4jif
From Proteopedia
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{{STRUCTURE_4jif| PDB=4jif | SCENE= }} | {{STRUCTURE_4jif| PDB=4jif | SCENE= }} | ||
===Co-crystal structure of ICAP1 PTB domain in complex with a KRIT1 peptide=== | ===Co-crystal structure of ICAP1 PTB domain in complex with a KRIT1 peptide=== | ||
+ | {{ABSTRACT_PUBMED_23695561}} | ||
==Disease== | ==Disease== | ||
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==Reference== | ==Reference== | ||
- | <references group="xtra"/><references/> | + | <ref group="xtra">PMID:023695561</ref><references group="xtra"/><references/> |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Boggon, T J.]] | [[Category: Boggon, T J.]] |
Revision as of 14:16, 10 July 2013
Contents |
Co-crystal structure of ICAP1 PTB domain in complex with a KRIT1 peptide
Template:ABSTRACT PUBMED 23695561
Disease
[KRIT1_HUMAN] Hereditary cerebral cavernous malformation. Cerebral cavernous malformations 1 (CCM1) [MIM:116860]: A congenital vascular anomaly of the central nervous system that can result in hemorrhagic stroke, seizures, recurrent headaches, and focal neurologic deficits. The lesions are characterized by grossly enlarged blood vessels consisting of a single layer of endothelium and without any intervening neural tissue, ranging in diameter from a few millimeters to several centimeters. Note=The disease is caused by mutations affecting the gene represented in this entry.[1]
Function
[ITBP1_HUMAN] Regulates integrin signaling by binding to the ITGB1 cytoplasmic tail and preventing the activation of integrin alpha-5/beta-1 (heterodimer of ITGA5 and ITGB1) by talin or FERMT1. May play a role in the recruitment of ITGB1 to focal contacts during integrin-dependent cell adhesion.[REFERENCE:8] [KRIT1_HUMAN] Component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity (By similarity). Negative regulator of angiogenesis. Inhibits endothelial proliferation, apoptosis, migration, lumen formation and sprouting angiogenesis in primary endothelial cells. Promotes AKT phosphorylation in a NOTCH-dependent and independent manner, and inhibits EKR1/2 phosphorylation indirectly through activation of the DELTA-NOTCH cascade. Acts in concert with CDH5 to establish and maintain correct endothelial cell polarity and vascular lumen and these effects are mediated by recruitment and activation of the Par polarity complex and RAP1B. Required for the localization of phosphorylated PRKCZ, PARD3, TIAM1 and RAP1B to the cell junction, and cell junction stabilization. Plays a role in integrin signaling via its interaction with ITGB1BP1; this prevents the interaction between ITGB1 and ITGB1BP1. Plays an important role in the maintenance of the intracellular reactive oxygen species (ROS) homeostasis to prevent oxidative cellular damage. Regulates the homeostasis of intracellular ROS through an antioxidant pathway involving FOXO1 and SOD2. Facilitates the down-regulation of cyclin-D1 (CCND1) levels required for cell transition from proliferative growth to quiescence by preventing the accumulation of intracellular ROS through the modulation of FOXO1 and SOD2 levels.[2] [3] [4] [5] [REFERENCE:17]
About this Structure
4jif is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- Liu W, Boggon TJ. Cocrystal structure of the ICAP1 PTB domain in complex with a KRIT1 peptide. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013 May;69(Pt 5):494-8. doi:, 10.1107/S1744309113010762. Epub 2013 Apr 27. PMID:23695561 doi:10.1107/S1744309113010762
- ↑ 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 Neuropathol. 2002 Sep;104(3):231-40. Epub 2002 Jun 26. PMID:12172908 doi:10.1007/s00401-002-0552-6
- ↑ Lampugnani MG, Orsenigo F, Rudini N, Maddaluno L, Boulday G, Chapon F, Dejana E. CCM1 regulates vascular-lumen organization by inducing endothelial polarity. J Cell Sci. 2010 Apr 1;123(Pt 7):1073-80. doi: 10.1242/jcs.059329. PMID:20332120 doi:10.1242/jcs.059329
- ↑ 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. 2010 Jul 26;5(7):e11786. doi: 10.1371/journal.pone.0011786. PMID:20668652 doi:10.1371/journal.pone.0011786
- ↑ Wustehube J, Bartol A, Liebler SS, Brutsch R, Zhu Y, Felbor U, Sure U, Augustin HG, Fischer A. Cerebral cavernous malformation protein CCM1 inhibits sprouting angiogenesis by activating DELTA-NOTCH signaling. Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12640-5. doi:, 10.1073/pnas.1000132107. Epub 2010 Jun 24. PMID:20616044 doi:10.1073/pnas.1000132107
- ↑ Liu JJ, Stockton RA, Gingras AR, Ablooglu AJ, Han J, Bobkov AA, Ginsberg MH. A mechanism of Rap1-induced stabilization of endothelial cell--cell junctions. Mol Biol Cell. 2011 Jul 15;22(14):2509-19. doi: 10.1091/mbc.E11-02-0157. Epub, 2011 Jun 1. PMID:21633110 doi:10.1091/mbc.E11-02-0157