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| - | [[Image:1xtn.gif|left|200px]]<br /><applet load="1xtn" size="450" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="1xtn, resolution 2.20Å" /> | |
| - | '''crystal structure of CISK-PX domain with sulfates'''<br /> | |
| | | | |
| - | ==Overview== | + | ==crystal structure of CISK-PX domain with sulfates== |
| - | The cytokine-independent survival kinase (CISK) in the serum and, glucocorticoid-regulated kinase family plays an important role in, mediating cell growth and survival. N-terminal to its catalytic kinase, domain, CISK contains a phox homology (PX) domain, a, phosphoinositide-binding motif that directs the membrane localization of, CISK and regulates CISK activity. We have determined the crystal, structures of the mouse CISK-PX domain to unravel the structural basis of, membrane targeting of CISK. In addition to the specific interactions, conferred by the phosphoinositide-binding pocket, the structure suggests, that a hydrophobic loop region and a hydrophilic beta-turn contribute to, the interactions with the membrane. Furthermore, biochemical studies, reveal that CISK-PX dimerizes in the presence of the linker between the PX, domain and kinase domain, suggesting a multivalent mechanism in membrane, localization of CISK. | + | <StructureSection load='1xtn' size='340' side='right'caption='[[1xtn]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1xtn]] is a 2 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=1XTN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XTN 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]] 2.2Å</td></tr> |
| | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=1xtn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xtn OCA], [https://pdbe.org/1xtn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xtn RCSB], [https://www.ebi.ac.uk/pdbsum/1xtn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xtn ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/SGK3_MOUSE SGK3_MOUSE] Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cell growth, proliferation, survival and migration. Up-regulates Na(+) channels: SCNN1A/ENAC and SCN5A, K(+) channels: KCNA3/KV1.3, KCNE1, KCNQ1 and KCNH2/HERG, epithelial Ca(2+) channels: TRPV5 and TRPV6, chloride channel: BSND, creatine transporter: SLC6A8, Na(+)/dicarboxylate cotransporter: SLC13A2/NADC1, Na(+)-dependent phosphate cotransporter: SLC34A2/NAPI-2B, amino acid transporters: SLC1A5/ASCT2 and SLC6A19, glutamate transporters: SLC1A3/EAAT1, SLC1A6/EAAT4 and SLC1A7/EAAT5, glutamate receptors: GRIA1/GLUR1 and GRIK2/GLUR6, Na(+)/H(+) exchanger: SLC9A3/NHE3, and the Na(+)/K(+) ATPase. Plays a role in the regulation of renal tubular phosphate transport and bone density. Phosphorylates NEDD4L and GSK3B. Positively regulates ER transcription activity through phosphorylation of FLII. Negatively regulates the function of ITCH/AIP4 via its phosphorylation and thereby prevents CXCR4 from being efficiently sorted to lysosomes.<ref>PMID:15774536</ref> <ref>PMID:15774535</ref> <ref>PMID:21113728</ref> <ref>PMID:21451460</ref> <ref>PMID:21865597</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/xt/1xtn_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=1xtn ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | The cytokine-independent survival kinase (CISK) in the serum and glucocorticoid-regulated kinase family plays an important role in mediating cell growth and survival. N-terminal to its catalytic kinase domain, CISK contains a phox homology (PX) domain, a phosphoinositide-binding motif that directs the membrane localization of CISK and regulates CISK activity. We have determined the crystal structures of the mouse CISK-PX domain to unravel the structural basis of membrane targeting of CISK. In addition to the specific interactions conferred by the phosphoinositide-binding pocket, the structure suggests that a hydrophobic loop region and a hydrophilic beta-turn contribute to the interactions with the membrane. Furthermore, biochemical studies reveal that CISK-PX dimerizes in the presence of the linker between the PX domain and kinase domain, suggesting a multivalent mechanism in membrane localization of CISK. |
| | | | |
| - | ==About this Structure==
| + | Structural basis of membrane targeting by the Phox homology domain of cytokine-independent survival kinase (CISK-PX).,Xing Y, Liu D, Zhang R, Joachimiak A, Songyang Z, Xu W J Biol Chem. 2004 Jul 16;279(29):30662-9. Epub 2004 May 4. PMID:15126499<ref>PMID:15126499</ref> |
| - | 1XTN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1XTN OCA].
