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<StructureSection load='6ncg' size='340' side='right'caption='[[6ncg]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
<StructureSection load='6ncg' size='340' side='right'caption='[[6ncg]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6ncg]] 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=6NCG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NCG FirstGlance]. <br>
<table><tr><td colspan='2'>[[6ncg]] is a 2 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=6NCG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NCG FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=KJD:4-[6-amino-5-(3,5-difluoro-4-hydroxyphenyl)pyridin-3-yl]benzene-1-sulfonamide'>KJD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.45&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VRK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KJD:4-[6-amino-5-(3,5-difluoro-4-hydroxyphenyl)pyridin-3-yl]benzene-1-sulfonamide'>KJD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></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=6ncg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ncg OCA], [https://pdbe.org/6ncg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ncg RCSB], [https://www.ebi.ac.uk/pdbsum/6ncg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ncg ProSAT]</span></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=6ncg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ncg OCA], [http://pdbe.org/6ncg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ncg RCSB], [http://www.ebi.ac.uk/pdbsum/6ncg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ncg ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/VRK2_HUMAN VRK2_HUMAN]] Serine/threonine kinase that regulates several signal transduction pathways. Isoform 1 modulates the stress response to hypoxia and cytokines, such as interleukin-1 beta (IL1B) and this is dependent on its interaction with MAPK8IP1, which assembles mitogen-activated protein kinase (MAPK) complexes. Inhibition of signal transmission mediated by the assembly of MAPK8IP1-MAPK complexes reduces JNK phosphorylation and JUN-dependent transcription. Phosphorylates 'Thr-18' of p53/TP53, histone H3, and may also phosphorylate MAPK8IP1. Phosphorylates BANF1 and disrupts its ability to bind DNA and reduces its binding to LEM domain-containing proteins. Downregulates the transactivation of transcription induced by ERBB2, HRAS, BRAF, and MEK1. Blocks the phosphorylation of ERK in response to ERBB2 and HRAS. Can also phosphorylate the following substrates that are commonly used to establish in vitro kinase activity: casein, MBP and histone H2B, but it is not sure that this is physiologically relevant.<ref>PMID:16704422</ref> <ref>PMID:14645249</ref> <ref>PMID:16495336</ref> <ref>PMID:17709393</ref> <ref>PMID:18617507</ref> <ref>PMID:18286207</ref> <ref>PMID:20679487</ref>  Isoform 2 phosphorylates 'Thr-18' of p53/TP53, as well as histone H3. Reduces p53/TP53 ubiquitination by MDM2, promotes p53/TP53 acetylation by EP300 and thereby increases p53/TP53 stability and activity.<ref>PMID:16704422</ref> <ref>PMID:14645249</ref> <ref>PMID:16495336</ref> <ref>PMID:17709393</ref> <ref>PMID:18617507</ref> <ref>PMID:18286207</ref> <ref>PMID:20679487</ref>
[https://www.uniprot.org/uniprot/VRK2_HUMAN VRK2_HUMAN] Serine/threonine kinase that regulates several signal transduction pathways. Isoform 1 modulates the stress response to hypoxia and cytokines, such as interleukin-1 beta (IL1B) and this is dependent on its interaction with MAPK8IP1, which assembles mitogen-activated protein kinase (MAPK) complexes. Inhibition of signal transmission mediated by the assembly of MAPK8IP1-MAPK complexes reduces JNK phosphorylation and JUN-dependent transcription. Phosphorylates 'Thr-18' of p53/TP53, histone H3, and may also phosphorylate MAPK8IP1. Phosphorylates BANF1 and disrupts its ability to bind DNA and reduces its binding to LEM domain-containing proteins. Downregulates the transactivation of transcription induced by ERBB2, HRAS, BRAF, and MEK1. Blocks the phosphorylation of ERK in response to ERBB2 and HRAS. Can also phosphorylate the following substrates that are commonly used to establish in vitro kinase activity: casein, MBP and histone H2B, but it is not sure that this is physiologically relevant.<ref>PMID:16704422</ref> <ref>PMID:14645249</ref> <ref>PMID:16495336</ref> <ref>PMID:17709393</ref> <ref>PMID:18617507</ref> <ref>PMID:18286207</ref> <ref>PMID:20679487</ref>  Isoform 2 phosphorylates 'Thr-18' of p53/TP53, as well as histone H3. Reduces p53/TP53 ubiquitination by MDM2, promotes p53/TP53 acetylation by EP300 and thereby increases p53/TP53 stability and activity.<ref>PMID:16704422</ref> <ref>PMID:14645249</ref> <ref>PMID:16495336</ref> <ref>PMID:17709393</ref> <ref>PMID:18617507</ref> <ref>PMID:18286207</ref> <ref>PMID:20679487</ref>  
 
==See Also==
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Arruda P]]
[[Category: Arruda, P]]
[[Category: Chiodi CG]]
[[Category: Chiodi, C G]]
[[Category: Counago RM]]
[[Category: Counago, R M]]
[[Category: Edwards AM]]
[[Category: Edwards, A M]]
[[Category: Elkins JM]]
[[Category: Elkins, J M]]
[[Category: Ferreira M]]
[[Category: Ferreira, M]]
[[Category: Gama F]]
[[Category: Gama, F]]
[[Category: Guimaraes C]]
[[Category: Guimaraes, C]]
[[Category: Mascarello A]]
[[Category: Mascarello, A]]
[[Category: Massirer KB]]
[[Category: Massirer, K B]]
[[Category: De Souza GP]]
[[Category: Reis, C V.dos]]
[[Category: Dos Reis CV]]
[[Category: Structural genomic]]
[[Category: Souza, G P.de]]
[[Category: Protein kinase domain]]
[[Category: Sgc]]
[[Category: Transferase]]
[[Category: Transferase-transferase inhibitor complex]]

Latest revision as of 06:49, 11 October 2023

Crystal Structure of Human Vaccinia-related kinase 2 (VRK-2) bound to pyridin-benzenesulfonamide inhibitor

6ncg, resolution 2.45Å

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