The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

PVRL1  -  poliovirus receptor-related 1 (herpesvirus...

Homo sapiens

Synonyms: CD111, CLPED1, ED4, HIgR, HV1S, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of PVRL1


High impact information on PVRL1

  • Mutation of PVRL1 is associated with sporadic, non-syndromic cleft lip/palate in northern Venezuela [5].
  • Nectin-1 is also the principal cell surface receptor for alpha-herpesviruses (HveC; ref. 7), and the high frequency of CLPED1 on Margarita Island in the Caribbean Sea might result from resistance of heterozygotes to infection by these viruses [1].
  • HveC was expressed in human cells of epithelial and neuronal origin; it is the prime candidate for the coreceptor that allows both HSV-1 and HSV-2 to infect epithelial cells on mucosal surfaces and spread to cells of the nervous system [6].
  • Incubation of HSV-1 with a secreted form of HveC inhibited subsequent infection of a variety of cell lines, suggesting that HveC interacts directly with the virus [6].
  • This membrane glycoprotein is poliovirus receptor-related protein 1 (Prr1), designated here as HveC [6].

Chemical compound and disease context of PVRL1


Biological context of PVRL1

  • PRR proteins were reported by others to mediate homophilic cell adhesion [9].
  • We have examined here the effect of trans-interacting nectin on non-trans-interacting E-cadherin endocytosis [10].
  • Together these data suggest that both rare and common mutations within PVRL1 make a minor contribution to disrupting the initiation and regulation of cell-to-cell adhesion and downstream morphogenesis of the embryonic face [11].
  • Exons 2-14 of the CLPTM1 and exons 1-6 of the PVRL1 gene were analysed by a direct sequencing method using DNA extracted from whole blood [12].
  • Binding of HSV gD prevents nectin-1-mediated cell aggregation [8].

Anatomical context of PVRL1


Associations of PVRL1 with chemical compounds

  • The sequence of herpesvirus Ig-like receptor (HIgR) predicts a transmembrane protein with an ectodomain consisting of three cysteine-bracketed domains, one V-like and two C-like [4].
  • The serine of the S112T variant position is conserved across all known PVRL1 sequences [11].
  • These receptors include the herpesvirus entry mediator (HVEM), nectin-1, nectin-2, and sites in heparan sulfate generated by specific 3-O-sulfotransferases [16].
  • Third, the V domain was sufficient to mediate HSV entry, as an engineered form of PRR1 in which the two C2 domains were deleted and the V domain was retained and fused to its transmembrane and cytoplasmic regions was still able to confer susceptibility, although at reduced efficiency relative to full-length receptor [17].
  • Vero cells and cells expressing either HVEM or nectin-1 were treated with cholesterol-sequestering drugs such as methyl-beta-cyclodextrin or nystatin and then exposed to virus [18].

Physical interactions of PVRL1


Co-localisations of PVRL1


Regulatory relationships of PVRL1

  • It has been shown mainly by use of cadherin-deficient L fibroblasts stably expressing each nectin that nectins first form homo-cis-dimers and then homo- or hetero-trans-dimers, causing cell-cell adhesion, and that the formation of the cis-dimers is necessary for the formation of the trans-dimers [22].
  • In conclusion, immature human hematopoietic progenitors express low levels of CD111 on their surface [23].

Other interactions of PVRL1

  • Neither PRR1 nor PRR2 binds poliovirus and it is assumed that their physiological functions differ from that of CD155 [9].
  • We have isolated nectin3/PRR3, the fourth human member of the nectin/PRR family, also described as the alpha herpes virus receptor family [14].
  • HIgR shares its ectodomain with and appears to be an alternative splice variant of the previously described protein PRR-1 (poliovirus receptor-related protein) [4].
  • One chimeric protein (nectin-1 amino acids 1-124 fused to CD4) failed to bind to soluble forms of HSV-1, HSV-2, PRV, and BHV-1 gD and, as expected, also failed to mediate entry of the viruses from which these gDs were derived [24].
  • We recently described Nectin-4, a 66-kDa adhesion molecule of the Nectin family, which is a valuable new histological and serological marker for breast carcinoma [25].

