Herpesvirus entry mediator

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Tumor necrosis factor receptor superfamily, member 14
Protein TNFRSF14 PDB 1jma.png
PDB rendering based on 1jma.
Available structures
PDB Ortholog search: PDBe, RCSB
External IDs OMIM602746 MGI2675303 HomoloGene2833 GeneCards: TNFRSF14 Gene
RNA expression pattern
PBB GE TNFRSF14 209354 at tn.png
More reference expression data
Species Human Mouse
Entrez 8764 230979
Ensembl ENSG00000157873 ENSMUSG00000042333
UniProt Q92956 B1AZN1
RefSeq (mRNA) NM_001297605 NM_178931
RefSeq (protein) NP_001284534 NP_849262
Location (UCSC) Chr 1:
2.56 – 2.57 Mb
Chr 4:
154.92 – 154.93 Mb
PubMed search [1] [2]

Herpesvirus entry mediator (HVEM), also known as tumor necrosis factor receptor superfamily member 14 (TNFRSF14), is a human cell surface receptor of the TNF-receptor superfamily.[1][2][3][4]


This protein was originally known as herpesvirus entry mediator A (HveA); HveB and HveC are structurally unrelated proteins of the immunoglobulin superfamily. It is also known as CD270 in the cluster of differentiation classification. Moreover it is also referred to as ATAR (another TRAF-associated receptor).


The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor was identified as a cellular mediator of herpes simplex virus (HSV) entry. Binding of HSV viral envelope glycoprotein D (gD) to this receptor protein has been shown to be part of the viral entry mechanism. The cytoplasmic region of this receptor was found to bind to several TRAF family members, which may mediate the signal transduction pathways that activate the immune response.[3]

In melanocytic cells TNFRSF14 gene expression may be regulated by MITF.[5]


TNFRSF14 has been shown to interact with TRAF2,[6][7] TNFSF14[8][9] and TRAF5.[6][7]

Clinical relevance[edit]

Mutations in this gene have been recurrently been associated to cases of diffuse large B-cell lymphoma.[10][11]


