Affinage

KRIT1

Krev interaction trapped protein 1 · UniProt O00522

Length
736 aa
Mass
84.3 kDa
Annotated
2026-04-28
100 papers in source corpus 19 papers cited in narrative 19 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KRIT1 is a multidomain scaffold protein that functions as a Rap1 GTPase effector at endothelial cell-cell junctions, where it suppresses stress fiber formation, stabilizes VE-cadherin/β-catenin complexes, restrains canonical Wnt/β-catenin transcription, and limits sprouting angiogenesis through DLL4-Notch signaling (PMID:17954608, PMID:20007487, PMID:20616044). Structurally, KRIT1 contains ankyrin repeats, a Nudix domain, three NPXY motifs, and a FERM domain; the FERM domain mediates junctional recruitment by HEG1 and Rap1, while the NPXY motifs bind ICAP-1 and CCM2, with crystal structures demonstrating that KRIT1 antagonizes ICAP-1-mediated β1-integrin inside-out activation by competing for the same binding surface (PMID:23317506, PMID:33977234, PMID:11854171). Loss of KRIT1 deregulates ROCK1-dependent contractility, increases NADPH oxidase/Nox4-driven ROS production and NF-κB activity, elevates VEGF-A/VEGFR2 signaling, and disrupts mechanosensitive KLF2/KLF4 dampening downstream of HEG1, collectively compromising endothelial barrier integrity and vascular morphogenesis (PMID:30030370, PMID:28811547, PMID:25320085, PMID:29364115). Truncating mutations in KRIT1 (CCM1) cause hereditary cerebral cavernous malformations (PMID:10508515).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1997 High

    The identity of KRIT1 as a Rap1A-interacting protein was unknown; yeast two-hybrid screening revealed that KRIT1 specifically binds Krev-1/Rap1A but not Ras, establishing it as a candidate Rap1 effector with ankyrin repeats and a C-terminal domain.

    Evidence Yeast two-hybrid screen of HeLa cDNA library with domain mapping

    PMID:9285558

    Open questions at the time
    • No cellular function assigned
    • No endothelial context established
    • Mechanism of Rap1 effector function unknown
  2. 1999 High

    The genetic basis of hereditary cerebral cavernous malformations (CCM1) was unresolved; positional cloning identified truncating mutations in KRIT1/CCM1 in affected families, establishing loss-of-function of KRIT1 as the cause of CCM1 disease.

    Evidence Positional cloning and mutation analysis in CCM1 families

    PMID:10508515

    Open questions at the time
    • No mechanism linking KRIT1 loss to vascular phenotype
    • Downstream signaling pathways unknown
  3. 2002 High

    How KRIT1 connects to integrin signaling was unknown; identification of the KRIT1–ICAP-1 interaction via an NPXY motif, combined with its microtubule association in endothelial cells, placed KRIT1 at the interface of integrin-cytoskeletal signaling.

    Evidence Yeast two-hybrid, GST pulldown, site-directed mutagenesis (ICAP-1 interaction); immunofluorescence and co-IP in endothelial cells (microtubule association)

    PMID:11854171 PMID:12140362

    Open questions at the time
    • Role at cell-cell junctions not yet identified
    • Functional consequence of ICAP-1 binding on integrin activation unknown
  4. 2007 High

    Whether KRIT1 functions as a true Rap1 effector at endothelial junctions was untested; KRIT1 was shown to localize to cell-cell junctions via its FERM domain under Rap1 control, and its depletion blocked Rap1-mediated junction stabilization and increased stress fibers, while CCM2 was identified as an additional NPXY-dependent partner.

    Evidence Co-IP, siRNA knockdown, Rap1 activation assays in endothelial cells; yeast two-hybrid and co-IP for CCM2 interaction

    PMID:17290187 PMID:17954608

    Open questions at the time
    • Downstream transcriptional consequences of junction destabilization unknown
    • ROCK isoform specificity not addressed
  5. 2009 High

    Whether KRIT1 regulates transcriptional signaling beyond junction stability was unknown; KRIT1 depletion was shown to cause β-catenin dissociation from VE-cadherin, nuclear accumulation, and increased β-catenin-dependent transcription, with in vivo validation in ApcMin/+ mice.

