Property Summary

NCBI Gene PubMed Count 90
PubMed Score 152.10
PubTator Score 174.55

Knowledge Summary

Patent

No data available

Expression

Protein-protein Interaction (4)

Gene RIF (70)

PMID Text
26356566 Studies suggest that the 3 proteins of the Cerebral Cavernous Malformations (CCM) complex KRIT1/CCM1, CCM2/malcavernin and CCM3/PDCD10 not only require one another for reciprocal stabilization, but also act as a platform for signal transduction.
25923142 KRIT1 protects endothelial integrity during mechanical stress and trap6 exposure.
25707093 Genetic analysis of familial cerebral cavernous malformation in Japanese involved the KRIT1 gene.
25525273 Data find that several disease-associated missense mutations in CCM2 have the potential to interrupt the KRIT1-CCM2 interaction by destabilizing the CCM2 PTB domain and that a KRIT1 mutation also disrupts this interaction
25413039 Case Report: cerebral cavernous malformations and unilateral moyamoya disease in a patient with a new mutation in the KRIT-1 /CCM1 gene.
25320085 Data indicate the regulatioin of vascular endothelial growth factor (VEGF) signaling in Krev-interaction trapped 1 (KRIT1)-depleted endothelial cells.
25203678 Valproic acid reduces intracellular ROS level by the modulation of KRIT1 and its correlated proteins, FoxO1, SOD2, and cyclin D1 in mesenchymal stromal cells.
25185960 Novel CCM1 deletion mutation segregated with cerebral cavernous angioma in a Chinese family.
25086949 Our findings demonstrate that CCM1 c.263-10A > G mutation is associated with cerebral cavernous malformations.
25059659 Data indicate that the major binding site for binding of sorting nexin 17 (SNX17) is confined to the NPXF2 motif in cytoplasmic adaptor protein Krev interaction trapped 1 (KRIT1).
24714220 Here we discuss nuclear functions of adhesion complex proteins with a special focus on the CCM-1/KRIT-1 protein, which may turn out to be yet another adhesion complex protein with a second life.
24705002 These preliminary data indicate a still undescribed and unknown role for KRIT1 inside the nucleus.
24466005 Prevalence, frequency and characterization of CCM1, CCM2 and CCM3 variants in cerebral cavernous malformation Spanish patients.
24291398 with the reported role of c-Jun in vascular dysfunctions triggered by oxidative stress, our findings shed new light on the molecular mechanisms underlying KRIT1 function and CCM pathogenesis.
24058906 The identification of other four new mutations in 40 sporadic patients with either single or multiple cerebral cavernous malformations, is reported.
24007869 DNA sequencing and deletion/duplication testing of the CCM1, CCM2, and CCM3 genes in the proband revealed a CCM1 c.601CNG mutation.
23872064 Our findings suggest that miR-21 promotes tumor cell growth, at least in part, by down-modulating the potential tumor suppressor KRIT1.
23814056 These data show that HEG1 can recruit the Rap1-KRIT complex to the plasma membrane.
23695561 A high resolution crystal structure and minimal binding region with integrin cytoplasmic domain-associated protein-1 (ICAP1) has been determined for KRIT1.
23584803 we present a rare and interesting case of monozygotic twins heterozygous for the CCM1 germline mutation and discuss their similar age and type of disease manifestation and their beginning divergent clinical course
23485406 KRIT1 mutations are associated with cerebral cavernous malformation in some Japanese patients.
23317506 The structural basis for KRIT1 antagonized ICAP1-modulated integrin-beta1 activation.
22699465 Genetic testing identified a truncating mutation in the KRIT1 gene in one individual and confirmed the diagnosis of familial cerebral cavernomas as the cause of epilepsy in a family.
22577140 Structural basis for small G protein effector interaction of Ras-related protein 1 (Rap1) and adaptor protein Krev interaction trapped 1 (KRIT1)
21633110 These studies establish that the direct physical interaction of Rap1 with KRIT1 enables the translocation of microtubule-sequestered KRIT1 to junctions, thereby supporting junctional integrity and cardiovascular development
21029238 Among familial cases of Cerebral cavernous malformations 67% had a mutation in CCM1, 5.5% in CCM2, and 5.5% in CCM3
20884211 Here we report a novel deletion of CCM1 that correlates strongly with cerebral cavernous malformations in a Chinese family. We predict this deletion produces a premature stop code (TGA) at NT 1228, resulting in a truncated protein of 409 amino acids.
20798775 We described the complete loss of 7q21.2 locus encompassing the KRIT1 gene and 4 flanking genes in a CCM family by using a dense set of 12 microsatellite markers.
20689144 Frame shift mutation in KRIT1 gene is associated with cerebral and multiple spinal cavernous malformations.
20419355 Genetic variations could interfere with the proper CCM1/CCM2/CCM3 protein complex, thus explaining the observed clinical variability in cerebral cavernous malformations in a large family.
20379614 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
20308363 The KRIT1-CCM2 interaction regulates endothelial junctional stability and vascular barrier function by suppressing activation of the RhoA/ROCK signaling pathway. This pathway is dysregulated in human cerebral cavernous malformation endothelium.
20306072 We have identified a novel mutation in the KRIT1/CCM1 gene in a patient with both CCM and retinal cavernous hemangioma.
19833796 Familial CCM1 cavernous malformations are unlikely to be associated with developmental venous anomalies, and sporadic malformations have a high rate of association with them
