KRIT1

KRIT1, ankyrin repeat containing
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsKRIT1 ; CAM; CCM1
External IDsOMIM: 604214 MGI: 1930618 HomoloGene: 12746 GeneCards: KRIT1 Gene
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez88979264
EnsemblENSG00000001631ENSMUSG00000000600
UniProtO00522Q6S5J6
RefSeq (mRNA)NM_001013406NM_001170552
RefSeq (protein)NP_001013424NP_001164023
Location (UCSC)Chr 7:
91.83 – 91.88 Mb		Chr 5:
3.8 – 3.84 Mb
PubMed search

Krev interaction trapped protein 1 is a protein that in humans is encoded by the CCM1 gene.[1][2][3] This gene contains 16 coding exons and is located on chromosome 7q21.2. Loss of function mutations in CCM1 result in the onset of Cerebral cavernous malformation.[4] Cerebral cavernous malformations (CCMs) are vascular malformations in the brain and spinal cord made of dilated capillary vessels.

Interactions

The normal CCM1 protein, KRIT1 (Krev Interaction Trapped), is 736 amino acids in length and has a variety of functions. KRIT1 has been shown to interact with multiple signaling pathways including; ITGB1BP1.,[5][6] reactive oxygen species,[7] cell death,[8] and angiogenesis.[9] Related to the CCM illness, this protein is required for maintaining the structural integrity of the vasculature.[10][11]

References

  1. ↑ Günel M, Awad IA, Anson J, Lifton RP (Jul 1995). "Mapping a gene causing cerebral cavernous malformation to 7q11.2-q21". Proceedings of the National Academy of Sciences of the United States of America 92 (14): 6620–4. doi:10.1073/pnas.92.14.6620. PMC 41570. PMID 7604043. Vancouver style error (help)
  2. ↑ Eerola I, McIntyre B, Vikkula M (Feb 2001). "Identification of eight novel 5'-exons in cerebral capillary malformation gene-1 (CCM1) encoding KRIT1". Biochimica Et Biophysica Acta 1517 (3): 464–7. doi:10.1016/s0167-4781(00)00303-1. PMID 11342228.
  3. ↑ "Entrez Gene: KRIT1 KRIT1, ankyrin repeat containing".
  4. ↑ Pagenstecher A, Stahl S, Sure U, Felbor U (Mar 2009). "A two-hit mechanism causes cerebral cavernous malformations: complete inactivation of CCM1, CCM2 or CCM3 in affected endothelial cells". Human Molecular Genetics 18 (5): 911–8. doi:10.1093/hmg/ddn420. PMC 2640205. PMID 19088124.
  5. ↑ Zhang J, Clatterbuck RE, Rigamonti D, Chang DD, Dietz HC (Dec 2001). "Interaction between krit1 and icap1alpha infers perturbation of integrin beta1-mediated angiogenesis in the pathogenesis of cerebral cavernous malformation". Human Molecular Genetics 10 (25): 2953–60. doi:10.1093/hmg/10.25.2953. PMID 11741838.
  6. ↑ Zawistowski JS, Serebriiskii IG, Lee MF, Golemis EA, Marchuk DA (Feb 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 11 (4): 389–96. doi:10.1093/hmg/11.4.389. PMID 11854171.
  7. ↑ Goitre L, Balzac F, Degani S, Degan P, Marchi S, Pinton P et al. (2010). Capogrossi MC, ed. "KRIT1 regulates the homeostasis of intracellular reactive oxygen species". PloS One 5 (7): e11786. doi:10.1371/journal.pone.0011786. PMC 2910502. PMID 20668652.
  8. ↑ Ito S, Greiss S, Gartner A, Derry WB (Feb 2010). "Cell-nonautonomous regulation of C. elegans germ cell death by kri-1". Current Biology 20 (4): 333–338. doi:10.1016/j.cub.2009.12.032. PMC 2829125. PMID 20137949.
  9. ↑ Wüstehube J, Bartol A, Liebler SS, Brütsch R, Zhu Y, Felbor U et al. (Jul 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 107 (28): 12640–12645. doi:10.1073/pnas.1000132107. PMC 2906569. PMID 20616044. Vancouver style error (help)
  10. ↑ Glading A, Han J, Stockton RA, Ginsberg MH (Oct 2007). "KRIT-1/CCM1 is a Rap1 effector that regulates endothelial cell cell junctions". The Journal of Cell Biology 179 (2): 247–254. doi:10.1083/jcb.200705175. PMC 2064761. PMID 17954608.
  11. ↑ Borikova AL, Dibble CF, Sciaky N, Welch CM, Abell AN, Bencharit S et al. (Apr 2010). "Rho kinase inhibition rescues the endothelial cell cerebral cavernous malformation phenotype". The Journal of Biological Chemistry 285 (16): 11760–11764. doi:10.1074/jbc.C109.097220. PMC 2852911. PMID 20181950.

