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O43557 (TNF14_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 141. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
Gene names
Name:TNFSF14
Synonyms:HVEML, LIGHT
ORF Names:UNQ391/PRO726
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length240 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 componentCell membrane
Cytoplasm
Membrane
Secreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   Molecular functionCytokine
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processT cell activation

Non-traceable author statement PubMed 12393901. Source: UniProtKB

T cell costimulation

Inferred from electronic annotation. Source: Ensembl

T cell homeostasis

Non-traceable author statement PubMed 12393901. Source: UniProtKB

T cell proliferation

Non-traceable author statement Ref.2. Source: UniProtKB

apoptotic process

Traceable author statement PubMed 10799510. Source: ProtInc

cellular response to mechanical stimulus

Inferred from expression pattern PubMed 19593445. Source: UniProtKB

immune response

Inferred from electronic annotation. Source: InterPro

negative regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from direct assay PubMed 12393901. Source: GOC

positive regulation of T cell chemotaxis

Inferred from electronic annotation. Source: Ensembl

release of cytoplasmic sequestered NF-kappaB

Inferred from direct assay PubMed 12393901. Source: UniProtKB

signal transduction

Non-traceable author statement PubMed 12393901. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular space

Inferred from electronic annotation. Source: UniProtKB-KW

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functioncysteine-type endopeptidase inhibitor activity involved in apoptotic process

Inferred from direct assay PubMed 12393901. Source: UniProtKB

receptor binding

Inferred from physical interaction PubMed 12393901. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

TNFRSF14Q929562EBI-524131,EBI-1056653
TNFRSF6BO954072EBI-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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 240240Tumor necrosis factor ligand superfamily member 14, membrane form
PRO_0000034532
Chain?83 – 240158Tumor necrosis factor ligand superfamily member 14, soluble form
PRO_0000034533

Regions

Topological domain1 – 3737Cytoplasmic Potential
Transmembrane38 – 5821Helical; Signal-anchor for type II membrane protein; Potential
Topological domain59 – 240182Extracellular Potential

Sites

Site82 – 832Cleavage Potential

Amino acid modifications

Glycosylation1021N-linked (GlcNAc...) Ref.9
Disulfide bond154 ↔ 187 Ref.9

Natural variations

Alternative sequence38 – 7336Missing in isoform 2.
VSP_006452
Natural variant321S → L.
Corresponds to variant rs2291667 [ dbSNP | Ensembl ].
VAR_027677
Natural variant1201L → V.
Corresponds to variant rs17851606 [ dbSNP | Ensembl ].
VAR_027678
Natural variant2141K → E. Ref.1 Ref.3 Ref.4 Ref.6 Ref.8
Corresponds to variant rs344560 [ dbSNP | Ensembl ].
VAR_027679

Secondary structure

............................. 240
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 30, 2010. Version 2.
Checksum: 49D0B1870F390B39

FASTA24026,350
        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 

« Hide

Isoform 2 (LIGHT delta-TM) [UniParc].

Checksum: FF97FD515DB2EB11
Show »

FASTA20422,395

References

« Hide '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. expand/collapse author list , 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. 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: 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. expand/collapse author list , 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. 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 (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.
RefSeqNP_003798.2. NM_003807.3.
NP_742011.2. NM_172014.2.
XP_005259727.1. XM_005259670.1.
UniGeneHs.129708.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4EN0X-ray2.59A/B/C83-240[»]
4J6GX-ray2.40A/B83-240[»]
4KG8X-ray2.25A/B/C83-240[»]
4KGGX-ray2.78A/B83-240[»]
4KGQX-ray2.27A/B83-240[»]
ProteinModelPortalO43557.
SMRO43557. Positions 93-240.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114277. 8 interactions.
DIPDIP-3016N.
IntActO43557. 3 interactions.
STRING9606.ENSP00000245912.

Proteomic databases

PaxDbO43557.
PRIDEO43557.

Protocols and materials databases

DNASU8740.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000245912; ENSP00000245912; ENSG00000125735. [O43557-2]
ENST00000326176; ENSP00000326940; ENSG00000125735. [O43557-2]
ENST00000599359; ENSP00000469049; ENSG00000125735. [O43557-1]
GeneID8740.
KEGGhsa:8740.
UCSCuc002mfj.2. human. [O43557-2]
uc002mfk.2. human. [O43557-1]

Organism-specific databases

CTD8740.
GeneCardsGC19M006663.
HGNCHGNC:11930. TNFSF14.
HPAHPA012700.
MIM604520. gene.
neXtProtNX_O43557.
PharmGKBPA36622.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG40950.
HOVERGENHBG061471.
InParanoidO43557.
KOK05477.
OMADGQTDIP.
OrthoDBEOG7V4B0Q.
PhylomeDBO43557.
TreeFamTF332169.

Gene expression databases

BgeeO43557.
CleanExHS_TNFSF14.
GenevestigatorO43557.

Family and domain databases

Gene3D2.60.120.40. 1 hit.
InterProIPR006053. TNF.
IPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
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

GeneWikiTNFSF14.
GenomeRNAi8740.
NextBio32787.
PROO43557.
SOURCESearch...

Entry information

Entry nameTNF14_HUMAN
AccessionPrimary (citable) accession number: O43557
Secondary accession number(s): A8K7M2 expand/collapse secondary AC list , C9J5H4, O75476, Q6FHA1, Q8WVF8, Q96LD2
Entry history
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: November 30, 2010
Last modified: April 16, 2014
This is version 141 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 19

Human chromosome 19: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries