Affinage

CELSR1

Cadherin EGF LAG seven-pass G-type receptor 1 · UniProt Q9NYQ6

Round 2 corrected
Length
3014 aa
Mass
329.5 kDa
Annotated
2026-04-28
130 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CELSR1 is an atypical seven-pass transmembrane cadherin (adhesion GPCR) that functions as a core component of the planar cell polarity (PCP) pathway, coordinating tissue-level polarity across diverse epithelia and neuronal populations. Its large extracellular region—comprising nine cadherin repeats, EGF-like, and laminin G domains organized into a compact CADH9-GAIN module—mediates weak, Ca²⁺-dependent homophilic adhesion through both trans- and cis-interactions that stabilize junctional puncta and organize asymmetric complexes containing Frizzled6 and Vangl2; disruption of cis-interactions (as in the Crash allele) abolishes junctional enrichment and PCP protein asymmetry (PMID:33529151, PMID:36712970, PMID:40295529). CELSR1 couples to Gαs independently of GAIN-domain autoproteolysis and tethered-agonist activation, distinguishing it from classical adhesion GPCRs (PMID:37224017). Loss of CELSR1 function disrupts neural tube closure, inner ear and oviduct ciliary orientation, lymphatic valve morphogenesis (via VE-cadherin/adherens junction destabilization), cortical neurogenesis (via retinoic acid signaling), and facial branchiomotor neuron migration (by de-repressing Wnt5a-mediated chemoattraction) (PMID:12842012, PMID:25406397, PMID:23792146, PMID:29257130, PMID:36325991); biallelic CELSR1 variants in humans cause brain malformations including pachygyria, periventricular heterotopia, and epilepsy (PMID:41530147).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1997 Medium

    Identification of CELSR1's unique domain architecture—nine cadherin repeats coupled to EGF-like, laminin G, and seven-transmembrane domains—established a new class of adhesion-GPCR hybrids with brain-enriched expression.

    Evidence cDNA cloning, domain analysis, in situ hybridization in mouse brain

    PMID:9339365

    Open questions at the time
    • No functional data; expression-based only
    • Signaling mechanism unknown
    • Ligand and adhesion properties not tested
  2. 2003 High

    Two independent ENU alleles (spin cycle, crash) demonstrated that Celsr1 is the first mammalian Flamingo homolog required for planar cell polarity and neural tube closure, transforming it from an uncharacterized orphan receptor to a core PCP component.

    Evidence ENU mutagenesis screen, organ of Corti hair cell orientation and neural tube closure analysis in homozygous mutant mice

    PMID:12842012

    Open questions at the time
    • Molecular mechanism of PCP disruption unknown
    • Downstream signaling effectors not identified
    • Relationship to other core PCP components (Vangl, Fz) not established
  3. 2010 High

    Functional studies expanded CELSR1's PCP role beyond the ear and neural tube to lung branching morphogenesis (upstream of Rho kinase), neuroepithelial basal polarity, and non-cell-autonomous regulation of facial branchiomotor neuron migration direction.

    Evidence Celsr1 Crash/KO mouse phenotyping in lung and hindbrain, ROCK inhibitor epistasis, conditional inactivation, FBM neuron fate mapping, neuroepithelial immunofluorescence

    PMID:20223754 PMID:20353824 PMID:20631168

    Open questions at the time
    • Signaling pathway between Celsr1 and ROCK not delineated
    • Floor plate vs. ventricular zone requirement not fully resolved
    • Multiple isoform significance unclear
  4. 2011 Medium

    Human CELSR1 missense variants from craniorachischisis patients were shown to impair plasma membrane trafficking, providing the first direct link between human NTD mutations and a defined cellular defect in CELSR1 function.

    Evidence Subcellular localization assays of multiple patient-derived CELSR1 variants in transfected cells, comparison to mouse Crash/spin cycle alleles

    PMID:22095531

    Open questions at the time
    • Overexpression system may not recapitulate endogenous trafficking
    • Functional rescue not performed
    • Interaction with PCP partners not systematically tested for all variants
  5. 2013 High

    Discovery that Celsr1 regulates lymphatic valve morphogenesis by inhibiting VE-cadherin stabilization revealed a PCP-adherens junction crosstalk mechanism operative in endothelial cells, expanding CELSR1 biology beyond epithelial and neuronal tissues.

    Evidence Celsr1-deficient mouse lymphatic analysis, live imaging of endothelial rearrangements, VE-cadherin dynamics assays

    PMID:23792146

    Open questions at the time
    • Biochemical mechanism of VE-cadherin destabilization unknown
    • Whether Celsr1 acts through Vangl2 or independently in this context not fully resolved
  6. 2014 High

    Celsr1 was shown to coordinate multilevel polarity in the oviduct (ciliary beat direction, cell elongation, epithelial fold alignment), while human spina bifida–associated variants were found to disrupt the CELSR1–VANGL2 physical interaction and VANGL2 junctional recruitment.

    Evidence Celsr1 KO mouse oviduct analysis with ciliary motion/mosaic studies; co-IP of patient-derived CELSR1 variants with VANGL2

    PMID:24632739 PMID:25406397

    Open questions at the time
    • Structural basis of CELSR1–VANGL2 interaction unknown
    • Oviduct-specific downstream effectors not identified
  7. 2016 High

    A gain-of-function CELSR1 variant (P870L) was demonstrated to upregulate both PCP and canonical WNT signaling, and conditional studies pinpointed the ventricular zone of r3–r5 as the critical site of Celsr1 action for suppressing aberrant FBM neuron migration.

    Evidence Cell-based PCP/WNT signaling assays and zebrafish injection for P870L; Cre-lox conditional KO in specific hindbrain domains with dye-fill tracing

    PMID:27395006 PMID:27756857

    Open questions at the time
    • Mechanism of P870L gain-of-function at receptor level unknown
    • Direct signal mediating non-cell-autonomous influence on FBM neurons not identified
  8. 2017 High

    Two studies revealed that Celsr1 controls cortical neurogenesis via retinoic acid signaling from meningeal-progenitor contacts, and coordinates vestibular hair cell stereociliary bundle orientation—extending its PCP repertoire to progenitor fate decisions and sensory organ patterning.

    Evidence Celsr1 KO mouse cortex (RA reporter, progenitor quantification, basal process morphology) and vestibular epithelium (hair bundle orientation, behavioral phenotyping)

    PMID:28159525 PMID:29257130

    Open questions at the time
    • Whether RA pathway engagement is direct or indirect not resolved
    • Vestibular compensation mechanisms not characterized
  9. 2021 High

    Super-resolution and biophysical studies established that CELSR1 forms both trans and cis homophilic interactions at junctions; the Crash mutation selectively disrupts cis-interactions, increasing receptor mobility and preventing asymmetric PCP complex assembly—demonstrating that lateral cis-clustering is the critical step for PCP establishment.

    Evidence STORM super-resolution microscopy, FRAP, co-IP, cell aggregation assays, ectopic cis-dimerization rescue of Crash phenotype

    PMID:33529151

    Open questions at the time
    • Structural basis of cis vs. trans interface not resolved at atomic level
    • Whether other PCP components modulate cis/trans equilibrium unknown
  10. 2021 High

    Dissection of intercellular (Celsr1-dependent) versus intracellular (CAMSAP3-dependent) basal body orientation in oviduct multiciliated cells clarified that CELSR1's role is specifically in coordinating polarity between neighboring cells rather than organizing the cytoskeleton within a single cell.

    Evidence Parallel analysis of Celsr1 and CAMSAP3 mutant mice with basal body and PCP factor localization imaging

    PMID:33468623

    Open questions at the time
    • Molecular link from junctional CELSR1 to cytoplasmic polarity machinery not identified
    • Whether this intercellular/intracellular division applies in other ciliated tissues unknown
  11. 2022 High

    Genetic epistasis showed that Celsr1 suppresses Wnt5a-mediated chemoattraction of FBM neurons, finally identifying the specific signal (Wnt5a) that Celsr1 counteracts to prevent aberrant rostral migration.

    Evidence Celsr1;Wnt5a double KO epistasis, Wnt5a-coated bead chemoattraction assays in hindbrain explants, Wnt5a overexpression in Celsr1 mutant

    PMID:36325991

    Open questions at the time
    • Whether Celsr1 modulates Wnt5a availability, receptor access, or downstream signaling not distinguished
    • Receptor on FBM neurons transducing Wnt5a not identified
  12. 2023 High

    Biochemical and signaling studies demonstrated that CELSR1 is cleavage-deficient at its GAIN domain yet couples to Gαs through a tethered-agonist-independent mechanism, fundamentally distinguishing its activation mode from canonical adhesion GPCRs. Separately, CELSR1 was confirmed as the dominant Celsr paralog for epidermal PCP based on its superior junctional stability relative to CELSR2.

    Evidence Autoproteolysis assays, Gαs BRET/cAMP coupling with TA mutants across CELSR family; CRISPR KO of Celsr1/Celsr2 in mouse epidermis with FRAP and co-IP

    PMID:36712970 PMID:37224017

    Open questions at the time
    • Structural mechanism of TA-independent Gαs activation unknown
    • Whether Gαs signaling is required for PCP function not tested
    • Basis for differential junctional stability of CELSR1 vs. CELSR2 at structural level unknown
  13. 2024 High

    Crystal structures of CELSR1 cadherin repeats EC1-7 revealed typical cadherin folds with a non-canonical flexible linker at EC5-6, and showed that isolated EC repeats support only weak adhesion while the C-terminal EC7-MAD10 region contributes significantly to dimerization.

    Evidence X-ray crystallography of EC1-4 and EC4-7, bead aggregation assays, AUC/SEC, MD simulations

    PMID:38307021

    Open questions at the time
    • Full-length extracellular region structure at high resolution not yet available from crystallography
    • Trans-dimer interface not resolved at atomic level
  14. 2025 High

    Cryo-EM at 3.8 Å resolved the compact CADH9-GAIN module of CELSR1 and showed Ca²⁺-dependent antiparallel dimerization mediated by cadherin repeats, with CADH1-8 required for cell adhesion and the CADH9-GAIN module regulating adhesion properties—providing the first near-complete structural view of the extracellular region.

    Evidence Cryo-EM reconstruction of mouse CELSR1 ECR, Ca²⁺-dependent dimerization assays, domain deletion cell adhesion assays

    PMID:40295529

    Open questions at the time
    • Structure of the 7TM domain and intracellular regions not resolved
    • Dimer interface at atomic resolution still lacking
    • Relationship between compact/extended conformations and signaling state unknown
  15. 2026 High

    Biallelic CELSR1 variants were identified as a cause of human brain malformations (pachygyria, periventricular heterotopia, corpus callosum abnormalities) with epilepsy, validated by fully penetrant corresponding phenotypes in Celsr1 KO mice—establishing CELSR1 as a Mendelian disease gene for cortical malformations beyond NTDs.

    Evidence Whole exome sequencing of human patients, Celsr1 KO mouse MRI/histology and seizure susceptibility testing

    PMID:41530147

    Open questions at the time
    • Specific cellular mechanism linking Celsr1 loss to heterotopia and pachygyria not defined
    • Genotype-phenotype correlations across different variant classes not established
    • Whether seizures are primary or secondary to malformation unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: (1) how the CADH9-GAIN compact module and conformational changes couple to Gαs activation in the absence of autoproteolysis; (2) whether Gαs signaling is required for CELSR1's PCP function or operates in a parallel pathway; and (3) the identity and structure of the intracellular signaling complexes that relay CELSR1 junctional asymmetry to cytoskeletal and transcriptional effectors.
  • No high-resolution structure of the 7TM or intracellular domain
  • Gαs pathway contribution to PCP not tested genetically
  • Direct intracellular effectors linking junctional CELSR1 to cytoskeletal polarity machinery remain unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 3 GO:0098772 molecular function regulator activity 2 GO:0060089 molecular transducer activity 1
Localization
GO:0005886 plasma membrane 6
Pathway
R-HSA-1266738 Developmental Biology 6 R-HSA-162582 Signal Transduction 5 R-HSA-1500931 Cell-Cell communication 4
Partners
DVL3FZD3FZD6VANGL1VANGL2
Complex memberships
PCP core complex (CELSR1–FZD6–VANGL2)

