6edx

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Crystal Structure of SGK3 PX domain

Structural highlights

6edx is a 1 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 2.009Å
Ligands:GOL
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SGK3_HUMAN 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] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21]

Publication Abstract from PubMed

Phox homology (PX) domains are membrane interacting domains that bind to phosphatidylinositol phospholipids or phosphoinositides, markers of organelle identity in the endocytic system. Although many PX domains bind the canonical endosome-enriched lipid PtdIns3P, others interact with alternative phosphoinositides, and a precise understanding of how these specificities arise has remained elusive. Here we systematically screen all human PX domains for their phospholipid preferences using liposome binding assays, biolayer interferometry and isothermal titration calorimetry. These analyses define four distinct classes of human PX domains that either bind specifically to PtdIns3P, non-specifically to various di- and tri-phosphorylated phosphoinositides, bind both PtdIns3P and other phosphoinositides, or associate with none of the lipids tested. A comprehensive evaluation of PX domain structures reveals two distinct binding sites that explain these specificities, providing a basis for defining and predicting the functional membrane interactions of the entire PX domain protein family.

Classification of the human phox homology (PX) domains based on their phosphoinositide binding specificities.,Chandra M, Chin YK, Mas C, Feathers JR, Paul B, Datta S, Chen KE, Jia X, Yang Z, Norwood SJ, Mohanty B, Bugarcic A, Teasdale RD, Henne WM, Mobli M, Collins BM Nat Commun. 2019 Apr 4;10(1):1528. doi: 10.1038/s41467-019-09355-y. PMID:30948714[22]

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

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Citations
26 reviews cite this structure
Novel roles of phosphoinositides in signaling, lipid transport, and disease.
Hammond et al. (2020)
25 more
37 other articles
No citations found