  1. ^ Montgomery RI, Warner MS, Lum BJ, Spear PG (Dec 1996). "Herpes simplex virus-1 entry into cells mediated by a novel member of the TNF/NGF receptor family". Cell 87 (3): 427–36. doi:10.1016/S0092-8674(00)81363-X. PMID 8898196. 
  2. ^ Kwon BS, Tan KB, Ni J, Oh KO, Lee ZH, Kim KK, Kim YJ, Wang S, Gentz R, Yu GL, Harrop J, Lyn SD, Silverman C, Porter TG, Truneh A, Young PR (June 1997). "A newly identified member of the tumor necrosis factor receptor superfamily with a wide tissue distribution and involvement in lymphocyte activation". J Biol Chem 272 (22): 14272–6. doi:10.1074/jbc.272.22.14272. PMID 9162061. 
  3. ^ a b "Entrez Gene: TNFRSF14 tumor necrosis factor receptor superfamily, member 14 (herpesvirus entry mediator)". 
  4. ^ Ware, Carl (2008). "Chapter 25: TNF-Related Cytokines in Immunity". In Paul, William. Fundamental Immunology (Book) (6th ed.). Philadelphia: Lippincott Williams & Wilkins. pp. 776–801. ISBN 0-7817-6519-6. 
  5. ^ Hoek KS, Schlegel NC, Eichhoff OM, et al. (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971. 
  6. ^ a b Hsu, H; Solovyev I; Colombero A; Elliott R; Kelley M; Boyle W J (May 1997). "ATAR, a novel tumor necrosis factor receptor family member, signals through TRAF2 and TRAF5". J. Biol. Chem. (UNITED STATES) 272 (21): 13471–4. doi:10.1074/jbc.272.21.13471. ISSN 0021-9258. PMID 9153189. 
  7. ^ a b Marsters, S A; Ayres T M; Skubatch M; Gray C L; Rothe M; Ashkenazi A (May 1997). "Herpesvirus entry mediator, a member of the tumor necrosis factor receptor (TNFR) family, interacts with members of the TNFR-associated factor family and activates the transcription factors NF-kappaB and AP-1". J. Biol. Chem. (UNITED STATES) 272 (22): 14029–32. doi:10.1074/jbc.272.22.14029. ISSN 0021-9258. PMID 9162022. 
  8. ^ Zhang, J; Salcedo T W, Wan X, Ullrich S, Hu B, Gregorio T, Feng P, Qi S, Chen H, Cho Y H, Li Y, Moore P A, Wu J (June 2001). "Modulation of T-cell responses to alloantigens by TR6/DcR3". J. Clin. Invest. (United States) 107 (11): 1459–68. doi:10.1172/JCI12159. ISSN 0021-9738. PMC 209323. PMID 11390428.  Cite uses deprecated parameter |coauthors= (help)
  9. ^ Yu, K Y; Kwon B; Ni J; Zhai Y; Ebner R; Kwon B S (May 1999). "A newly identified member of tumor necrosis factor receptor superfamily (TR6) suppresses LIGHT-mediated apoptosis". J. Biol. Chem. (UNITED STATES) 274 (20): 13733–6. doi:10.1074/jbc.274.20.13733. ISSN 0021-9258. PMID 10318773. 
  10. ^ Morin, Ryan D.; Mendez-Lago, Maria; Mungall, Andrew J.; Goya, Rodrigo; Mungall, Karen L.; Corbett, Richard D.; Johnson, Nathalie A.; Severson, Tesa M.; Chiu, Readman; Field, Matthew; Jackman, Shaun; Krzywinski, Martin; Scott, David W.; Trinh, Diane L.; Tamura-Wells, Jessica; Li, Sa; Firme, Marlo R.; Rogic, Sanja; Griffith, Malachi; Chan, Susanna; Yakovenko, Oleksandr; Meyer, Irmtraud M.; Zhao, Eric Y.; Smailus, Duane; Moksa, Michelle; Chittaranjan, Suganthi; Rimsza, Lisa; Brooks-Wilson, Angela; Spinelli, John J.; Ben-Neriah, Susana; Meissner, Barbara; Woolcock, Bruce; Boyle, Merrill; McDonald, Helen; Tam, Angela; Zhao, Yongjun; Delaney, Allen; Zeng, Thomas; Tse, Kane; Butterfield, Yaron; Birol, Inanç; Holt, Rob; Schein, Jacqueline; Horsman, Douglas E.; Moore, Richard; Jones, Steven J. M.; Connors, Joseph M.; Hirst, Martin; Gascoyne, Randy D.; Marra, Marco A. (2011). "Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma". Nature 476 (7360): 298–303. doi:10.1038/nature10351. ISSN 0028-0836. PMC 3210554. PMID 21796119. 
  11. ^ Lohr, JG; Stojanov, P, Lawrence, MS, Auclair, D, Chapuy, B, Sougnez, C, Cruz-Gordillo, P, Knoechel, B, Asmann, YW, Slager, SL, Novak, AJ, Dogan, A, Ansell, SM, Link, BK, Zou, L, Gould, J, Saksena, G, Stransky, N, Rangel-Escareño, C, Fernandez-Lopez, JC, Hidalgo-Miranda, A, Melendez-Zajgla, J, Hernández-Lemus, E, Schwarz-Cruz Y Celis, A, Imaz-Rosshandler, I, Ojesina, AI, Jung, J, Pedamallu, CS, Lander, ES, Habermann, TM, Cerhan, JR, Shipp, MA, Getz, G, Golub, TR (Feb 17, 2012). "Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing.". Proceedings of the National Academy of Sciences of the United States of America 109 (10): 3879–84. doi:10.1073/pnas.1121343109. PMC 3309757. PMID 22343534.  Cite uses deprecated parameter |coauthors= (help)

Further reading[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.