4tkn: Difference between revisions
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''' | ==Structure of the SNX17 FERM domain bound to the second NPxF motif of KRIT1== | ||
<StructureSection load='4tkn' size='340' side='right' caption='[[4tkn]], [[Resolution|resolution]] 3.00Å' scene=''> | |||
The entry | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4tkn]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TKN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TKN FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4tkn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tkn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4tkn RCSB], [http://www.ebi.ac.uk/pdbsum/4tkn PDBsum]</span></td></tr> | |||
<table> | |||
== Disease == | |||
[[http://www.uniprot.org/uniprot/KRIT1_HUMAN KRIT1_HUMAN]] Hereditary cerebral cavernous malformation. Cerebral cavernous malformations 1 (CCM1) [MIM:[http://omim.org/entry/116860 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.<ref>PMID:12172908</ref> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/SNX17_HUMAN SNX17_HUMAN]] Critical regulator of endosomal recycling of numerous receptors, channels, and other transmembrane proteins. Binds to NPxY sequences in the cytoplasmic tails of target cargos. Plays a role in the sorting of endocytosed LRP1 and APP, and prevents their degradation. Required for maintenance of normal cell surface levels of APP and LRP1. Recycles internalized integrins ITGB1, ITGB5 and their associated alpha subunits, preventing them from lysosomal degradation. Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)).<ref>PMID:15121882</ref> <ref>PMID:15769472</ref> <ref>PMID:16712798</ref> <ref>PMID:19005208</ref> <ref>PMID:22492727</ref> <ref>PMID:21512128</ref> [[http://www.uniprot.org/uniprot/KRIT1_HUMAN 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.<ref>PMID:20332120</ref> <ref>PMID:20668652</ref> <ref>PMID:20616044</ref> <ref>PMID:21633110</ref> [REFERENCE:17] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Boggon, T J.]] | |||
[[Category: Liu, W.]] | |||
[[Category: Stiegler, A L.]] | |||
[[Category: Zhang, R.]] | |||
[[Category: Ferm domain]] | |||
[[Category: Npxf motif]] | |||
[[Category: Npxy motif]] | |||
[[Category: Protein transport-signaling protein complex]] | |||