| + | |
| | | | |
| - | ==Reference==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | Structural basis of membrane targeting by the Phox homology domain of cytokine-independent survival kinase (CISK-PX)., Xing Y, Liu D, Zhang R, Joachimiak A, Songyang Z, Xu W, J Biol Chem. 2004 Jul 16;279(29):30662-9. Epub 2004 May 4. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15126499 15126499]
| + | </div> |
| - | [[Category: Mus musculus]]
| + | <div class="pdbe-citations 1xtn" style="background-color:#fffaf0;"></div> |
| - | [[Category: Non-specific serine/threonine protein kinase]]
| + | |
| - | [[Category: Single protein]]
| + | |
| - | [[Category: Joachimiak, A.]]
| + | |
| - | [[Category: Liu, D]]
| + | |
| - | [[Category: Songyang, Z.]]
| + | |
| - | [[Category: Xing, Y.]]
| + | |
| - | [[Category: Xu, W.]]
| + | |
| - | [[Category: Zhang, R.]]
| + | |
| - | [[Category: SO4]]
| + | |
| - | [[Category: cisk]]
| + | |
| - | [[Category: crystal structure]]
| + | |
| - | [[Category: px domain]]
| + | |
| | | | |
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 06:20:12 2007''
| + | ==See Also== |
| | + | *[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]] |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | + | [[Category: Mus musculus]] |
| | + | [[Category: Joachimiak A]] |
| | + | [[Category: Liu D]] |
| | + | [[Category: Songyang Z]] |
| | + | [[Category: Xing Y]] |
| | + | [[Category: Xu W]] |
| | + | [[Category: Zhang R]] |
| Structural highlights
Function
SGK3_MOUSE Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cell growth, proliferation, survival and migration. Up-regulates Na(+) channels: SCNN1A/ENAC and SCN5A, K(+) channels: KCNA3/KV1.3, KCNE1, KCNQ1 and KCNH2/HERG, epithelial Ca(2+) channels: TRPV5 and TRPV6, chloride channel: BSND, creatine transporter: SLC6A8, Na(+)/dicarboxylate cotransporter: SLC13A2/NADC1, Na(+)-dependent phosphate cotransporter: SLC34A2/NAPI-2B, amino acid transporters: SLC1A5/ASCT2 and SLC6A19, glutamate transporters: SLC1A3/EAAT1, SLC1A6/EAAT4 and SLC1A7/EAAT5, glutamate receptors: GRIA1/GLUR1 and GRIK2/GLUR6, Na(+)/H(+) exchanger: SLC9A3/NHE3, and the Na(+)/K(+) ATPase. Plays a role in the regulation of renal tubular phosphate transport and bone density. Phosphorylates NEDD4L and GSK3B. Positively regulates ER transcription activity through phosphorylation of FLII. Negatively regulates the function of ITCH/AIP4 via its phosphorylation and thereby prevents CXCR4 from being efficiently sorted to lysosomes.[1] [2] [3] [4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The cytokine-independent survival kinase (CISK) in the serum and glucocorticoid-regulated kinase family plays an important role in mediating cell growth and survival. N-terminal to its catalytic kinase domain, CISK contains a phox homology (PX) domain, a phosphoinositide-binding motif that directs the membrane localization of CISK and regulates CISK activity. We have determined the crystal structures of the mouse CISK-PX domain to unravel the structural basis of membrane targeting of CISK. In addition to the specific interactions conferred by the phosphoinositide-binding pocket, the structure suggests that a hydrophobic loop region and a hydrophilic beta-turn contribute to the interactions with the membrane. Furthermore, biochemical studies reveal that CISK-PX dimerizes in the presence of the linker between the PX domain and kinase domain, suggesting a multivalent mechanism in membrane localization of CISK.