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Missense mutations in mouse Celsr1 (spin cycle and crash alleles) disrupt planar cell polarity of inner ear hair cells and cause severe neural tube defects due to failure to initiate neural tube closure, establishing Celsr1 as the first mammalian Flamingo/Starry night homolog required for planar cell polarity. ENU mutagenesis, genetic mapping, in vivo phenotypic analysis of homozygous mutant mice (organ of Corti hair cell orientation, neural tube closure) Current biology : CB High 12842012
2011 Human CELSR1 missense variants associated with craniorachischisis impair subcellular trafficking to the plasma membrane, as demonstrated by reduced or abolished membrane localization compared to wild-type CELSR1, mirroring the crash and spin cycle mouse mutant phenotypes. Subcellular protein localization assays in transfected cells, protein-protein interaction assays, comparison with mouse Celsr1 mutant alleles Human mutation Medium 22095531
2010 Celsr1 (Crash allele) mutant mice show disrupted lung branching morphogenesis with fewer branches, thickened interstitial mesenchyme, and defective saccular formation; Rho kinase inhibition recapitulates these defects, and epithelial integrity and cytoskeletal remodelling are perturbed, placing Celsr1 upstream of Rho kinase in lung epithelial PCP signaling. Analysis of Celsr1Crsh mutant mouse lungs, Rho kinase inhibitor treatment, endoderm branching assays with FGF10, Celsr1 protein localization in lung epithelium Human molecular genetics High 20223754
2013 Celsr1 regulates dynamic endothelial cell movements during lymphatic valve morphogenesis by inhibiting stabilization of VE-cadherin and maturation of adherens junctions; Celsr1 and Vangl2 are recruited from filopodia to discrete membrane domains at cell-cell contacts during valve formation. Celsr1- and Vangl2-deficient mouse analysis, live imaging of endothelial cell rearrangements, VE-cadherin dynamics assays, subcellular localization of Celsr1/Vangl2 by immunofluorescence Developmental cell High 23792146
2010 Celsr1 regulates the direction of facial branchiomotor (FBM) neuron migration in a non-cell-autonomous manner; Celsr1 is expressed in floor plate and ventricular zone but not in FBM neurons, and conditional inactivation in ventricular zone of r3–r5 causes rostral misdirection of FBM neurons. Celsr2 is epistatic to Celsr1 in this context. Celsr1 knockout and Crash allele mice, conditional inactivation, FBM neuron fate mapping, hindbrain patterning analysis, epistasis analysis The Journal of neuroscience : the official journal of the Society for Neuroscience High 20631168
2014 Celsr1 is required for multilevel polarity in the mouse oviduct: it concentrates at specific cellular boundaries perpendicular to the ovary-uterus axis, coordinates ciliary beat direction, controls epithelial cell elongation/orientation, and directs epithelial fold alignment. Mosaic analysis indicates cell geometry is primarily regulated by Celsr1. Celsr1-deficient mouse analysis, immunofluorescence localization, ciliary motion analysis, mosaic analysis, postnatal oviduct development characterization Development (Cambridge, England) High 25406397
2014 CELSR1 TG dinucleotide repeat variants found in spina bifida patients alter subcellular localization of CELSR1 protein and impair physical association between CELSR1 and VANGL2, thereby diminishing recruitment of VANGL2 to cell-cell contacts. In vitro subcellular localization assays, co-immunoprecipitation of CELSR1 and VANGL2, functional analysis of patient-derived variants PloS one Medium 24632739
2010 Celsr1 protein is enriched at the basal surface of neuroepithelial cells in the neural tube and in ventricular zone cells at the midline of the developing spinal cord; this basal enrichment is lost in Celsr1 homozygous mutant embryos. The basal Celsr1 distribution correlates with dorsal sensory tract morphogenesis and suggests multiple protein isoforms with distinct signaling potential. Immunofluorescence/protein localization in wild-type and mutant mouse embryos, subcellular fractionation approaches, in vivo analysis Molecular and cellular neurosciences Medium 20353824
2016 CELSR1 P870L, identified in both NTD and CHD patients, is a gain-of-function mutation that upregulates both the PCP pathway and canonical WNT signaling in cells, and induces both NTDs and CHDs when expressed in zebrafish embryos. In vitro cell-based signaling assays, in vivo zebrafish embryo injection, patient variant characterization Clinical science (London, England : 1979) Medium 27756857
2021 Mouse Celsr1 engages in both trans- (cell-cell bridging) and cis- (lateral, same-cell) interactions and organizes into dense, highly stable junctional puncta. The PCP-mutant Celsr1Crsh variant selectively impairs lateral cis-interactions, increases receptor mobility, diminishes junctional enrichment, and fails to engage in homophilic adhesion with wild-type Celsr1, preventing organization of Frizzled6 and Vangl2 into asymmetric junctional complexes. Ectopic cis-dimerization rescues these defects. Biochemical assays (co-IP), super-resolution microscopy (STORM), FRAP, cell aggregation assays, epistasis with Celsr1Crsh mutant eLife High 33529151
2021 CELSR1 coordinates intercellular (between-cell) coordination of basal body orientation in oviduct multi-ciliated cells, while CAMSAP3 controls intracellular basal body orientation. Loss of CELSR1 disrupts intercellular coordination but only moderately affects intracellular polarity, whereas CAMSAP3 mutation disrupts intracellular BB orientation and microtubule interconnection without affecting PCP factor localization. Celsr1 mutant mouse analysis, CAMSAP3 mutant analysis, immunofluorescence localization of basal bodies and PCP factors, microtubule imaging Journal of cell science High 33468623
2017 Celsr1 is asymmetrically distributed at cell boundaries between hair cells and supporting cells in developing vestibular and auditory sensory epithelia. Loss of Celsr1 causes misorientation of vestibular hair cell stereociliary bundles relative to neighbors, predominantly in cristae of semicircular canals, causing vestibular behavioral defects (circling). Celsr1 KO mouse analysis, immunofluorescence showing asymmetric Celsr1 distribution, hair bundle orientation analysis, behavioral phenotyping Developmental biology High 28159525
2017 Celsr1 controls branching of apical neural progenitor cell (aNPC) basal processes that abut the meninges, and thereby regulates retinoic acid (RA)-dependent neurogenesis. Loss of Celsr1 decreases endfeet number, modifies RA-dependent transcriptional activity, and biases aNPC commitment toward self-renewal at the expense of basal progenitor and neuron production, resulting in microcephaly. Celsr1 KO mouse analysis, RA signaling reporter assays, quantification of neural progenitor subtypes and neuron numbers, basal process morphology analysis Molecular psychiatry High 29257130
