Herpesvirus entry mediator

Tumor necrosis factor receptor superfamily, member 14
PDB rendering based on 1jma.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1JMA​, 2AW2​, 4FHQ​, 4RSU​
Identifiers
Symbols	TNFRSF14 ; ATAR; CD270; HVEA; HVEM; LIGHTR; TR2
External IDs	OMIM: 602746 MGI: 2675303 HomoloGene: 2833 GeneCards: TNFRSF14 Gene
Gene ontology Molecular function • virus receptor activity • tumor necrosis factor-activated receptor activity • protein binding • ubiquitin protein ligase binding Cellular component • plasma membrane • integral component of plasma membrane • external side of plasma membrane Biological process • positive regulation of cytokine secretion involved in immune response • immune response • cell surface receptor signaling pathway • T cell costimulation • tumor necrosis factor-mediated signaling pathway • negative regulation of alpha-beta T cell proliferation • viral entry into host cell • positive regulation of peptidyl-tyrosine phosphorylation • defense response to Gram-negative bacterium • defense response to Gram-positive bacterium • positive regulation of T cell migration Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
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

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]

Nomenclature

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).

Function

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]

Interactions

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

Clinical relevance

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

References

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. "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. 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. 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

• Hsu H, Solovyev I, Colombero A, et al. (1997). "ATAR, a novel tumor necrosis factor receptor family member, signals through TRAF2 and TRAF5". J. Biol. Chem. 272 (21): 13471–4. doi:10.1074/jbc.272.21.13471. PMID 9153189.
• Marsters SA, Ayres TM, Skubatch M, et al. (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. 272 (22): 14029–32. doi:10.1074/jbc.272.22.14029. PMID 9162022.
• Mauri DN, Ebner R, Montgomery RI, et al. (1998). "LIGHT, a new member of the TNF superfamily, and lymphotoxin alpha are ligands for herpesvirus entry mediator". Immunity 8 (1): 21–30. doi:10.1016/S1074-7613(00)80455-0. PMID 9462508.
• Lee CH, Chinpaisal C, Wei LN (1998). "Cloning and Characterization of Mouse RIP140, a Corepressor for Nuclear Orphan Receptor TR2". Mol. Cell. Biol. 18 (11): 6745–55. PMC 109258. PMID 9774688.
• Kelly K, Manos E, Jensen G, et al. (2000). "APRIL/TRDL-1, a tumor necrosis factor-like ligand, stimulates cell death". Cancer Res. 60 (4): 1021–7. PMID 10706119.
• Zhang J, Salcedo TW, Wan X, et al. (2001). "Modulation of T-cell responses to alloantigens by TR6/DcR3". J. Clin. Invest. 107 (11): 1459–68. doi:10.1172/JCI12159. PMC 209323. PMID 11390428.
• Franco PJ, Farooqui M, Seto E, Wei LN (2001). "The orphan nuclear receptor TR2 interacts directly with both class I and class II histone deacetylases". Mol. Endocrinol. 15 (8): 1318–28. doi:10.1210/mend.15.8.0682. PMID 11463856.
• Carfí A, Willis SH, Whitbeck JC, et al. (2001). "Herpes simplex virus glycoprotein D bound to the human receptor HveA". Mol. Cell 8 (1): 169–79. doi:10.1016/S1097-2765(01)00298-2. PMID 11511370.
• Bobik A, Kalinina N (2002). "Tumor necrosis factor receptor and ligand superfamily family members TNFRSF14 and LIGHT: new players in human atherogenesis". Arterioscler. Thromb. Vasc. Biol. 21 (12): 1873–5. PMID 11742858.
• Struyf F, Posavad CM, Keyaerts E, et al. (2002). "Search for polymorphisms in the genes for herpesvirus entry mediator, nectin-1, and nectin-2 in immune seronegative individuals". J. Infect. Dis. 185 (1): 36–44. doi:10.1086/338116. PMID 11756979.
• Carfí A, Gong H, Lou H, et al. (2002). "Crystallization and preliminary diffraction studies of the ectodomain of the envelope glycoprotein D from herpes simplex virus 1 alone and in complex with the ectodomain of the human receptor HveA". Acta Crystallogr. D Biol. Crystallogr. 58 (Pt 5): 836–8. doi:10.1107/S0907444902001270. PMID 11976496.
• Hu YC, Shyr CR, Che W, et al. (2002). "Suppression of estrogen receptor-mediated transcription and cell growth by interaction with TR2 orphan receptor". J. Biol. Chem. 277 (37): 33571–9. doi:10.1074/jbc.M203531200. PMID 12093804.
• Gill RM, Ni J, Hunt JS (2003). "Differential Expression of LIGHT and Its Receptors in Human Placental Villi and Amniochorion Membranes". Am. J. Pathol. 161 (6): 2011–7. doi:10.1016/S0002-9440(10)64479-3. PMC 1850908. PMID 12466117.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Bender FC, Whitbeck JC, Ponce de Leon M, et al. (2003). "Specific Association of Glycoprotein B with Lipid Rafts during Herpes Simplex Virus Entry". J. Virol. 77 (17): 9542–52. doi:10.1128/JVI.77.17.9542-9552.2003. PMC 187402. PMID 12915568.
• Clark HF, Gurney AL, Abaya E, et al. (2003). "The Secreted Protein Discovery Initiative (SPDI), a Large-Scale Effort to Identify Novel Human Secreted and Transmembrane Proteins: A Bioinformatics Assessment". Genome Res. 13 (10): 2265–70. doi:10.1101/gr.1293003. PMC 403697. PMID 12975309.
• Jung HW, La SJ, Kim JY, et al. (2004). "High levels of soluble herpes virus entry mediator in sera of patients with allergic and autoimmune diseases". Experimental & Molecular Medicine 35 (6): 501–8. doi:10.1038/emm.2003.65. PMID 14749527.
• Krummenacher C, Baribaud F, Ponce de Leon M, et al. (2004). "Comparative usage of herpesvirus entry mediator A and nectin-1 by laboratory strains and clinical isolates of herpes simplex virus". Virology 322 (2): 286–99. doi:10.1016/j.virol.2004.02.005. PMID 15110526.

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