19454328 C329X in KRIT1 is a founder mutation among CCM patients in Sardinia.
19453802 CCM1 is the most frequently mutated gene in cutaneous vascular malformations-familial cerebral cavernous malformations patients.
19199464 The Multiplex Ligation-dependent Probe Amplification analysis revealed a new mutation, a heterozygous exon 9/10 deletion of Krit1, in the proband and in all affected family members.
19182478 mutations in the KRIT1 gene may cause phenotypically heterogeneous cutaneous vascular lesions other than those previously described as HCCVMs.
19092252 Sequencing of KRIT1 identified a novel frameshift mutation in exon 15 (c.1561delC or p.Leu551X) which cosegregated with the phenotype observed in a family with cerebral cavernous malformations.
19088124 Complete localized loss of either CCM1, CCM2 or CCM3 protein expression depend on the inherited mutation in cerebral cavernous malformations.
19088123 Biallelic germline and somatic mutations were identified in CCM1, CCM2 or PDCD10 from all forms of inherited cerebral cavernous malformations.
18812969 Krit1 and integrin cytoplasmic domain-associated protein-1 alpha (icap1alpha) act concordantly to play a critical role in beta 1-integrin-mediated cell proliferation.
18300272 data are in agreement with a loss-of-function mechanism for CCM mutations, uncover an N-terminal CCM2 domain required for CCM1 binding, and demonstrate full-length CCM2 as the essential core protein in the CCM1/CCM2/CCM3 complex
17954608 Rap1 increases KRIT-1 targeting to endothelial cell-cell junctions where it suppresses stress fibers and stabilizes junctional integrity.
17562932 Three novel and 2 described mutations were found in KRIT1. The families included 33 KRIT1 mutation carriers, 57.6% of whom had no symptoms.
17440989 we found a novel CCM1 gene mutation (Q66X) in a family with apparently asymptomatic old-aged mutation carriers and patients who either had skin angiomas alone or the full association of cerebral, spinal, and skin lesions
17290187 Krit1 interacts with malcavernin and may shuttle it through the nucleus via nuclear export signals, thereby regulating cellular function.
17148043 Mutations in CCM1/KRIT1 may be found in asymptomatic patients with retinal cavernous hemangioma.
17043900 Two new mutations in the KRIT1 gene in two Italian families affected by cerebral cavernous malformations.
16769843 Five percent of patients with familial cerebral cavernomas have retinal cavernomas. These lesions are clinically asymptomatic. They can be associated with any of the 3 cerebral cavernous malformation genes.
16712798 SNX17 has a role in the indicated KRIT1 function in cell adhesion processes by integrin signaling
16529293 Results confirm the conclusion that KRIT1 haploinsufficiency may be the underlying mechanism of cerebral cavernous malformations.
16373645 CCM1 and CCM2 have similar expression patterns during development and are involved in the same pathway important for central nervous system vascular development
16321204 Observational study of gene-disease association. (HuGE Navigator)
16239636 KRIT1, Malcavernin, and PDCD10 are differentially expressed in cerebral venous malformations and cerebral cavernous malformations
15718512 biallelic CCM1 somatic and germ line truncating mutation identification strongly supports the "two-hit" mechanism in this cerebral cavernous malformation lesion
15079030 Observational study of genotype prevalence. (HuGE Navigator)
15079030 The CCM1 gene was screened in 35 sporadic cases with either single or multiple CCM. It was found that 29% of the individuals with multiple CCM have a CCM1 mutation, whereas cases with only one malformation have none
15046662 KRIT1 is also present in cells and structures integral to the cerebral angiogenesis and formation of the blood-brain barrier, namely, endothelial cells and astrocytic foot processes, as well as pyramidal neurons in the cerebral cortex.
12877753 We report a mutation causing a premature termination triplet in exon 17 of the Krit1 gene in a family with diagnoses of cerebral cavernous angioma
12810002 Identification of a novel KRIT1 mutation in an Italian family with cerebral cavernous malformation by the protein truncation test.
12682320 Mutations in Krit1 are associated with familial cerebral cavernous malformations, but seldom a cause of sporadic cavernomas
12204286 Krit1 mRNA expression in adult tissues
12172908 Experimentally determined alternatively spliced variants in the 5' coding region that alter the open reading frame and lead to premature translation termination codons. Determined that the 3' UTR is larger than previously found.
11941540 RNA analysis reveals that two point mutations actually activate cryptic splice-donor sites, causing aberrant splicing and leading to a frameshift and protein truncation
11914398 In familial CCM1 samples, two new Krit1 mutations have been reported in four new upstream exons and six additional mutations have been discovered in the previously identified exons, demonstrating a mutation frequency of 47% in the 27 families studied.
11854171 Integrin-binding protein also interacts with Krit 1 protein, cause of CCM1. (ICAP-1, integrin cytoplasmic domain-associated protein 1)
11831930 KRIT1/CCM1 mutation in a patient with retinal and cerebral cavernous angiomas.
11342228 Experimentally determined additional 5' UTR alternatively spliced variants. Determined gene contains 20 exons.
11161805 Experimentally determined additional 5' UTR variants and additional mutations (in CCM1 study families) in coding exons that lead to frameshifts and premature truncations in the protein.

