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Reviewed, UniProtKB/Swiss-Prot O43557 (TNF14_HUMAN)

Last modified October 13, 2009. Version 96. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Complete 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.

The soluble form of isoform 1 derives from the membrane form by proteolytic processing.

Sequence similarities

Belongs to the tumor necrosis factor family.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

TNFRSF6BO954071EBI-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 – 5821Signal-anchor for type II membrane protein Potential
Topological domain59 – 240182Extracellular Potential

Sites

Site82 – 832Cleavage Potential

Amino acid modifications

Glycosylation1021N-linked (GlcNAc...)
Disulfide bond154 ↔ 187 Potential

Natural variations

Alternative sequence38 – 7336Missing in isoform 2.
VSP_006452
Natural variant321S → L: dbSNP rs2291667.
VAR_027677
Natural variant1201L → V: dbSNP rs17851606.
VAR_027678
Natural variant2141E → K: dbSNP rs344560. Ref.2 Ref.5
VAR_027679

Sequences

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

Last modified June 1, 1998. Version 1.
Checksum: 49D0BF67E1390B39

FASTA24026,351
        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 

« Hide

Isoform 2 (LIGHT delta-TM).

Checksum: FF97F3B1B3B2EB11
Show »

FASTA20422,396

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: 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. 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: 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. 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: 14702039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT LYS-214.
Tissue: Spleen.
+Additional computationally mapped references.

Cross-references

Sequence databases

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.
IPIIPI00221341.
IPI00307531.
RefSeqNP_003798.2.
NP_742011.1.
UniGeneHs.129708

3D structure databases

HSSPHSSP built from PDB template 4TSV based on UniProtKB P01375.
ModBaseSearch...

Protein-protein interaction databases

IntActO43557. 3 interactions.
STRINGO43557.

Genome annotation databases

EnsemblENST00000245912; ENSP00000245912; ENSG00000125735; Homo sapiens. [Genome view]
ENST00000326176; ENSP00000326940; ENSG00000125735; Homo sapiens. [Genome view]
ENST00000366236; ENSP00000406518; ENSG00000125735; Homo sapiens. [Genome view]
GeneID8740.
KEGGhsa:8740.
UCSCuc002mfj.1. human.
uc002mfk.1. human.

Organism-specific databases

CTD8740.
GeneCardsGC19M006615.
HGNCHGNC:11930. TNFSF14.
HPAHPA012700.
HPA026919.
MIM604520. gene.
PharmGKBPA36622.
GenAtlasSearch...

Phylogenomic databases

HOGENOMO43557.
HOVERGENO43557.

Gene expression databases

ArrayExpressO43557.
BgeeO43557.
CleanExHS_TNFSF14.
GenevestigatorO43557.
GermOnlineENSG00000125735. Homo sapiens.

Family and domain databases

InterProIPR006052. TNF_family.
IPR008983. Tumour_necrosis_fac-like.
[Graphical view]
Gene3DG3DSA:2.60.120.40. Tumour_necrosis_fac-like. 1 hit.
PfamPF00229. TNF. 1 hit.
[Graphical view]
ProDomPD002012. TNF_subf. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00207. TNF. 1 hit.
[Graphical view]
PROSITEPS00251. TNF_1. False negative.
PS50049. TNF_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio32787.
SOURCESearch...

Entry information

Entry nameTNF14_HUMAN
AccessionPrimary (citable) accession number: O43557
Secondary accession number(s): A8K7M2 expand/collapse secondary AC list , 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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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.

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

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Index of human polymorphisms and disease mutations

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SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents