1k40: Difference between revisions

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-[[Image:1k40.gif|left|200px]]<br /><applet load="1k40" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1k40, resolution 2.25&Aring;" />
-'''crystal structure of the FAT domain of focal adhesion kinase'''<br />
-==Overview==
+==crystal structure of the FAT domain of focal adhesion kinase==
-Focal adhesion kinase (FAK) is a tyrosine kinase found in focal adhesions, intracellular signaling complexes that are formed following engagement of, the extracellular matrix by integrins. The C-terminal 'focal adhesion, targeting' (FAT) region is necessary and sufficient for localizing FAK to, focal adhesions. We have determined the crystal structure of FAT and show, that it forms a four-helix bundle that resembles those found in two other, proteins involved in cell adhesion, alpha-catenin and vinculin. The, binding of FAT to the focal adhesion protein, paxillin, requires the, integrity of the helical bundle, whereas binding to another focal adhesion, protein, talin, does not. We show by mutagenesis that paxillin binding, involves two hydrophobic patches on opposite faces of the bundle and, propose a model in which two LD motifs of paxillin adopt amphipathic, helices that augment the hydrophobic core of FAT, creating a six-helix, bundle.
+<StructureSection load='1k40' size='340' side='right'caption='[[1k40]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1k40]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K40 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1K40 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.25&#8491;</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1k40 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1k40 OCA], [https://pdbe.org/1k40 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1k40 RCSB], [https://www.ebi.ac.uk/pdbsum/1k40 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1k40 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/FAK1_MOUSE FAK1_MOUSE] Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 9 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription (By similarity).<ref>PMID:7997267</ref> <ref>PMID:7478517</ref> <ref>PMID:9148935</ref> <ref>PMID:10373530</ref> <ref>PMID:10806474</ref> <ref>PMID:11278462</ref> <ref>PMID:11369769</ref> <ref>PMID:12941275</ref> <ref>PMID:12702722</ref> <ref>PMID:15967814</ref> <ref>PMID:16000375</ref> <ref>PMID:16391003</ref> <ref>PMID:17093062</ref> <ref>PMID:18206965</ref> <ref>PMID:19473962</ref> <ref>PMID:19147981</ref> <ref>PMID:22056317</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k4/1k40_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1k40 ConSurf].
+<div style="clear:both"></div>
-==About this Structure==
+==See Also==
-K40 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Active as [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1K40 OCA].
+*[[Focal adhesion kinase 3D structures|Focal adhesion kinase 3D structures]]
+== References ==
-==Reference==
+<references/>
-The focal adhesion targeting (FAT) region of focal adhesion kinase is a four-helix bundle that binds paxillin., Hayashi I, Vuori K, Liddington RC, Nat Struct Biol. 2002 Feb;9(2):101-6. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11799401 11799401]
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
 [[Category: Mus musculus]]
-[[Category: Single protein]]
+[[Category: Hayashi I]]
-[[Category: Transferase]]
+[[Category: Liddington RC]]
-[[Category: Hayashi, I.]]
+[[Category: Vuori K]]
-[[Category: Liddington, R.C.]]
-[[Category: Vuori, K.]]
-[[Category: helix bundle]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 18:50:29 2007''