KRIT1 explained

Krev interaction trapped protein 1 or Cerebral cavernous malformations 1 protein is a protein that in humans is encoded by the KRIT1 gene.^{[1] [2] [3] [4]} This gene contains 16 coding exons and is located on chromosome 7q21.2. Loss of function mutations in KRIT1 result in the onset of cerebral cavernous malformation.^[5] Cerebral cavernous malformations (CCMs) are vascular malformations in the brain and spinal cord made of dilated capillary vessels.

Interactions

The KRIT1 protein, is 736 amino acids in length and has a variety of functions. KRIT1 has been shown to interact with multiple signaling pathways including; ITGB1BP1.,^{[6] [7]} reactive oxygen species,^[8] cell death,^[9] and angiogenesis.^[10] Related to cerebral cavernous malformations, this protein is required for maintaining the structural integrity of the vasculature.^{[11] [12]}

Further reading

• Verlaan DJ, Davenport WJ, Stefan H, Sure U, Siegel AM, Rouleau GA . Cerebral cavernous malformations: mutations in Krit1 . Neurology . 58 . 6 . 853–7 . Mar 2002 . 11914398 . 10.1212/wnl.58.6.853 . 12113924 .
• Marchuk DA, Gallione CJ, Morrison LA, Clericuzio CL, Hart BL, Kosofsky BE, Louis DN, Gusella JF, Davis LE, Prenger VL . A locus for cerebral cavernous malformations maps to chromosome 7q in two families . Genomics . 28 . 2 . 311–4 . Jul 1995 . 8530042 . 10.1006/geno.1995.1147 .
• Serebriiskii I, Estojak J, Sonoda G, Testa JR, Golemis EA . 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 . Aug 1997 . 9285558 . 10.1038/sj.onc.1201268 .
• Deloulme JC, Prichard L, Delattre O, Storm DR . 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 . Oct 1997 . 9341188 . 10.1074/jbc.272.43.27369 . free .
• Laberge-le Couteulx S, Jung HH, Labauge P, Houtteville JP, Lescoat C, Cecillon M, Marechal E, Joutel A, Bach JF, Tournier-Lasserve E . Truncating mutations in CCM1, encoding KRIT1, cause hereditary cavernous angiomas . Nature Genetics . 23 . 2 . 189–93 . Oct 1999 . 10508515 . 10.1038/13815 . 22297740 .
• Sahoo T, Johnson EW, Thomas JW, Kuehl PM, Jones TL, Dokken CG, Touchman JW, Gallione CJ, Lee-Lin SQ, Kosofsky B, Kurth JH, Louis DN, Mettler G, Morrison L, Gil-Nagel A, Rich SS, Zabramski JM, Boguski MS, Green ED, Marchuk DA . Mutations in the gene encoding KRIT1, a Krev-1/rap1a binding protein, cause cerebral cavernous malformations (CCM1) . Human Molecular Genetics . 8 . 12 . 2325–33 . Nov 1999 . 10545614 . 10.1093/hmg/8.12.2325 . free .
• Eerola I, Plate KH, Spiegel R, Boon LM, Mulliken JB, Vikkula M . KRIT1 is mutated in hyperkeratotic cutaneous capillary-venous malformation associated with cerebral capillary malformation . Human Molecular Genetics . 9 . 9 . 1351–5 . May 2000 . 10814716 . 10.1093/hmg/9.9.1351 . free .
• Zhang J, Clatterbuck RE, Rigamonti D, Dietz HC . Cloning of the murine Krit1 cDNA reveals novel mammalian 5' coding exons . Genomics . 70 . 3 . 392–5 . Dec 2000 . 11161791 . 10.1006/geno.2000.6410 .
• Sahoo T, Goenaga-Diaz E, Serebriiskii IG, Thomas JW, Kotova E, Cuellar JG, Peloquin JM, Golemis E, Beitinjaneh F, Green ED, Johnson EW, Marchuk DA . Computational and experimental analyses reveal previously undetected coding exons of the KRIT1 (CCM1) gene . Genomics . 71 . 1 . 123–6 . Jan 2001 . 11161805 . 10.1006/geno.2000.6426 .
• Zhang J, Clatterbuck RE, Rigamonti D, Chang DD, Dietz HC . 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 . Dec 2001 . 11741838 . 10.1093/hmg/10.25.2953 . free .
• Couteulx SL, Brézin AP, Fontaine B, Tournier-Lasserve E, Labauge P . A novel KRIT1/CCM1 truncating mutation in a patient with cerebral and retinal cavernous angiomas . Archives of Ophthalmology . 120 . 2 . 217–8 . Feb 2002 . 11831930 .
• Zawistowski JS, Serebriiskii IG, Lee MF, Golemis EA, Marchuk DA . 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 . Feb 2002 . 11854171 . 10.1093/hmg/11.4.389 . free .
• Verlaan DJ, Siegel AM, Rouleau GA . Krit1 missense mutations lead to splicing errors in cerebral cavernous malformation . American Journal of Human Genetics . 70 . 6 . 1564–7 . Jun 2002 . 11941540 . 379143 . 10.1086/340604 .
• Gunel M, Laurans MS, Shin D, DiLuna ML, Voorhees J, Choate K, Nelson-Williams C, Lifton RP . 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 . Aug 2002 . 12140362 . 125011 . 10.1073/pnas.122354499 . 2002PNAS...9910677G . free .
• Kehrer-Sawatzki H, Wilda M, Braun VM, Richter HP, Hameister H . Mutation and expression analysis of the KRIT1 gene associated with cerebral cavernous malformations (CCM1) . Acta Neuropathologica . 104 . 3 . 231–40 . Sep 2002 . 12172908 . 10.1007/s00401-002-0552-6 . 1909964 .
• Denier C, Gasc JM, Chapon F, Domenga V, Lescoat C, Joutel A, Tournier-Lasserve E . 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 . Sep 2002 . 12204286 . 10.1016/S0925-4773(02)00209-5 . 12682438 .

