Affinage

CRB2

Protein crumbs homolog 2 · UniProt Q5IJ48

Length
1285 aa
Mass
134.3 kDa
Annotated
2026-04-28
65 papers in source corpus 32 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CRB2 functions as a conserved scaffold protein operating in two distinct biological contexts: DNA damage checkpoint signaling in fission yeast and apicobasal polarity maintenance in mammalian epithelia. In fission yeast, Crb2 is recruited to DNA double-strand breaks through tandem Tudor domains that bind H4-K20me2 (deposited by Set9) and BRCT domains that bind γ-H2A and mediate homo-oligomerization; a parallel CDK-dependent pathway involving Cdc2 phosphorylation at T215 and Cut5 interaction provides redundant checkpoint activation, while Rad3-phosphorylated SQ/TQ motifs in Crb2 directly recruit and activate Chk1, with T215 phosphorylation governing checkpoint recovery (PMID:17190600, PMID:15550243, PMID:15226425, PMID:15229228, PMID:22792081, PMID:10488332). In mammals, CRB2 is a transmembrane Crumbs complex component essential for photoreceptor and Müller glia adhesion, retinal lamination, RPE tight junction integrity, and podocyte slit diaphragm formation and actin cytoskeleton organization, with its loss activating YAP mechanosignaling and increasing podocyte contractility; disease-associated CRB2 variants causing steroid-resistant nephrotic syndrome are retained in the ER due to impaired PDIA3-dependent disulfide bond formation (PMID:23001562, PMID:34654837, PMID:40062402, PMID:36549870, PMID:25557779). CRB2 forms homo- and heteromeric complexes with CRB1 through its extracellular domain in the retina (PMID:38570189).

Mechanistic history

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

    Establishing Crb2 as a checkpoint mediator upstream of Chk1 resolved how DNA damage signals are relayed to cell cycle arrest machinery in fission yeast.

    Evidence Two-hybrid, co-IP, and genetic epistasis in S. pombe showing Crb2 interacts with Cut5 and Chk1 and acts upstream of Chk1 activation

    PMID:9407031

    Open questions at the time
    • Biochemical mechanism of Crb2-Chk1 activation not yet defined
    • Direct binding interface not characterized
  2. 1999 High

    Identifying Cdc2-mediated T215 phosphorylation as necessary for checkpoint recovery revealed how cells re-enter the cell cycle after DNA repair, separating checkpoint activation from termination.

    Evidence In vitro kinase assay with purified Cdc2 and T215A mutant analysis in S. pombe

    PMID:10488332

    Open questions at the time
    • Mechanism by which T215 phosphorylation inactivates Crb2 checkpoint function unknown
    • Phosphatase(s) acting on Crb2 not identified
  3. 2003 High

    Visualizing Crb2 recruitment to DSB foci in living cells and showing that Rad3/Rad1/Rad17 are needed for retention but not initial recruitment established a two-step assembly model.

    Evidence Live-cell fluorescence microscopy in S. pombe with checkpoint mutant backgrounds

    PMID:12917337

    Open questions at the time
    • Initial recruitment signal not identified at this point
    • Stoichiometry of Crb2 at foci unknown
  4. 2004 High

    Discovery that γ-H2A and H4-K20 methylation constitute the two chromatin marks that cooperatively recruit Crb2 to DSBs, with BRCT-mediated oligomerization being the essential function of BRCT domains, defined the chromatin-reading mechanism of the checkpoint mediator.

    Evidence Genetic epistasis, fluorescence microscopy (γ-H2A mutants), Set9 methyltransferase mutants, biochemical oligomerization assays, heterologous dimerization rescue

    PMID:14739927 PMID:15226425 PMID:15229228 PMID:15550243

    Open questions at the time
    • Structural basis for γ-H2A recognition by BRCT not yet resolved
    • Whether oligomerization enhances chromatin binding affinity unknown
  5. 2006 High

    Structural determination of the Tudor domain–H4K20me2 interface and definition of two parallel DSB recruitment pathways (histone-modification-dependent and CDK/Cut5-dependent) provided a comprehensive mechanistic model for Crb2 activation.

    Evidence X-ray crystallography and NMR of Tudor–H4K20me2 complex; mutational dissection of Tudor/BRCT/T215 pathways at HO-induced DSBs

    PMID:16778077 PMID:17190600

    Open questions at the time
    • Whether both pathways operate simultaneously or sequentially at endogenous DSBs unclear
    • Relative contribution under physiological damage levels not quantified
  6. 2008 High

    Crystal structure of the BRCT2 domain revealed how dimerization and γ-H2A binding are structurally separable, with dimerization mutants failing checkpoint activation while phosphopeptide-binding mutants primarily affecting DNA repair.

