Affinage

NECTIN1

Nectin-1 · UniProt Q15223

Length
517 aa
Mass
57.2 kDa
Annotated
2026-04-29
100 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Nectin-1 is a Ca²⁺-independent immunoglobulin-superfamily cell adhesion molecule that organizes adherens junctions and modulates intercellular signaling through homophilic and heterophilic V-domain–mediated trans-interactions. It forms cis-dimers through its first Ig-like domain, engages nectin-3 (Kd ~1 nM) and nectin-4 heterophilically via the C-C′-C″ beta-strand surface, and is recruited to cadherin-based junctions through its C-terminal PDZ-binding motif interacting with afadin; downstream, it signals through Rap1-ERK to regulate keratinocyte differentiation and through FGFR (via its Ig3 module) to promote neurite outgrowth and neuronal survival (PMID:10225955, PMID:11544254, PMID:17472964, PMID:22955284). The same V-domain adhesive interface serves as the principal entry receptor for HSV-1 and HSV-2 through direct binding of glycoprotein D, which competitively disrupts nectin-1 dimerization and displaces it from junctions to facilitate viral entry and cell-to-cell spread; nectin-1 is essential for HSV neuronal infection and encephalitis in vivo (PMID:9861033, PMID:21980294, PMID:19805039). Nectin-1 additionally engages the NK cell receptor CD96 at the same canonical interface, undergoes NMDA-receptor–triggered ADAM10-mediated ectodomain shedding followed by γ-secretase processing in neurons, and its expression is transcriptionally regulated by p63 in stratified epithelia (PMID:30759143, PMID:20501653, PMID:25387952).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1998 High

    Identifying nectin-1's V domain as sufficient for HSV gD binding and viral entry established the minimal receptor determinant and defined the molecular basis of herpesvirus tropism.

    Evidence Deletion mutants, soluble V-domain competition, and chimeric receptor entry assays in transfected cells

    PMID:9861033

    Open questions at the time
    • Structural basis of gD–V-domain interaction unknown at this stage
    • Relative contribution of nectin-1 vs. other HSV receptors (HVEM) in vivo not resolved
  2. 1999 High

    Demonstrating that nectin-1 binds afadin via its PDZ-binding motif and localizes to cadherin-based adherens junctions revealed its primary cell-biological function as a junctional adhesion molecule independent of its viral receptor role.

    Evidence Co-immunoprecipitation, colocalization imaging, and Ca²⁺-independent adhesion assays in EL cells

    PMID:10225955

    Open questions at the time
    • How nectin-1/afadin interaction coordinates with cadherin-catenin complex assembly not defined
    • Signaling downstream of nectin-1 at junctions unknown
  3. 2001 High

    Mapping the gD-binding and nectin heterophilic interaction sites to the same C-C′-C″ region of the V domain established that HSV hijacks the canonical cell adhesion interface, and showing nectin-1 mediates direct cell-to-cell HSV spread linked receptor function to viral pathogenesis.

    Evidence Chimeric nectin-1/PVR constructs with functional entry readout; antibody blockade of cell-to-cell spread; Fc-fusion binding for nectin-3 and nectin-4 heterophilic interactions

    PMID:10729168 PMID:11483743 PMID:11544254

    Open questions at the time
    • Atomic-resolution structure of the adhesive interface not yet available
    • Affinity measurements for heterophilic interactions not yet quantified
  4. 2002 High

    Quantifying binding affinities (nectin-3 Kd ~1 nM, nectin-4 Kd ~100 nM) and showing gD competition for the same V-domain surface established the thermodynamic hierarchy of nectin-1 interactions and the competitive mechanism of HSV receptor usurpation.

    Evidence Affinity measurements, competition binding with mAbs and gD, chimeric receptor strand substitutions

    PMID:12011057 PMID:12072525

    Open questions at the time
    • Structural basis of competition at atomic resolution still lacking
    • Whether differential affinities determine tissue-specific junction composition unknown
  5. 2003 Medium

    Showing that gD displaces nectin-1 from adherens junctions in living infected cells and substitutes for nectin-1 in trans explained how HSV remodels cell junctions to promote spread.

    Evidence Live-cell imaging of nectin-1-GFP, immunofluorescence colocalization during HSV infection

    PMID:12885915

    Open questions at the time
    • Kinetics of junction disassembly during infection not quantified
    • Whether afadin redistribution accompanies nectin-1 displacement not examined
  6. 2004 High

    Demonstrating that nectin-1 can route HSV entry through either plasma membrane fusion or endocytosis depending on membrane context (lipid rafts, chimeric receptor signaling) resolved the long-standing question of how the same receptor mediates different entry pathways.

    Evidence Chimeric nectin-1-EGFR1 receptors, GPI-anchored nectin-1, pharmacological inhibitors of endocytosis and acidification

    PMID:15507614

    Open questions at the time
    • Endogenous signals that determine nectin-1 membrane microdomain sorting in vivo not identified
    • Whether integrin-mediated relocalization occurs in neuronal entry not tested at this point
  7. 2007 High

    Nectin-1 KO mice revealed a cell-autonomous role for nectin-1 in regulating keratinocyte terminal differentiation through Rap1-ERK–dependent loricrin expression, establishing a signaling function beyond adhesion; separately, CD96 was identified as an immune receptor ligand for nectin-1.

    Evidence Nectin-1 KO mouse epidermis analysis, ERK inhibition in primary keratinocytes; CD96 binding assay with mAb blockade

    PMID:17472964 PMID:17971293

    Open questions at the time
    • How nectin-1 activates Rap1 (direct or indirect) not resolved
    • Functional consequence of CD96–nectin-1 interaction for NK or T cell cytotoxicity not fully tested
  8. 2009 High

    Genetic demonstration that nectin-1 is the essential HSV entry receptor in CNS neurons in vivo (HVEM dispensable) resolved the long-standing receptor-redundancy question for neuronal infection.

    Evidence Nectin-1 KO, HVEM KO, and double-KO mice with intracranial HSV inoculation and immunohistology

    PMID:19805039

    Open questions at the time
    • Whether nectin-1 is equally essential for peripheral sensory neuron entry not addressed by intracranial route
    • Mechanism by which loss of nectin-1 blocks neuronal entry (failure of attachment vs. fusion) not distinguished
  9. 2010 High

    Identifying ADAM10 as the NMDA-receptor–activated α-secretase for nectin-1 ectodomain shedding, followed by γ-secretase processing, established a regulated proteolytic mechanism linking synaptic activity to nectin-1 turnover.

    Evidence ADAM10 KO/KD neurons, pharmacological NMDA/AMPA antagonists, γ-secretase inhibitors in primary cortical neurons

    PMID:20501653

    Open questions at the time
    • Physiological consequence of nectin-1 ICD release by γ-secretase unknown
    • Whether ADAM10-mediated shedding affects HSV susceptibility at synapses not tested
  10. 2011 High

    Crystal structures of the nectin-1 cis-dimer and the gD–nectin-1 complex provided the atomic basis for adhesion and viral hijacking: gD occupies the same dimerization interface, competitively disrupting nectin-1 cis-dimers and trans-adhesion.

    Evidence X-ray crystallography of nectin-1 ectodomain and gD–nectin-1 complex (two independent labs), site-directed mutagenesis with entry assays

    PMID:21325282 PMID:21980294 PMID:22146396

    Open questions at the time
    • Structure of nectin-1/nectin-3 heterophilic trans-complex not determined
    • Whether gD-induced dimer disruption is sufficient to trigger endocytosis or requires additional signaling
  11. 2012 High

    Demonstrating that nectin-1's Ig3 module directly binds and activates FGFR to promote neurite outgrowth and neuronal survival established a second signaling axis independent of afadin-mediated junction assembly.

    Evidence NMR structure of Ig3, SPR binding to FGFR isoforms, FGFR inhibitor and dominant-negative FGFR1 in hippocampal/cerebellar neurons

    PMID:22955284

    Open questions at the time
    • Whether FGFR signaling through nectin-1 operates in non-neuronal tissues unknown
    • How Ig3-FGFR interaction is coordinated with V-domain adhesive interactions not resolved
  12. 2019 Medium

    Confirming that human nectin-1 binds NK receptor CD96 at its canonical V-domain adhesive interface with affinity comparable to gD established nectin-1 as an immune-modulatory ligand and extended the shared-interface paradigm to immunosurveillance.

    Evidence SPR-equivalent binding, K562 nectin-1 expression with NK-92 cytotoxicity assay

    PMID:30759143

    Open questions at the time
    • In vivo immunological consequence of nectin-1–CD96 interaction not demonstrated
    • Whether CD96 engagement competes with HSV gD for the same residues not structurally resolved
    • Single-lab binding study awaits independent confirmation

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full structural picture of nectin-1 heterophilic trans-complexes (nectin-1/nectin-3, nectin-1/nectin-4) and the mechanism by which nectin-1 activates Rap1 signaling remain unresolved.
  • No crystal structure of nectin-1/nectin-3 or nectin-1/nectin-4 trans-complex
  • Molecular mechanism linking nectin-1 to Rap1 activation not identified
  • Functional significance of γ-secretase-released nectin-1 ICD unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0001618 virus receptor activity 5 GO:0098631 cell adhesion mediator activity 5 GO:0060089 molecular transducer activity 4
Localization
GO:0005886 plasma membrane 5 GO:0005576 extracellular region 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-162582 Signal Transduction 2 R-HSA-168256 Immune System 2
Partners
ADAM10AFDNCD96FGFR1NECTIN3NECTIN4
Complex memberships
Nectin-1 cis-homodimerNectin-afadin complex