    Evidence siRNA knockdown, β-catenin reporter assays, nuclear fractionation, ApcMin/+ mouse cross

    PMID:20007487

    Open questions at the time
    • Specific transcriptional targets of β-catenin in CCM context not fully defined
    • Connection to VEGF-A upregulation not yet made
  6. 2010 High

    How KRIT1 controls angiogenic sprouting was unclear; KRIT1 was found to suppress sprouting angiogenesis by inducing DLL4-Notch signaling, with Notch inhibition rescuing the effect, linking KRIT1 to endothelial quiescence control.

    Evidence siRNA knockdown in endothelial cells, SCID mouse xenograft model, Notch pathway inhibition, phosphorylation assays

    PMID:20616044

    Open questions at the time
    • Whether Notch induction is direct or secondary to β-catenin signaling unclear
    • Interplay with VEGF signaling not resolved
  7. 2013 High

    The structural basis of KRIT1–ICAP-1 competition with integrin β1 was unknown; co-crystal structures revealed KRIT1 binds ICAP-1 via a bidentate surface that directly competes with the integrin β1 tail, and loss of CCM1 was shown to destabilize ICAP-1, increase β1-integrin activation, RhoA-dependent contractility, and aberrant fibronectin remodeling.

    Evidence X-ray crystallography at 2.54 Å and 3.0 Å resolution, competition binding assays, traction force microscopy, β1-integrin activation assays, CCM mouse models

    PMID:23317506 PMID:23918940

    Open questions at the time
    • Structural basis of KRIT1-Rap1 interaction at junctions not resolved
    • Whether ICAP-1 destabilization is sufficient to drive CCM lesions alone unclear
  8. 2014 High

    The link between KRIT1 loss, β-catenin transcription, and autocrine VEGF signaling was not established; KRIT1 depletion was shown to upregulate VEGF-A via nuclear β-catenin, activating VEGFR2 and altering cytoskeletal organization and barrier function in vitro and in vivo.

    Evidence siRNA knockdown, western blot, VEGFR2 signaling assays, β-catenin reporter, in vivo permeability in Krit1+/- mice

    PMID:25320085

    Open questions at the time
    • Therapeutic targeting of VEGF pathway in CCM not tested
    • Contribution of VEGF versus other β-catenin targets to lesion formation unknown
  9. 2017 High

    The roles of ROS and ROCK isoform balance downstream of KRIT1 loss were uncharacterized; KRIT1 depletion was found to increase Nox4/NADPH oxidase-driven ROS and NF-κB activity (rescued by targeted antioxidants in vivo), and KRIT1 oligomerization via NPXY-FERM interactions was demonstrated, expanding the KRIT1 interactome to 28 PTB/PH-domain proteins.

    Evidence siRNA knockdown, intravital microscopy in Krit1+/- mice with targeted antioxidant rescue, Nox4 expression analysis; molecular cloning and binding assays with structural modeling

    PMID:28698152 PMID:28811547

    Open questions at the time
    • Functional significance of KRIT1 oligomerization in vivo untested
    • Relative contribution of ROS versus contractility to barrier loss not delineated
  10. 2018 High

    How KRIT1 integrates mechanosensing and ROCK isoform balance was unclear; HEG1 was shown to stabilize Krit1 to dampen flow-induced klf2a expression and regulate cardiac valve formation, while the CCM1-CCM2 complex was found to scaffold ROCK2 at VE-cadherin and restrain ROCK1, with ROCK1 silencing rescuing ccm1 mutant zebrafish.

    Evidence Zebrafish genetic mutants with flow manipulation; isoform-specific siRNA knockdown, traction force microscopy, VE-cadherin co-IP, zebrafish rescue experiments

    PMID:29364115 PMID:30030370

    Open questions at the time
    • Direct mechanosensor identity upstream of KRIT1 in mammalian endothelium unresolved
    • Structural basis of ROCK1 versus ROCK2 selectivity by CCM complex unknown
  11. 2021 High

    How HEG1 recruits KRIT1 at the structural level was not defined; a crystal structure of a small-molecule inhibitor bound to the KRIT1 FERM domain confirmed the HEG1 cytoplasmic tail binding pocket, and acute pharmacological disruption increased KLF2/KLF4 and Akt signaling.

    Evidence High-throughput screening, crystal structure of inhibitor–KRIT1 FERM complex, endothelial reporter assays, zebrafish klf2a expression analysis

    PMID:33977234

    Open questions at the time
    • In vivo pharmacological modulation in mammalian CCM models not demonstrated
    • Full structural model of KRIT1 in complex with Rap1 and HEG1 simultaneously lacking
  12. 2022 High

    How KRIT1 expression itself is epigenetically regulated was unknown; NGBR was shown to maintain CCM1/CCM2 transcription via HBO1-mediated H4K5/H4K12 acetylation at their promoters, with NGBR loss in endothelial cells phenocopying CCM.

    Evidence Endothelial-specific Ngbr knockout mice, RNA-seq, ChIP-qPCR for HBO1 and acetylated histones at CCM1/CCM2 promoters

    PMID:35316220

    Open questions at the time
    • Whether HBO1-mediated regulation is specific to endothelial cells or general is untested
    • Chromatin accessibility landscape at the KRIT1 locus not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • A complete structural model of the full-length KRIT1 protein in complex with Rap1, HEG1, and CCM2 simultaneously is lacking, and the relative contributions of individual KRIT1-regulated pathways (β-catenin, ROCK1, Nox4/ROS, integrin activation) to CCM lesion initiation versus progression remain unresolved.
  • No full-length KRIT1 structure available
  • Pathway hierarchy in CCM pathogenesis not established by epistasis in mammalian models
  • Whether KRIT1 oligomerization is required for in vivo function untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4
Localization
GO:0005886 plasma membrane 2 GO:0005634 nucleus 1 GO:0005856 cytoskeleton 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1500931 Cell-Cell communication 3 R-HSA-1643685 Disease 3 R-HSA-1266738 Developmental Biology 2
Partners
CCM2CDH5CTNNB1HEG1ICAP1RAP1AROCK1ROCK2
Complex memberships
CCM1-CCM2 complex