    Evidence X-ray crystallography of BRCT2, structure-guided mutagenesis with in vivo checkpoint and repair readouts in S. pombe

    PMID:18676809 PMID:18826944

    Open questions at the time
    • Full-length Crb2 structure not available
    • How dimerization and γ-H2A binding are coordinated in 3D not resolved
  7. 2010 High

    Identification of specific BRCT2 residues (S548, K619) that contact γ-H2A phosphate, with additive effects when combined with T215A, completed the molecular map of Crb2 chromatin engagement.

    Evidence Structure-guided mutagenesis with IRIF quantification and checkpoint assays in S. pombe

    PMID:20679485 PMID:20679488

    Open questions at the time
    • Quantitative binding affinities for individual and combined interactions not measured
  8. 2011 High

    Demonstration that mouse Crb2 is essential for epiblast apicobasal polarity and gastrulation established the mammalian gene as a polarity determinant distinct from its yeast checkpoint role.

    Evidence Constitutive knockout mice with embryonic lethality and disrupted epiblast polarity at primitive streak

    PMID:22072575

    Open questions at the time
    • Which Crumbs complex partners mediate epiblast polarity not defined
    • Whether the intracellular FERM-binding or PDZ-binding motif is required not tested
  9. 2012 High

    Defining how Rad3-phosphorylated SQ/TQ motifs in Crb2 directly recruit Chk1 via a 19-aa peptide, with artificial tethering bypassing the need for full-length Crb2, demonstrated that Crb2's essential checkpoint function is to bring Chk1 to DSBs for Rad3-mediated phosphorylation.

    Evidence In vitro binding with phosphorylated peptides, Crb2-Chk1 and Rad22-SQ/TQ fusion rescue experiments in S. pombe

    PMID:22792081

    Open questions at the time
    • Whether multiple Chk1 molecules are activated per Crb2 oligomer unknown
    • Signal amplification mechanism not addressed
  10. 2012 High

    Conditional retinal knockout of CRB2 causing photoreceptor disorganization, adherens junction disruption, and progenitor cell overproliferation established CRB2 as essential for retinal lamination and cell fate control.

    Evidence Conditional knockout mice with OCT, ERG, histology, and confocal imaging

    PMID:23001562

    Open questions at the time
    • Whether phenotype is cell-autonomous in photoreceptors vs. Müller glia not yet distinguished
  11. 2014 High

    Zebrafish and human genetic studies linking CRB2 loss-of-function to podocyte foot process defects and nephrotic syndrome, with photoreceptor-specific vs. Müller cell-specific knockout defining cell-autonomous requirements, solidified CRB2 as a disease gene for steroid-resistant nephrotic syndrome.

    Evidence Zebrafish crb2b mutants with human CRB2 variant complementation; cell-type-specific conditional KO and AAV-Cre delivery in mouse retina

    PMID:24493795 PMID:25557779

    Open questions at the time
    • CRB2 intracellular signaling partners in podocytes not identified
    • Whether CRB2 directly binds nephrin or acts indirectly unknown
  12. 2021 High

    Podocyte-specific Crb2 knockout producing massive albuminuria and FSGS, with decreased F-actin and increased apoptosis, and parallel findings in RPE showing CRB2 is needed for tight junction maintenance and immune privilege, defined CRB2 as a master regulator of epithelial integrity across tissue types.

    Evidence Podocyte-specific conditional KO with EM; siRNA knockdown in human RPE and mouse in vivo

    PMID:34262913 PMID:34654837

    Open questions at the time
    • Direct link between CRB2 loss and F-actin disorganization mechanism unresolved
    • Whether CRB2 signals through Hippo pathway in RPE not tested
  13. 2022 Medium

    Identification that disease-associated CRB2 variants are retained in the ER due to failed PDIA3-dependent disulfide bond formation explained the molecular pathogenesis of many nephrotic syndrome-causing mutations.

    Evidence Live-cell imaging of GFP-tagged CRB2 variants with PM reporter; PDIA3 knockdown phenocopying ER retention

    PMID:36549870

    Open questions at the time
    • Which specific disulfide bonds are disrupted per variant not mapped
    • Whether chaperone-based therapies could rescue trafficking not tested
    • Independent replication needed
  14. 2022 Medium

    Linking CRB2 to ezrin phosphorylation and demonstrating that anti-CRB2 autoantibodies phenocopy CRB2 loss in podocytes revealed a potential autoimmune mechanism for membranous nephropathy through CRB2-cytoskeleton uncoupling.

    Evidence Immunization model and anti-CRB2 antibody treatment of podocyte cell line with phospho-ezrin and actin readouts

    PMID:35985815

    Open questions at the time
    • Whether CRB2 directly binds ezrin or acts through an adaptor unknown
    • Pathogenic role of anti-CRB2 antibodies in human disease not confirmed
    • Single lab finding
  15. 2025 Medium

    CRB2 deficiency activating YAP mechanosignaling and increasing podocyte contractility in a stiffness-dependent manner connected CRB2 to the Hippo pathway and mechanotransduction, explaining how polarity loss translates to cytoskeletal and adhesion phenotypes.

    Evidence siRNA knockdown with YAP reporter assays and Elastic Resonator Interference Stress Microscopy in podocytes

    PMID:40062402

    Open questions at the time
    • Whether CRB2 directly regulates Hippo kinase cascade or acts indirectly through junctional tension unknown
    • In vivo validation of YAP activation upon CRB2 loss not performed
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis for mammalian CRB2 extracellular domain interactions (homo/heteromeric complexes with CRB1), the precise mechanism connecting CRB2 to Hippo/YAP regulation in vivo, and whether CRB2's polarity and checkpoint functions share any conserved molecular logic remain unresolved.
  • No structure of mammalian CRB2 extracellular or transmembrane domains
  • No unified model connecting CRB2 to Hippo pathway across tissues
  • Evolutionary relationship between yeast checkpoint and mammalian polarity functions unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4 GO:0042393 histone binding 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005694 chromosome 4 GO:0005634 nucleus 3 GO:0005886 plasma membrane 3 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-73894 DNA Repair 6 R-HSA-1500931 Cell-Cell communication 3 R-HSA-1640170 Cell Cycle 3 R-HSA-162582 Signal Transduction 2
Partners
CHK1CRB1CUT5EZRINPDIA3RAD3
Complex memberships
Crumbs polarity complex