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Nectin-1 (PRR1) directly interacts with the PDZ domain of afadin via its C-terminal consensus motif (A/EXYV), and is recruited to cadherin-based cell-cell adherens junctions through this interaction; nectin-1 shows Ca2+-independent cell-cell adhesion activity. Co-immunoprecipitation, colocalization imaging, adhesion assays in EL cells The Journal of cell biology High 10225955
1998 The V domain of nectin-1 (HIgR/PRR1) is the major functional region mediating HSV-1 entry into cells; a single V domain is sufficient for physical interaction with HSV glycoprotein D (gD) in vitro and for conferring cell susceptibility to HSV-1 entry. Deletion mutants, soluble V-domain competition assay, in vitro binding (Co-IP/pulldown), entry assay with engineered chimeric receptors Proceedings of the National Academy of Sciences of the United States of America High 9861033
2001 Nectin-1 mediates direct cell-to-cell spread of wild-type HSV-1 through a gD-receptor interaction; a monoclonal antibody blocking nectin-1 also blocks cell-to-cell spread, and spread from receptor-positive to receptor-negative cells does not occur. Plaque assay, antibody blockade, receptor-negative J cell lines expressing nectin1 Journal of virology High 10729168
2001 Nectin-4 trans-interacts heterophilically with nectin-1 through V domain-to-V domain interactions; the V domain of nectin-1 is the major functional region involved in trans-heterointeraction with both nectin-3 and nectin-4. Soluble Fc-fusion binding to cells, co-immunoprecipitation, in vitro binding between recombinant proteins The Journal of biological chemistry High 11544254
2002 Nectin-1 trans-heterophilic interactions with nectin-3 (Kd ~1 nM) and nectin-4 (Kd ~100 nM) are mediated through V-to-V domain contacts; nectin-3 and nectin-4 share a common binding region on nectin-1 mapped to the C-C'-C"-D beta-strands of the V domain, and HSV-1 gD competes with both for binding to this region. Affinity measurements, competition binding with monoclonal antibodies and gD, chimeric nectin1/PVR receptors with strand substitutions The Journal of biological chemistry High 12011057
2011 Crystal structure of HSV-1 gD bound to nectin-1 (at 4.0 Å) reveals that gD uses both its N- and C-terminal extensions to contact the first Ig domain of nectin-1 at the same surface used for nectin-1 homophilic dimerization; Phe129 at the tip of nectin-1's FG loop inserts into a groove on gD, and mutation F129A abolishes nectin-1 binding to gD and HSV entry. X-ray crystallography, site-directed mutagenesis, HSV entry assay PLoS pathogens High 21980294
2011 Crystal structure of the nectin-1 extracellular region reveals that it forms a V-shaped cis-dimer through the first Ig-like domain; four residues in the first Ig domain are essential for cis-dimerization, homophilic adhesion, and heterophilic adhesion activity. X-ray crystallography, site-directed mutagenesis, cell-surface cis-dimerization assay, homophilic and heterophilic adhesion assays The Journal of biological chemistry High 21325282
2011 The gD/nectin-1 complex structure shows that gD binds nectin-1 in a mode similar to the nectin-1 homodimer interaction, using the same key residues for dimerization; gD binding to nectin-1 would preclude nectin-1 dimerization and abolish its cell adhesion function. X-ray crystallography of gD–nectin-1 complex Nature communications High 22146396
2014 Crystal structures of HSV-2 gD unbound and bound to nectin-1 demonstrate a conserved receptor-binding mode between HSV-1 and HSV-2; nectin-1 residue I80 is important for gD interaction, confirmed by surface plasmon resonance and cell fusion assays. X-ray crystallography, surface plasmon resonance, site-directed mutagenesis, cell-based fusion assay Journal of virology High 25231300
