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==The crystal structure of the PH domain of human AKT3 protein kinase==
The line below this paragraph, containing "STRUCTURE_2x18", creates the "Structure Box" on the page.
<StructureSection load='2x18' size='340' side='right'caption='[[2x18]], [[Resolution|resolution]] 1.46&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)  
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[2x18]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2X18 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2X18 FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.46&#8491;</td></tr>
-->
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene></td></tr>
{{STRUCTURE_2x18| PDB=2x18 |  SCENE= }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2x18 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x18 OCA], [https://pdbe.org/2x18 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2x18 RCSB], [https://www.ebi.ac.uk/pdbsum/2x18 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2x18 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/AKT3_HUMAN AKT3_HUMAN] Hemimegalencephaly;Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome. AKT3 is a key modulator of several tumors like melanoma, glioma and ovarian cancer. Active AKT3 increases progressively during melanoma tumor progression with highest levels present in advanced-stage metastatic melanomas. Promotes melanoma tumorigenesis by decreasing apoptosis. Plays a key role in the genesis of ovarian cancers through modulation of G2/M phase transition. With AKT2, plays a pivotal role in the biology of glioblastoma.  The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/AKT3_HUMAN AKT3_HUMAN] AKT3 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT3 is the least studied AKT isoform. It plays an important role in brain development and is crucial for the viability of malignant glioma cells. AKT3 isoform may also be the key molecule in up-regulation and down-regulation of MMP13 via IL13. Required for the coordination of mitochondrial biogenesis with growth factor-induced increases in cellular energy demands. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis.<ref>PMID:18524868</ref> <ref>PMID:21191416</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/x1/2x18_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=2x18 ConSurf].
<div style="clear:both"></div>


===THE CRYSTAL STRUCTURE OF THE PH DOMAIN OF HUMAN AKT3 PROTEIN KINASE===
==See Also==
 
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
 
== References ==
==About this Structure==
<references/>
[[2x18]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2X18 OCA].
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Large Structures]]
[[Category: Arrowsmith, C H.]]
[[Category: Arrowsmith CH]]
[[Category: Bountra, C.]]
[[Category: Bountra C]]
[[Category: Burgess-Brown, N.]]
[[Category: Burgess-Brown N]]
[[Category: Chaikuad, A.]]
[[Category: Chaikuad A]]
[[Category: Delft, F Von.]]
[[Category: Edwards A]]
[[Category: Edwards, A.]]
[[Category: Elkins JM]]
[[Category: Elkins, J M.]]
[[Category: Knapp S]]
[[Category: Knapp, S.]]
[[Category: Pike ACW]]
[[Category: Pike, A C.W.]]
[[Category: Vollmar M]]
[[Category: Vollmar, M.]]
[[Category: Wang J]]
[[Category: Wang, J.]]
[[Category: Weigelt J]]
[[Category: Weigelt, J.]]
[[Category: Zhang Y]]
[[Category: Zhang, Y.]]
[[Category: Von Delft F]]
[[Category: Atp-binding]]
[[Category: Kinase]]
[[Category: Membrane]]
[[Category: Transferase]]

Latest revision as of 13:21, 20 December 2023

The crystal structure of the PH domain of human AKT3 protein kinaseThe crystal structure of the PH domain of human AKT3 protein kinase

Structural highlights

2x18 is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.46Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

AKT3_HUMAN Hemimegalencephaly;Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome. AKT3 is a key modulator of several tumors like melanoma, glioma and ovarian cancer. Active AKT3 increases progressively during melanoma tumor progression with highest levels present in advanced-stage metastatic melanomas. Promotes melanoma tumorigenesis by decreasing apoptosis. Plays a key role in the genesis of ovarian cancers through modulation of G2/M phase transition. With AKT2, plays a pivotal role in the biology of glioblastoma. The disease is caused by variants affecting the gene represented in this entry.

Function

AKT3_HUMAN AKT3 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT3 is the least studied AKT isoform. It plays an important role in brain development and is crucial for the viability of malignant glioma cells. AKT3 isoform may also be the key molecule in up-regulation and down-regulation of MMP13 via IL13. Required for the coordination of mitochondrial biogenesis with growth factor-induced increases in cellular energy demands. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis.[1] [2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ Wright GL, Maroulakou IG, Eldridge J, Liby TL, Sridharan V, Tsichlis PN, Muise-Helmericks RC. VEGF stimulation of mitochondrial biogenesis: requirement of AKT3 kinase. FASEB J. 2008 Sep;22(9):3264-75. PMID:18524868 doi:10.1096/fj.08-106468
  2. ↑ Moriya C, Jinnin M, Yamane K, Maruo K, Muchemwa FC, Igata T, Makino T, Fukushima S, Ihn H. Expression of matrix metalloproteinase-13 is controlled by IL-13 via PI3K/Akt3 and PKC-δ in normal human dermal fibroblasts. J Invest Dermatol. 2011 Mar;131(3):655-61. PMID:21191416 doi:10.1038/jid.2010.361

2x18, resolution 1.46Å

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