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 Crb2 (fission yeast 53BP1 homolog) contains tandem tudor domains that directly bind histone H4 specifically dimethylated at Lys20 (H4-K20me2), with a five-residue binding cage that accommodates dimethyllysine but excludes trimethyllysine, establishing the structural basis for methylation state-specific recruitment to DNA double-strand breaks. X-ray crystallography, NMR spectroscopy, in vitro binding assays Cell High 17190600
2004 Set9-mediated methylation of histone H4-K20 is required for Crb2 localization to sites of DNA damage; loss of Set9 or mutation of H4-K20 impairs Crb2 focus formation and compromises checkpoint-mediated cell cycle arrest in fission yeast. Genetic epistasis, chromatin immunoprecipitation, fluorescence microscopy of Crb2 foci Cell High 15550243
1997 Crb2 interacts with Cut5 (TopBP1 homolog) and Chk1 in fission yeast, acts upstream of Chk1 in the DNA damage checkpoint pathway, and is transiently phosphorylated upon UV damage in a manner requiring other damage-sensing checkpoint proteins but not Chk1. Two-hybrid interaction, co-immunoprecipitation, genetic epistasis, phosphorylation assays Genes & development High 9407031
2004 Gamma-H2A (phosphorylated histone H2A) controls large-scale recruitment of Crb2 to damaged DNA in fission yeast; H2A-AQE mutations defective in phosphorylation impair Crb2 and Chk1 phosphorylation and cause failure to recruit large amounts of Crb2 to DSBs. Genetic analysis, fluorescence microscopy, phosphorylation assays, epistasis with rad22Δ Molecular and cellular biology High 15226425
1999 Cdc2 kinase phosphorylates Crb2 at threonine-215 in vitro and in vivo; this phosphorylation is required for cells to re-enter the cell cycle after DNA damage checkpoint arrest, and non-phosphorylatable T215A cells remain arrested with Chk1 kinase maintained in a phosphorylated state even after repair. In vitro kinase assay with purified Cdc2, mutational analysis (T215A), phosphorylation timing experiments Molecular cell High 10488332
2002 Cdc2-cyclin B kinase activity links Crb2 to topoisomerase III (Top3) function in recombinational repair during G2; low Cdc2-cyclin B activity disrupts proper regulation of Top3 via Crb2, affecting a recombination step after Rhp51 focus assembly. Genetic epistasis, fluorescence microscopy of Rhp51 foci, cyclin B mutant analysis Genes & development Medium 12023299
2003 Crb2 localizes to distinct nuclear foci representing sites of DNA double-strand breaks in live fission yeast cells; Crb2 colocalizes with Rad22 at persistent foci; Rad1, Rad3, and Rad17 complexes are required for retention but not initial recruitment of Crb2 to DSBs. Live-cell fluorescence microscopy, genetic analysis of checkpoint mutants Molecular and cellular biology High 12917337
2006 Two parallel recruitment pathways bring Crb2 to DSBs in fission yeast: one requires histone H4-K20 methylation (Tudor domain) and gamma-H2A (BRCT domain) acting cooperatively; a second CDK-dependent pathway requires phosphorylation of the Cut5-binding site (T215) in Crb2 and mediates Cut5 association, providing checkpoint activation even in the absence of histone modifications. Fluorescence microscopy of HO-induced DSBs, mutational analysis of Tudor and BRCT motifs, genetic epistasis Genes & development High 16778077
2004 Crb2 oligomerizes through its tandem BRCT domains; this homo-oligomerization is the essential function of the BRCT domains for DNA damage checkpoint signaling, as heterologous dimerization motifs can substitute for BRCT domains. In vitro biochemical analysis, dominant-negative overexpression, functional complementation with heterologous dimerization motifs The Journal of biological chemistry High 15229228
2004 Crb2 dynamically interacts with Rad3, Chk1, and Cut5 in a temporal manner during the DNA damage checkpoint; active Crb2-Chk1 complex formation is regulated by Rad3 and requires Crb2 BRCT domain; Chk1 activation in vitro requires the presence of Crb2 BRCT domain; Crb2 directly interacts with Rad3 in an inhibitory manner to Rad3 activity. Co-immunoprecipitation, in vitro Chk1 activation assay, two-hybrid analysis The EMBO journal High 14739927
2008 Crystal structure of Crb2-BRCT2 domain reveals structural basis for dimerization and direct interaction with gamma-H2A.1 peptide; dimerization mutants are genotoxin sensitive and defective in checkpoint signaling and Crb2 IRIF formation, while phosphopeptide-binding mutants show DNA repair defects (slowed Rpa1 foci, reduced Rad22 foci) with only slight IR sensitivity. X-ray crystallography, in vitro mutational analysis, in vivo phenotypic analysis (checkpoint, IRIF, repair foci) Genes & development High 18676809