2000 Nectin-3 (PRR3) interacts with afadin through its C-terminal A/EXYV motif (PDZ-domain binding), and both proteins co-localize at intercellular junctions. In vivo co-immunoprecipitation with long and short afadin isoforms, colocalization imaging Gene Medium 11024295
2003 During HSV infection, nectin-1 is displaced from adherens junctions in a gD-dependent manner; newly synthesized gD substitutes for nectin-1 at junctions by trans-interacting with nectin-1 on adjacent noninfected cells, redirecting nectin-1 localization and facilitating virus spread. Live-cell imaging with nectin-1-GFP fusions, immunofluorescence colocalization, HSV entry/spread assay in cells with/without afadin interaction disrupted Journal of virology Medium 12885915
2009 Nectin-1 expression is necessary for HSV infection of neurons in the CNS and for development of encephalitis after intracranial inoculation; HVEM is largely dispensable for neuronal infection by this route, while nectin-1 KO mice show no detectable virus in brain parenchyma. Genetic KO mice (nectin-1 KO, HVEM KO, double KO), intracranial inoculation, immunohistology Proceedings of the National Academy of Sciences of the United States of America High 19805039
2003 Amino acids 77 and 85 in the V domain of nectin-1 are critical for HSV-1 and HSV-2 gD binding and entry but not for pseudorabies virus (PRV) or bovine herpesvirus 1 (BHV-1) entry, demonstrating overlapping but distinct gD binding footprints for different herpesviruses on nectin-1. Site-directed mutagenesis, soluble gD binding assay, viral entry assay Journal of virology High 12072525
2001 The HSV entry site on nectin-1 maps to residues 64–94 of the V domain (likely the C, C', C" beta-strands and loops); the gD-binding site maps to the same region, while the epitope for the entry-blocking mAb R1.302 additionally requires residues 95–102. Chimeric nectin1/PVR receptor constructs, HSV entry functional assay, mAb epitope mapping Journal of virology High 11483743
2003 N-terminal deletions in HSV-1 or HSV-2 gD that abolish interactions with HVEM, nectin-2, and 3-O-sulfated heparan sulfate do not impair functional interactions with nectin-1, demonstrating that gD's N-terminus is dispensable for nectin-1 binding and cell fusion. Cell fusion assay, soluble gD:Fc binding assay, site-directed mutagenesis Journal of virology High 12915538
2008 After trans-interaction with gD expressed on adjacent cells, nectin-1 is internalized and degraded via a low-pH-dependent pathway in cells where HSV enters endosomally; this down-regulation correlates with gD-mediated virion internalization. Co-culture of gD-expressing cells with nectin-1-expressing cells, receptor internalization assay, pH inhibitors (bafilomycin, NH4Cl), flow cytometry Virology Medium 18076965
2004 HSV entry mediated by nectin-1 can occur via either plasma membrane fusion or an endocytic route depending on cellular context; a chimeric nectin-1-EGFR1 receptor routes HSV through clathrin-dependent endocytosis requiring EGFR tyrosine kinase activity and acidic endosomes, while nectin-1 sorted to lipid rafts via GPI anchor also routes entry through acid endosomes. Chimeric receptor constructs, endosome acidification inhibitors, kinase inhibitors (AG1478), wortmannin, viral entry assays Journal of virology High 15507614
2011 αVβ3-integrin relocalizes nectin-1 to lipid rafts independently of HSV, thereby routing HSV to a lipid raft-dependent acidic endosome entry pathway; this integrin-induced relocalization is the mechanistic basis for αVβ3-integrin's control of HSV entry route. Lipid raft fractionation, co-expression of nectin-1 and αVβ3-integrin, HSV entry assay with pharmacological inhibitors Journal of virology Medium 22171266
2010 NMDA receptor activation (but not AMPA or mGluR) induces Ca2+/calmodulin-dependent α-secretase (ADAM10) cleavage of nectin-1 ectodomain and subsequent γ-secretase processing in primary cortical neurons; ADAM10 is identified as the major α-secretase responsible for nectin-1 ectodomain shedding. Primary cortical neuron stimulation, pharmacological receptor antagonists, ADAM10 knockdown/KO neurons, gamma-secretase inhibitors, western blot for cleavage products The Journal of biological chemistry High 20501653
