Herpesvirus entry mediator

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(Redirected from TNFRSF14)
Available structures
PDBOrtholog search: PDBe RCSB
AliasesTNFRSF14, ATAR, CD270, HVEA, HVEM, LIGHTR, TR2, tumor necrosis factor receptor superfamily member 14, TNF receptor superfamily member 14
External IDsOMIM: 602746 MGI: 2675303 HomoloGene: 2833 GeneCards: TNFRSF14
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 1: 2.56 – 2.57 MbChr 4: 155.01 – 155.01 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

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[5][6][7][8] encoded by the TNFRSF14 gene.[7]


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. The cytoplasmic region of this receptor was found to bind to several TNF receptor associated factor (TRAF) family members, which may mediate the signal transduction pathways that activate the immune response.[7]

In melanocytic cells TNFRSF14 gene expression may be regulated by MITF.[9]


TNFRSF14 has been shown to interact with TRAF2,[10][11] TNFSF14[12][13] and TRAF5.[10][11]

Clinical relevance[edit]

Mutations in this gene have been recurrently been associated to cases of diffuse large B-cell lymphoma[14][15] and pediatric-type follicular lymphoma.[16]

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.[7]


  1. ^ a b c ENSG00000157873 GRCh38: Ensembl release 89: ENSG00000273936, ENSG00000157873 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000042333 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Montgomery RI, Warner MS, Lum BJ, Spear PG (November 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. S2CID 14626053.
  6. ^ 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 (May 1997). "A newly identified member of the tumor necrosis factor receptor superfamily with a wide tissue distribution and involvement in lymphocyte activation". The Journal of Biological Chemistry. 272 (22): 14272–6. doi:10.1074/jbc.272.22.14272. PMID 9162061.
  7. ^ a b c d "TNFRSF14 TNF receptor superfamily member 14 [ Homo sapiens (human) ]". Gene. National Library of Medicine, National Center for Biotechnology Information. 23 November 2023. Retrieved 5 January 2024.
  8. ^ Ware, Carl (2008). "Chapter 25: TNF-Related Cytokines in Immunity". In Paul, William (ed.). Fundamental Immunology (Book) (6th ed.). Philadelphia: Lippincott Williams & Wilkins. pp. 776–801. ISBN 978-0-7817-6519-0.
  9. ^ Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (December 2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.
  10. ^ a b Hsu H, Solovyev I, Colombero A, Elliott R, Kelley M, Boyle WJ (May 1997). "ATAR, a novel tumor necrosis factor receptor family member, signals through TRAF2 and TRAF5". The Journal of Biological Chemistry. 272 (21): 13471–4. doi:10.1074/jbc.272.21.13471. PMID 9153189.
  11. ^ a b Marsters SA, Ayres TM, Skubatch M, Gray CL, 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". The Journal of Biological Chemistry. 272 (22): 14029–32. doi:10.1074/jbc.272.22.14029. PMID 9162022.
  12. ^ Zhang J, Salcedo TW, Wan X, Ullrich S, Hu B, Gregorio T, Feng P, Qi S, Chen H, Cho YH, Li Y, Moore PA, Wu J (June 2001). "Modulation of T-cell responses to alloantigens by TR6/DcR3". The Journal of Clinical Investigation. 107 (11): 1459–68. doi:10.1172/JCI12159. PMC 209323. PMID 11390428.
  13. ^ Yu KY, Kwon B, Ni J, Zhai Y, Ebner R, Kwon BS (May 1999). "A newly identified member of tumor necrosis factor receptor superfamily (TR6) suppresses LIGHT-mediated apoptosis". The Journal of Biological Chemistry. 274 (20): 13733–6. doi:10.1074/jbc.274.20.13733. PMID 10318773.
  14. ^ Morin RD, Mendez-Lago M, Mungall AJ, Goya R, Mungall KL, Corbett RD, Johnson NA, Severson TM, Chiu R, Field M, Jackman S, Krzywinski M, Scott DW, Trinh DL, Tamura-Wells J, Li S, Firme MR, Rogic S, Griffith M, Chan S, Yakovenko O, Meyer IM, Zhao EY, Smailus D, Moksa M, Chittaranjan S, Rimsza L, Brooks-Wilson A, Spinelli JJ, Ben-Neriah S, Meissner B, Woolcock B, Boyle M, McDonald H, Tam A, Zhao Y, Delaney A, Zeng T, Tse K, Butterfield Y, Birol I, Holt R, Schein J, Horsman DE, Moore R, Jones SJ, Connors JM, Hirst M, Gascoyne RD, Marra MA (August 2011). "Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma". Nature. 476 (7360): 298–303. Bibcode:2011Natur.476..298M. doi:10.1038/nature10351. PMC 3210554. PMID 21796119.
  15. ^ 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 (March 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. Bibcode:2012PNAS..109.3879L. doi:10.1073/pnas.1121343109. PMC 3309757. PMID 22343534.
  16. ^ Koo M, Ohgami RS (May 2017). "Pediatric-type Follicular Lymphoma and Pediatric Nodal Marginal Zone Lymphoma: Recent Clinical, Morphologic, Immunophenotypic, and Genetic Insights". Advances in Anatomic Pathology. 24 (3): 128–135. doi:10.1097/PAP.0000000000000144. PMID 28277421.

Further reading[edit]

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