Further reading

  • Verlaan DJ, Davenport WJ, Stefan H, Sure U, Siegel AM, Rouleau GA (Mar 2002). "Cerebral cavernous malformations: mutations in Krit1". Neurology 58 (6): 853–7. doi:10.1212/wnl.58.6.853. PMID 11914398.
  • Marchuk DA, Gallione CJ, Morrison LA, Clericuzio CL, Hart BL, Kosofsky BE et al. (Jul 1995). "A locus for cerebral cavernous malformations maps to chromosome 7q in two families". Genomics 28 (2): 311–4. doi:10.1006/geno.1995.1147. PMID 8530042.
  • Serebriiskii I, Estojak J, Sonoda G, Testa JR, Golemis EA (Aug 1997). "Association of Krev-1/rap1a with Krit1, a novel ankyrin repeat-containing protein encoded by a gene mapping to 7q21-22". Oncogene 15 (9): 1043–9. doi:10.1038/sj.onc.1201268. PMID 9285558.
  • Deloulme JC, Prichard L, Delattre O, Storm DR (Oct 1997). "The prooncoprotein EWS binds calmodulin and is phosphorylated by protein kinase C through an IQ domain". The Journal of Biological Chemistry 272 (43): 27369–77. doi:10.1074/jbc.272.43.27369. PMID 9341188.
  • Laberge-le Couteulx S, Jung HH, Labauge P, Houtteville JP, Lescoat C, Cecillon M et al. (Oct 1999). "Truncating mutations in CCM1, encoding KRIT1, cause hereditary cavernous angiomas". Nature Genetics 23 (2): 189–93. doi:10.1038/13815. PMID 10508515.
  • Sahoo T, Johnson EW, Thomas JW, Kuehl PM, Jones TL, Dokken CG et al. (Nov 1999). "Mutations in the gene encoding KRIT1, a Krev-1/rap1a binding protein, cause cerebral cavernous malformations (CCM1)". Human Molecular Genetics 8 (12): 2325–33. doi:10.1093/hmg/8.12.2325. PMID 10545614.
  • Eerola I, Plate KH, Spiegel R, Boon LM, Mulliken JB, Vikkula M (May 2000). "KRIT1 is mutated in hyperkeratotic cutaneous capillary-venous malformation associated with cerebral capillary malformation". Human Molecular Genetics 9 (9): 1351–5. doi:10.1093/hmg/9.9.1351. PMID 10814716.
  • Zhang J, Clatterbuck RE, Rigamonti D, Dietz HC (Dec 2000). "Cloning of the murine Krit1 cDNA reveals novel mammalian 5' coding exons". Genomics 70 (3): 392–5. doi:10.1006/geno.2000.6410. PMID 11161791.
  • Sahoo T, Goenaga-Diaz E, Serebriiskii IG, Thomas JW, Kotova E, Cuellar JG et al. (Jan 2001). "Computational and experimental analyses reveal previously undetected coding exons of the KRIT1 (CCM1) gene". Genomics 71 (1): 123–6. doi:10.1006/geno.2000.6426. PMID 11161805.
  • Zhang J, Clatterbuck RE, Rigamonti D, Chang DD, Dietz HC (Dec 2001). "Interaction between krit1 and icap1alpha infers perturbation of integrin beta1-mediated angiogenesis in the pathogenesis of cerebral cavernous malformation". Human Molecular Genetics 10 (25): 2953–60. doi:10.1093/hmg/10.25.2953. PMID 11741838.
  • Couteulx SL, Brézin AP, Fontaine B, Tournier-Lasserve E, Labauge P (Feb 2002). "A novel KRIT1/CCM1 truncating mutation in a patient with cerebral and retinal cavernous angiomas". Archives of Ophthalmology 120 (2): 217–8. PMID 11831930. Vancouver style error (help)
  • Zawistowski JS, Serebriiskii IG, Lee MF, Golemis EA, Marchuk DA (Feb 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 11 (4): 389–96. doi:10.1093/hmg/11.4.389. PMID 11854171.
  • Verlaan DJ, Siegel AM, Rouleau GA (Jun 2002). "Krit1 missense mutations lead to splicing errors in cerebral cavernous malformation". American Journal of Human Genetics 70 (6): 1564–7. doi:10.1086/340604. PMC 379143. PMID 11941540.
  • Gunel M, Laurans MS, Shin D, DiLuna ML, Voorhees J, Choate K et al. (Aug 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 99 (16): 10677–82. doi:10.1073/pnas.122354499. PMC 125011. PMID 12140362.
  • Kehrer-Sawatzki H, Wilda M, Braun VM, Richter HP, Hameister H (Sep 2002). "Mutation and expression analysis of the KRIT1 gene associated with cerebral cavernous malformations (CCM1)". Acta Neuropathologica 104 (3): 231–40. doi:10.1007/s00401-002-0552-6. PMID 12172908.
  • Denier C, Gasc JM, Chapon F, Domenga V, Lescoat C, Joutel A et al. (Sep 2002). "Krit1/cerebral cavernous malformation 1 mRNA is preferentially expressed in neurons and epithelial cells in embryo and adult". Mechanisms of Development 117 (1-2): 363–7. doi:10.1016/S0925-4773(02)00209-5. PMID 12204286.