2008 The tandem tudor domains of Crb2 preferentially bind di-methylated H4K20 (not tri-methylated); disruption of either the tudor-binding motif or the H4K20 methylating enzyme Set9 ablates Crb2 localization to DSBs and impairs checkpoint function and cell survival after DNA damage. In vitro binding assays with mono/di/tri-methyl H4K20 peptides, fluorescence microscopy, genetic analysis The Journal of biological chemistry High 18826944
2010 Crb2 BRCT2 domain directly binds phospho-H2A (gamma-H2A) through polar interactions of serine-548 and lysine-619 with the phosphate group; these interactions are critical for Crb2 IRIF formation and checkpoint function, and mutations have additive effects; combining these BRCT2 mutations with T215A completely abrogates Crb2 IRIF and function. Mutational analysis, fluorescence microscopy (IRIF), checkpoint assays, in vitro phosphopeptide binding Molecular and cellular biology High 20679485 20679488
2005 Cooperative control of Crb2 by ATM family kinases (through gamma-H2A) and Cdc2 (through T215 phosphorylation) is essential for the DNA damage checkpoint; crb2-T215A cells can initiate but not sustain checkpoint response; gamma-H2A is essential for checkpoint in crb2-T215A cells; Cdc2 inactivation in gamma-H2A-defective cells impairs Crb2-dependent Chk1 signaling. Genetic epistasis, checkpoint signaling assays, Chk1 phosphorylation analysis Molecular and cellular biology High 16314498
2012 Crb2 recruits Chk1 to DSBs through direct physical interaction; Rad3-phosphorylated SQ/TQ motifs in Crb2 are required for Chk1 recruitment and activation; a 19-aa peptide containing these motifs is sufficient for Chk1 binding in vitro when phosphorylated; tethering a Crb2-Chk1 fusion or Rad22-SQ/TQ fusion to DSBs can bypass the need for full-length Crb2 and even the 9-1-1 complex. Co-immunoprecipitation, in vitro binding assays, mutational analysis, artificial tethering experiments PLoS genetics High 22792081
2010 Human CRB2 inhibits gamma-secretase cleavage of amyloid precursor protein (APP) by binding to the presenilin complex; the transmembrane domain of CRB2 is indispensable for this inhibition and mediates binding to the gamma-secretase complex; CRB2 is not a competitive substrate but functions as an inhibitory binding protein. Transfection/knockdown in HEK293 and SH-SY5Y cells, cell-free gamma-secretase assay, co-immunoprecipitation, domain deletion analysis The Journal of biological chemistry Medium 20299451
2014 Loss of Crb2 in zebrafish podocytes impairs podocyte foot process arborization, slit diaphragm formation, and proper nephrin trafficking; complementation experiments with human CRB2 mutations confirm loss-of-function causing nephrotic syndrome. Zebrafish crb2b loss-of-function analysis, nephrin trafficking assay, complementation with human CRB2 mutants American journal of human genetics High 25557779
2011 Mouse Crb2 is required for epiblast cell polarity at the primitive streak; loss of Crb2 disturbs apical polarity of epiblast cells, affecting epithelial-to-mesenchymal transition during gastrulation and impairing mesoderm/endoderm formation, causing embryonic lethality by E12.5. Gene-targeted knockout mice, histological and immunofluorescence analysis Developmental dynamics High 22072575
2012 Conditional deletion of mouse CRB2 in the retina causes progressive disorganization of photoreceptor layer, disruption of adherens junctions between photoreceptors, Müller glia and progenitor cells, and increased proliferation of late-born progenitor cells; CRB2 is essential for proper lamination and suppression of late-born retinal progenitor cell proliferation. Conditional knockout mice, OCT imaging, ERG, histological and confocal analysis Human molecular genetics High 23001562
2013 Loss of both CRB1 and CRB2 in retinal progenitor cells dysregulates Notch1 and YAP/Hippo signaling pathways, increases P120-catenin levels, and alters progenitor cell cycle distribution (decrease in late G1, increase in S and G2/M phase), leading to expanded late-born cell types. Conditional double-knockout mice, transcriptome analysis, cell cycle analysis, immunostaining PLoS genetics Medium 24339791