AA Sequence

MGNPENIEDAYVAVIRPKNTASLNSREYRAKSYEILLHEVPIEGQKKKRKKVLLETKLQGNSEITQGILD      1 - 70
YVVETTKPISPANQGIRGKRVVLMKKFPLDGEKMGREASLFIVPSVVKDNTKYTYTPGCPIFYCLQDIMR     71 - 140
VCSESSTHFATLTARMLIALDKWLDERHAQSHFIPALFRPSPLERIKTNVINPAYATESGQTENSLHMGY    141 - 210
SALEIKSKMLALEKADTCIYNPLFGSDLQYTNRVDKVVINPYFGLGAPDYSKIQIPKQEKWQRSMSSVTE    211 - 280
DKERQWVDDFPLHRSACEGDSELLSRLLSERFSVNQLDSDHWAPIHYACWYGKVEATRILLEKGKCNPNL    281 - 350
LNGQLSSPLHFAAGGGHAEIVQILLNHPETDRHITDQQGRSPLNICEENKQNNWEEAAKLLKEAINKPYE    351 - 420
KVRIYRMDGSYRSVELKHGNNTTVQQIMEGMRLSQETQQYFTIWICSENLSLQLKPYHKPLQHVRDWPEI    421 - 490
LAELTNLDPQRETPQLFLRRDVRLPLEVEKQIEDPLAILILFDEARYNLLKGFYTAPDAKLITLASLLLQ    491 - 560
IVYGNYESKKHKQGFLNEENLKSIVPVTKLKSKAPHWTNRILHEYKNLSTSEGVSKEMHHLQRMFLQNCW    561 - 630
EIPTYGAAFFTGQIFTKASPSNHKVIPVYVGVNIKGLHLLNMETKALLISLKYGCFMWQLGDTDTCFQIH    631 - 700
SMENKMSFIVHTKQAGLVVKLLMKLNGQLMPTERNS                                      701 - 736
//