2012 The third membrane-proximal Ig module (Ig3) of nectin-1 directly binds fibroblast growth factor receptors (FGFRs) as measured by surface plasmon resonance; this interaction induces FGFR1c phosphorylation, neurite outgrowth in hippocampal and cerebellar neurons, and neuronal survival, all abolished by FGFR inhibitor SU5402 or dominant-negative FGFR1. NMR structure of Ig3 module, surface plasmon resonance (SPR) binding to FGFR isoforms, dominant-negative FGFR1 transfection, FGFR inhibitor, neurite outgrowth assay, cell survival assay The Journal of biological chemistry High 22955284
2007 Nectin-1 regulates loricrin expression in keratinocytes through a Ca2+-induced Rap1-ERK signaling pathway; nectin-1 knockout mice show markedly reduced loricrin in the epidermis, and inhibition of ERK reduces loricrin in wild-type keratinocytes. Nectin-1 KO mice, primary keratinocyte culture, ERK activation assay, Western blot for loricrin/repetin/SPRR The Journal of biological chemistry High 17472964
2008 Nectin-1 and l-afadin cluster at developing hippocampal synapses in an F-actin-dependent manner, co-localizing with N-cadherin-catenin at excitatory synapses; actin depolymerization disrupts nectin-1/afadin synaptic clusters and triggers nectin-1 ectodomain shedding, suggesting a role in synaptic plasticity. Immunofluorescence in primary hippocampal neurons, actin depolymerizing agents (latrunculin, cytochalasin D), live imaging The Journal of comparative neurology Medium 18181141
2004 Nectin-1 trans-interaction with nectin-3 modulates E-cadherin-based adhesion differently depending on which nectin is expressed at high vs. low levels; heterodimers of nectin-1/nectin-3 adhere more strongly than homodimers, and the direction of trans-interaction (nectin-1 interacting with nectin-3 or vice versa) determines whether E-cadherin adhesion is agonized or not. Dual-pipette cell separation force measurement, L cell transfection with nectin-1 or nectin-3 at varying levels, soluble nectin ectodomain competition The Journal of biological chemistry Medium 15550395
2015 p63 directly transcriptionally regulates Pvrl1 (nectin-1) gene expression in stratified epithelia; ChIP demonstrates p63 binding to two conserved intronic Pvrl1 enhancer regions, and p63-null skin/keratinocytes show strongly reduced nectin-1 expression. ChIP, p63 KO mouse model, siRNA knockdown, qRT-PCR and western blot Experimental dermatology Medium 25387952
2010 miR-661 targets the 3'-UTR of nectin-1 mRNA, destabilizing it downstream of SNAI1-induced EMT; re-expression of nectin-1 lacking the 3'-UTR counteracts SNAI1-induced invasion of breast cancer cells, establishing nectin-1 downregulation as mechanistically contributing to EMT-driven invasion. miRNA overexpression, luciferase 3'-UTR reporter assay, nectin-1 rescue construct (without 3'-UTR), invasion assay Oncogene Medium 20543867
2019 Human nectin-1 directly interacts with the NK receptor CD96 via its V-domain canonical adhesive interface; the affinity of nectin-1 for CD96 is similar to its affinity for HSV gD; overexpression of nectin-1 in K562 cells increases susceptibility to NK-92 cell cytotoxicity. In vitro binding assay (SPR-equivalent), K562 cell expression of nectin-1-GFP, NK cytotoxicity assay, HSV entry assay PloS one Medium 30759143
2007 Murine CD96 binds nectin-1 in addition to CD155, demonstrating that nectin-1 is a ligand for the CD96 adhesion receptor; anti-CD96 and anti-CD155 antibodies block CD96/CD155 complex formation and T cell adhesion. Binding assay with monoclonal antibodies, T cell adhesion to insect cells expressing CD155, flow cytometry Biochemical and biophysical research communications Medium 17971293