Analytical, diagnostic and therapeutic context of PVRL1


  1. Mutations of PVRL1, encoding a cell-cell adhesion molecule/herpesvirus receptor, in cleft lip/palate-ectodermal dysplasia. Suzuki, K., Hu, D., Bustos, T., Zlotogora, J., Richieri-Costa, A., Helms, J.A., Spritz, R.A. Nat. Genet. (2000) [Pubmed]
  2. Restoration of E-cadherin-based cell-cell adhesion by overexpression of nectin in HSC-39 cells, a human signet ring cell gastric cancer cell line. Peng, Y.F., Mandai, K., Nakanishi, H., Ikeda, W., Asada, M., Momose, Y., Shibamoto, S., Yanagihara, K., Shiozaki, H., Monden, M., Takeichi, M., Takai, Y. Oncogene (2002) [Pubmed]
  3. Requirement of interaction of nectin-1alpha/HveC with afadin for efficient cell-cell spread of herpes simplex virus type 1. Sakisaka, T., Taniguchi, T., Nakanishi, H., Takahashi, K., Miyahara, M., Ikeda, W., Yokoyama, S., Peng, Y.F., Yamanishi, K., Takai, Y. J. Virol. (2001) [Pubmed]
  4. The ectodomain of a novel member of the immunoglobulin subfamily related to the poliovirus receptor has the attributes of a bona fide receptor for herpes simplex virus types 1 and 2 in human cells. Cocchi, F., Menotti, L., Mirandola, P., Lopez, M., Campadelli-Fiume, G. J. Virol. (1998) [Pubmed]
  5. Mutation of PVRL1 is associated with sporadic, non-syndromic cleft lip/palate in northern Venezuela. Sözen, M.A., Suzuki, K., Tolarova, M.M., Bustos, T., Fernández Iglesias, J.E., Spritz, R.A. Nat. Genet. (2001) [Pubmed]
  6. Entry of alphaherpesviruses mediated by poliovirus receptor-related protein 1 and poliovirus receptor. Geraghty, R.J., Krummenacher, C., Cohen, G.H., Eisenberg, R.J., Spear, P.G. Science (1998) [Pubmed]
  7. Mutations in the N termini of herpes simplex virus type 1 and 2 gDs alter functional interactions with the entry/fusion receptors HVEM, nectin-2, and 3-O-sulfated heparan sulfate but not with nectin-1. Yoon, M., Zago, A., Shukla, D., Spear, P.G. J. Virol. (2003) [Pubmed]
  8. Cellular localization of nectin-1 and glycoprotein D during herpes simplex virus infection. Krummenacher, C., Baribaud, I., Eisenberg, R.J., Cohen, G.H. J. Virol. (2003) [Pubmed]
  9. The poliovirus receptor CD155 mediates cell-to-matrix contacts by specifically binding to vitronectin. Lange, R., Peng, X., Wimmer, E., Lipp, M., Bernhardt, G. Virology (2001) [Pubmed]
  10. Regulation of E-cadherin endocytosis by nectin through afadin, Rap1, and p120ctn. Hoshino, T., Sakisaka, T., Baba, T., Yamada, T., Kimura, T., Takai, Y. J. Biol. Chem. (2005) [Pubmed]
  11. PVRL1 variants contribute to non-syndromic cleft lip and palate in multiple populations. Avila, J.R., Jezewski, P.A., Vieira, A.R., Orioli, I.M., Castilla, E.E., Christensen, K., Daack-Hirsch, S., Romitti, P.A., Murray, J.C. Am. J. Med. Genet. A (2006) [Pubmed]
  12. Mutation analysis of CLPTM 1 and PVRL 1 genes in patients with non-syndromic clefts of lip, alveolus and palate. Turhani, D., Item, C.B., Watzinger, E., Sinko, K., Watzinger, F., Lauer, G., Ewers, R. Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery. (2005) [Pubmed]
  13. Nectin-like molecule-1/TSLL1/SynCAM3: a neural tissue-specific immunoglobulin-like cell-cell adhesion molecule localizing at non-junctional contact sites of presynaptic nerve terminals, axons and glia cell processes. Kakunaga, S., Ikeda, W., Itoh, S., Deguchi-Tawarada, M., Ohtsuka, T., Mizoguchi, A., Takai, Y. J. Cell. Sci. (2005) [Pubmed]