2016 Celsr1 suppresses inappropriate rostral FBM neuron migration non-cell-autonomously by acting in the ventricular zone of r3-r5 (not the floor plate). Conditional inactivation of Celsr1 specifically in the ventricular zone of r3-r5 phenocopies the full Celsr1 mutant migration defect. Conditional (Cre-lox) Celsr1 inactivation in specific cell types, dye-fill tracing of FBM neuron origin, hindbrain explant analysis Developmental biology High 27395006
2022 Celsr1 suppresses Wnt5a-mediated chemoattraction to prevent inappropriate rostral migration of FBM neurons. In Celsr1; Wnt5a double mutants, rostral migration is abolished; FBM neurons migrate rostrally toward Wnt5a-coated beads in wild-type explants; and rostral migration is enhanced in Celsr1 mutants overexpressing Wnt5a in r3. Genetic epistasis (Celsr1; Wnt5a double mutants), Wnt5a-coated bead assays in hindbrain explants, Wnt5a overexpression in Celsr1 mutant background Development (Cambridge, England) High 36325991
2020 CELSR1 promotes neuroprotection after cerebral ischemia by reducing apoptosis in peri-infarct cortex and promoting neurogenesis and angiogenesis in the subventricular zone, mainly through the Wnt/PKC signaling pathway. Knockdown of Celsr1 in the SVZ with lentivirus reduced neuroblast proliferation, CD31+ cell numbers, and motor function, and decreased p-PKC expression. Lentiviral Celsr1 knockdown in MCAO rat SVZ, immunohistochemistry for neuroblasts and CD31, Western blot for p-PKC, behavioral testing International journal of molecular sciences Medium 32070035
2016 CELSR1 is a positive regulator of endothelial cell migration, proliferation, and tube formation, and its effects on migration and tube formation are mediated through dishevelled segment polarity protein 3 (Dvl3). TALE-VP64 activator (gain-of-function) and shRNA knockdown of CELSR1 in human aortic endothelial cells, MTT proliferation assay, scratch/transwell migration assays, tube formation assay, Dvl3 epistasis Biochemistry. Biokhimiia Medium 27301287
2023 CELSR1 and CELSR3 are cleavage-deficient adhesion GPCRs (they do not undergo autoproteolytic cleavage at the GAIN domain), while CELSR2 is efficiently cleaved. Despite differential autoproteolysis, CELSR1-3 all engage GαS. CELSR1 tethered agonist (TA) point mutants retain GαS coupling activity, indicating that CELSR1 signals via a tethered-agonist-independent mechanism distinct from classical aGPCR activation. Autoproteolysis assays, G protein coupling assays (GαS BRET/cAMP), TA point mutagenesis, comparison across CELSR1-3 and LPHN3 Cell reports High 37224017
2023 Celsr1 is the major Celsr family member for epidermal PCP: removal of Celsr1 alone abolishes PCP protein asymmetry and hair follicle polarization, while loss of Celsr2 alone has no effect. Celsr1 stably enriches at junctional interfaces (low FRAP mobility), whereas Celsr2 is much less efficiently recruited to junctions. Both proteins interact equivalently with Vangl2 and Fz6, suggesting that differences in homophilic adhesion underlie differential PCP involvement. CRISPR/Cas9 Celsr1 and Celsr2 KO mice, PCP protein asymmetry assays, hair follicle orientation analysis, FRAP, junctional enrichment assays, co-IP with Vangl2 and Fz6 Frontiers in cell and developmental biology High 36712970
2025 Cryo-EM reconstruction of mouse CELSR1 ECR (3.8 Å) reveals that 14 of its 23 adhesion domains form a compact module mediated by conserved interactions between the CADH9 and C-terminal GAIN domains. In the presence of Ca2+, the CELSR1 ECR forms a dimer species mediated by cadherin repeats in a putative antiparallel fashion. Cell-based assays show the N-terminal CADH1-8 repeat is required for cell-cell adhesion while the C-terminal CADH9-GAIN compact module regulates cellular adhesion. Cryo-EM structure determination (3.8 Å), Ca2+-dependent dimerization assays, cell-based adhesion assays with domain deletion constructs Nature communications High 40295529
2024 Crystal structures of human CELSR1 EC1-4 and EC4-7 reveal typical cadherin folds and a non-canonical linker between EC5 and EC6. CELSR1 EC repeats alone support only weak homophilic adhesion in bead aggregation assays; EC1-4 dimerizes only at high concentration; EC7-MAD10 mediates dimerization in solution. MD simulations and experiments indicate flexibility at EC5-6. X-ray crystallography (EC1-4, EC4-7), bead aggregation assays, analytical ultracentrifugation/SEC, MD simulations Structure (London, England : 1993) High 38307021
2024 Preprint (later published): 4.3 Å cryo-EM of mCELSR1 ECR resolves 13 domains forming a compact module with contact between N- and C-terminal domains; Ca2+ promotes an extended species proposed to represent the antiparallel cadherin dimer. CADH1-8 is necessary for cell adhesion and CADH9-GAIN module regulates G protein signaling. Cryo-EM, Ca2+-dependent biophysical assays, cell adhesion assays, G protein coupling assays with domain deletion constructs bioRxivpreprint Medium 38328199
2020 Somatic CELSR1 p.Gln2125His mutation found in NTD fetal tissue; FZD6 p.Gln88Glu disrupts colocalization of CELSR1 and FZD6, and VANGL1 p.Arg374His impairs colocalization of CELSR1 and VANGL1, indicating that CELSR1 co-localizes with FZD6 and VANGL1 at cell membranes as part of the PCP complex, and this is disrupted by partner mutations. Subcellular colocalization assays in transfected cells, Western blot, luciferase non-canonical Wnt signaling assay, cell migration assay Human genetics Medium 32356230
2026 Biallelic CELSR1 variants in humans cause brain malformations (pachygyria, periventricular nodular heterotopia, corpus callosum abnormalities), neurodevelopmental delay, and epilepsy. Celsr1 knockout mice exhibit partial corpus callosum agenesis, periventricular heterotopia, irregular ventricular/subventricular zone shape, enlarged lateral ventricles (fully penetrant), and increased seizure susceptibility. Whole exome sequencing of human patients, Celsr1 KO mouse generation and analysis (MRI/histology of brain malformations, seizure susceptibility testing) Nature communications High 41530147
1997 Celsr1 encodes a developmentally regulated seven-pass transmembrane protein whose extracellular domain contains nine cadherin repeats followed by EGF-like and laminin A G-type repeats, a unique domain architecture coupling adhesion motifs to a 7TM domain. Expression in adult brain is localized principally to ependymal cell layer, choroid plexus, and area postrema. cDNA cloning, domain analysis, chromosomal mapping (EUCIB, BXD, FISH), RT-PCR, in situ hybridization Genomics Medium 9339365
2021 Loss of Celsr1 in vestibular hair cells causes ~50% reduction in canal-dependent vestibulo-ocular reflex gain across all tested frequencies and ~30% reduction in otolith-dependent function, demonstrating that the highly organized PCP-dependent polarization of hair cells is critical for accurate vestibular encoding. Video-oculography in Celsr1 KO mice, sinusoidal rotation, angular velocity steps, off-vertical axis rotation, static/dynamic head tilt assays Frontiers in neuroscience Medium 34790090

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2005 Chromosome-wide mapping of estrogen receptor binding reveals long-range regulation requiring the forkhead protein FoxA1. Cell 1126 16009131
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
1999 The DNA sequence of human chromosome 22. Nature 808 10591208
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1999 A striking organization of a large family of human neural cadherin-like cell adhesion genes. Cell 602 10380929
2000 Phylogenetic analysis of the cadherin superfamily allows identification of six major subfamilies besides several solitary members. Journal of molecular biology 576 10835267
2003 Mutation of Celsr1 disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse. Current biology : CB 495 12842012
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2011 Mutations in the planar cell polarity genes CELSR1 and SCRIB are associated with the severe neural tube defect craniorachischisis. Human mutation 156 22095531
2017 RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain and is required for ubiquitination. BMC biology 135 29117863
2010 The PCP genes Celsr1 and Vangl2 are required for normal lung branching morphogenesis. Human molecular genetics 128 20223754
2013 Planar cell polarity protein Celsr1 regulates endothelial adherens junctions and directed cell rearrangements during valve morphogenesis. Developmental cell 118 23792146
2010 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. Molecular medicine (Cambridge, Mass.) 108 20379614
2014 Wnt signaling in midbrain dopaminergic neuron development and regenerative medicine for Parkinson's disease. Journal of molecular cell biology 98 24431302
2000 Large exons encoding multiple ectodomains are a characteristic feature of protocadherin genes. Proceedings of the National Academy of Sciences of the United States of America 98 10716726
2010 Atypical cadherins Celsr1-3 differentially regulate migration of facial branchiomotor neurons in mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 97 20631168
1985 Conjugal transfer from Streptococcus lactis ME2 of plasmids encoding phage resistance, nisin resistance and lactose-fermenting ability: evidence for a high-frequency conjugative plasmid responsible for abortive infection of virulent bacteriophage. Journal of general microbiology 88 3930657
2011 Mindbomb 1, an E3 ubiquitin ligase, forms a complex with RYK to activate Wnt/β-catenin signaling. The Journal of cell biology 85 21875946
2012 Role of the planar cell polarity gene CELSR1 in neural tube defects and caudal agenesis. Birth defects research. Part A, Clinical and molecular teratology 82 22371354
1998 EWS/FLI1 up regulates mE2-C, a cyclin-selective ubiquitin conjugating enzyme involved in cyclin B destruction. Oncogene 82 9798675
2014 Celsr1 is required for the generation of polarity at multiple levels of the mouse oviduct. Development (Cambridge, England) 81 25406397
2002 Differential expression of the seven-pass transmembrane cadherin genes Celsr1-3 and distribution of the Celsr2 protein during mouse development. Developmental dynamics : an official publication of the American Association of Anatomists 79 11891983
2017 A Single Adaptable Cochaperone-Scaffold Complex Delivers Nascent Iron-Sulfur Clusters to Mammalian Respiratory Chain Complexes I-III. Cell metabolism 78 28380382
2009 Identification of CELSR1 as a susceptibility gene for ischemic stroke in Japanese individuals by a genome-wide association study. Atherosclerosis 77 19403135
2011 Me2-NHC based robust Ir catalyst for efficient water oxidation. Chemical communications (Cambridge, England) 73 21225028
2014 Identification of novel CELSR1 mutations in spina bifida. PloS one 72 24632739
2001 The flamingo-related mouse Celsr family (Celsr1-3) genes exhibit distinct patterns of expression during embryonic development. Mechanisms of development 70 11677057
1997 Celsr1, a neural-specific gene encoding an unusual seven-pass transmembrane receptor, maps to mouse chromosome 15 and human chromosome 22qter. Genomics 61 9339365
2017 Seven pass Cadherins CELSR1-3. Seminars in cell & developmental biology 53 28716607
1992 Molecular characterization of a second abortive phage resistance gene present in Lactococcus lactis subsp. lactis ME2. Journal of bacteriology 53 1429469
2021 Competitive binding of E3 ligases TRIM26 and WWP2 controls SOX2 in glioblastoma. Nature communications 51 34732716
2023 SIRT5-mediated ME2 desuccinylation promotes cancer growth by enhancing mitochondrial respiration. Cell death and differentiation 50 38007551
2016 A novel mutation in CELSR1 is associated with hereditary lymphedema. Vascular cell 48 26855770
2001 In vivo antitumor activity of bis(4,7-dimethyl-1,10-phenanthroline) sulfatooxovanadium(IV) (METVAN [VO(SO4)(Me2-Phen)2]). Clinical cancer research : an official journal of the American Association for Cancer Research 47 11448932
2012 Celsr1-3 cadherins in PCP and brain development. Current topics in developmental biology 45 23140629
1988 Restriction and modification activities from Streptococcus lactis ME2 are encoded by a self-transmissible plasmid, pTN20, that forms cointegrates during mobilization of lactose-fermenting ability. Journal of bacteriology 44 2841286
2017 Celsr1 coordinates the planar polarity of vestibular hair cells during inner ear development. Developmental biology 41 28159525
2016 Planar cell polarity genes Celsr1 and Vangl2 are necessary for kidney growth, differentiation, and rostrocaudal patterning. Kidney international 41 27597235
2008 Combination of 2-methoxyestradiol (2-ME2) and eugenol for apoptosis induction synergistically in androgen independent prostate cancer cells. The Journal of steroid biochemistry and molecular biology 40 19084597
1994 Expression of basic-helix-loop-helix transcription factor ME2 during brain development and in the regions of neuronal plasticity in the adult brain. Brain research. Molecular brain research 40 7984047
2023 Protein interaction studies in human induced neurons indicate convergent biology underlying autism spectrum disorders. Cell genomics 38 36950384
1998 The effect of Me2+ cofactors at the initial stages of V(D)J recombination. The Journal of biological chemistry 38 9632694