Structural basis of membrane targeting by the Phox homology domain of cytokine-independent survival kinase (CISK-PX).,Xing Y, Liu D, Zhang R, Joachimiak A, Songyang Z, Xu W J Biol Chem. 2004 Jul 16;279(29):30662-9. Epub 2004 May 4. PMID:15126499[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Strutz-Seebohm N, Seebohm G, Mack AF, Wagner HJ, Just L, Skutella T, Lang UE, Henke G, Striegel M, Hollmann M, Rouach N, Nicoll RA, McCormick JA, Wang J, Pearce D, Lang F. Regulation of GluR1 abundance in murine hippocampal neurones by serum- and glucocorticoid-inducible kinase 3. J Physiol. 2005 Jun 1;565(Pt 2):381-90. Epub 2005 Mar 17. PMID:15774536 doi:http://dx.doi.org/10.1113/jphysiol.2004.079582
- ↑ Strutz-Seebohm N, Seebohm G, Shumilina E, Mack AF, Wagner HJ, Lampert A, Grahammer F, Henke G, Just L, Skutella T, Hollmann M, Lang F. Glucocorticoid adrenal steroids and glucocorticoid-inducible kinase isoforms in the regulation of GluR6 expression. J Physiol. 2005 Jun 1;565(Pt 2):391-401. Epub 2005 Mar 17. PMID:15774535 doi:http://dx.doi.org/10.1113/jphysiol.2004.079624
- ↑ Pasham V, Rotte A, Bhandaru M, Eichenmuller M, Frohlich H, Mack AF, Bobbala D, Yang W, Pearce D, Lang F. Regulation of gastric acid secretion by the serum and glucocorticoid inducible kinase isoform SGK3. J Gastroenterol. 2011 Mar;46(3):305-17. doi: 10.1007/s00535-010-0348-8. Epub 2010, Nov 27. PMID:21113728 doi:http://dx.doi.org/10.1007/s00535-010-0348-8
- ↑ Bhandaru M, Kempe DS, Rotte A, Capuano P, Pathare G, Sopjani M, Alesutan I, Tyan L, Huang DY, Siraskar B, Judenhofer MS, Stange G, Pichler BJ, Biber J, Quintanilla-Martinez L, Wagner CA, Pearce D, Foller M, Lang F. Decreased bone density and increased phosphaturia in gene-targeted mice lacking functional serum- and glucocorticoid-inducible kinase 3. Kidney Int. 2011 Jul;80(1):61-7. doi: 10.1038/ki.2011.67. Epub 2011 Mar 30. PMID:21451460 doi:http://dx.doi.org/10.1038/ki.2011.67
- ↑ He P, Lee SJ, Lin S, Seidler U, Lang F, Fejes-Toth G, Naray-Fejes-Toth A, Yun CC. Serum- and glucocorticoid-induced kinase 3 in recycling endosomes mediates acute activation of Na+/H+ exchanger NHE3 by glucocorticoids. Mol Biol Cell. 2011 Oct;22(20):3812-25. doi: 10.1091/mbc.E11-04-0328. Epub 2011, Aug 24. PMID:21865597 doi:http://dx.doi.org/10.1091/mbc.E11-04-0328
- ↑ Xing Y, Liu D, Zhang R, Joachimiak A, Songyang Z, Xu W. Structural basis of membrane targeting by the Phox homology domain of cytokine-independent survival kinase (CISK-PX). J Biol Chem. 2004 Jul 16;279(29):30662-9. Epub 2004 May 4. PMID:15126499 doi:10.1074/jbc.M404107200
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