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Direct regulation of the NADPH oxidase RBOHD by the PRR-associated kinase BIK1 during plant immunity. Molecular cell 709 24630626
1999 Nectin/PRR: an immunoglobulin-like cell adhesion molecule recruited to cadherin-based adherens junctions through interaction with Afadin, a PDZ domain-containing protein. The Journal of cell biology 450 10225955
2001 Nectin4/PRR4, a new afadin-associated member of the nectin family that trans-interacts with nectin1/PRR1 through V domain interaction. The Journal of biological chemistry 272 11544254
2020 Stepwise selection on homeologous PRR genes controlling flowering and maturity during soybean domestication. Nature genetics 269 32231277
2004 Functional characterization of DNAM-1 (CD226) interaction with its ligands PVR (CD155) and nectin-2 (PRR-2/CD112). International immunology 226 15039383
2011 Structure of herpes simplex virus glycoprotein D bound to the human receptor nectin-1. PLoS pathogens 150 21980294
2019 The receptor for advanced glycation end-products (RAGE) is an important pattern recognition receptor (PRR) for inflammaging. Biogerontology 133 30968282
2002 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. The Journal of biological chemistry 118 12011057
1990 The optional E. coli prr locus encodes a latent form of phage T4-induced anticodon nuclease. The EMBO journal 117 1691706
2010 miR-661 expression in SNAI1-induced epithelial to mesenchymal transition contributes to breast cancer cell invasion by targeting Nectin-1 and StarD10 messengers. Oncogene 107 20543867
2020 Intimate Association of PRR- and NLR-Mediated Signaling in Plant Immunity. Molecular plant-microbe interactions : MPMI 106 33048599
1998 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. Proceedings of the National Academy of Sciences of the United States of America 106 9861033
2003 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. Journal of virology 98 12915538
2000 Cell-to-cell spread of wild-type herpes simplex virus type 1, but not of syncytial strains, is mediated by the immunoglobulin-like receptors that mediate virion entry, nectin1 (PRR1/HveC/HIgR) and nectin2 (PRR2/HveB). Journal of virology 94 10729168
2011 Binding of herpes simplex virus glycoprotein D to nectin-1 exploits host cell adhesion. Nature communications 91 22146396
2015 PRR-signaling pathways: Learning from microbial tactics. Seminars in immunology 90 25911384
1973 Characteristics and purification of PRR1, an RNA phage specific for the broad host range Pseudomonas R1822 drug resistance plasmid. Journal of virology 89 4128383
2021 Roles of PRR-Mediated Signaling Pathways in the Regulation of Oxidative Stress and Inflammatory Diseases. International journal of molecular sciences 86 34299310
2009 Chitosan as a MAMP, searching for a PRR. Plant signaling & behavior 86 19704712
2013 The PRR family of transcriptional regulators reflects the complexity and evolution of plant circadian clocks. Current opinion in plant biology 82 23856081
2007 The murine pan T cell marker CD96 is an adhesion receptor for CD155 and nectin-1. Biochemical and biophysical research communications 79 17971293
2009 Infection of neurons and encephalitis after intracranial inoculation of herpes simplex virus requires the entry receptor nectin-1. Proceedings of the National Academy of Sciences of the United States of America 76 19805039
2004 Entry of herpes simplex virus mediated by chimeric forms of nectin1 retargeted to endosomes or to lipid rafts occurs through acidic endosomes. Journal of virology 76 15507614
2018 Identification of the fungal ligand triggering cytotoxic PRR-mediated NK cell killing of Cryptococcus and Candida. Nature communications 73 29467448
2010 The Drosophila PRR GNBP3 assembles effector complexes involved in antifungal defenses independently of its Toll-pathway activation function. European journal of immunology 72 20201042
2015 Activation of ENaC in collecting duct cells by prorenin and its receptor PRR: involvement of Nox4-derived hydrogen peroxide. American journal of physiology. Renal physiology 68 26697985
1994 The Escherichia coli prr region encodes a functional type IC DNA restriction system closely integrated with an anticodon nuclease gene. Journal of molecular biology 67 8145241
2018 Enhanced Sensitivity of Patient-Derived Pediatric High-Grade Brain Tumor Xenografts to Oncolytic HSV-1 Virotherapy Correlates with Nectin-1 Expression. Scientific reports 66 30224769
2003 Cellular localization of nectin-1 and glycoprotein D during herpes simplex virus infection. Journal of virology 64 12885915
2017 Targeting Pattern Recognition Receptors (PRR) for Vaccine Adjuvantation: From Synthetic PRR Agonists to the Potential of Defective Interfering Particles of Viruses. Viruses 62 28703784
1999 A fission yeast gene (prr1(+)) that encodes a response regulator implicated in oxidative stress response. Journal of biochemistry 61 10348908
2000 Human nectin3/PRR3: a novel member of the PVR/PRR/nectin family that interacts with afadin. Gene 60 11024295
2008 The herpes simplex virus receptor nectin-1 is down-regulated after trans-interaction with glycoprotein D. Virology 54 18076965
2004 Separation force measurements reveal different types of modulation of E-cadherin-based adhesion by nectin-1 and -3. The Journal of biological chemistry 54 15550395
2013 Early signaling network in rice PRR-mediated and R-mediated immunity. Current opinion in plant biology 53 23927868