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2016 Genetic analysis of rare coding mutations of CELSR1-3 in congenital heart and neural tube defects in Chinese people. Clinical science (London, England : 1979) 37 27756857
2010 Basal enrichment within neuroepithelia suggests novel function(s) for Celsr1 protein. Molecular and cellular neurosciences 35 20353824
2003 2-Methoxyestradiol exhibits a biphasic effect on VEGF-A in tumor cells and upregulation is mediated through ER-alpha: a possible signaling pathway associated with the impact of 2-ME2 on proliferative cells. Neoplasia (New York, N.Y.) 34 14670179
2024 AKT1 phosphorylation of cytoplasmic ME2 induces a metabolic switch to glycolysis for tumorigenesis. Nature communications 33 38263319
2019 Increasing evidence of hereditary lymphedema caused by CELSR1 loss-of-function variants. American journal of medical genetics. Part A 33 31215153
2019 The RNA-mediated estrogen receptor α interactome of hormone-dependent human breast cancer cell nuclei. Scientific data 32 31527615
2015 Alkane metathesis with the tantalum methylidene [(≡SiO)Ta(═CH2)Me2]/[(≡SiO)2Ta(═CH2)Me] generated from well-defined surface organometallic complex [(≡SiO)Ta(V)Me4]. Journal of the American Chemical Society 32 25557135
2021 Overexpression of circ_CELSR1 facilitates paclitaxel resistance of ovarian cancer by regulating miR-149-5p/SIK2 axis. Anti-cancer drugs 30 33735118
1982 The structure of the EF-Tu . GDP . Me2+ complex. European journal of biochemistry 30 7200884
2015 Enhanced cytosolic NADP-ME2 activity in A. thaliana affects plant development, stress tolerance and specific diurnal and nocturnal cellular processes. Plant science : an international journal of experimental plant biology 29 26475199
2012 Planar cell polarity genes, Celsr1-3, in neural development. Neuroscience bulletin 29 22622831
2018 Global assessment of its network dynamics reveals that the kinase Plk1 inhibits the phosphatase PP6 to promote Aurora A activity. Science signaling 28 29764989
2017 Neural progenitor fate decision defects, cortical hypoplasia and behavioral impairment in Celsr1-deficient mice. Molecular psychiatry 28 29257130
1995 Differential expression and distinct DNA-binding specificity of ME1a and ME2 suggest a unique role during differentiation and neuronal plasticity. Brain research. Molecular brain research 27 7769987
2023 The adhesion GPCRs CELSR1-3 and LPHN3 engage G proteins via distinct activation mechanisms. Cell reports 26 37224017
2021 Plant defense compound triggers mycotoxin synthesis by regulating H2B ub1 and H3K4 me2/3 deposition. The New phytologist 26 34480757
2020 Somatic mutations in planar cell polarity genes in neural tissue from human fetuses with neural tube defects. Human genetics 26 32356230
2016 Sediment PAH source apportionment in the Liaohe River using the ME2 approach: A comparison to the PMF model. The Science of the total environment 26 26925728
2023 TRIM67 drives tumorigenesis in oligodendrogliomas through Rho GTPase-dependent membrane blebbing. Neuro-oncology 25 36215168
2022 A dual-activity topoisomerase complex regulates mRNA translation and turnover. Nucleic acids research 25 35748872
2010 Association of genetic variants with hemorrhagic stroke in Japanese individuals. International journal of molecular medicine 25 20198315
2020 circCELSR1 facilitates ovarian cancer proliferation and metastasis by sponging miR-598 to activate BRD4 signals. Molecular medicine (Cambridge, Mass.) 24 32640974
2017 Sex-Based Genetic Association Study Identifies CELSR1 as a Possible Chronic Obstructive Pulmonary Disease Risk Locus among Women. American journal of respiratory cell and molecular biology 24 27854507
2015 A small-molecule inhibitor suppresses the tumor-associated mitochondrial NAD(P)+-dependent malic enzyme (ME2) and induces cellular senescence. Oncotarget 24 26008970
2025 ACAT1-Mediated ME2 Acetylation Drives Chemoresistance in Ovarian Cancer by Linking Glutaminolysis to Lactate Production. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 23 39951294
2019 Sex-limited penetrance of lymphedema to females with CELSR1 haploinsufficiency: A second family. Clinical genetics 23 31403174
2023 Inhibition of miR-214-3p attenuates ferroptosis in myocardial infarction via regulating ME2. Biochemical and biophysical research communications 22 37087800
2022 ESCPE-1 mediates retrograde endosomal sorting of the SARS-CoV-2 host factor Neuropilin-1. Proceedings of the National Academy of Sciences of the United States of America 22 35696571
2013 Atypical cadherins Celsr1-3 and planar cell polarity in vertebrates. Progress in molecular biology and translational science 22 23481196
2022 CELSR1 variants are associated with partial epilepsy of childhood. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 21 36453712
2021 Intercellular and intracellular cilia orientation is coordinated by CELSR1 and CAMSAP3 in oviduct multi-ciliated cells. Journal of cell science 21 33468623
2021 ME2 Promotes Proneural-Mesenchymal Transition and Lipogenesis in Glioblastoma. Frontiers in oncology 20 34381734
2022 CELSR1 Risk Alleles in Familial Bicuspid Aortic Valve and Hypoplastic Left Heart Syndrome. Circulation. Genomic and precision medicine 19 35133174
2023 Celsr1 and Celsr2 exhibit distinct adhesive interactions and contributions to planar cell polarity. Frontiers in cell and developmental biology 18 36712970
2017 Miz1 Controls Schwann Cell Proliferation via H3K36me2 Demethylase Kdm8 to Prevent Peripheral Nerve Demyelination. The Journal of neuroscience : the official journal of the Society for Neuroscience 18 29217679
2014 Discovery of a novel inhibitor of NAD(P)(+)-dependent malic enzyme (ME2) by high-throughput screening. Acta pharmacologica Sinica 18 24681895
2009 Mitochondrial malic enzyme (ME2) in pancreatic islets of the human, rat and mouse and clonal insulinoma cells. Archives of biochemistry and biophysics 18 19691144
2016 The atypical cadherin Celsr1 functions non-cell autonomously to block rostral migration of facial branchiomotor neurons in mice. Developmental biology 17 27395006
2020 CELSR1 Promotes Neuroprotection in Cerebral Ischemic Injury Mainly Through the Wnt/PKC Signaling Pathway. International journal of molecular sciences 16 32070035
