Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
The Database for Annotation, Visualization and Integrated Discovery
0
DAVID Functional Annotation Table
Gene Report
Help and Manual

Right-click and select 'Save Target As' to download results Download File
nectin cell adhesion molecule 1(NECTIN1) nectin cell adhesion molecule 1(NECTIN1) Related Genes Homo sapiens
CHROMOSOME 11,
CYTOBAND 11q23.3,
ENSEMBL_GENE_ID ENSG00000110400,
GENERIF_SUMMARY evidence that nectin-1 confined to adherens junctions in epithelial cells is not very accessible to virus, whereas dissociation of cell junctions releases nectin-1 to serve more efficiently as an entry receptor, Regions of nectin-1 protein important for herpesvirus entry activity and homotypic nectin-nectin interactions are overlapping but not identical., association of HVEM and nectin-1 with lipid rafts during herpes simplex virus entry, both nectin 1 and HVEM receptors play a role during HSV infection in vivo and both are highly efficient even at low levels of expression, Nectin-1-Delta2 exhibited a severely reduced ability to mediate HSV entry and accumulated in the endoplasmic reticulum but retained the ability to interact with its HSV ligand, gD., trans-interacting nectin inhibits non-trans-interacting E-cadherin endocytosis through afadin, Rap1, and p120ctn and further accumulates non-trans-interacting E-cadherin to the nectin-based cell-cell adhesion sites for the formation of adherens junctions, mutations at codons 185 and 323, especially the W185X mutation, do not participate in the formation of cleft lip and palate within the Taiwanese population examined, Mutations within the PVRL1 gene represent risk factors for non-syndromic cleft lip with or without cleft palate., Access to nectin-1 contributes to preferential apical infection of human epithelial cells by herpes simplex virus., the role of PVRL1 in the sporadic forms of orofacial clefting in multiple populations was studied., nectin-1 may be used as a marker to predict the sensitivity of a tumor to herpes oncolytic therapy, These data suggest that the determinants of gD-mediated internalization of nectin-1 may direct HSV to an endocytic pathway during entry., Novel non-synonymous PVRL1 mutation of the substitution of valine by methionine a position 395 in a conserved sequence suggests a possible etiologic role of PVRL1 in non-syndromic CL/P across different populations., Western blot analyses demonstrated that accumulation of host nectin-1 is decreased by 85 % at 48 hours post-infection (h.p.i.) in Chlamydia trachomatis serovar E-infected HeLa cells., Antibodies against nectin-1, but not HVEM, were able to block HSV-1 infection.Anti-nectin-1 antibodies and F-actin depolymerizers were also successful in blocking the cytoskeletal changes that occur upon HSV-1 entry into cells, These results indicate that nectin-1 is degraded by chlamydial protease-like activity factor (CPAF) in Chlamydia trachomatis-infected genital epithelial cells, a novel strategy that Chlamydiae may use to aid their dissemination., There is no relationship between nonsyndromic cleft lip and/or palate and PVRL1exon3 in Han People., Insertional mutations of gB reduced cell fusion activity when PILRalpha was overexpressed much more than nectin-1., results suggest that PVRL1 may play a minor role in susceptibility to the occurrence of nsCL/P in some Caucasian populations, and that variation involving the beta (HIgR) isoform might have particular importance for risk of orofacial clefts, alpha- and gamma-secretase processing of nectin-1 is a Ca(2+)/calmodulin-regulated event that occurs under conditions of activity-dependent synaptic plasticity and ADAM10 and gamma-secretase are responsible for these cleavage events., A nonpredicted link between SNAI1-triggered EMT and the down-regulation of Nectin-1 and StarD10 through the up-regulation of miR-661, which may contribute to the invasion of breast cancer cells and poor disease outcome., Structure of herpes simplex virus glycoprotein D bound to the human receptor nectin-1., alphaVbeta3-integrin relocalizes nectin1 to lipid rafts, independently of herpes simplex virus 1., NSCL/P-associated mutations of PVRL1, This study demonistated that increased expression of nectin-1 in MS lesions plays a role in the pathogenesis of MS through participation in axonal responses to injury and mediation of altered neuron-glia interactions relevant to myelination., Nectin-1 Ig3 induced phosphorylation of FGFR1c in the same manner