  14. Human nectin3/PRR3: a novel member of the PVR/PRR/nectin family that interacts with afadin. Reymond, N., Borg, J.P., Lecocq, E., Adelaide, J., Campadelli-Fiume, G., Dubreuil, P., Lopez, M. Gene (2000) [Pubmed]
  15. Nectin-1/HveC Mediates herpes simplex virus type 1 entry into primary human sensory neurons and fibroblasts. Simpson, S.A., Manchak, M.D., Hager, E.J., Krummenacher, C., Whitbeck, J.C., Levin, M.J., Freed, C.R., Wilcox, C.L., Cohen, G.H., Eisenberg, R.J., Pizer, L.I. J. Neurovirol. (2005) [Pubmed]
  16. Mutations in herpes simplex virus glycoprotein D that prevent cell entry via nectins and alter cell tropism. Manoj, S., Jogger, C.R., Myscofski, D., Yoon, M., Spear, P.G. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  17. The V domain of herpesvirus Ig-like receptor (HIgR) contains a major functional region in herpes simplex virus-1 entry into cells and interacts physically with the viral glycoprotein D. Cocchi, F., Lopez, M., Menotti, L., Aoubala, M., Dubreuil, P., Campadelli-Fiume, G. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  18. Specific association of glycoprotein B with lipid rafts during herpes simplex virus entry. Bender, F.C., Whitbeck, J.C., Ponce de Leon, M., Lou, H., Eisenberg, R.J., Cohen, G.H. J. Virol. (2003) [Pubmed]
  19. Herpes simplex virus glycoprotein D can bind to poliovirus receptor-related protein 1 or herpesvirus entry mediator, two structurally unrelated mediators of virus entry. Krummenacher, C., Nicola, A.V., Whitbeck, J.C., Lou, H., Hou, W., Lambris, J.D., Geraghty, R.J., Spear, P.G., Cohen, G.H., Eisenberg, R.J. J. Virol. (1998) [Pubmed]
  20. Mutations in the N-terminal domains of nectin-1 and nectin-2 reveal differences in requirements for entry of various alphaherpesviruses and for nectin-nectin interactions. Struyf, F., Martinez, W.M., Spear, P.G. J. Virol. (2002) [Pubmed]
  21. Disruption of adherens junctions liberates nectin-1 to serve as receptor for herpes simplex virus and pseudorabies virus entry. Yoon, M., Spear, P.G. J. Virol. (2002) [Pubmed]
  22. Role of each immunoglobulin-like loop of nectin for its cell-cell adhesion activity. Yasumi, M., Shimizu, K., Honda, T., Takeuchi, M., Takai, Y. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  23. Functional characterization of human CD34+ cells that express low or high levels of the membrane antigen CD111 (nectin 1). Belaaloui, G., Imbert, A.M., Bardin, F., Tonnelle, C., Dubreuil, P., Lopez, M., Chabannon, C. Leukemia (2003) [Pubmed]
  24. Use of chimeric nectin-1(HveC)-related receptors to demonstrate that ability to bind alphaherpesvirus gD is not necessarily sufficient for viral entry. Geraghty, R.J., Fridberg, A., Krummenacher, C., Cohen, G.H., Eisenberg, R.J., Spear, P.G. Virology (2001) [Pubmed]
  25. Nectin-4, a new serological breast cancer marker, is a substrate for tumor necrosis factor-alpha-converting enzyme (TACE)/ADAM-17. Fabre-Lafay, S., Garrido-Urbani, S., Reymond, N., Gonçalves, A., Dubreuil, P., Lopez, M. J. Biol. Chem. (2005) [Pubmed]
  26. Nectin-1 Expression by Squamous Cell Carcinoma is a Predictor of Herpes Oncolytic Sensitivity. Yu, Z., Adusumilli, P.S., Eisenberg, D.P., Darr, E., Ghossein, R.A., Li, S., Liu, S., Singh, B., Shah, J.P., Fong, Y., Wong, R.J. Mol. Ther. (2007) [Pubmed]
WikiGenes - Universities