SGK1_HUMAN
ID SGK1_HUMAN Reviewed; 431 AA.
AC O00141; B7UUP7; B7UUP8; B7UUP9; B7Z5B2; E1P583; Q5TCN2; Q5TCN3; Q5TCN4;
AC Q5VY65; Q9UN56;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 2.
DT 03-AUG-2022, entry version 211.
DE RecName: Full=Serine/threonine-protein kinase Sgk1;
DE EC=2.7.11.1;
DE AltName: Full=Serum/glucocorticoid-regulated kinase 1;
GN Name=SGK1; Synonyms=SGK;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9114008; DOI=10.1073/pnas.94.9.4440;
RA Waldegger S., Barth P., Raber G., Lang F.;
RT "Cloning and characterization of a putative human serine/threonine protein
RT kinase transcriptionally modified during anisotonic and isotonic
RT alterations of cell volume.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:4440-4445(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORM 1).
RX PubMed=9722955; DOI=10.1006/geno.1998.5258;
RA Waldegger S., Erdel M., Nagl U.O., Barth P., Raber G., Steuer S.,
RA Utermann G., Paulmichl M., Lang F.;
RT "Genomic organization and chromosomal localization of the human SGK protein
RT kinase gene.";
RL Genomics 51:299-302(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, ALTERNATIVE PROMOTER
RP USAGE, INDUCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=18753299; DOI=10.1152/ajprenal.90239.2008;
RA Raikwar N.S., Snyder P.M., Thomas C.P.;
RT "An evolutionarily conserved N-terminal Sgk1 variant with enhanced
RT stability and improved function.";
RL Am. J. Physiol. 295:F1440-F1448(2008).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3; 4 AND 5), AND ALTERNATIVE
RP PROMOTER USAGE.
RC TISSUE=Glioblastoma, Hippocampus, and Skin;
RA Hall B.A., Blakeley S., Daniels N.A., Jamieson D., Brickley D.,
RA Reynolds N.J., Conzen S.D., Jackson T.R.;
RT "Transcriptional variants of serum/glucocorticoid regulated kinase 1 show
RT differential localisation and regulation.";
RL Submitted (AUG-2008) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Hair follicle dermal papilla;
RA Kim M.K., Kim Y.H., Seo J.M., Lee H.M., Chung H.J., Sohn M.Y., Hwang S.Y.,
RA Im S.U., Jung E.J., Lee J.H., Kim J.C.;
RT "A catalogue of genes in the human dermal papilla cells as identified by
RT expressed sequence tags.";
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Cervix;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP TISSUE SPECIFICITY.
RX PubMed=10548550; DOI=10.1042/bj3440189;
RA Kobayashi T., Deak M., Morrice N., Cohen P.;
RT "Characterization of the structure and regulation of two novel isoforms of
RT serum- and glucocorticoid-induced protein kinase.";
RL Biochem. J. 344:189-197(1999).
RN [11]
RP PHOSPHORYLATION AT THR-256 AND SER-422, AND MUTAGENESIS OF THR-256 AND
RP SER-422.
RC TISSUE=Brain;
RX PubMed=10191262; DOI=10.1042/bj3390319;
RA Kobayashi T., Cohen P.;
RT "Activation of serum- and glucocorticoid-regulated protein kinase by
RT agonists that activate phosphatidylinositide 3-kinase is mediated by 3-
RT phosphoinositide-dependent protein kinase-1 (PDK1) and PDK2.";
RL Biochem. J. 339:319-328(1999).
RN [12]
RP CHARACTERIZATION.
RX PubMed=10884438; DOI=10.1073/pnas.97.14.8157;
RA Lang F., Klingel K., Wagner C.A., Stegen C., Waerntges S., Friedrich B.,
RA Lanzendoerfer M., Melzig J., Moschen I., Steuer S., Waldegger S.,
RA Sauter M., Paulmichl M., Gerke V., Risler T., Gamba G., Capasso G.,
RA Kandolf R., Hebert S.C., Massry S.G., Broer S.;
RT "Deranged transcriptional regulation of cell-volume-sensitive kinase hSGK
RT in diabetic nephropathy.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:8157-8162(2000).
RN [13]
RP PHOSPHORYLATION AT SER-78 BY MAPK7, AND INTERACTION WITH MAPK7.
RX PubMed=11254654; DOI=10.1074/jbc.c000838200;
RA Hayashi M., Tapping R.I., Chao T.H., Lo J.F., King C.C., Yang Y., Lee J.D.;
RT "BMK1 mediates growth factor-induced cell proliferation through direct
RT cellular activation of serum and glucocorticoid-inducible kinase.";
RL J. Biol. Chem. 276:8631-8634(2001).
RN [14]
RP PHOSPHORYLATION AT THR-369 BY PKA.
RX PubMed=11096081; DOI=10.1074/jbc.m007052200;
RA Perrotti N., He R.A., Phillips S.A., Haft C.R., Taylor S.I.;
RT "Activation of serum- and glucocorticoid-induced protein kinase (Sgk) by
RT cyclic AMP and insulin.";
RL J. Biol. Chem. 276:9406-9412(2001).
RN [15]
RP FUNCTION IN PHOSPHORYLATION OF BRAF.
RX PubMed=11410590; DOI=10.1074/jbc.m102808200;
RA Zhang B.H., Tang E.D., Zhu T., Greenberg M.E., Vojtek A.B., Guan K.L.;
RT "Serum- and glucocorticoid-inducible kinase SGK phosphorylates and
RT negatively regulates B-Raf.";
RL J. Biol. Chem. 276:31620-31626(2001).
RN [16]
RP FUNCTION.
RX PubMed=11154281; DOI=10.1128/mcb.21.3.952-965.2001;
RA Brunet A., Park J., Tran H., Hu L.S., Hemmings B.A., Greenberg M.E.;
RT "Protein kinase SGK mediates survival signals by phosphorylating the
RT forkhead transcription factor FKHRL1 (FOXO3a).";
RL Mol. Cell. Biol. 21:952-965(2001).
RN [17]
RP INTERACTION WITH NEDD4 AND NEDD4L, MUTAGENESIS OF LYS-127; TYR-298 AND
RP SER-422, AND FUNCTION.
RX PubMed=11696533; DOI=10.1074/jbc.c100623200;
RA Snyder P.M., Olson D.R., Thomas B.C.;
RT "Serum and glucocorticoid-regulated kinase modulates Nedd4-2-mediated
RT inhibition of the epithelial Na+ channel.";
RL J. Biol. Chem. 277:5-8(2002).
RN [18]
RP FUNCTION IN REGULATION OF NA(+)/K(+) ATPASE.
RX PubMed=12590200; DOI=10.1159/000068699;
RA Henke G., Setiawan I., Boehmer C., Lang F.;
RT "Activation of Na+/K+-ATPase by the serum and glucocorticoid-dependent
RT kinase isoforms.";
RL Kidney Blood Press. Res. 25:370-374(2002).
RN [19]
RP FUNCTION.
RX PubMed=12397388; DOI=10.1007/s00424-002-0873-2;
RA Gamper N., Fillon S., Feng Y., Friedrich B., Lang P.A., Henke G.,
RA Huber S.M., Kobayashi T., Cohen P., Lang F.;
RT "K(+) channel activation by all three isoforms of serum- and
RT glucocorticoid-dependent protein kinase SGK.";
RL Pflugers Arch. 445:60-66(2002).
RN [20]
RP FUNCTION, AND INTERACTION WITH SLC9A3R2/NHERF2 AND KCNJ1/ROMK1.
RX PubMed=14623317; DOI=10.1016/j.bbrc.2003.10.037;
RA Palmada M., Embark H.M., Yun C., Bohmer C., Lang F.;
RT "Molecular requirements for the regulation of the renal outer medullary
RT K(+) channel ROMK1 by the serum- and glucocorticoid-inducible kinase
RT SGK1.";
RL Biochem. Biophys. Res. Commun. 311:629-634(2003).
RN [21]
RP FUNCTION IN REGULATION OF SCN5A.
RX PubMed=12650886; DOI=10.1016/s0008-6363(02)00837-4;
RA Boehmer C., Wilhelm V., Palmada M., Wallisch S., Henke G., Brinkmeier H.,
RA Cohen P., Pieske B., Lang F.;
RT "Serum and glucocorticoid inducible kinases in the regulation of the
RT cardiac sodium channel SCN5A.";
RL Cardiovasc. Res. 57:1079-1084(2003).
RN [22]
RP FUNCTION IN PHOSPHORYLATION OF MAP3K3/MEKK3.
RX PubMed=12761204; DOI=10.1093/jb/mvg010;
RA Chun J., Kwon T., Kim D.J., Park I., Chung G., Lee E.J., Hong S.K.,
RA Chang S.I., Kim H.Y., Kang S.S.;
RT "Inhibition of mitogen-activated kinase kinase kinase 3 activity through
RT phosphorylation by the serum- and glucocorticoid-induced kinase 1.";
RL J. Biochem. 133:103-108(2003).
RN [23]
RP FUNCTION IN REGULATION OF KCNA3/KV1.3, AND MUTAGENESIS OF LYS-127 AND
RP SER-422.
RX PubMed=12911626; DOI=10.1046/j.1471-4159.2003.01937.x;
RA Boehmer C., Henke G., Schniepp R., Palmada M., Rothstein J.D., Broeer S.,
RA Lang F.;
RT "Regulation of the glutamate transporter EAAT1 by the ubiquitin ligase
RT Nedd4-2 and the serum and glucocorticoid-inducible kinase isoforms SGK1/3
RT and protein kinase B.";
RL J. Neurochem. 86:1181-1188(2003).
RN [24]
RP NUCLEAR LOCALIZATION SIGNAL.
RX PubMed=12631736; DOI=10.1091/mbc.e02-03-0170;
RA Maiyar A.C., Leong M.L., Firestone G.L.;
RT "Importin-alpha mediates the regulated nuclear targeting of serum- and
RT glucocorticoid-inducible protein kinase (Sgk) by recognition of a nuclear
RT localization signal in the kinase central domain.";
RL Mol. Biol. Cell 14:1221-1239(2003).
RN [25]
RP FUNCTION IN REGULATION OF KCNE1 AND KCNQ1.
RX PubMed=12634932; DOI=10.1007/s00424-002-0982-y;
RA Embark H.M., Boehmer C., Vallon V., Luft F., Lang F.;
RT "Regulation of KCNE1-dependent K(+) current by the serum and
RT glucocorticoid-inducible kinase (SGK) isoforms.";
RL Pflugers Arch. 445:601-606(2003).
RN [26]
RP FUNCTION IN REGULATION OF SLC34A2/NAPI-2B, AND FUNCTION IN PHOSPHORYLATION
RP OF NEDD4L.
RX PubMed=15044175; DOI=10.1152/ajpgi.00121.2003;
RA Palmada M., Dieter M., Speil A., Boehmer C., Mack A.F., Wagner H.J.,
RA Klingel K., Kandolf R., Murer H., Biber J., Closs E.I., Lang F.;
RT "Regulation of intestinal phosphate cotransporter NaPi IIb by ubiquitin
RT ligase Nedd4-2 and by serum- and glucocorticoid-dependent kinase 1.";
RL Am. J. Physiol. 287:G143-G150(2004).
RN [27]
RP FUNCTION IN REGULATION OF SLC13A2/NADC1.
RX PubMed=14706641; DOI=10.1016/j.bbrc.2003.12.011;
RA Boehmer C., Embark H.M., Bauer A., Palmada M., Yun C.H., Weinman E.J.,
RA Endou H., Cohen P., Lahme S., Bichler K.H., Lang F.;
RT "Stimulation of renal Na+ dicarboxylate cotransporter 1 by Na+/H+ exchanger
RT regulating factor 2, serum and glucocorticoid inducible kinase isoforms,
RT and protein kinase B.";
RL Biochem. Biophys. Res. Commun. 313:998-1003(2004).
RN [28]
RP FUNCTION IN REGULATION OF TRPV5.
RX PubMed=15319523; DOI=10.1159/000080329;
RA Embark H.M., Setiawan I., Poppendieck S., van de Graaf S.F., Boehmer C.,
RA Palmada M., Wieder T., Gerstberger R., Cohen P., Yun C.C., Bindels R.J.,
RA Lang F.;
RT "Regulation of the epithelial Ca2+ channel TRPV5 by the NHE regulating
RT factor NHERF2 and the serum and glucocorticoid inducible kinase isoforms
RT SGK1 and SGK3 expressed in Xenopus oocytes.";
RL Cell. Physiol. Biochem. 14:203-212(2004).
RN [29]
RP FUNCTION.
RX PubMed=15234985; DOI=10.1074/jbc.m403260200;
RA Diakov A., Korbmacher C.;
RT "A novel pathway of epithelial sodium channel activation involves a
RT serum- and glucocorticoid-inducible kinase consensus motif in the C
RT terminus of the channel's alpha-subunit.";
RL J. Biol. Chem. 279:38134-38142(2004).
RN [30]
RP FUNCTION, AND MUTAGENESIS OF LYS-127 AND SER-422.
RX PubMed=15040001; DOI=10.1002/jcp.10430;
RA Henke G., Maier G., Wallisch S., Boehmer C., Lang F.;
RT "Regulation of the voltage gated K+ channel Kv1.3 by the ubiquitin ligase
RT Nedd4-2 and the serum and glucocorticoid inducible kinase SGK1.";
RL J. Cell. Physiol. 199:194-199(2004).
RN [31]
RP FUNCTION IN REGULATION OF BSND.
RX PubMed=15496163; DOI=10.1111/j.1523-1755.2004.00966.x;
RA Embark H.M., Boehmer C., Palmada M., Rajamanickam J., Wyatt A.W.,
RA Wallisch S., Capasso G., Waldegger P., Seyberth H.W., Waldegger S.,
RA Lang F.;
RT "Regulation of CLC-Ka/barttin by the ubiquitin ligase Nedd4-2 and the
RT serum- and glucocorticoid-dependent kinases.";
RL Kidney Int. 66:1918-1925(2004).
RN [32]
RP FUNCTION IN PHOSPHORYLATION OF SLC9A3/NHE3.
RX PubMed=15888551; DOI=10.1152/ajpcell.00597.2004;
RA Wang D., Sun H., Lang F., Yun C.C.;
RT "Activation of NHE3 by dexamethasone requires phosphorylation of NHE3 at
RT Ser663 by SGK1.";
RL Am. J. Physiol. 289:C802-C810(2005).
RN [33]
RP FUNCTION IN REGULATION OF SLC1A5/ASCT2.
RX PubMed=15845389; DOI=10.1016/j.bbrc.2005.03.159;
RA Palmada M., Speil A., Jeyaraj S., Boehmer C., Lang F.;
RT "The serine/threonine kinases SGK1, 3 and PKB stimulate the amino acid
RT transporter ASCT2.";
RL Biochem. Biophys. Res. Commun. 331:272-277(2005).
RN [34]
RP FUNCTION IN REGULATION OF SLC1A7/EAAT5.
RX PubMed=15737648; DOI=10.1016/j.bbrc.2005.02.035;
RA Boehmer C., Rajamanickam J., Schniepp R., Kohler K., Wulff P., Kuhl D.,
RA Palmada M., Lang F.;
RT "Regulation of the excitatory amino acid transporter EAAT5 by the serum and
RT glucocorticoid dependent kinases SGK1 and SGK3.";
RL Biochem. Biophys. Res. Commun. 329:738-742(2005).
RN [35]
RP FUNCTION IN REGULATION OF SLC6A8.
RX PubMed=16036218; DOI=10.1016/j.bbrc.2005.06.164;
RA Shojaiefard M., Christie D.L., Lang F.;
RT "Stimulation of the creatine transporter SLC6A8 by the protein kinases SGK1
RT and SGK3.";
RL Biochem. Biophys. Res. Commun. 334:742-746(2005).
RN [36]
RP FUNCTION IN PHOSPHORYLATION OF CREB1, AND INTERACTION WITH CREB1.
RX PubMed=15733869; DOI=10.1016/j.febslet.2005.01.040;
RA David S., Kalb R.G.;
RT "Serum/glucocorticoid-inducible kinase can phosphorylate the cyclic AMP
RT response element binding protein, CREB.";
RL FEBS Lett. 579:1534-1538(2005).
RN [37]
RP UBIQUITINATION.
RX PubMed=15576372; DOI=10.1074/jbc.m411053200;
RA Zhou R., Snyder P.M.;
RT "Nedd4-2 phosphorylation induces serum and glucocorticoid-regulated kinase
RT (SGK) ubiquitination and degradation.";
RL J. Biol. Chem. 280:4518-4523(2005).
RN [38]
RP FUNCTION IN REGULATION OF SLC2A1/GLUT1.
RX PubMed=16443776; DOI=10.2337/diabetes.55.02.06.db05-0720;
RA Palmada M., Boehmer C., Akel A., Rajamanickam J., Jeyaraj S., Keller K.,
RA Lang F.;
RT "SGK1 kinase upregulates GLUT1 activity and plasma membrane expression.";
RL Diabetes 55:421-427(2006).
RN [39]
RP FUNCTION IN PHOSPHORYLATION OF MAPT/TAU, AND INTERACTION WITH MAPT/TAU.
RX PubMed=16982696; DOI=10.1128/mcb.01017-06;
RA Yang Y.C., Lin C.H., Lee E.H.;
RT "Serum- and glucocorticoid-inducible kinase 1 (SGK1) increases neurite
RT formation through microtubule depolymerization by SGK1 and by SGK1
RT phosphorylation of tau.";
RL Mol. Cell. Biol. 26:8357-8370(2006).
RN [40]
RP SUBCELLULAR LOCATION.