as the whole nectin-1 ectodomain, and promoted survival of cerebellar granule neurons induced to undergo apoptosis., Glycoprotein D (gD) epitope core structure maps to the external surface of herpesvirus (HSV) gD, corresponding to the binding sites of two receptors, herpesvirus entry mediator (HVEM) and nectin-1, which mediate HSV infection., These results suggest that HVEM might play more important roles than CD28 in ConA-mediated T cell proliferation, The conformation of the N-terminus of herpes simplex virus gD is induced by direct binding to HVEM and nectin-1., We identified new supportive evidence that the association between PVRL1 gene and nsCL/P in Turkish patients., The results showed that the interface between the BV gD and nectin-1 molecule is not geometrically complementary., These data provided solid structural and functional evidence that herpes simplex virus 1 and herpes simplex virus 2 gD proteins recognize nectin-1 via the same binding mode., Authors show that the same key residues in the BC and FG loops of nectin-4 govern binding to the measles virus attachment protein hemagglutinin (H) and cell entry, nectin-4 homodimerization, and heterodimerization with nectin-1., data suggests that E-cadherin regulates assembly of nectin junctions through alpha-catenin-induced remodeling of the actin cytoskeleton around the cadherin clusters., Host nectin-1 is required for efficient Chlamydia trachomatis serovar E development., mutations in exons 2 and 5 of PVRL1, and T334A, A391T, G1183A in the alpha-spliced transcript, and G1082T in the beta-spliced transcript do not participate in the development of non-syndromic cleft of the lip and/or palate in patients from Guangdong.,
OFFICIAL_GENE_SYMBOL NECTIN1,
OMIM_DISEASE Cleft lip/palate-ectodermal dysplasia syndrome, Orofacial cleft 7,
SP_COMMENT disease:Defects in PVRL1 are the cause of ectodermal dysplasia Margarita Island type (EDMI) [MIM:225060]; also known as Zlotogora-Ogur syndrome, cleft lip/palate-ectodermal dysplasia syndrome (CLPED1) or ectodermal dysplasia 4. Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. EDMI is an autosomal recessive syndrome characterized by the association of cleft lip/palate, ectodermal dysplasia (sparse short and dry scalp hair, sparse eyebrows and eyelashes), and partial syndactyly of the fingers and/or toes. Two thirds of the patients do not manifest oral cleft but present with abnormal teeth and nails., disease:Defects in PVRL1 are the cause of non-syndromic orofacial cleft type 7 (OFC7) [MIM:225060]. Non-syndromic orofacial cleft is a common birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum., function:Promotes cell-cell contacts by forming homophilic or heterophilic trans-dimers. Heterophilic interactions have been detected between PVRL1/nectin-1 and PVRL3/nectin-3 and between PVRL1/nectin-1 and PVRL4/nectin-4., similarity:Belongs to the nectin family., similarity:Contains 1 Ig-like V-type (immunoglobulin-like) domain., similarity:Contains 2 Ig-like C2-type (immunoglobulin-like) domains., subunit:Can form trans-heterodimers with PVRL3/nectin-3 and with PVRL4/nectin-4. Interacts (via C-terminus) with afadin (via PDZ domain); this interaction recruits PVRL1 to cadherin-based adherens junctions. Interacts with integrin alphaV/beta3. Interacts with herpes simplex virus 1 and 2, and pseudorabies virus glycoprotein gD and act as a receptor for these viruses.,
nectin cell adhesion molecule 2(NECTIN2) nectin cell adhesion molecule 2(NECTIN2) Related Genes Homo sapiens
CHROMOSOME 19,
CYTOBAND 19q13.2,
ENSEMBL_GENE_ID ENSG00000130202,
GENERIF_SUMMARY Regions of nectin-2 protein important for herpesvirus entry activity and homotypic nectin-nectin interactions are overlapping but not identical., Data show that both PVR and Nectin-2 represent specific ligands for the DNAM-1 triggering receptor., differences in the N termini of herpes simplex virus type 1 and 2 gDs that influence functional interactions with the human entry receptor Nectin-2, Analysis of the ligands for triggering NK receptors revealed the consistent expression of cd155 and cd112 in myeloid leukemias, and less frequent expression in lymphoblastic leukemias, There is an allelic association of sequence variation in PVRL2 and the severity of multiple sclerosis., CD226/CD112 (DNAM-1/Nectin-2) mast cell stimulation has a role in the allergic process, no statistically significant association between this marker allele and non-syndromic clefting, identified PVRL2 as a new