2007 Nectin-1 expression by squamous cell carcinoma is a predictor of herpes oncolytic sensitivity. Molecular therapy : the journal of the American Society of Gene Therapy 53 17164781
2001 Transcription from the gene encoding the herpesvirus entry receptor nectin-1 (HveC) in nervous tissue of adult mouse. Virology 53 11531408
2020 Cytokinin response induces immunity and fungal pathogen resistance, and modulates trafficking of the PRR LeEIX2 in tomato. Molecular plant pathology 49 32841497
2011 Herpesvirus entry mediator and nectin-1 mediate herpes simplex virus 1 infection of the murine cornea. Journal of virology 49 21795335
2012 The transcription factors Pap1 and Prr1 collaborate to activate antioxidant, but not drug tolerance, genes in response to H2O2. Nucleic acids research 48 22344694
2011 αVβ3-integrin relocalizes nectin1 and routes herpes simplex virus to lipid rafts. Journal of virology 46 22171266
2010 Activity-dependent alpha-cleavage of nectin-1 is mediated by a disintegrin and metalloprotease 10 (ADAM10). The Journal of biological chemistry 46 20501653
2005 Enhanced nectin-1 expression and herpes oncolytic sensitivity in highly migratory and invasive carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 46 16000587
2011 Crystal Structure of the cis-Dimer of Nectin-1: implications for the architecture of cell-cell junctions. The Journal of biological chemistry 45 21325282
2002 Amino acid substitutions in the V domain of nectin-1 (HveC) that impair entry activity for herpes simplex virus types 1 and 2 but not for Pseudorabies virus or bovine herpesvirus 1. Journal of virology 41 12072525
2014 Crystal structure of herpes simplex virus 2 gD bound to nectin-1 reveals a conserved mode of receptor recognition. Journal of virology 39 25231300
2003 The domains of glycoprotein D required to block apoptosis induced by herpes simplex virus 1 are largely distinct from those involved in cell-cell fusion and binding to nectin1. Journal of virology 39 12610150
2001 Novel, soluble isoform of the herpes simplex virus (HSV) receptor nectin1 (or PRR1-HIgR-HveC) modulates positively and negatively susceptibility to HSV infection. Journal of virology 39 11356977
2004 Herpes simplex virus entry receptor nectin-1 is widely expressed in the murine eye. Current eye research 38 15590476
2002 Role of fission yeast Tup1-like repressors and Prr1 transcription factor in response to salt stress. Molecular biology of the cell 38 12221110
2015 Role of Nectin-1 and Herpesvirus Entry Mediator as Cellular Receptors for Herpes Simplex Virus 1 on Primary Murine Dermal Fibroblasts. Journal of virology 36 26136572
2002 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. Journal of virology 35 12438620
2000 The Prr1 response regulator is essential for transcription of ste11+ and for sexual development in fission yeast. Molecular & general genetics : MGG 35 11129048
2010 Pseudo-response regulator (PRR) homologues of the moss Physcomitrella patens: insights into the evolution of the PRR family in land plants. DNA research : an international journal for rapid publication of reports on genes and genomes 34 21186242
2020 Inhibition of IRF4 in dendritic cells by PRR-independent and -dependent signals inhibit Th2 and promote Th17 responses. eLife 33 32014112
2019 Interaction between nectin-1 and the human natural killer cell receptor CD96. PloS one 32 30759143
2009 Generation of herpesvirus entry mediator (HVEM)-restricted herpes simplex virus type 1 mutant viruses: resistance of HVEM-expressing cells and identification of mutations that rescue nectin-1 recognition. Journal of virology 32 19129446
2015 p63-dependent and independent mechanisms of nectin-1 and nectin-4 regulation in the epidermis. Experimental dermatology 31 25387952
2008 Temporal and spatial localization of nectin-1 and l-afadin during synaptogenesis in hippocampal neurons. The Journal of comparative neurology 31 18181141
2001 Chimeric nectin1-poliovirus receptor molecules identify a nectin1 region functional in herpes simplex virus entry. Journal of virology 31 11483743
2018 PRR Function of Innate Immune Receptors in Recognition of Bacteria or Bacterial Ligands. Advances in experimental medicine and biology 30 30637703
2016 Adipose tissue (P)RR regulates insulin sensitivity, fat mass and body weight. Molecular metabolism 30 27689008
1999 Characterization of the regulatory elements of the maize P-rr gene by transient expression assays. Plant molecular biology 30 10080705
2022 EDS1 complexes are not required for PRR responses and execute TNL-ETI from the nucleus in Nicotiana benthamiana. The New phytologist 29 36151929
2006 Complete genome sequence of the broad host range single-stranded RNA phage PRR1 places it in the Levivirus genus with characteristics shared with Alloleviviruses. Journal of virology 28 16940544
2012 Nectin-1 binds and signals through the fibroblast growth factor receptor. The Journal of biological chemistry 27 22955284
2007 Up-regulation of loricrin expression by cell adhesion molecule nectin-1 through Rap1-ERK signaling in keratinocytes. The Journal of biological chemistry 27 17472964
2022 Concerted actions of PRR- and NLR-mediated immunity. Essays in biochemistry 26 35762737
2009 Role of nectin-1, HVEM, and PILR-alpha in HSV-2 entry into human retinal pigment epithelial cells. Investigative ophthalmology & visual science 26 19234349