Text Mined References (90)

PMID Year Title
26356566 2015 The cerebral cavernous malformations proteins.
25923142 2015 Role of Krev Interaction Trapped-1 in Prostacyclin-Induced Protection against Lung Vascular Permeability Induced by Excessive Mechanical Forces and Thrombin Receptor Activating Peptide 6.
25814554 2015 Phospho-tyrosine dependent protein-protein interaction network.
25707093 2014 A Japanese pedigree of familial cerebral cavernous malformations--a case report.
25525273 2015 Structural basis for the disruption of the cerebral cavernous malformations 2 (CCM2) interaction with Krev interaction trapped 1 (KRIT1) by disease-associated mutations.
25413039 2014 Cerebral cavernous malformations and unilateral moyamoya in a patient with a new mutation in the KRIT-1 /CCM1 gene.
25320085 2014 KRIT1 protein depletion modifies endothelial cell behavior via increased vascular endothelial growth factor (VEGF) signaling.
25203678 2015 Proteomic analysis reveals KRIT1 as a modulator for the antioxidant effects of valproic acid in human bone-marrow mesenchymal stromal cells.
25185960 2014 Familial cerebral cavernous angiomas: clinical and genetic features in a Chinese family with a frame-shift mutation in the CCM1 gene (krit1).
25086949 2014 A novel CCM1 mutation associated with multiple cerebral and vertebral cavernous malformations.
25059659 2014 Structural determinants for binding of sorting nexin 17 (SNX17) to the cytoplasmic adaptor protein Krev interaction trapped 1 (KRIT1).
24714220 2014 CCM1 and the second life of proteins in adhesion complexes.
24705002 2014 Unexpected distribution of KRIT1 inside the nucleus: new insight in a complex molecular pathway.
24466005 2014 Mutation prevalence of cerebral cavernous malformation genes in Spanish patients.
24291398 2014 KRIT1 loss of function causes a ROS-dependent upregulation of c-Jun.
24058906 2013 Sporadic cerebral cavernous malformations: report of further mutations of CCM genes in 40 Italian patients.
24007869 2013 Identification of a c.601C>G mutation in the CCM1 gene in a kindred with multiple skin, spinal and cerebral cavernous malformations.
23872064 2013 miR-21 coordinates tumor growth and modulates KRIT1 levels.
23814056 2013 The structure of the ternary complex of Krev interaction trapped 1 (KRIT1) bound to both the Rap1 GTPase and the heart of glass (HEG1) cytoplasmic tail.
23695561 2013 Cocrystal structure of the ICAP1 PTB domain in complex with a KRIT1 peptide.
23584803 2013 Two-hit mechanism in cerebral cavernous malformation? A case of monozygotic twins with a CCM1/KRIT1 germline mutation.
23485406 2013 Genomic causes of multiple cerebral cavernous malformations in a Japanese population.
23317506 2013 Mechanism for KRIT1 release of ICAP1-mediated suppression of integrin activation.
23007647 2012 Structural basis of the junctional anchorage of the cerebral cavernous malformations complex.
22699465 2011 Familial cerebral cavernomas due to a KRIT1 mutation presenting with epilepsy.
22664934 2012 Comparison of tear protein levels in breast cancer patients and healthy controls using a de novo proteomic approach.
22577140 2012 Structural basis for small G protein effector interaction of Ras-related protein 1 (Rap1) and adaptor protein Krev interaction trapped 1 (KRIT1).
21633110 2011 A mechanism of Rap1-induced stabilization of endothelial cell--cell junctions.
21029238 2011 Mutation analysis of CCM1, CCM2 and CCM3 genes in a cohort of Italian patients with cerebral cavernous malformation.