recurrent partner gene of the TRA@ locus in peripheral T-cell lymphoma, Crystallization and preliminary X-ray analysis of the V domain of human nectin-2 are reported., TIGIT is expressed by all NK cells, it binds PVR and PVRL2 but not PVRL3, and it inhibits NK cytotoxicity, The authors now show that human cytomegalovirus targets CD112 for proteasome-mediated degradation by 48 h post-infection, thus removing both activating ligands for DNAM-1 from the cell surface during productive infection., The CD112 is highly expressed in colon carcinoma tissues and cell lines., a possible etiologic role of PRR2 in nonsyndromic cleft lip with or without cleft palate, Data show that a high expression of CD112 and CD155 (DNAM-1 ligands) on leukemic blasts., Structure of Nectin-2 reveals determinants of homophilic and heterophilic interactions that control cell-cell adhesion., Chorionic gonadotropin induces vascular endothelial growth factor (VEGFA)-dependent downregulation of nectin 2, which increases the endothelial permeability in the coculture system., Nectin-3 trans-interacts with Nectin-2 to promote lymphocyte and monocyte extravasation., PVRL2, TOMM40 and APOE might be associated with human longevity., Soluble form of nectin-2 is required for exerting the resistance against HSV-2 infection.,
OFFICIAL_GENE_SYMBOL NECTIN2,
SP_COMMENT function:Probable cell adhesion protein., similarity:Belongs to the nectin family., similarity:Contains 1 Ig-like V-type (immunoglobulin-like) domain., similarity:Contains 2 Ig-like C2-type (immunoglobulin-like) domains., subunit:Can form trans-heterodimers with PVRL3/nectin-3 (By similarity). Interacts with CD226. Receptor for alphaherpesvirus (HSV-1, HSV-2 and pseudorabies virus) entry into cells. Binds with low affinity to TIGIT., tissue specificity:Ubiquitous.,
nectin cell adhesion molecule 3(NECTIN3) nectin cell adhesion molecule 3(NECTIN3) Related Genes Homo sapiens
CHROMOSOME 3,
CYTOBAND 3q13,
ENSEMBL_GENE_ID ENSG00000177707,
GENERIF_SUMMARY Data suggest that expression of nectin-3 is up-regulated in eutopic endometrium of patients with endometriosis as compared with control subjects and up-regulated in all endometriotic lesions investigated compared with eutopic endometrium., Nectin-3 trans-interacts with Nectin-2 to promote lymphocyte and monocyte extravasation., Nectin-3 is associated with the formation of cell junctions and be a putative suppressor molecule to the invasion of breast cancer cells., Expression of nectin-3 in pancreatic cancer can be a prognostic factor., PVRL3 is a physiologically relevant binding partner that can serve as a target for the prevention of TcdB-induced cytotoxicity in C. difficile infection., Data suggest that 3 independent regions of TcdB (Clostridium difficile toxin B; 1372-1493, 1493-1848, 1851-2366) contribute to binding and entry of TcdB into mammalian cells; residues 1372-1493 are sufficient for interaction with PVRL3.,
OFFICIAL_GENE_SYMBOL NECTIN3,
SP_COMMENT function:Plays a role in cell-cell adhesion through heterophilic trans-interactions with nectin-like proteins or nectins, such as trans-interaction with PVRL2/nectin-2 at Sertoli-spermatid junctions. Trans-interaction with PVR induces activation of CDC42 and RAC small G proteins through common signaling molecules such as SRC and RAP1. Also involved in the formation of cell-cell junctions, including adherens junctions and synapses. Induces endocytosis-mediated down-regulation of PVR from the cell surface, resulting in reduction of cell movement and proliferation. Plays a role in the morphology of the ciliary body., similarity:Belongs to the nectin family., similarity:Contains 1 Ig-like V-type (immunoglobulin-like) domain., similarity:Contains 2 Ig-like C2-type (immunoglobulin-like) domains., subunit:Cis- and trans-homodimer. Can form trans-heterodimers with PVRL1/nectin-1, PVRL2/nectin-2, PVR, IGSF4B/Necl-1 and with IGSF4. Interacts with MLLT4/afadin. Binds with low affinity to TIGIT., tissue specificity:Predominantly expressed in testis and placenta as well as in many cell lines, including epithelial cell lines.,
nectin cell adhesion molecule 4(NECTIN4) nectin cell adhesion molecule 4(NECTIN4) Related Genes Homo sapiens
CHROMOSOME 1,
CYTOBAND 1q22-q23.2,
ENSEMBL_GENE_ID ENSG00000143217,
