524171

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O43557-1)

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: O43557-2)

Also known as: LIGHT delta-TM;

The sequence of this isoform differs from the canonical sequence as follows:
     38-73: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 240	240	Tumor necrosis factor ligand superfamily member 14, membrane form		PRO_0000034532
	Chain	?83 – 240	158	Tumor necrosis factor ligand superfamily member 14, soluble form		PRO_0000034533
Regions
	Topological domain	1 – 37	37	Cytoplasmic Potential
	Transmembrane	38 – 58	21	Signal-anchor for type II membrane protein Potential
	Topological domain	59 – 240	182	Extracellular Potential
Sites
	Site	82 – 83	2	Cleavage Potential
Amino acid modifications
	Glycosylation	102	1	N-linked (GlcNAc...)
	Disulfide bond	154 ↔ 187		Potential
Natural variations
	Alternative sequence	38 – 73	36	Missing in isoform 2.		VSP_006452
	Natural variant	32	1	S → L: dbSNP rs2291667.		VAR_027677
	Natural variant	120	1	L → V: dbSNP rs17851606.		VAR_027678
	Natural variant	214	1	E → K: dbSNP rs344560. Ref.2 Ref.5		VAR_027679

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: 49D0BF67E1390B39	FASTA	240	26,351
	10 20 30 40 50 60 MEESVVRPSV FVVDGQTDIP FTRLGRSHRR QSCSVARVGL GLLLLLMGAG LAVQGWFLLQ 70 80 90 100 110 120 LHWRLGEMVT RLPDGPAGSW EQLIQERRSH EVNPAAHLTG ANSSLTGSGG PLLWETQLGL 130 140 150 160 170 180 AFLRGLSYHD GALVVTKAGY YYIYSKVQLG GVGCPLGLAS TITHGLYKRT PRYPEELELL 190 200 210 220 230 240 VSQQSPCGRA TSSSRVWWDS SFLGGVVHLE AGEEVVVRVL DERLVRLRDG TRSYFGAFMV
	Isoform 2 (LIGHT delta-TM). Checksum: FF97F3B1B3B2EB11	FASTA	204	22,396
	10 20 30 40 50 60 MEESVVRPSV FVVDGQTDIP FTRLGRSHRR QSCSVARDGP AGSWEQLIQE RRSHEVNPAA 70 80 90 100 110 120 HLTGANSSLT GSGGPLLWET QLGLAFLRGL SYHDGALVVT KAGYYYIYSK VQLGGVGCPL 130 140 150 160 170 180 GLASTITHGL YKRTPRYPEE LELLVSQQSP CGRATSSSRV WWDSSFLGGV VHLEAGEEVV 190 200 VRVLDERLVR LRDGTRSYFG AFMV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"LIGHT, a new member of the TNF superfamily, and lymphotoxin alpha are ligands for herpesvirus entry mediator." Mauri D.N., Ebner R., Montgomery R.I., Kochel K.D., Cheung T.C., Yu G.-L., Ruben S., Murphy M., Eisenberg R.J., Cohen G.H., Spear P.G., Ware C.F. Immunity 8:21-30(1998) [PubMed: 9462508] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Herpesvirus entry mediator ligand (HVEM-L), a novel ligand for HVEM/TR2, stimulates proliferation of T cells and inhibits HT29 cell growth." Harrop J.A., McDonnell P.C., Brigham-Burke M., Lyn S.D., Minton J., Tan K.B., Dede K., Spampanato J., Silverman C., Hensley P., DiPrinzio R., Emery J.G., Deen K., Eichman C., Chabot-Fletcher M., Truneh A., Young P.R. J. Biol. Chem. 273:27548-27556(1998) [PubMed: 9765287] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION, VARIANT LYS-214. Tissue: Liver.
[3]	"Genomic characterization of LIGHT reveals linkage to an immune response locus on chromosome 19p13.3 and distinct isoforms generated by alternate splicing or proteolysis." Granger S.W., Butrovich K.D., Houshmand P., Edwards W.R., Ware C.F. J. Immunol. 167:5122-5128(2001) [PubMed: 11673523] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEOLYTIC PROCESSING.
[4]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT LYS-214. Tissue: Spleen.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF036581 mRNA. Translation: AAC39563.1. AF064090 mRNA. Translation: AAC25169.1. AY028261 mRNA. Translation: AAK26160.1. AY358812 mRNA. Translation: AAQ89171.1. AK292037 mRNA. Translation: BAF84726.1.
IPI	IPI00221341. IPI00307531.
RefSeq	NP_003798.2. NP_742011.1.
UniGene	Hs.129708
3D structure databases
HSSP	HSSP built from PDB template 4TSV based on UniProtKB P01375.
ModBase	Search...
Protein-protein interaction databases
IntAct	O43557. 3 interactions.
STRING	O43557.
Genome annotation databases
Ensembl	ENST00000245912; ENSP00000245912; ENSG00000125735; Homo sapiens. [Genome view] ENST00000326176; ENSP00000326940; ENSG00000125735; Homo sapiens. [Genome view] ENST00000366236; ENSP00000406518; ENSG00000125735; Homo sapiens. [Genome view]
GeneID	8740.
KEGG	hsa:8740.
UCSC	uc002mfj.1. human. uc002mfk.1. human.
Organism-specific databases
CTD	8740.
GeneCards	GC19M006615.
HGNC	HGNC:11930. TNFSF14.
HPA	HPA012700. HPA026919.
MIM	604520. gene.
PharmGKB	PA36622.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O43557.
HOVERGEN	O43557.
Gene expression databases
ArrayExpress	O43557.
Bgee	O43557.
CleanEx	HS_TNFSF14.
Genevestigator	O43557.
GermOnline	ENSG00000125735. Homo sapiens.
Family and domain databases
InterPro	IPR006052. TNF_family. IPR008983. Tumour_necrosis_fac-like. [Graphical view]
Gene3D	G3DSA:2.60.120.40. Tumour_necrosis_fac-like. 1 hit.
Pfam	PF00229. TNF. 1 hit. [Graphical view]
ProDom	PD002012. TNF_subf. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00207. TNF. 1 hit. [Graphical view]
PROSITE	PS00251. TNF_1. False negative. PS50049. TNF_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	32787.
SOURCE	Search...

Entry information

Entry name

TNF14_HUMAN

Accession

Primary (citable) accession number: O43557
Secondary accession number(s): A8K7M2 , O75476, Q8WVF8, Q96LD2

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	June 1, 1998
Last modified:	October 13, 2009
This is version 96 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.