2009 Assessment of a polymorphism of SDK1 with hypertension in Japanese Individuals. American journal of hypertension 15 19851296
1976 Me2+-(13 S) ATPase from Micrococcus sp. ATCC 398E. The effect of trypsin on the purified enzyme. Biochimica et biophysica acta 15 131581
2006 Innovative effect of illite on improved microbiological conversion of L-tyrosine to 3,4 dihydroxy phenyl L-alanine (L-DOPA) by Aspergillus oryzae ME2 under acidic reaction conditions. Current microbiology 13 17039388
2001 Apoptosis inducing novel anti-leukemic agent, bis(4,7-dimethyl-1,10 phenanthroline) sulfatooxovanadium(IV) [VO(SO4)(Me2-Phen)2] depolarizes mitochondrial membranes. Leukemia & lymphoma 13 11378580
1985 Linkage between the loci for mitochondrial malic enzyme (ME2) and coagulation factor XIIIA subunit (F13A). Human genetics 13 2860058
2016 CELSR1 Is a Positive Regulator of Endothelial Cell Migration and Angiogenesis. Biochemistry. Biokhimiia 12 27301287
2015 Implementing constrained multi-time approach with bootstrap analysis in ME-2: An application to PM2.5 data from Florence (Italy). The Science of the total environment 12 26414851
2023 Targeting human mitochondrial NAD(P)+-dependent malic enzyme (ME2) impairs energy metabolism and redox state and exhibits antileukemic activity in acute myeloid leukemia. Cellular oncology (Dordrecht, Netherlands) 10 37079187
2021 Implication of Vestibular Hair Cell Loss of Planar Polarity for the Canal and Otolith-Dependent Vestibulo-Ocular Reflexes in Celsr1 Mice. Frontiers in neuroscience 10 34790090
2025 Structural basis for regulation of CELSR1 by a compact module in its extracellular region. Nature communications 7 40295529
2024 Structure of the extracellular region of the adhesion GPCR CELSR1 reveals a compact module which regulates G protein-coupling. bioRxiv : the preprint server for biology 7 38328199
2020 CELSR1 Acts as an Oncogene Regulated by miR-199a-5p in Glioma. Cancer management and research 7 33061581
2016 The level and distribution pattern of HP1β in the embryonic brain correspond to those of H3K9me1/me2 but not of H3K9me3. Histochemistry and cell biology 7 26794325
2014 Dynamic effects dictate the mechanism and selectivity of dehydration-rearrangement reactions of protonated alcohols [Me2 (R)CCH(OH2 )Me](+) (R=Me, Et, iPr) in the gas phase. Chemistry (Weinheim an der Bergstrasse, Germany) 7 25179304
2023 Lymphedema is associated with CELSR1 in Phelan-McDermid syndrome. Clinical genetics 6 37232218
2014 The CELSR1 polymorphisms rs6007897 and rs4044210 are associated with ischaemic stroke in Chinese Han population. Annals of human biology 6 25117632
2001 Mutational analysis of the neuronal cadherin gene CELSR1 and exclusion as a candidate for catatonic schizophrenia in a large family. Psychiatric genetics 6 11807409
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2023 Cucumber malate decarboxylase, CsNADP-ME2, functions in the balance of carbon and amino acid metabolism in fruit. Horticulture research 5 38077499
2022 Study on the Effect of Key Genes ME2 and adhE during Luzhou-Flavor Baijiu Brewing. Foods (Basel, Switzerland) 5 35267332
2021 Lymphedema complicated by protein-losing enteropathy with a 22q13.3 deletion and the potential role of CELSR1: A case report. Medicine 5 34128868
2013 Association of genetic variants of CELSR1 and 3q28 with hypertension in community-dwelling individuals. Biomedical reports 5 24649039
2003 Genetic variation in the seven-pass transmembrane cadherin CELSR1: lack of association with schizophrenia. Psychiatric genetics 5 12782967
1982 Induction of 2H+/Me2+ exchange in rat-liver mitochondria. European journal of biochemistry 5 6293824
2024 NADP-malic Enzyme OsNADP-ME2 Modulates Plant Height Involving in Gibberellin Signaling in Rice. Rice (New York, N.Y.) 4 39152344
2023 The adhesion GPCRs CELSR1-3 and LPHN3 engage G proteins via distinct activation mechanisms. bioRxiv : the preprint server for biology 4 37066404
2023 Ureteropelvic junction obstruction with primary lymphoedema associated with CELSR1 variants. Journal of medical genetics 4 37225411
2023 Upregulation of CELSR1 expression promotes ovarian cancer cell proliferation, migration, and invasion. Medical oncology (Northwood, London, England) 4 38070011
2019 Genome-wide identification of histone methylation (H3K9me2) and acetylation (H4K12ac) marks in two ecotypes of switchgrass (Panicum virgatum L.). BMC genomics 4 31438854
2015 Metabolic vulnerability in melanoma: a ME2 (me too) story. The Journal of investigative dermatology 4 25666673
2003 Xstir polymorphism and absence of sex linkage in Xenopus laevis ME2 gene. Folia biologica 4 12859020
2024 De novo heterozygous missense variants in CELSR1 as cause of fetal pleural effusions and progressive fetal hydrops. Journal of medical genetics 3 38272662
2024 ME2 Deficiency Is Associated With Recessive Neurodevelopmental Disorder. Clinical genetics 3 39401966
2024 PRMT1-mediated methylation of ME2 promotes hepatocellular carcinoma growth by inhibiting ubiquitination. Cell death & disease 3 39528487
2023 ME2 Promotes Hepatocellular Carcinoma Cell Migration through Pyruvate. Metabolites 3 37110198
2018 Preparation and Properties of Nanoparticles, tRNA-Bivalent Metal Cation (Me2+) Complexes, and Prospects of Their Practical Use. Doklady. Biochemistry and biophysics 3 29779113
2026 Biallelic variants in CELSR1 cause brain malformations, neurodevelopmental disorders and epilepsy in humans. Nature communications 2 41530147
2022 Celsr1 suppresses Wnt5a-mediated chemoattraction to prevent incorrect rostral migration of facial branchiomotor neurons. Development (Cambridge, England) 1 36325991
2013 (N,N-diethyldithiocarbamato)[tris(3,5-dimethylpyrazol-1-yl)hydroborato]copper(II): a new copper(II) dithiocarbamate compound with the classic Tp(Me2) scorpionate. Acta crystallographica. Section C, Crystal structure communications 1 24005503
2025 CYP4F11 promotes lung cancer progression through the miR-195/ME2 pathway. Frontiers of medicine 0 41359237
2024 A Targeted Octahedral DNA Nanostructure Co-delivers siME3 and Doxorubicin to Enhance Collateral Lethality in ME2-Deficient Pancreatic Cancer. Nano letters 0 39602246
2014 Competitive reaction pathways for the gas-phase reactivity of [Me2 AlNH2 ]3. Chemphyschem : a European journal of chemical physics and physical chemistry 0 24976567