KRIT1

KRIT1
Available structures PDB Ortholog search: C9JD81 PDBe C9JD81 RCSB List of PDB id codes 3U7D, 4DX8, 4DXA, 4HDO, 4HDQ, 4JIF, 4TKN, 5D68
Identifiers
Aliases	KRIT1 , ankyrin repeat containing, CAM, CCM1
External IDs	OMIM: 604214; MGI: 1930618; HomoloGene: 12746; GeneCards: KRIT1; OMA:KRIT1 - orthologs
Gene location (Mouse) Chr. Chromosome 5 (mouse) [1] Band 5 A1|5 2.26 cM Start 3,853,184 bp [1] End 3,895,564 bp [1]
RNA expression pattern Bgee Human Mouse (ortholog) n/a Top expressed in Rostral migratory stream interventricular septum mammillary body lateral septal nucleus dorsomedial hypothalamic nucleus anterior amygdaloid area tail of embryo spermatocyte lateral hypothalamus genital tubercle BioGPS More reference expression data
Gene ontology Molecular function microtubule binding protein binding phosphatidylinositol-4,5-bisphosphate binding protein-containing complex binding GTPase regulator activity Cellular component cytoskeleton membrane microtubule plasma membrane cytoplasm cell-cell junction cell junction extracellular space Biological process regulation of establishment of cell polarity negative regulation of angiogenesis small GTPase mediated signal transduction angiogenesis negative regulation of endothelial cell proliferation negative regulation of endothelial cell apoptotic process negative regulation of endothelial cell migration positive regulation of protein binding cell redox homeostasis regulation of catalytic activity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 889 79264 Ensembl ENSG00000001631 ENSMUSG00000000600 UniProt O00522 Q6S5J6 RefSeq (mRNA) NM_001013406 NM_004912 NM_194454 NM_194455 NM_194456 NM_001170552 NM_030675 RefSeq (protein) NP_001013424 NP_004903 NP_919436 NP_919437 NP_919438 NP_001337598 NP_001337599 NP_001337600 NP_001337601 NP_001337602 NP_001337603 NP_001337604 NP_001337605 NP_001337606 NP_001337607 NP_001337608 NP_001337609 NP_001337610 NP_001337611 NP_001337612 NP_001337613 NP_001337614 NP_001337615 NP_001337616 NP_001337617 NP_001337618 NP_001337619 NP_001337620 NP_001337621 NP_001337622 NP_001337623 NP_001337624 NP_001337625 NP_001337626 NP_001164023 NP_109600 Location (UCSC) n/a Chr 5: 3.85 – 3.9 Mb PubMed search [2] [3]
Wikidata
View/Edit Human View/Edit Mouse

Krev interaction trapped protein 1 or Cerebral cavernous malformations 1 protein is a protein that in humans is encoded by the KRIT1 gene. ^{[4] [5] [6] [7]} 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. ^[8] 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., ^{[9] [10]} reactive oxygen species, ^[11] cell death, ^[12] and angiogenesis. ^[13] Related to cerebral cavernous malformations, this protein is required for maintaining the structural integrity of the vasculature. ^{[14] [15]}

References

1. GRCm38: Ensembl release 89: ENSMUSG00000000600 – Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "UniProt". www.uniprot.org. Retrieved 12 July 2023.
5. 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. Bibcode:1995PNAS...92.6620G. doi: 10.1073/pnas.92.14.6620 . PMC   41570 . PMID   7604043.
6. 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.
7. "Entrez Gene: KRIT1 KRIT1, ankyrin repeat containing".
8. 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.
9. 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.
10. 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.
11. Goitre L, Balzac F, Degani S, Degan P, Marchi S, Pinton P, Retta SF (2010). Capogrossi MC (ed.). "KRIT1 regulates the homeostasis of intracellular reactive oxygen species". PLOS ONE. 5 (7) e11786. Bibcode:2010PLoSO...511786G. doi: 10.1371/journal.pone.0011786 . PMC   2910502 . PMID   20668652.
12. 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. Bibcode:2010CBio...20..333I. doi:10.1016/j.cub.2009.12.032. PMC   2829125 . PMID   20137949.
13. Wüstehube J, Bartol A, Liebler SS, Brütsch R, Zhu Y, Felbor U, Sure U, Augustin HG, Fischer A (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.
14. 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.
15. Borikova AL, Dibble CF, Sciaky N, Welch CM, Abell AN, Bencharit S, Johnson GL (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. S2CID   12113924.
• Marchuk DA, Gallione CJ, Morrison LA, Clericuzio CL, Hart BL, Kosofsky BE, Louis DN, Gusella JF, Davis LE, Prenger VL (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, Marechal E, Joutel A, Bach JF, Tournier-Lasserve E (Oct 1999). "Truncating mutations in CCM1, encoding KRIT1, cause hereditary cavernous angiomas". Nature Genetics. 23 (2): 189–93. doi:10.1038/13815. PMID   10508515. S2CID   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 (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, Peloquin JM, Golemis E, Beitinjaneh F, Green ED, Johnson EW, Marchuk DA (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.
• 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, Nelson-Williams C, Lifton RP (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. Bibcode:2002PNAS...9910677G. 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. S2CID   1909964.
• Denier C, Gasc JM, Chapon F, Domenga V, Lescoat C, Joutel A, Tournier-Lasserve E (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. S2CID   12682438.