GENERIF_SUMMARY the active form of TACE is overexpressed in breast tumors and may indicate that TACE is responsible for Nectin-4 shedding not only in vitro but also in vivo, Nectin-4 was not detected in normal breast epithelium; by contrast Nectin-4 was expressed in ductal breast carcinoma., Nectin-4 might play a significant role in lung carcinogenesis, and it should be a new candidate serum and tissue biomarker, as well as a therapeutic target., Ectodermal dysplasia-syndactyly syndrome is the second known "nectinopathy" caused by mutations in a nectin adhesion molecule., nectin 4 may serve as a potential biomarker that helps discriminate benign gynecologic diseases from ovarian cancer in a panel with CA125., Ectoderma dysplasia-syndactyly syndrome. Second example of "nectinopathy"., Sequence analysis revealed a homozygous missense mutation (c.635C>G; p.Pro212Arg) in the recently reported PVRL4 gene causing EDSS1, The findings of study suggest that increased expression of Nectin-4 may indicate a worse prognosis in breast cancer patients., Measles virus infection reduced PVRL4 surface expression in MCF7 cells, a property that is characteristic of receptor-associated viral infections., measles virus targets nectin-4 to emerge in the airways, crystals of nectin-4 diffracted to 1.8 A resolution and belonged to space group P2(1), with unit-cell parameters a = 33.1, b = 51.7, c = 56.9 A, beta = 94.7 degrees, Data suggest that expression of nectin-4 is up-regulated in eutopic endometrium of patients with endometriosis compared with control subjects., We show that human nectin4 is fully functional as a canince distemper virus receptor., structure of the membrane-distal domain of nectin-4 in complex with measles virus hemagglutinin (MV-H; structure shows nectin-4 binds the MV-H beta4-beta5 groove exclusively via its N-terminal IgV domain; the contact interface is dominated by hydrophobic interactions, Transformation of breast cancer cells is dependent on PVRL4., Thus, while nectin-4 and CD46 interact functionally with the measles virus H protein beta4-beta5 hydrophobic groove, SLAM merely covers it., Ablation of nectin4 binding compromises CD46 usage by a hybrid vesicular stomatitis virus/measles virus., data outline a synergistic action of nectin-1 and -4 in the early steps of AJ formation and implicate this interaction in modulating the Rac1 signaling pathway, Ovarian tissue expression and serum nectin 4 appear to be potential markers in ovarian cancer., Authors show that the same key residues in the BC and FG loops of nectin-4 govern binding to the measles virus attachment protein hemagglutinin (H) and cell entry, nectin-4 homodimerization, and heterodimerization with nectin-1., The present study described clinical investigation of the EDSS1 identified in a large consanguineous family; DNA sequence analysis revealed a novel homozygous nonsense mutation (181C>T, p.Asp61*) in the PVRL4 gene., Nectin-4 is a significant prognostic predictor, and may play a critical role in pancreatic cancer. Nectin-4 may be novel therapeutic target for pancreatic cancer., In airway epithelial cells, measles virus spread requires the nectin-4/afadin complex and is based on cytoplasm transfer between columnar cells., The data presented in this study suggested that nectin-4 may be a therapeutic target for systemic lupus erythematous through affecting the cell apoptosis, Nectin-4 is critical for gallbladder cancer cell progression via PI3K/AKT pathway activation of Rac1., Nectin-4 expression, when compared with control group, was higher in endometriotic lesions of patients having ovarian endometriosis and peritoneal endometriosis. This difference was significant in the endometrium of patients having endometriosis.,
OFFICIAL_GENE_SYMBOL NECTIN4,
OMIM_DISEASE Ectodermal dysplasia-syndactyly syndrome 1,
SP_COMMENT function:Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with PVRL2/nectin-1. Does not act as receptor for alpha-herpesvirus entry into cells., PTM:The soluble form is produced by proteolytic cleavage at the cell surface (shedding), probably by ADAM17/TACE., similarity:Belongs to the nectin family., similarity:Contains 1 Ig-like V-type (immunoglobulin-like) domain., similarity:Contains 2 Ig-like C2-type (immunoglobulin-like) domains., subcellular location:Colocalizes with MLLT4 at cadherin-based adherens junctions., subcellular location:The secreted form is found in breast tumor patients., subunit:Self-associates. Interacts via its Ig-like V-type domain with PVRL1/nectin-1 Ig-like V-type domain. Interacts via its C-terminus with MLLT4., tissue specificity:Predominantly expressed in placenta. Not detected in normal breast epithelium but expressed in breast carcinoma.,