2014 CRB2 has essential functions specifically in photoreceptors (not redundant in Müller cells) in developing mouse retina; photoreceptor-specific loss causes early-onset abnormal lamination, while Müller cell-specific loss causes late-onset disorganization; short-term adult loss of CRB2 in photoreceptors causes sporadic loss of adhesion between photoreceptors and Müller cells. Cell-type-specific conditional knockout, AAV-Cre delivery, OCT imaging, ERG Human molecular genetics High 24493795
2021 Podocyte-specific Crb2 knockout mice develop massive albuminuria and FSGS; CRB2-deficient human podocytes show decreased F-actin positive area and increased susceptibility to apoptosis, demonstrating that CRB2 is required for actin cytoskeleton organization and podocyte survival. Podocyte-specific conditional knockout, electron microscopy, siRNA knockdown of human podocytes, F-actin staining, apoptosis assays Scientific reports High 34654837
2022 CRB2 depletion or anti-CRB2 autoantibody binding in podocytes increases phosphorylation of ezrin (which connects CRB2 to the cytoskeleton) and alters CRB2 localization and actin distribution, linking CRB2 to cytoskeletal organization at podocyte foot processes. Immunization model, anti-CRB2 antibody treatment of podocyte cell line, immunofluorescence, phosphorylation assay Journal of the American Society of Nephrology Medium 35985815
2025 CRB2 knockdown in podocytes induces YAP transcriptional activity and upregulates YAP-mediated mechanosignaling; CRB2 deficiency increases focal adhesion density, F-actin, and podocyte contractility in a substrate stiffness-dependent manner as measured by ERISM, demonstrating impaired mechanosensing. siRNA knockdown, YAP reporter assays, F-actin staining, Elastic Resonator Interference Stress Microscopy (ERISM), pharmacological YAP inhibition American journal of physiology. Renal physiology Medium 40062402
2022 Disease-associated CRB2 variants causing nephrotic syndrome remain predominantly at the ER rather than reaching the plasma membrane; WT CRB2 is retained in the ER in cells lacking protein disulfide isomerase A3 (PDIA3), demonstrating that disulfide bridge formation is a crucial posttranslational modification required for CRB2 plasma membrane transport. Live-cell imaging with GFP-tagged CRB2 variants, BFP-labeled plasma membrane reporter, PDIA3 knockdown Life science alliance Medium 36549870
2024 Human CRB1 and CRB2 form homo- and heteromeric complexes; CRB1 was enriched in CRB2 pull-downs from retina; co-immunoprecipitation shows canonical CRB1 interacts with CRB1 and CRB2 but not CRB3 (which lacks an extracellular domain), indicating interaction is mediated through the extracellular domain. Retina-specific pull-down, co-immunoprecipitation, co-localization in human retina and iPSC-derived organoids Life science alliance Medium 38570189
2015 CRB2 localizes to the apicolateral membrane of mouse RPE cells at tight junctions, completing a fully expressed Crumbs complex in the retinal pigment epithelium. Immunofluorescence with specific antibody, confocal microscopy, subcellular fractionation Scientific reports Medium 26404741
2021 CRB2 plays a key role in tight junction maintenance and cell cycle arrest in human RPE cells during polarization; in vivo CRB2 knockdown in mouse RPE disrupts distribution of apical polarity proteins and results in invasion of activated microglial cells into the subretinal space. Human fetal RPE culture, siRNA knockdown in vivo and in vitro, immunostaining of polarity and junction proteins Frontiers in cell and developmental biology Medium 34262913
2026 In HNSCC, CRB2 hindered the interaction between the E8A isoform of LSD1 and deubiquitinase USP7, facilitating degradation of LSD1(E8A) and increasing H4K20 dimethylation at the SLC7A11 promoter, epigenetically suppressing SLC7A11 transcription and inducing ferroptosis. Co-immunoprecipitation, ChIP, overexpression/knockdown, in vivo tumor models, ubiquitination assays Cancer research Medium 40991301
2022 CRB2 loss in podocytes leads to dysfunction of slit diaphragm-related proteins (podocin, nephrin, ZO-1) by reducing phosphorylation of sphingosine 1-phosphate receptor 1 (S1PR1), while the podocytic cytoskeleton (synaptopodin) remains unaffected, revealing a distinct SD-related mechanism. CRB2 knockdown in podocytes, immunostaining, phosphorylation assays, patient kidney biopsy analysis Pediatric nephrology Low 37452832
2018 CRB2 overexpression in GBM cells activates NF-κB signaling by increasing phosphorylation of IKKα and reducing IκB protein levels, enhancing cell proliferation, migration, invasion and therapy resistance. Lentiviral knockdown, overexpression, Western blot for IKKα phosphorylation and IκB, bioinformatics correlation Experimental cell research Low 35219647

Source papers

Stage 0 corpus · 65 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair. Cell 800 17190600
2004 Methylation of histone H4 lysine 20 controls recruitment of Crb2 to sites of DNA damage. Cell 442 15550243
1997 Damage and replication checkpoint control in fission yeast is ensured by interactions of Crb2, a protein with BRCT motif, with Cut5 and Chk1. Genes & development 223 9407031
2004 Histone H2A phosphorylation controls Crb2 recruitment at DNA breaks, maintains checkpoint arrest, and influences DNA repair in fission yeast. Molecular and cellular biology 158 15226425
2002 Cdc2-cyclin B kinase activity links Crb2 and Rqh1-topoisomerase III. Genes & development 140 12023299
2006 Histone modification-dependent and -independent pathways for recruitment of checkpoint protein Crb2 to double-strand breaks. Genes & development 128 16778077
2014 Defects of CRB2 cause steroid-resistant nephrotic syndrome. American journal of human genetics 85 25557779
2003 Retention but not recruitment of Crb2 at double-strand breaks requires Rad1 and Rad3 complexes. Molecular and cellular biology 85 12917337
2005 Characterization of the Crumbs homolog 2 (CRB2) gene and analysis of its role in retinitis pigmentosa and Leber congenital amaurosis. Molecular vision 79 15851977
2019 Human iPSC-Derived Retinas Recapitulate the Fetal CRB1 CRB2 Complex Formation and Demonstrate that Photoreceptors and Müller Glia Are Targets of AAV5. Stem cell reports 78 30956116
1999 Cdc2 phosphorylation of Crb2 is required for reestablishing cell cycle progression after the damage checkpoint. Molecular cell 73 10488332
2012 Loss of CRB2 in the mouse retina mimics human retinitis pigmentosa due to mutations in the CRB1 gene. Human molecular genetics 71 23001562
2013 Targeted ablation of CRB1 and CRB2 in retinal progenitor cells mimics Leber congenital amaurosis. PLoS genetics 64 24339791
2011 Deficiency in Crumbs homolog 2 (Crb2) affects gastrulation and results in embryonic lethality in mice. Developmental dynamics : an official publication of the American Association of Anatomists 64 22072575
2008 Structural and functional analysis of the Crb2-BRCT2 domain reveals distinct roles in checkpoint signaling and DNA damage repair. Genes & development 57 18676809
2008 Di-methyl H4 lysine 20 targets the checkpoint protein Crb2 to sites of DNA damage. The Journal of biological chemistry 56 18826944
2004 Regulation of checkpoint kinases through dynamic interaction with Crb2. The EMBO journal 48 14739927
2014 CRB2 acts as a modifying factor of CRB1-related retinal dystrophies in mice. Human molecular genetics 46 24565864
2014 Targeted ablation of Crb2 in photoreceptor cells induces retinitis pigmentosa. Human molecular genetics 40 24493795
2016 Expansion of phenotype and genotypic data in CRB2-related syndrome. European journal of human genetics : EJHG 39 27004616
2013 Microarray and morphological analysis of early postnatal CRB2 mutant retinas on a pure C57BL/6J genetic background. PloS one 34 24324803
2019 Loss of CRB2 in Müller glial cells modifies a CRB1-associated retinitis pigmentosa phenotype into a Leber congenital amaurosis phenotype. Human molecular genetics 33 30239717
2005 The fission yeast Crb2/Chk1 pathway coordinates the DNA damage and spindle checkpoint in response to replication stress induced by topoisomerase I inhibitor. Molecular and cellular biology 31 16107732
2004 Homo-oligomerization is the essential function of the tandem BRCT domains in the checkpoint protein Crb2. The Journal of biological chemistry 28 15229228
2018 CRB2 mutation causes autosomal recessive retinitis pigmentosa. Experimental eye research 27 30593785
2018 CRB2 in immature photoreceptors determines the superior-inferior symmetry of the developing retina to maintain retinal structure and function. Human molecular genetics 25 29893966
2010 Human CRB2 inhibits gamma-secretase cleavage of amyloid precursor protein by binding to the presenilin complex. The Journal of biological chemistry 24 20299451
2010 BRCT domain interactions with phospho-histone H2A target Crb2 to chromatin at double-strand breaks and maintain the DNA damage checkpoint. Molecular and cellular biology 23 20679485
2016 Expanding the phenotype of CRB2 mutations - A new ciliopathy syndrome? Clinical genetics 22 26925547
2005 Cooperative control of Crb2 by ATM family and Cdc2 kinases is essential for the DNA damage checkpoint in fission yeast. Molecular and cellular biology 22 16314498
2020 AAV-CRB2 protects against vision loss in an inducible CRB1 retinitis pigmentosa mouse model. Molecular therapy. Methods & clinical development 21 33575434
2018 Rev7 and 53BP1/Crb2 prevent RecQ helicase-dependent hyper-resection of DNA double-strand breaks. eLife 21 29697047
2022 A Novel Mouse Model of Idiopathic Nephrotic Syndrome Induced by Immunization with the Podocyte Protein Crb2. Journal of the American Society of Nephrology : JASN 18 35985815
2012 Phosphorylation-dependent interactions between Crb2 and Chk1 are essential for DNA damage checkpoint. PLoS genetics 18 22792081
2021 Podocyte-specific Crb2 knockout mice develop focal segmental glomerulosclerosis. Scientific reports 17 34654837
2016 Altered expression of Crb2 in podocytes expands a variation of CRB2 mutations in steroid-resistant nephrotic syndrome. Pediatric nephrology (Berlin, Germany) 17 27942854
2015 CRB2 completes a fully expressed Crumbs complex in the Retinal Pigment Epithelium. Scientific reports 16 26404741
2019 CRB2 Loss in Rod Photoreceptors Is Associated with Progressive Loss of Retinal Contrast Sensitivity. International journal of molecular sciences 15 31438467
2010 Requirement for the phospho-H2AX binding module of Crb2 in double-strand break targeting and checkpoint activation. Molecular and cellular biology 15 20679488
2023 Bi-allelic variations in CRB2, encoding the crumbs cell polarity complex component 2, lead to non-communicating hydrocephalus due to atresia of the aqueduct of sylvius and central canal of the medulla. Acta neuropathologica communications 14 36803301
2022 CRB2 enhances malignancy of glioblastoma via activation of the NF-κB pathway. Experimental cell research 12 35219647
2022 Six new cases of CRB2-related syndrome and a review of clinical findings in 28 reported patients. Clinical genetics 12 36071576
1999 The S/M checkpoint at 37 degrees C and the recovery of viability of the mutant poldeltats3 require the crb2+/rhp9+ gene in fission yeast. Molecular & general genetics : MGG 12 9928931
2021 Key Role for CRB2 in the Maintenance of Apicobasal Polarity in Retinal Pigment Epithelial Cells. Frontiers in cell and developmental biology 11 34262913
2019 Targeted deletion of Crb1/Crb2 in the optic vesicle models key features of leber congenital amaurosis 8. Developmental biology 11 31145883
2023 Characterization and AAV-mediated CRB gene augmentation in human-derived CRB1KO and CRB1KOCRB2+/- retinal organoids. Molecular therapy. Methods & clinical development 10 37886604
2003 High dosage Rhp51 suppression of the MMS sensitivity of DNA structure checkpoint mutants reveals a relationship between Crb2 and Rhp51. Genes to cells : devoted to molecular & cellular mechanisms 9 12839619
2018 Expression and localization of the polarity protein CRB2 in adult mouse brain: a comparison with the CRB1rd8 mutant mouse model. Scientific reports 8 30076417
2007 Overexpression of human CRB1 or related isoforms, CRB2 and CRB3, does not regulate the human presenilin complex in culture cells. Biochemistry 8 17988153
2023 Novel variants in CRB2 targeting the malfunction of slit diaphragm related to focal segmental glomerulosclerosis. Pediatric nephrology (Berlin, Germany) 6 37452832
2022 Loss of surface transport is a main cellular pathomechanism of CRB2 variants causing podocytopathies. Life science alliance 6 36549870
2024 Human CRB1 and CRB2 form homo- and heteromeric protein complexes in the retina. Life science alliance 5 38570189
2018 A case report of CRB2 mutation identified in a Chinese boy with focal segmental glomerulosclerosis. Medicine 5 30212996
2014 Hyperactive Cdc2 kinase interferes with the response to broken replication forks by trapping S.pombe Crb2 in its mitotic T215 phosphorylated state. Nucleic acids research 5 24861625
2025 CRB2 depletion induces YAP signaling and disrupts mechanosensing in podocytes. American journal of physiology. Renal physiology 3 40062402
2022 Exome Sequencing Revealed a Novel Splice Site Variant in the CRB2 Gene Underlying Nephrotic Syndrome. Medicina (Kaunas, Lithuania) 3 36556986
2003 Expression, purification and preliminary X-ray analysis of the BRCT domain from Rhp9/Crb2. Acta crystallographica. Section D, Biological crystallography 2 12832769
2026 CRB2 Activates an Epigenetic Axis to Promote Ferroptosis in Head and Neck Squamous Cell Carcinoma. Cancer research 0 40991301
2026 CRB2 Facilitates Epithelial Ovarian Cancer Progression by Inducing Polarity Changes via Activation of the Wnt/PCP Signalling Pathway. Journal of cellular and molecular medicine 0 41906249
2025 CRISPR/Cas9-mediated generation of a homozygous CRB2 knockout H1 human embryonic stem cell line. Stem cell research 0 39987590
2025 Expanded CRB2-related disease phenotype: multisystem involvement and post-transplant complications in monozygotic twins. Pediatric nephrology (Berlin, Germany) 0 40456931
2025 CRB2-Related Syndrome in 2 New Patients: Three Novel Variants. Molecular syndromology 0 40734719
2025 Heterozygous variants of uncertain significance in NPHS1 and CRB2 in a newborn with congenital nephrotic syndrome of the Finnish type and multiple fetal anomalies: a case report. AME case reports 0 40761226
2024 CRB2 Depletion Induces YAP Signaling and Disrupts Mechanosensing in Podocytes. bioRxiv : the preprint server for biology 0 39484460
2024 Biochemical characterization and structure prediction of the Cerrado soil CRB2(1) metagenomic dioxygenase. Enzyme and microbial technology 0 39527864