See Also

References

  1. ↑ Dai F, Yu L, He H, Chen Y, Yu J, Yang Y, Xu Y, Ling W, Zhao S. Human serum and glucocorticoid-inducible kinase-like kinase (SGKL) phosphorylates glycogen syntheses kinase 3 beta (GSK-3beta) at serine-9 through direct interaction. Biochem Biophys Res Commun. 2002 May 17;293(4):1191-6. doi:, 10.1016/S0006-291X(02)00349-2. PMID:12054501 doi:http://dx.doi.org/10.1016/S0006-291X(02)00349-2
  2. ↑ Gamper N, Fillon S, Feng Y, Friedrich B, Lang PA, Henke G, Huber SM, Kobayashi T, Cohen P, Lang F. K+ channel activation by all three isoforms of serum- and glucocorticoid-dependent protein kinase SGK. Pflugers Arch. 2002 Oct;445(1):60-6. Epub 2002 Aug 28. PMID:12397388 doi:http://dx.doi.org/10.1007/s00424-002-0873-2
  3. ↑ Henke G, Setiawan I, Bohmer C, Lang F. Activation of Na+/K+-ATPase by the serum and glucocorticoid-dependent kinase isoforms. Kidney Blood Press Res. 2002;25(6):370-4. PMID:12590200 doi:http://dx.doi.org/68699
  4. ↑ Friedrich B, Feng Y, Cohen P, Risler T, Vandewalle A, Broer S, Wang J, Pearce D, Lang F. The serine/threonine kinases SGK2 and SGK3 are potent stimulators of the epithelial Na+ channel alpha,beta,gamma-ENaC. Pflugers Arch. 2003 Mar;445(6):693-6. doi: 10.1007/s00424-002-0993-8. Epub 2003, Jan 21. PMID:12632189 doi:http://dx.doi.org/10.1007/s00424-002-0993-8
  5. ↑ Embark HM, Bohmer C, Vallon V, Luft F, Lang F. Regulation of KCNE1-dependent K(+) current by the serum and glucocorticoid-inducible kinase (SGK) isoforms. Pflugers Arch. 2003 Feb;445(5):601-6. Epub 2002 Dec 4. PMID:12634932 doi:http://dx.doi.org/10.1007/s00424-002-0982-y
  6. ↑ Boehmer C, Wilhelm V, Palmada M, Wallisch S, Henke G, Brinkmeier H, Cohen P, Pieske B, Lang F. Serum and glucocorticoid inducible kinases in the regulation of the cardiac sodium channel SCN5A. Cardiovasc Res. 2003 Mar 15;57(4):1079-84. PMID:12650886
  7. ↑ Boehmer C, Henke G, Schniepp R, Palmada M, Rothstein JD, Broer S, Lang F. Regulation of the glutamate transporter EAAT1 by the ubiquitin ligase Nedd4-2 and the serum and glucocorticoid-inducible kinase isoforms SGK1/3 and protein kinase B. J Neurochem. 2003 Sep;86(5):1181-8. PMID:12911626
  8. ↑ Boehmer C, Embark HM, Bauer A, Palmada M, Yun CH, Weinman EJ, Endou H, Cohen P, Lahme S, Bichler KH, Lang F. Stimulation of renal Na+ dicarboxylate cotransporter 1 by Na+/H+ exchanger regulating factor 2, serum and glucocorticoid inducible kinase isoforms, and protein kinase B. Biochem Biophys Res Commun. 2004 Jan 23;313(4):998-1003. PMID:14706641
  9. ↑ Henke G, Maier G, Wallisch S, Boehmer C, Lang F. Regulation of the voltage gated K+ channel Kv1.3 by the ubiquitin ligase Nedd4-2 and the serum and glucocorticoid inducible kinase SGK1. J Cell Physiol. 2004 May;199(2):194-9. PMID:15040001 doi:10.1002/jcp.10430
  10. ↑ Palmada M, Dieter M, Speil A, Bohmer C, Mack AF, Wagner HJ, Klingel K, Kandolf R, Murer H, Biber J, Closs EI, Lang F. Regulation of intestinal phosphate cotransporter NaPi IIb by ubiquitin ligase Nedd4-2 and by serum- and glucocorticoid-dependent kinase 1. Am J Physiol Gastrointest Liver Physiol. 2004 Jul;287(1):G143-50. Epub 2004 Mar, 25. PMID:15044175 doi:http://dx.doi.org/10.1152/ajpgi.00121.2003
  11. ↑ Embark HM, Setiawan I, Poppendieck S, van de Graaf SF, Boehmer C, Palmada M, Wieder T, Gerstberger R, Cohen P, Yun CC, Bindels RJ, Lang F. Regulation of the epithelial Ca2+ channel TRPV5 by the NHE regulating factor NHERF2 and the serum and glucocorticoid inducible kinase isoforms SGK1 and SGK3 expressed in Xenopus oocytes. Cell Physiol Biochem. 2004;14(4-6):203-12. PMID:15319523 doi:http://dx.doi.org/10.1159/000080329
  12. ↑ Embark HM, Bohmer C, Palmada M, Rajamanickam J, Wyatt AW, Wallisch S, Capasso G, Waldegger P, Seyberth HW, Waldegger S, Lang F. Regulation of CLC-Ka/barttin by the ubiquitin ligase Nedd4-2 and the serum- and glucocorticoid-dependent kinases. Kidney Int. 2004 Nov;66(5):1918-25. PMID:15496163 doi:http://dx.doi.org/10.1111/j.1523-1755.2004.00966.x
  13. ↑ Boehmer C, Rajamanickam J, Schniepp R, Kohler K, Wulff P, Kuhl D, Palmada M, Lang F. Regulation of the excitatory amino acid transporter EAAT5 by the serum and glucocorticoid dependent kinases SGK1 and SGK3. Biochem Biophys Res Commun. 2005 Apr 8;329(2):738-42. PMID:15737648 doi:http://dx.doi.org/10.1016/j.bbrc.2005.02.035
  14. ↑ Palmada M, Speil A, Jeyaraj S, Bohmer C, Lang F. The serine/threonine kinases SGK1, 3 and PKB stimulate the amino acid transporter ASCT2. Biochem Biophys Res Commun. 2005 May 27;331(1):272-7. PMID:15845389 doi:http://dx.doi.org/10.1016/j.bbrc.2005.03.159
  15. ↑ Shojaiefard M, Christie DL, Lang F. Stimulation of the creatine transporter SLC6A8 by the protein kinases SGK1 and SGK3. Biochem Biophys Res Commun. 2005 Sep 2;334(3):742-6. PMID:16036218 doi:http://dx.doi.org/10.1016/j.bbrc.2005.06.164
  16. ↑ Slagsvold T, Marchese A, Brech A, Stenmark H. CISK attenuates degradation of the chemokine receptor CXCR4 via the ubiquitin ligase AIP4. EMBO J. 2006 Aug 23;25(16):3738-49. doi: 10.1038/sj.emboj.7601267. Epub 2006 Aug , 3. PMID:16888620 doi:http://dx.doi.org/10.1038/sj.emboj.7601267
  17. ↑ Maier G, Palmada M, Rajamanickam J, Shumilina E, Bohmer C, Lang F. Upregulation of HERG channels by the serum and glucocorticoid inducible kinase isoform SGK3. Cell Physiol Biochem. 2006;18(4-5):177-86. doi: 10.1159/000097666. PMID:17167223 doi:http://dx.doi.org/10.1159/000097666
  18. ↑ Bohmer C, Palmada M, Kenngott C, Lindner R, Klaus F, Laufer J, Lang F. Regulation of the epithelial calcium channel TRPV6 by the serum and glucocorticoid-inducible kinase isoforms SGK1 and SGK3. FEBS Lett. 2007 Dec 11;581(29):5586-90. Epub 2007 Nov 20. PMID:18005662 doi:http://dx.doi.org/10.1016/j.febslet.2007.11.006
  19. ↑ Xu J, Liao L, Qin J, Xu J, Liu D, Songyang Z. Identification of Flightless-I as a substrate of the cytokine-independent survival kinase CISK. J Biol Chem. 2009 May 22;284(21):14377-85. doi: 10.1074/jbc.M807770200. Epub 2009, Mar 17. PMID:19293151 doi:http://dx.doi.org/10.1074/jbc.M807770200
  20. ↑ Bohmer C, Sopjani M, Klaus F, Lindner R, Laufer J, Jeyaraj S, Lang F, Palmada M. The serum and glucocorticoid inducible kinases SGK1-3 stimulate the neutral amino acid transporter SLC6A19. Cell Physiol Biochem. 2010;25(6):723-32. doi: 10.1159/000315092. Epub 2010 May, 18. PMID:20511718 doi:http://dx.doi.org/10.1159/000315092
  21. ↑ 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
  22. ↑ Chandra M, Chin YK, Mas C, Feathers JR, Paul B, Datta S, Chen KE, Jia X, Yang Z, Norwood SJ, Mohanty B, Bugarcic A, Teasdale RD, Henne WM, Mobli M, Collins BM. Classification of the human phox homology (PX) domains based on their phosphoinositide binding specificities. Nat Commun. 2019 Apr 4;10(1):1528. doi: 10.1038/s41467-019-09355-y. PMID:30948714 doi:http://dx.doi.org/10.1038/s41467-019-09355-y

Contents


PDB ID 6edx

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