O43557 (TNF14_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tumor necrosis factor ligand superfamily member 14

Alternative name(s):
Herpes virus entry mediator ligand
Short name=HVEM-L
Short name=Herpesvirus entry mediator ligand
CD_antigen=CD258

Cleaved into the following 2 chains:

1. Tumor necrosis factor ligand superfamily member 14, membrane form
2. Tumor necrosis factor ligand superfamily member 14, soluble form

Gene names

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

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	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. Ref.9 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 Transmembrane helix
Molecular function	Cytokine
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	T cell homeostasis Non-traceable author statement PubMed 12393901. Source: UniProtKB T cell proliferation Non-traceable author statement Ref.2. Source: UniProtKB cellular response to mechanical stimulus Inferred from expression pattern PubMed 19593445. Source: UniProtKB immune response Inferred from electronic annotation. Source: InterPro induction of apoptosis Traceable author statement PubMed 10799510. Source: ProtInc release of cytoplasmic sequestered NF-kappaB Inferred from direct assay PubMed 12393901. 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-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	cysteine-type endopeptidase inhibitor activity involved in apoptotic process Inferred from direct assay PubMed 12393901. Source: UniProtKB receptor binding Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TNFRSF14	Q92956	2	EBI-524131,EBI-1056653
TNFRSF6B	O95407	2	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

Helical; 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...) Ref.9

Disulfide bond

154 ↔ 187

Ref.9

Natural variations

Alternative sequence

38 – 73

36

Missing in isoform 2.

VSP_006452

Natural variant

32

1

S → L.
Corresponds to variant rs2291667 [ dbSNP | Ensembl ].

VAR_027677

Natural variant

120

1

L → V.
Corresponds to variant rs17851606 [ dbSNP | Ensembl ].

VAR_027678

Natural variant

214

1

K → E. Ref.1 Ref.3 Ref.4 Ref.6 Ref.8
Corresponds to variant rs344560 [ dbSNP | Ensembl ].

VAR_027679

Secondary structure

1

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240

Helix Strand Turn

Details...

Beta strand

95 – 102

8

Helix

106 – 108

3

Beta strand

113 – 118

6

Beta strand

122 – 129

8

Beta strand

132 – 137

6

Beta strand

139 – 152

14

Beta strand

162 – 169

8

Beta strand

176 – 184

9

Helix

186 – 189

4

Beta strand

197 – 209

13

Beta strand

214 – 221

8

Helix

229 – 232

4

Beta strand

234 – 239

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 30, 2010. Version 2. Checksum: 49D0B1870F390B39	FASTA	240	26,350
	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 AGEKVVVRVL DERLVRLRDG TRSYFGAFMV
	Isoform 2 (LIGHT delta-TM) [UniParc]. Checksum: FF97FD515DB2EB11	FASTA	204	22,395
	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 VHLEAGEKVV 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLU-214.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION. 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEOLYTIC PROCESSING, VARIANT GLU-214.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT GLU-214.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Spleen.
[6]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT GLU-214.
[7]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT GLU-214.
[9]	"Crystal structure of LIGHT." New York structural genomics research consortium (NYSGRC) Submitted (MAY-2012) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS) OF 83-240, GLYCOSYLATION AT ASN-102, DISULFIDE BOND.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.
CR541854 mRNA. Translation: CAG46652.1.
CR541871 mRNA. Translation: CAG46669.1.
AC008760 Genomic DNA. No translation available.
CH471139 Genomic DNA. Translation: EAW69072.1.

IPI

IPI00221341.
IPI00307531.

RefSeq

NP_003798.2. NM_003807.3.
NP_742011.2. NM_172014.2.

UniGene

Hs.129708.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4EN0	X-ray	2.59	A/B/C	83-240	[»]
4J6G	X-ray	2.40	A/B	83-240	[»]

ProteinModelPortal

O43557.

SMR

O43557. Positions 93-240.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-3016N.

IntAct

O43557. 3 interactions.

STRING

9606.ENSP00000245912.

Proteomic databases

PaxDb

O43557.

PRIDE

O43557.

Protocols and materials databases

DNASU

8740.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000245912; ENSP00000245912; ENSG00000125735.
ENST00000326176; ENSP00000326940; ENSG00000125735.
ENST00000599359; ENSP00000469049; ENSG00000125735.

GeneID

8740.

KEGG

hsa:8740.

UCSC

uc002mfj.2. human.
uc002mfk.2. human.

Organism-specific databases

CTD

8740.

GeneCards

GC19M006663.

HGNC

HGNC:11930. TNFSF14.

HPA

HPA012700.

MIM

604520. gene.

neXtProt

NX_O43557.

PharmGKB

PA36622.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG40950.

HOVERGEN

HBG061471.

InParanoid

O43557.

KO

K05477.

OMA

ITHGLYK.

OrthoDB

EOG4MKNHT.

PhylomeDB

O43557.

Gene expression databases

Bgee

O43557.

CleanEx

HS_TNFSF14.

Genevestigator

O43557.

GermOnline

ENSG00000125735. 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

PS00251. TNF_1. False negative.
PS50049. TNF_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

8740.

NextBio

32787.

SOURCE

Search...

Entry information

Entry name

TNF14_HUMAN

Accession

Primary (citable) accession number: O43557
Secondary accession number(s): A8K7M2 , C9J5H4, O75476, Q6FHA1, Q8WVF8, Q96LD2

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	November 30, 2010
Last modified:	May 1, 2013
This is version 132 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.