Notes and References

1. Web site: UniProt . www.uniprot.org . 12 July 2023.
2. Günel M, Awad IA, Anson J, Lifton RP . 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 . Jul 1995 . 7604043 . 41570 . 10.1073/pnas.92.14.6620 . 1995PNAS...92.6620G . free .
3. Eerola I, McIntyre B, Vikkula M . Identification of eight novel 5'-exons in cerebral capillary malformation gene-1 (CCM1) encoding KRIT1 . Biochimica et Biophysica Acta . 1517 . 3 . 464–7 . Feb 2001 . 11342228 . 10.1016/s0167-4781(00)00303-1 .
4. Web site: Entrez Gene: KRIT1 KRIT1, ankyrin repeat containing.
5. Pagenstecher A, Stahl S, Sure U, Felbor U . 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 . Mar 2009 . 19088124 . 2640205 . 10.1093/hmg/ddn420 .
6. Zhang J, Clatterbuck RE, Rigamonti D, Chang DD, Dietz HC . 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 . Dec 2001 . 11741838 . 10.1093/hmg/10.25.2953 . free .
7. Zawistowski JS, Serebriiskii IG, Lee MF, Golemis EA, Marchuk DA . 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 . Feb 2002 . 11854171 . 10.1093/hmg/11.4.389 . free .
8. Goitre L, Balzac F, Degani S, Degan P, Marchi S, Pinton P, Retta SF . KRIT1 regulates the homeostasis of intracellular reactive oxygen species . PLOS ONE . 5 . 7 . e11786 . 2010 . 20668652 . 2910502 . 10.1371/journal.pone.0011786 . 2010PLoSO...511786G . Capogrossi . Maurizio C. . free .
9. Ito S, Greiss S, Gartner A, Derry WB . Cell-nonautonomous regulation of C. elegans germ cell death by kri-1 . Current Biology . 20 . 4 . 333–338 . Feb 2010 . 20137949 . 2829125 . 10.1016/j.cub.2009.12.032 .
10. Wüstehube J, Bartol A, Liebler SS, Brütsch R, Zhu Y, Felbor U, Sure U, Augustin HG, Fischer A . 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 . Jul 2010 . 20616044 . 2906569 . 10.1073/pnas.1000132107 . free .
11. Glading A, Han J, Stockton RA, Ginsberg MH . KRIT-1/CCM1 is a Rap1 effector that regulates endothelial cell cell junctions . The Journal of Cell Biology . 179 . 2 . 247–254 . Oct 2007 . 17954608 . 2064761 . 10.1083/jcb.200705175 .
12. Borikova AL, Dibble CF, Sciaky N, Welch CM, Abell AN, Bencharit S, Johnson GL . Rho kinase inhibition rescues the endothelial cell cerebral cavernous malformation phenotype . The Journal of Biological Chemistry . 285 . 16 . 11760–11764 . Apr 2010 . 20181950 . 2852911 . 10.1074/jbc.C109.097220 . free .