Serine/threonine-protein kinase Sgk3

Details

Name
Serine/threonine-protein kinase Sgk3
Synonyms
  • 2.7.11.1
  • CISK
  • Cytokine-independent survival kinase
  • Serum/glucocorticoid-regulated kinase 3
  • Serum/glucocorticoid-regulated kinase-like
  • SGKL
Gene Name
SGK3
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051951|Serine/threonine-protein kinase Sgk3
MQRDHTMDYKESCPSVSIPSSDEHREKKKRFTVYKVLVSVGRSEWFVFRRYAEFDKLYNT
LKKQFPAMALKIPAKRIFGDNFDPDFIKQRRAGLNEFIQNLVRYPELYNHPDVRAFLQMD
SPKHQSDPSEDEDERSSQKLHSTSQNINLGPSGNPHAKPTDFDFLKVIGKGSFGKVLLAK
RKLDGKFYAVKVLQKKIVLNRKEQKHIMAERNVLLKNVKHPFLVGLHYSFQTTEKLYFVL
DFVNGGELFFHLQRERSFPEHRARFYAAEIASALGYLHSIKIVYRDLKPENILLDSVGHV
VLTDFGLCKEGIAISDTTTTFCGTPEYLAPEVIRKQPYDNTVDWWCLGAVLYEMLYGLPP
FYCRDVAEMYDNILHKPLSLRPGVSLTAWSILEELLEKDRQNRLGAKEDFLEIQNHPFFE
SLSWADLVQKKIPPPFNPNVAGPDDIRNFDTAFTEETVPYSVCVSSDYSIVNASVLEADD
AFVGFSYAPPSEDLFL
Number of residues
496
Molecular Weight
57107.655
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / calcium channel regulator activity / chloride channel regulator activity / phosphatidylinositol binding / potassium channel regulator activity / protein kinase activity / protein serine/threonine kinase activity / sodium channel regulator activity
Processes
intracellular signal transduction / ion transmembrane transport / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / peptidyl-serine phosphorylation / positive regulation of transporter activity / protein phosphorylation / regulation of apoptotic process / regulation of cell growth / regulation of cell migration / regulation of cell proliferation / regulation of DNA binding transcription factor activity
Components
cytoplasmic vesicle / cytosol / early endosome / recycling endosome
General Function
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.
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasmic vesicle
Gene sequence
>lcl|BSEQ0051952|Serine/threonine-protein kinase Sgk3 (SGK3)
ATGCAAAGAGATCACACCATGGACTACAAGGAAAGCTGCCCAAGTGTAAGCATTCCCAGC
TCCGATGAACACAGAGAGAAAAAGAAGAGGTTTACTGTTTATAAAGTTCTGGTTTCAGTG
GGAAGAAGTGAATGGTTTGTCTTCAGGAGATATGCAGAGTTTGATAAACTTTATAACACT
TTAAAAAAACAGTTTCCTGCTATGGCCCTGAAGATTCCTGCCAAGAGAATATTTGGTGAT
AATTTTGATCCAGATTTTATTAAACAAAGACGAGCAGGACTAAACGAATTCATTCAGAAC
CTAGTTAGGTATCCAGAACTTTATAACCATCCAGATGTCAGAGCATTCCTTCAAATGGAC
AGTCCAAAACACCAGTCAGATCCATCTGAAGATGAGGATGAAAGAAGTTCTCAGAAGCTA
CACTCTACCTCACAGAACATCAACCTGGGACCGTCTGGAAATCCTCATGCCAAACCAACT
GACTTTGATTTCTTAAAAGTTATTGGAAAAGGCAGCTTTGGCAAGGTTCTTCTTGCAAAA
CGGAAACTGGATGGAAAATTTTATGCTGTCAAAGTGTTACAGAAAAAAATAGTTCTCAAC
AGAAAAGAGCAAAAACATATTATGGCTGAACGTAATGTGCTCTTGAAAAATGTGAAACAT
CCGTTTTTGGTTGGATTGCATTATTCCTTCCAAACAACTGAAAAGCTTTATTTTGTTCTG
GATTTTGTTAATGGAGGGGAGCTTTTTTTCCACTTACAAAGAGAACGGTCCTTTCCTGAG
CACAGAGCTAGGTTTTACGCTGCTGAAATTGCTAGTGCATTGGGTTACTTACATTCCATC
AAAATAGTATACAGAGACTTGAAACCAGAAAATATTCTTTTGGATTCAGTAGGACATGTT
GTCTTAACAGATTTTGGGCTTTGTAAAGAAGGAATTGCTATTTCTGACACCACTACCACA
TTTTGTGGGACACCAGAGTATCTTGCACCTGAAGTAATTAGAAAACAGCCCTATGACAAT
ACTGTAGATTGGTGGTGCCTTGGGGCTGTTCTGTATGAAATGCTGTATGGATTGCCTCCT
TTTTATTGCCGAGATGTTGCTGAAATGTATGACAATATCCTTCACAAACCCCTAAGTTTG
AGGCCAGGAGTGAGTCTTACAGCCTGGTCCATTCTGGAAGAACTCCTAGAAAAAGACAGG
CAAAATCGACTTGGTGCCAAGGAAGACTTTCTTGAAATTCAGAATCATCCTTTTTTTGAA
TCACTCAGCTGGGCTGACCTTGTACAAAAGAAGATTCCACCACCATTTAATCCTAATGTG
GCTGGACCAGATGATATCAGAAACTTTGACACAGCATTTACAGAAGAAACAGTTCCATAT
TCTGTGTGTGTATCTTCTGACTATTCTATAGTGAATGCCAGTGTATTGGAGGCAGATGAT
GCATTCGTTGGTTTCTCTTATGCACCTCCTTCAGAAGACTTATTTTTGTGA
Chromosome Location
8
Locus
8q13.1
External Identifiers
ResourceLink
UniProtKB IDQ96BR1
UniProtKB Entry NameSGK3_HUMAN
HGNC IDHGNC:10812
General References
  1. Kobayashi T, Deak M, Morrice N, Cohen P: Characterization of the structure and regulation of two novel isoforms of serum- and glucocorticoid-induced protein kinase. Biochem J. 1999 Nov 15;344 Pt 1:189-97. [Article]
  2. Dai F, Yu L, He H, Zhao Y, Yang J, Zhang X, Zhao S: Cloning and mapping of a novel human serum/glucocorticoid regulated kinase-like gene, SGKL, to chromosome 8q12.3-q13.1. Genomics. 1999 Nov 15;62(1):95-7. [Article]
  3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
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  5. 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. [Article]
  6. 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. [Article]
  7. 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. [Article]
  8. 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. [Article]
  9. 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. [Article]
  10. 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. [Article]
  11. 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. Epub 2003 Jan 21. [Article]
  12. 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. [Article]
  13. 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. [Article]
  14. 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. [Article]
  15. Nilsen T, Slagsvold T, Skjerpen CS, Brech A, Stenmark H, Olsnes S: Peroxisomal targeting as a tool for assaying potein-protein interactions in the living cell: cytokine-independent survival kinase (CISK) binds PDK-1 in vivo in a phosphorylation-dependent manner. J Biol Chem. 2004 Feb 6;279(6):4794-801. Epub 2003 Nov 6. [Article]
  16. 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. [Article]
  17. 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. [Article]
  18. 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. [Article]
  19. 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. [Article]
  20. 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. [Article]
  21. 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. [Article]
  22. 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. Epub 2006 Aug 3. [Article]
  23. Tessier M, Woodgett JR: Role of the Phox homology domain and phosphorylation in activation of serum and glucocorticoid-regulated kinase-3. J Biol Chem. 2006 Aug 18;281(33):23978-89. Epub 2006 Jun 21. [Article]
  24. 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. [Article]
  25. 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. [Article]
  26. 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. [Article]
  27. 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. [Article]
  28. Wang Y, Zhou D, Phung S, Masri S, Smith D, Chen S: SGK3 is an estrogen-inducible kinase promoting estrogen-mediated survival of breast cancer cells. Mol Endocrinol. 2011 Jan;25(1):72-82. doi: 10.1210/me.2010-0294. Epub 2010 Nov 17. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails