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6fd0

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Human KIBRA C2 domain mutant M734I S735A

Structural highlights

6fd0 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	6fb4
Gene:	WWC1, KIAA0869 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[KIBRA_HUMAN] Probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in tumor suppression by restricting proliferation and promoting apoptosis. Along with NF2 can synergistically induce the phosphorylation of LATS1 and LATS2 and can probably function in the regulation of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway. Acts as a transcriptional coactivator of ESR1 which plays an essential role in DYNLL1-mediated ESR1 transactivation. Regulates collagen-stimulated activation of the ERK/MAPK cascade. Modulates directional migration of podocytes. Acts as a substrate for PRKCZ. Plays a role in cognition and memory performance.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Publication Abstract from PubMed

KIBRA, a multi-functional scaffold protein with around twenty known binding partners, is involved in memory and cognition, organ size control via the Hippo pathway, cell polarity, and membrane trafficking. KIBRA includes tandem N-terminal WW domains, a C2 domain and motifs for binding aPKC and PDZ domains. A naturally occurring human KIBRA variant involving residue changes at positions 734 (M-to-I) and 735 (S-to-A) within the C2 domain affects cognitive performance. We have elucidated 3D structures, and calcium and phosphoinositide binding properties, of human KIBRA C2 domain. Both wild type and variant C2 adopt a canonical type I topology C2 domain fold. Neither Ca(2+) nor any other metal ion was bound to wild type or variant KIBRA C2 in crystal structures, and Ca(2+) titration produced no significant reproducible changes in NMR spectra. NMR and X-ray diffraction data indicate that KIBRA C2 binds phosphoinositides via an atypical site involving beta-strands 5, 2, 1, and 8. Molecular dynamics simulations indicate that KIBRA C2 interacts with membranes via primary and secondary sites on the same domain face as the experimentally identified phosphoinositide binding site. Our results indicate that KIBRA C2 domain association with membranes is calcium-independent and involves distinctive C2 domain-membrane relative orientations.

Distinctive phosphoinositide and Ca(2+) binding properties of normal and cognitive performance-linked variant forms of KIBRA C2 domain.,Posner MG, Upadhyay A, Ishima R, Kalli AC, Harris G, Kremerskothen J, Sansom MSP, Crennell SJ, Bagby S J Biol Chem. 2018 May 3. pii: RA118.002279. doi: 10.1074/jbc.RA118.002279. PMID:29724824^[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Buther K, Plaas C, Barnekow A, Kremerskothen J. KIBRA is a novel substrate for protein kinase Czeta. Biochem Biophys Res Commun. 2004 May 7;317(3):703-7. PMID:15081397 doi:http://dx.doi.org/10.1016/j.bbrc.2004.03.107
↑ Rayala SK, den Hollander P, Manavathi B, Talukder AH, Song C, Peng S, Barnekow A, Kremerskothen J, Kumar R. Essential role of KIBRA in co-activator function of dynein light chain 1 in mammalian cells. J Biol Chem. 2006 Jul 14;281(28):19092-9. Epub 2006 May 9. PMID:16684779 doi:10.1074/jbc.M600021200
↑ Hilton HN, Stanford PM, Harris J, Oakes SR, Kaplan W, Daly RJ, Ormandy CJ. KIBRA interacts with discoidin domain receptor 1 to modulate collagen-induced signalling. Biochim Biophys Acta. 2008 Mar;1783(3):383-93. doi: 10.1016/j.bbamcr.2007.12.007., Epub 2008 Jan 9. PMID:18190796 doi:http://dx.doi.org/10.1016/j.bbamcr.2007.12.007
↑ Duning K, Schurek EM, Schluter M, Bayer M, Reinhardt HC, Schwab A, Schaefer L, Benzing T, Schermer B, Saleem MA, Huber TB, Bachmann S, Kremerskothen J, Weide T, Pavenstadt H. KIBRA modulates directional migration of podocytes. J Am Soc Nephrol. 2008 Oct;19(10):1891-903. doi: 10.1681/ASN.2007080916. Epub, 2008 Jul 2. PMID:18596123 doi:10.1681/ASN.2007080916
↑ Johannsen S, Duning K, Pavenstadt H, Kremerskothen J, Boeckers TM. Temporal-spatial expression and novel biochemical properties of the memory-related protein KIBRA. Neuroscience. 2008 Sep 9;155(4):1165-73. doi: 10.1016/j.neuroscience.2008.06.054., Epub 2008 Jul 3. PMID:18672031 doi:http://dx.doi.org/10.1016/j.neuroscience.2008.06.054
↑ Yu J, Zheng Y, Dong J, Klusza S, Deng WM, Pan D. Kibra functions as a tumor suppressor protein that regulates Hippo signaling in conjunction with Merlin and Expanded. Dev Cell. 2010 Feb 16;18(2):288-99. doi: 10.1016/j.devcel.2009.12.012. PMID:20159598 doi:http://dx.doi.org/10.1016/j.devcel.2009.12.012
↑ Duning K, Wennmann DO, Bokemeyer A, Reissner C, Wersching H, Thomas C, Buschert J, Guske K, Franzke V, Floel A, Lohmann H, Knecht S, Brand SM, Poter M, Rescher U, Missler M, Seelheim P, Propper C, Boeckers TM, Makuch L, Huganir R, Weide T, Brand E, Pavenstadt H, Kremerskothen J. Common exonic missense variants in the C2 domain of the human KIBRA protein modify lipid binding and cognitive performance. Transl Psychiatry. 2013 Jun 18;3:e272. doi: 10.1038/tp.2013.49. PMID:23778582 doi:http://dx.doi.org/10.1038/tp.2013.49
↑ Posner MG, Upadhyay A, Ishima R, Kalli AC, Harris G, Kremerskothen J, Sansom MSP, Crennell SJ, Bagby S. Distinctive phosphoinositide and Ca(2+) binding properties of normal and cognitive performance-linked variant forms of KIBRA C2 domain. J Biol Chem. 2018 May 3. pii: RA118.002279. doi: 10.1074/jbc.RA118.002279. PMID:29724824 doi:http://dx.doi.org/10.1074/jbc.RA118.002279

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6fd0"

@@ Line 3: / Line 3: @@
 <StructureSection load='6fd0' size='340' side='right' caption='[[6fd0]], [[Resolution|resolution]] 2.64&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6fd0]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FD0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FD0 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6fd0]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FD0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FD0 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6fb4|6fb4]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">WWC1, KIAA0869 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6fd0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fd0 OCA], [http://pdbe.org/6fd0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fd0 RCSB], [http://www.ebi.ac.uk/pdbsum/6fd0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fd0 ProSAT]</span></td></tr>
 </table>
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Bagby, S]]
 [[Category: Crennell, S J]]

6fd0

From Proteopedia

Current revision

Human KIBRA C2 domain mutant M734I S735A

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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