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 KRIT1 (Krev Interaction Trapped 1) was identified as a binding partner of Krev-1/Rap1A GTPase via yeast two-hybrid screening of a HeLa cell cDNA library. The protein contains an N-terminal ankyrin repeat domain and a C-terminal domain; it interacts strongly with Krev-1/Rap1A but only weakly with Ras, suggesting specificity for Rap1A signaling. Yeast two-hybrid screen, domain mapping Oncogene High 9285558
1999 Truncating mutations in CCM1, which encodes KRIT1, cause hereditary cerebral cavernous angiomas (CCM1 families), establishing loss-of-function of KRIT1 as the molecular basis of CCM1 disease and implicating the RAP1A signal transduction pathway in vasculogenesis or angiogenesis. Positional cloning, mutation analysis in CCM1 families Nature genetics High 10508515
2002 KRIT1 associates with integrin cytoplasmic domain-associated protein-1 (ICAP-1) via an NPXY motif at the N-terminus of KRIT1; mutagenesis of this NPXY sequence completely abrogates the KRIT1/ICAP-1 interaction, suggesting KRIT1 is involved in integrin-cytoskeleton signaling. Yeast two-hybrid screening, GST pulldown of endogenous ICAP-1 from 293T cells, site-directed mutagenesis Human molecular genetics High 11854171
2002 KRIT1 colocalizes with microtubules in endothelial cells during interphase and localizes to spindle pole bodies, mitotic spindle, and microtubule plus ends during mitosis, establishing KRIT1 as a microtubule-associated protein potentially involved in microtubule targeting and endothelial cell shape. Immunofluorescence microscopy, coimmunoprecipitation with anti-KRIT1 antibodies in endothelial cells Proceedings of the National Academy of Sciences of the United States of America Medium 12140362
2007 KRIT1 is a Rap1 effector in endothelial cells: KRIT1 is present at cell-cell junctions via its FERM domain, colocalizes and physically associates with junctional proteins, and Rap1 activity regulates junctional localization of KRIT1. KRIT1 depletion by siRNA blocks Rap1-mediated stabilization of endothelial junctions and leads to increased actin stress fibers. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, Rap1 activation assays in endothelial cells The Journal of cell biology High 17954608
2007 KRIT1 interacts with CCM2 (malcavernin) through its NPXY motifs; malcavernin independently binds to two of the three NPXY motifs in KRIT1, and at steady state malcavernin shuttles between nucleus and cytoplasm, with KRIT1 potentially regulating its nuclear localization. Yeast two-hybrid, in vivo coimmunoprecipitation, epitope mapping, immunocytochemistry Neurosurgery Medium 17290187
2008 Loss of ccm1 in zebrafish embryos leads to severe progressive dilation of major vessels with endothelial cell spreading and thinning of vessel walls despite normal cell-cell contacts; ccm1 function is cell-autonomous in endothelial cells, establishing that CCM1 regulates endothelial cellular morphogenesis. Zebrafish genetic mutant analysis, mosaic rescue experiments, electron microscopy, cell transplantation Human molecular genetics High 18469344
2008 KRIT1 depletion reduces endothelial cell proliferation and decreases phosphorylation along the β1-integrin/FAK/ERK/MAPK pathway; KRIT1 colocalizes with ICAP-1α in nucleus and cytoplasm and stabilizes/shuttles ICAP-1α, modulating β1-integrin-mediated signal transduction. siRNA knockdown in HeLa, HUVEC, and microvascular endothelial cells; western blot for pathway phosphorylation; immunocytochemistry Neurosurgery Medium 18812969
2009 KRIT1 and Rap1 are negative regulators of canonical β-catenin signaling; depletion of endothelial KRIT1 causes β-catenin to dissociate from VE-cadherin and accumulate in the nucleus with increased β-catenin-dependent transcription. This effect requires intact cell-cell junctions and KRIT1. Hemizygous Krit1 deficiency in vivo increases intestinal polyps in ApcMin/+ mice. siRNA knockdown, Rap1 activation, β-catenin reporter assays, ApcMin/+ mouse cross, nuclear fractionation Disease models & mechanisms High 20007487
2010 CCM1/KRIT1 inhibits sprouting angiogenesis by strongly inducing DLL4-NOTCH signaling in endothelial cells, promoting AKT phosphorylation while reducing ERK phosphorylation; blocking NOTCH activity alleviates CCM1 effects. Loss of CCM1 leads to excessive capillary sprouting. siRNA knockdown in primary human endothelial cells, SCID mouse xenograft model, NOTCH pathway inhibition, phosphorylation assays Proceedings of the National Academy of Sciences of the United States of America High 20616044