2007 Global transcriptional responses of Pseudomonas aeruginosa to phage PRR1 infection. Journal of virology 26 18077716
2018 Losartan prevents the elevation of blood pressure in adipose-PRR deficient female mice while elevated circulating sPRR activates the renin-angiotensin system. American journal of physiology. Heart and circulatory physiology 25 30550352
2012 Molecular view on PRR cross-talk in antifungal immunity. Cellular microbiology 25 22233321
2012 The (pro)renin receptor ((P)RR) can act as a repressor of Wnt signalling. Biochemical pharmacology 25 23022225
2024 Pattern-Triggered Immunity  and Effector-Triggered Immunity: crosstalk and cooperation of PRR and NLR-mediated plant defense pathways during host-pathogen interactions. Physiology and molecular biology of plants : an international journal of functional plant biology 23 38737322
2002 Differential expression of the CO2 fixation operons of Rhodobacter sphaeroides by the Prr/Reg two-component system during chemoautotrophic growth. Journal of bacteriology 23 12426354
2024 Shared signals, different fates: Calcium and ROS in plant PRR and NLR immunity. Cell reports 22 39471173
2006 Expression of nectin-1 in normal and herpes simplex virus type 1-infected murine brain. Applied immunohistochemistry & molecular morphology : AIMM 22 16932027
2007 Characterization of Circadian-associated pseudo-response regulators: I. Comparative studies on a series of transgenic lines misexpressing five distinctive PRR Genes in Arabidopsis thaliana. Bioscience, biotechnology, and biochemistry 21 17284849
2006 Chemokine production and pattern recognition receptor (PRR) expression in whole blood stimulated with pathogen-associated molecular patterns (PAMPs). Cytokine 21 16406558
2003 Characterization of the Prr1 response regulator with special reference to sexual development in Schizosaccharomyces pombe. Bioscience, biotechnology, and biochemistry 21 12723602
2019 Positional Cloning of the Flowering Time QTL qFT12-1 Reveals the Link Between the Clock Related PRR Homolog With Photoperiodic Response in Soybeans. Frontiers in plant science 20 31681389
2012 Chronological lifespan extension by Ecl1 family proteins depends on Prr1 response regulator in fission yeast. Genes to cells : devoted to molecular & cellular mechanisms 20 22212525
2008 MyoD- and nerve-dependent maintenance of MyoD expression in mature muscle fibres acts through the DRR/PRR element. BMC developmental biology 20 18215268
2017 Prorenin receptor (PRR)-mediated NADPH oxidase (Nox) signaling regulates VEGF synthesis under hyperglycemic condition in ARPE-19 cells. Journal of receptor and signal transduction research 18 28840773
2015 Macrophages polarization is mediated by the combination of PRR ligands and distinct inflammatory cytokines. International journal of clinical and experimental pathology 18 26617814
2015 Mosla scabra flavonoids ameliorate the influenza A virus-induced lung injury and water transport abnormality via the inhibition of PRR and AQP signaling pathways in mice. Journal of ethnopharmacology 18 26719287
2014 Different roles of the three loops forming the adhesive interface of nectin-4 in measles virus binding and cell entry, nectin-4 homodimerization, and heterodimerization with nectin-1. Journal of virology 18 25275122
2008 The capsid of the small RNA phage PRR1 is stabilized by metal ions. Journal of molecular biology 18 18786545
2004 The herpes simplex virus JMP mutant enters receptor-negative J cells through a novel pathway independent of the known receptors nectin1, HveA, and nectin2. Journal of virology 18 15078954
2022 An Overview of PRR- and NLR-Mediated Immunities: Conserved Signaling Components across the Plant Kingdom That Communicate Both Pathways. International journal of molecular sciences 17 36361764
2021 (Pro)renin receptor involves in myocardial fibrosis and oxidative stress in diabetic cardiomyopathy via the PRR-YAP pathway. Scientific reports 17 33547400
2021 Effects of (Pro)renin Receptor on Diabetic Cardiomyopathy Pathological Processes in Rats via the PRR-AMPK-YAP Pathway. Frontiers in physiology 17 34122131
2013 PRR repeats in the intracellular domain of KISS1R are important for its export to cell membrane. Molecular endocrinology (Baltimore, Md.) 17 23608644
2006 Nectin-1 expression in the normal and neoplastic human uterine cervix. Archives of pathology & laboratory medicine 17 16879022
2004 Effects of linker-insertion mutations in herpes simplex virus 1 gD on glycoprotein-induced fusion with cells expressing HVEM or nectin-1. Virology 17 14972557
2001 Comparison of murine and human nectin1 binding to herpes simplex virus glycoprotein D (gD) reveals a weak interaction of murine nectin1 to gD and a gD-dependent pathway of entry. Virology 17 11289808
2018 Variegated Transcription of the WC1 Hybrid PRR/Co-Receptor Genes by Individual γδ T Cells and Correlation With Pathogen Responsiveness. Frontiers in immunology 16 29867919
2018 Role of a fluid-phase PRR in fighting an intracellular pathogen: PTX3 in Shigella infection. PLoS pathogens 16 30532257
2002 Substitution in the murine nectin1 receptor of a single conserved amino acid at a position distal from the herpes simplex virus gD binding site confers high-affinity binding to gD. Journal of virology 16 11991974
2022 Linking nutrient sensing, mitochondrial function, and PRR immune cell signaling in liver disease. Trends in immunology 15 36216719