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Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Gene Section Mini Review PVRL4 (poliovirus receptor-related 4) Marc Lopez Centre de Recherches en Cancérologie de Marseille, Inserm UMR599, 27 bvd Leiroure, 13009 Marseille, France Published in Atlas Database: January 2008 Online updated version: http://AtlasGeneticsOncology.org/Genes/PVRL4ID44141ch1q23.html DOI: 10.4267/2042/38578 This work is licensed under a Creative Commons Attribution-Non-commercial-No Derivative Works 2.0 France Licence. © 2008 Atlas of Genetics and Cytogenetics in Oncology and Haematology C-terminus region binds to the scaffold F-actin binding protein AF-6/afadin. Nectin-4 ectodomain is shedded from cell surface by the metalloprotease TACE/ ADAM-17. Identity Hugo: PVRL4 Other names: LNIR; PRR4; Nectin-4 Location: 1q23.3 Description Nectin-4 protein is 510 aminoacid long. Molecular weight is 66 kDa. DNA/RNA Expression The PVRL4 gene spans 17.85 kb, consists of 9 exons and 8 introns. Nectin-4 expression in mainly expressed during development. In mice Nectin-4 transcript are detected at day 11 d.p.c. In human Nectin-4 is not expressed in adult tissues. Transcription Localisation The human Nectin-4 mRNA consists of 1458 or 1533 bases (alternative splice forms). Nectin-4 is expressed at epithelial adherens junctions. In tumors Nectin-4 expression can be observed in the cytoplasm. Description Protein Function Note: Nectin-4 belongs to the family of adhesion molecules: Nectins. Four members have been described (Nectin-1, Nectin-2, Nectin-3 and Nectin-4). Nectins belong to the immunoglobulin superfamily and exhibit three Ig-like domain in their extracellular region. Nectin-4 binds Nectin-1 through IgV domain interaction. Nectin-1 is involved in development. Nectin-4 increases tumor cell migration. Homology With other members of the family. Implicated in Breast carcinoma of basal subtypes Disease Nectin-4 is found in breast tumors and its expression correlates with the basal subtype. The soluble form is detected in sera of patients with metastatic breast carcinoma and is a marker of disease progression. Prognosis Adverse prognosis. Oncogenesis Related to tumor cell migration. Extracellular region of dimeric Nectin-4 is composed with three Ig domains of Ig V and IgC types. The last 4 aminoacids in the Atlas Genet Cytogenet Oncol Haematol. 2008;12(5) 387 PVRL4 (poliovirus receptor-related 4) Lopez M References converting enzyme (TACE)/ADAM-17. J Biol Chem 2005;280 (20); 19543-19550. Reymond N, Fabre S, Lecocq E, Adélaïde J, Dubreuil P, Lopez M. Nectin4/PRR4, a new afadin-associated member of the nectin family that trans-interacts with nectin1/PRR1 through V domain interaction. J Biol Chem 2001;276 (46):43205-43215. Fabre-Lafay S, Monville F, Garrido-Urbani S, Berruyer-Pouyet C, Ginestier C, Reymond N, Finetti P, Sauvan R, Adélaïde J, Geneix J, Lecocq E, Popovici C, Dubreuil P, Viens P, Lopez M. Nectin-4 is a new histological and serological tumor associated marker for breast cancer. BMC Cancer 2007;7:73. Fabre S, Reymond N, Cocchi F, Menotti L, Dubreuil P, Campadelli-Fiume G, Lopez M. Prominent role of the Ig-like V domain in trans-interactions of nectins. Nectin3 and nectin 4 bind to the predicted C-C'-C'-D beta-strands of the nectin1 V domain. J Biol Chem 2002;277 (30):27006-27013. This article should be referenced as such: Lopez M. PVRL4 (poliovirus receptor-related 4). Atlas Genet Cytogenet Oncol Haematol.2008;12(5):387-388. Fabre-Lafay S, Garrido-Urbani S, Reymond N, Gonçalves A, Dubreuil P, Lopez M. Nectin-4, a new serological breast cancer marker, is a substrate for tumor necrosis factor-alpha- Atlas Genet Cytogenet Oncol Haematol. 2008;12(5) 388