2013 Crystal structures of KRIT1 bound to ICAP1 and ICAP1 bound to integrin β1 cytoplasmic tail were solved to 2.54 Å and 3.0 Å resolution. KRIT1 binds ICAP1 via a bidentate surface that directly competes with integrin β1, antagonizing ICAP1-mediated suppression of integrin inside-out activation. KRIT1 also contains an N-terminal Nudix domain previously considered unstructured. X-ray crystallography (co-crystal structures), competition binding assays, integrin activation functional assays Molecular cell High 23317506
2013 The CCM1-ICAP-1 complex controls β1 integrin-dependent endothelial contractility and ECM remodeling; loss of CCM1/2 destabilizes ICAP-1, increases β1 integrin activation, and leads to increased RhoA-dependent contractility and aberrant fibronectin remodeling, destabilizing endothelial barrier function via a positive feedback loop between aberrant ECM and cellular tension. siRNA knockdown, traction force microscopy, β1 integrin activation assays, CCM1/2 mouse models, RhoA activity assays The Journal of cell biology High 23918940
2014 Loss of KRIT1 (but not CCM2) increases nuclear β-catenin signaling and up-regulates VEGF-A protein expression in endothelial cells; increased VEGF-A leads to VEGFR2 activation with consequent altered cytoskeletal organization, migration, barrier function, and in vivo endothelial permeability in KRIT1-deficient animals. siRNA knockdown, western blot, VEGFR2 signaling assays, β-catenin reporter, in vivo permeability measurements in Krit1+/- mice The Journal of biological chemistry High 25320085
2017 KRIT1 depletion increases endothelial ROS production via NADPH oxidase/Nox4 signaling and NF-κB-dependent promoter activity, directly contributing to loss of barrier function; targeted antioxidant delivery reversed permeability increases in KRIT1 heterozygous mice in vivo. siRNA knockdown, intravital microscopy in Krit1+/- mice with targeted antioxidant enzymes, Nox4 expression analysis, NF-κB reporter assay Scientific reports High 28811547
2018 Zebrafish Krit1 regulates cardiac valve formation; HEG1 expression is induced by blood flow, Heg1 stabilizes Krit1 protein levels, and Heg1/Krit1 dampen mechanosensitive klf2a expression. Loss of Krit1 increases klf2a and notch1b throughout the endocardium and prevents valve leaflet formation. Zebrafish genetic mutants, morpholino knockdown, blood flow manipulation, in situ hybridization, protein level analysis eLife High 29364115
2018 The CCM1-CCM2 complex controls complementary functions of ROCK1 and ROCK2: CCM proteins act as a scaffold promoting ROCK2 interactions with VE-cadherin and limiting ROCK1 kinase activity. Loss of CCM1 produces excessive ROCK1-dependent actin stress fibers; silencing ROCK1 (but not ROCK2) restores endothelial homeostasis and rescues ccm1 mutant zebrafish cardiovascular defects. siRNA knockdown of CCM1/CCM2 and ROCK isoforms, traction force microscopy, VE-cadherin co-IP, zebrafish ccm1 mutant rescue experiments Journal of cell science High 30030370
2021 HEG1 directly binds to and recruits KRIT1 to endothelial junctions via the KRIT1 FERM domain; a crystal structure of a small-molecule HEG1-KRIT1 inhibitor (HKi2) bound to the KRIT1 FERM domain revealed it occupies the same binding pocket as the HEG1 cytoplasmic tail. Acute inhibition of HEG1-KRIT1 interaction increases KLF4 and KLF2 expression and activates Akt signaling in endothelial cells. High-throughput screening, crystal structure of inhibitor-KRIT1 FERM complex, in vitro colocalization assay, endothelial cell reporter assays, zebrafish klf2a expression analysis FASEB bioAdvances High 33977234
2017 CCM1/KRIT1 contains three NPXY motifs that interact with a spectrum of PTB and PH domain-containing proteins; the KRIT1 F3 lobe of the FERM domain acts as a functional PH domain to interact with NPXY motifs, and KRIT1 can form oligomers through intermolecular interaction between its F3 FERM lobe and an NPXY motif. Twenty-eight novel cellular partners of CCM1 containing PTB or PH domains were identified. Molecular cloning, protein binding assays, structural simulation combined with existing X-ray crystallography and NMR data, RT-qPCR Biochimica et biophysica acta. Proteins and proteomics Medium 28698152
2022 NGBR (NOGOB receptor) is required for maintaining CCM1/2 expression in endothelial cells via HBO1-mediated histone H4 acetylation; loss of NGBR reduces HBO1 and histone acetylation at CCM1 and CCM2 promoters (H4K5 and H4K12), resulting in CCM1/2 deficiency and cerebrovascular lesions. Endothelial-specific Ngbr knockout mice, RNA-seq, ChIP-qPCR for HBO1 and acetylated histone H4K5/H4K12 at CCM1/CCM2 promoters The Journal of clinical investigation High 35316220

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Sensitivity of CaM kinase II to the frequency of Ca2+ oscillations. Science (New York, N.Y.) 1032 9422695
1994 The CaM kinase II hypothesis for the storage of synaptic memory. Trends in neurosciences 421 7530878
2001 Ca(2+)/CaM-dependent kinases: from activation to function. Annual review of pharmacology and toxicology 411 11264466
1999 Truncating mutations in CCM1, encoding KRIT1, cause hereditary cavernous angiomas. Nature genetics 367 10508515
2015 The pineapple genome and the evolution of CAM photosynthesis. Nature genetics 344 26523774
1995 Axonin-1, Nr-CAM, and Ng-CAM play different roles in the in vivo guidance of chick commissural neurons. Neuron 290 7541632
2019 CaM Kinase: Still Inspiring at 40. Neuron 272 31394063
2007 KRIT-1/CCM1 is a Rap1 effector that regulates endothelial cell cell junctions. The Journal of cell biology 265 17954608
1999 The role of CD146 (Mel-CAM) in biology and pathology. The Journal of pathology 202 10451481
1999 Expression of Ep-CAM in normal, regenerating, metaplastic, and neoplastic liver. The Journal of pathology 180 10398165
1997 Association of Krev-1/rap1a with Krit1, a novel ankyrin repeat-containing protein encoded by a gene mapping to 7q21-22. Oncogene 178 9285558
2004 Ecophysiology of Crassulacean Acid Metabolism (CAM). Annals of botany 173 15150072
2010 Cerebral cavernous malformation protein CCM1 inhibits sprouting angiogenesis by activating DELTA-NOTCH signaling. Proceedings of the National Academy of Sciences of the United States of America 165 20616044
2002 KRIT1 association with the integrin-binding protein ICAP-1: a new direction in the elucidation of cerebral cavernous malformations (CCM1) pathogenesis. Human molecular genetics 159 11854171
2008 A two-hit mechanism causes cerebral cavernous malformations: complete inactivation of CCM1, CCM2 or CCM3 in affected endothelial cells. Human molecular genetics 155 19088124
1995 Postsynaptic injection of CA2+/CaM induces synaptic potentiation requiring CaMKII and PKC activity. Neuron 155 7646896
1994 N-CAM and N-cadherin expression during in vitro chondrogenesis. Experimental cell research 151 7982473
2000 The regulation of phosphoenolpyruvate carboxylase in CAM plants. Trends in plant science 137 10664617
2014 Facultative crassulacean acid metabolism (CAM) plants: powerful tools for unravelling the functional elements of CAM photosynthesis. Journal of experimental botany 136 24642847
2015 A roadmap for research on crassulacean acid metabolism (CAM) to enhance sustainable food and bioenergy production in a hotter, drier world. The New phytologist 134 26153373
2004 Expression profiling-based identification of CO2-responsive genes regulated by CCM1 controlling a carbon-concentrating mechanism in Chlamydomonas reinhardtii. Plant physiology 134 15235119
2005 Biallelic somatic and germ line CCM1 truncating mutations in a cerebral cavernous malformation lesion. Stroke 130 15718512
2021 Cancer-secreted exosomal miR-21-5p induces angiogenesis and vascular permeability by targeting KRIT1. Cell death & disease 127 34088891
2001 Ccm1, a regulatory gene controlling the induction of a carbon-concentrating mechanism in Chlamydomonas reinhardtii by sensing CO2 availability. Proceedings of the National Academy of Sciences of the United States of America 118 11287669
1987 Formation of heterotypic adherens-type junctions between L-CAM-containing liver cells and A-CAM-containing lens cells. Cell 106 3621349
2016 Transcript, protein and metabolite temporal dynamics in the CAM plant Agave. Nature plants 104 27869799
2011 Analysis of CaM-kinase signaling in cells. Cell calcium 100 21529938
2009 Rap1 and its effector KRIT1/CCM1 regulate beta-catenin signaling. Disease models & mechanisms 98 20007487
1985 Specific regulation of N-CAM/D2-CAM cell adhesion molecule during skeletal muscle development. The EMBO journal 98 3891323
2006 Derepression of pathological cardiac genes by members of the CaM kinase superfamily. Cardiovascular research 97 17217938
2002 KRIT1, a gene mutated in cerebral cavernous malformation, encodes a microtubule-associated protein. Proceedings of the National Academy of Sciences of the United States of America 94 12140362
2019 The KN-93 Molecule Inhibits Calcium/Calmodulin-Dependent Protein Kinase II (CaMKII) Activity by Binding to Ca2+/CaM. Journal of molecular biology 92 30753871
2004 Neurobiology of Acupuncture: Toward CAM. Evidence-based complementary and alternative medicine : eCAM 92 15257325
2004 Loss of p53 sensitizes mice with a mutation in Ccm1 (KRIT1) to development of cerebral vascular malformations. The American journal of pathology 92 15509522
2018 The chick chorioallantoic membrane (CAM) as a versatile patient-derived xenograft (PDX) platform for precision medicine and preclinical research. American journal of cancer research 90 30210932
2008 ccm1 cell autonomously regulates endothelial cellular morphogenesis and vascular tubulogenesis in zebrafish. Human molecular genetics 90 18469344
1992 Decoding calcium signals by multifunctional CaM kinase. Cell calcium 88 1324121
2004 Clinical features of cerebral cavernous malformations patients with KRIT1 mutations. Annals of neurology 87 14755725
2013 CCM1-ICAP-1 complex controls β1 integrin-dependent endothelial contractility and fibronectin remodeling. The Journal of cell biology 86 23918940
2008 L1-CAM in cancerous tissues. Expert opinion on biological therapy 85 18847309
2019 Ecophysiology of constitutive and facultative CAM photosynthesis. Journal of experimental botany 83 30810162
1991 Regulation of Cl- channels by multifunctional CaM kinase. Neuron 77 1849722
2013 Mechanism for KRIT1 release of ICAP1-mediated suppression of integrin activation. Molecular cell 71 23317506
2000 Mutations in KRIT1 in familial cerebral cavernous malformations. Neurosurgery 70 10807272
1995 Refined localization of the cerebral cavernous malformation gene (CCM1) to a 4-cM interval of chromosome 7q contained in a well-defined YAC contig. Genome research 68 8750196
2007 Interaction between krit1 and malcavernin: implications for the pathogenesis of cerebral cavernous malformations. Neurosurgery 66 17290187
2014 Shared origins of a key enzyme during the evolution of C4 and CAM metabolism. Journal of experimental botany 65 24638902
2011 Ccm3 functions in a manner distinct from Ccm1 and Ccm2 in a zebrafish model of CCM vascular disease. Developmental biology 65 22182521
2002 Cerebral cavernous malformations: mutations in Krit1. Neurology 58 11914398
2014 KRIT1 protein depletion modifies endothelial cell behavior via increased vascular endothelial growth factor (VEGF) signaling. The Journal of biological chemistry 53 25320085
2010 Mutation analysis of CCM1, CCM2 and CCM3 genes in a cohort of Italian patients with cerebral cavernous malformation. Brain pathology (Zurich, Switzerland) 53 21029238
2015 L1-CAM and N-CAM: From Adhesion Proteins to Pharmacological Targets. Trends in pharmacological sciences 52 26478212
2018 Heg1 and Ccm1/2 proteins control endocardial mechanosensitivity during zebrafish valvulogenesis. eLife 50 29364115
2017 Up-regulation of NADPH oxidase-mediated redox signaling contributes to the loss of barrier function in KRIT1 deficient endothelium. Scientific reports 49 28811547
2015 Neurogranin regulates CaM dynamics at dendritic spines. Scientific reports 46 26084473
2004 KRIT1/cerebral cavernous malformation 1 protein localizes to vascular endothelium, astrocytes, and pyramidal cells of the adult human cerebral cortex. Neurosurgery 45 15046662
2001 Alx4 binding to LEF-1 regulates N-CAM promoter activity. The Journal of biological chemistry 45 11696550
2017 Temporal and spatial transcriptomic and microRNA dynamics of CAM photosynthesis in pineapple. The Plant journal : for cell and molecular biology 43 28670834
2014 Synthetic biology as it relates to CAM photosynthesis: challenges and opportunities. Journal of experimental botany 42 24567493
2005 CCM2 expression parallels that of CCM1. Stroke 41 16373645
2018 The CCM1-CCM2 complex controls complementary functions of ROCK1 and ROCK2 that are required for endothelial integrity. Journal of cell science 40 30030370
2002 Krit1/cerebral cavernous malformation 1 mRNA is preferentially expressed in neurons and epithelial cells in embryo and adult. Mechanisms of development 40 12204286
1991 Expression of polysialylated N-CAM during rat heart development. Differentiation; research in biological diversity 40 1955110
2000 Elevated concentration of N-CAM VASE isoforms in schizophrenia. Journal of psychiatric research 39 10696830
1997 Cell signalling and CAM-mediated neurite outgrowth. Society of General Physiologists series 39 9210232
2001 Germline mutations in the CCM1 gene, encoding Krit1, cause cerebral cavernous malformations. Annals of neurology 38 11310633
2017 Hepatic Activation of the FAM3C-HSF1-CaM Pathway Attenuates Hyperglycemia of Obese Diabetic Mice. Diabetes 36 28246289
2020 Cadherins, Selectins, and Integrins in CAM-DR in Leukemia. Frontiers in oncology 35 33425742
2008 Krit1 modulates beta 1-integrin-mediated endothelial cell proliferation. Neurosurgery 35 18812969
2000 Cloning of the murine Krit1 cDNA reveals novel mammalian 5' coding exons. Genomics 34 11161791
2023 The CAM lineages of planet Earth. Annals of botany 33 37698538
2015 CaM Kinases: From Memories to Addiction. Trends in pharmacological sciences 33 26674562
2014 PTEN/PI3K/Akt/VEGF signaling and the cross talk to KRIT1, CCM2, and PDCD10 proteins in cerebral cavernous malformations. Neurosurgical review 33 25403688
1997 Familial cavernous malformations in a large French kindred: mapping of the gene to the CCM1 locus on chromosome 7q. Journal of neurology, neurosurgery, and psychiatry 31 9221966
2019 Understanding trait diversity associated with crassulacean acid metabolism (CAM). Current opinion in plant biology 30 31284077
2007 Highly variable penetrance in subjects affected with cavernous cerebral angiomas (CCM) carrying novel CCM1 and CCM2 mutations. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 30 17440989
2001 Identification of eight novel 5'-exons in cerebral capillary malformation gene-1 (CCM1) encoding KRIT1. Biochimica et biophysica acta 29 11342228
2019 Shared expression of crassulacean acid metabolism (CAM) genes pre-dates the origin of CAM in the genus Yucca. Journal of experimental botany 27 30870557
1996 Shared cell adhesion molecule (CAM) homology domains point to CAMs signalling via FGF receptors. Perspectives on developmental neurobiology 27 9168198
2020 Ca2+-CaM Dependent Inactivation of RyR2 Underlies Ca2+ Alternans in Intact Heart. Circulation research 26 33375811
2003 Molecular genetic investigations in the CCM1 gene in sporadic cerebral cavernomas. Neurology 26 12682320
2015 Activity dependent CAM cleavage and neurotransmission. Frontiers in cellular neuroscience 25 26321910
2018 Grip and slip of L1-CAM on adhesive substrates direct growth cone haptotaxis. Proceedings of the National Academy of Sciences of the United States of America 24 29483251
2018 Two Novel KRIT1 and CCM2 Mutations in Patients Affected by Cerebral Cavernous Malformations: New Information on CCM2 Penetrance. Frontiers in neurology 24 30487773
2011 Cell adhesion molecules in context: CAM function depends on the neighborhood. Cell adhesion & migration 24 20948304
2021 Establishment, characterization, and transfection potential of a new continuous fish cell line (CAM) derived from the muscle tissue of grass goldfish (Carassius auratus). In vitro cellular & developmental biology. Animal 23 34725799
2022 NOGOB receptor deficiency increases cerebrovascular permeability and hemorrhage via impairing histone acetylation-mediated CCM1/2 expression. The Journal of clinical investigation 21 35316220
2013 miR-21 coordinates tumor growth and modulates KRIT1 levels. Biochemical and biophysical research communications 21 23872064
2012 Regulation of neuronal mRNA translation by CaM-kinase I phosphorylation of eIF4GII. The Journal of neuroscience : the official journal of the Society for Neuroscience 20 22514323
2014 Genomic analyses of the CAM plant pineapple. Journal of experimental botany 19 24692645
2021 Electrical therapies act on the Ca2+ /CaM signaling pathway to enhance bone regeneration with bioactive glass [S53P4] and allogeneic grafts. Journal of biomedical materials research. Part B, Applied biomaterials 18 34008329
2021 Tetrahydropalmatine Regulates BDNF through TrkB/CAM Interaction to Alleviate the Neurotoxicity Induced by Methamphetamine. ACS chemical neuroscience 18 34448569
2020 Biosystems Design to Accelerate C3-to-CAM Progression. Biodesign research 17 37849902
2016 Australia lacks stem succulents but is it depauperate in plants with crassulacean acid metabolism (CAM)? Current opinion in plant biology 17 27088716
2008 Significance of zinc in a regulatory protein, CCM1, which regulates the carbon-concentrating mechanism in Chlamydomonas reinhardtii. Plant & cell physiology 17 18202004
2003 Identification of a novel KRIT1 mutation in an Italian family with cerebral cavernous malformation by the protein truncation test. Journal of the neurological sciences 17 12810002
2021 Inhibition of the HEG1-KRIT1 interaction increases KLF4 and KLF2 expression in endothelial cells. FASEB bioAdvances 16 33977234
2017 MicroRNA-1185 Induces Endothelial Cell Apoptosis by Targeting UVRAG and KRIT1. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 16 28441650
2017 Novel functions of CCM1 delimit the relationship of PTB/PH domains. Biochimica et biophysica acta. Proteins and proteomics 16 28698152
2016 CRISPR-Cas-Assisted Multiplexing (CAM): Simple Same-Day Multi-Locus Engineering in Yeast. Journal of cellular physiology 16 26991244