20884211 2011 A novel CCM1 gene mutation causes cerebral cavernous malformation in a Chinese family.
20798775 2010 Small deletion at the 7q21.2 locus in a CCM family detected by real-time quantitative PCR.
20689144 2010 A novel KRIT1 gene mutation in a patient with cerebral and multiple spinal cavernous malformations.
20668652 2010 KRIT1 regulates the homeostasis of intracellular reactive oxygen species.
20616044 2010 Cerebral cavernous malformation protein CCM1 inhibits sprouting angiogenesis by activating DELTA-NOTCH signaling.
20419355 2010 Genetic variations within KRIT1/CCM1, MGC4607/CCM2 and PDCD10/CCM3 in a large Italian family harbouring a Krit1/CCM1 mutation.
20379614 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
20332120 2010 CCM1 regulates vascular-lumen organization by inducing endothelial polarity.
20308363 2010 Cerebral cavernous malformations proteins inhibit Rho kinase to stabilize vascular integrity.
20306072 2010 Novel KRIT1/CCM1 mutation in a patient with retinal cavernous hemangioma and cerebral cavernous malformation.
19833796 2010 Familial versus sporadic cavernous malformations: differences in developmental venous anomaly association and lesion phenotype.
19454328 C329X in KRIT1 is a founder mutation among CCM patients in Sardinia.
19453802 2009 Frequency and phenotypes of cutaneous vascular malformations in a consecutive series of 417 patients with familial cerebral cavernous malformations.
19199464 2009 Molecular screening test in familial forms of cerebral cavernous malformation: the impact of the Multiplex Ligation-dependent Probe Amplification approach.
19182478 2009 Cutaneous venous malformations in familial cerebral cavernomatosis caused by KRIT1 gene mutations.
19092252 2009 Novel KRIT1 mutation and no molecular evidence of anticipation in a family with cerebral and spinal cavernous malformations.
19088124 2009 A two-hit mechanism causes cerebral cavernous malformations: complete inactivation of CCM1, CCM2 or CCM3 in affected endothelial cells.
19088123 2009 Biallelic somatic and germline mutations in cerebral cavernous malformations (CCMs): evidence for a two-hit mechanism of CCM pathogenesis.
18812969 2008 Krit1 modulates beta 1-integrin-mediated endothelial cell proliferation.
18300272 2008 Novel CCM1, CCM2, and CCM3 mutations in patients with cerebral cavernous malformations: in-frame deletion in CCM2 prevents formation of a CCM1/CCM2/CCM3 protein complex.
17954608 2007 KRIT-1/CCM1 is a Rap1 effector that regulates endothelial cell cell junctions.
17916086 2007 Krit 1 interactions with microtubules and membranes are regulated by Rap1 and integrin cytoplasmic domain associated protein-1.
17657516 2007 CCM3 interacts with CCM2 indicating common pathogenesis for cerebral cavernous malformations.
17562932 2007 Clinical, magnetic resonance imaging, and genetic study of 5 Italian families with cerebral cavernous malformation.
17440989 2007 Highly variable penetrance in subjects affected with cavernous cerebral angiomas (CCM) carrying novel CCM1 and CCM2 mutations.
17290187 2007 Interaction between krit1 and malcavernin: implications for the pathogenesis of cerebral cavernous malformations.
17148043 2006 A splice-site mutation in CCM1/KRIT1 is associated with retinal and cerebral cavernous hemangioma.
17043900 2007 Identification of two novel mutations and of a novel critical region in the KRIT1 gene.
16769843 2006 Frequency of retinal cavernomas in 60 patients with familial cerebral cavernomas: a clinical and genetic study.
16712798 2006 Sorting nexin 17, a non-self-assembling and a PtdIns(3)P high class affinity protein, interacts with the cerebral cavernous malformation related protein KRIT1.
16529293 2006 A novel deletion mutation in CCM1 gene (krit1) is detected in a Chinese family with cerebral cavernous malformations.
16373645 2006 CCM2 expression parallels that of CCM1.
16321204 2005 [Analysis of CCM1 gene mutations in Chinese patients with intracranial cavernous malformations].
16239636 2005 Cerebral venous malformations have distinct genetic origin from cerebral cavernous malformations.
16037064 2005 CCM1 and CCM2 protein interactions in cell signaling: implications for cerebral cavernous malformations pathogenesis.
15718512 2005 Biallelic somatic and germ line CCM1 truncating mutations in a cerebral cavernous malformation lesion.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15079030 2004 CCM1 mutation screen of sporadic cases with cerebral cavernous malformations.
15046662 2004 KRIT1/cerebral cavernous malformation 1 protein localizes to vascular endothelium, astrocytes, and pyramidal cells of the adult human cerebral cortex.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12877753 2003 Variable expression of cerebral cavernous malformations in carriers of a premature termination codon in exon 17 of the Krit1 gene.
12853948 2003 The DNA sequence of human chromosome 7.
12810002 2003 Identification of a novel KRIT1 mutation in an Italian family with cerebral cavernous malformation by the protein truncation test.
12690205 2003 Human chromosome 7: DNA sequence and biology.
12682320 2003 Molecular genetic investigations in the CCM1 gene in sporadic cerebral cavernomas.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12204286 2002 Krit1/cerebral cavernous malformation 1 mRNA is preferentially expressed in neurons and epithelial cells in embryo and adult.
12172908 2002 Mutation and expression analysis of the KRIT1 gene associated with cerebral cavernous malformations (CCM1).
12140362 2002 KRIT1, a gene mutated in cerebral cavernous malformation, encodes a microtubule-associated protein.
11941540 2002 Krit1 missense mutations lead to splicing errors in cerebral cavernous malformation.
11854171 2002 KRIT1 association with the integrin-binding protein ICAP-1: a new direction in the elucidation of cerebral cavernous malformations (CCM1) pathogenesis.
11741838 2001 Interaction between krit1 and icap1alpha infers perturbation of integrin beta1-mediated angiogenesis in the pathogenesis of cerebral cavernous malformation.
11342228 2001 Identification of eight novel 5'-exons in cerebral capillary malformation gene-1 (CCM1) encoding KRIT1.
11161805 2001 Computational and experimental analyses reveal previously undetected coding exons of the KRIT1 (CCM1) gene.
11161791 2000 Cloning of the murine Krit1 cDNA reveals novel mammalian 5' coding exons.
10814716 2000 KRIT1 is mutated in hyperkeratotic cutaneous capillary-venous malformation associated with cerebral capillary malformation.
10545614 1999 Mutations in the gene encoding KRIT1, a Krev-1/rap1a binding protein, cause cerebral cavernous malformations (CCM1).
10508515 1999 Truncating mutations in CCM1, encoding KRIT1, cause hereditary cavernous angiomas.
9285558 1997 Association of Krev-1/rap1a with Krit1, a novel ankyrin repeat-containing protein encoded by a gene mapping to 7q21-22.
8530042 1995 A locus for cerebral cavernous malformations maps to chromosome 7q in two families.
7604043 1995 Mapping a gene causing cerebral cavernous malformation to 7q11.2-q21.