RX PubMed=17202226; DOI=10.1152/ajpcell.00399.2006;
RA Cordas E., Naray-Fejes-Toth A., Fejes-Toth G.;
RT "Subcellular location of serum- and glucocorticoid-induced kinase-1 in
RT renal and mammary epithelial cells.";
RL Am. J. Physiol. 292:C1971-C1981(2007).
RN [41]
RP FUNCTION IN PHOSPHORYLATION OF SLC2A4/GLUT4.
RX PubMed=17382906; DOI=10.1016/j.bbrc.2007.03.029;
RA Jeyaraj S., Boehmer C., Lang F., Palmada M.;
RT "Role of SGK1 kinase in regulating glucose transport via glucose
RT transporter GLUT4.";
RL Biochem. Biophys. Res. Commun. 356:629-635(2007).
RN [42]
RP FUNCTION IN REGULATION OF TRPV6.
RX PubMed=18005662; DOI=10.1016/j.febslet.2007.11.006;
RA Boehmer C., Palmada M., Kenngott C., Lindner R., Klaus F., Laufer J.,
RA Lang F.;
RT "Regulation of the epithelial calcium channel TRPV6 by the serum and
RT glucocorticoid-inducible kinase isoforms SGK1 and SGK3.";
RL FEBS Lett. 581:5586-5590(2007).
RN [43]
RP FUNCTION IN PHOSPHORYLATION OF APBB1/FE65.
RX PubMed=18304449; DOI=10.5483/bmbrep.2008.41.1.041;
RA Lee E.J., Chun J., Hyun S., Ahn H.R., Jeong J.M., Hong S.K., Hong J.T.,
RA Chang I.K., Jeon H.Y., Han Y.S., Auh C.K., Park J.I., Kang S.S.;
RT "Regulation Fe65 localization to the nucleus by SGK1 phosphorylation of its
RT Ser566 residue.";
RL BMB Rep. 41:41-47(2008).
RN [44]
RP PHOSPHORYLATION AT SER-422 BY MTORC2.
RX PubMed=18925875; DOI=10.1042/bj20081668;
RA Garcia-Martinez J.M., Alessi D.R.;
RT "mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and
RT activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1).";
RL Biochem. J. 416:375-385(2008).
RN [45]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-74; SER-397 AND SER-401, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [46]
RP ALTERNATIVE PROMOTER USAGE (ISOFORMS 2 AND 3).
RX PubMed=18334630; DOI=10.1073/pnas.0800958105;
RA Arteaga M.F., Coric T., Straub C., Canessa C.M.;
RT "A brain-specific SGK1 splice isoform regulates expression of ASIC1 in
RT neurons.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:4459-4464(2008).
RN [47]
RP PHOSPHORYLATION AT SER-397 AND SER-401.
RX PubMed=19068477; DOI=10.1074/jbc.m807502200;
RA Chen W., Chen Y., Xu B.E., Juang Y.C., Stippec S., Zhao Y., Cobb M.H.;
RT "Regulation of a third conserved phosphorylation site in SGK1.";
RL J. Biol. Chem. 284:3453-3460(2009).
RN [48]
RP FUNCTION IN PHOSPHORYLATION OF MAPK1/ERK2, AND INTERACTION WITH MAPK3/ERK1;
RP MAPK1/ERK2; MAP2K1/MEK1 AND MAP2K2/MEK2.
RX PubMed=19447520; DOI=10.1016/j.jhep.2009.02.027;
RA Won M., Park K.A., Byun H.S., Kim Y.R., Choi B.L., Hong J.H., Park J.,
RA Seok J.H., Lee Y.H., Cho C.H., Song I.S., Kim Y.K., Shen H.M., Hur G.M.;
RT "Protein kinase SGK1 enhances MEK/ERK complex formation through the
RT phosphorylation of ERK2: implication for the positive regulatory role of
RT SGK1 on the ERK function during liver regeneration.";
RL J. Hepatol. 51:67-76(2009).
RN [49]
RP FUNCTION IN PHOSPHORYLATION OF MDM2.
RX PubMed=19756449; DOI=10.1007/s00109-009-0525-5;
RA Amato R., D'Antona L., Porciatti G., Agosti V., Menniti M., Rinaldo C.,
RA Costa N., Bellacchio E., Mattarocci S., Fuiano G., Soddu S., Paggi M.G.,
RA Lang F., Perrotti N.;
RT "Sgk1 activates MDM2-dependent p53 degradation and affects cell
RT proliferation, survival, and differentiation.";
RL J. Mol. Med. 87:1221-1239(2009).
RN [50]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-74; SER-397 AND SER-401, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [51]
RP FUNCTION IN REGULATION OF SLC6A19.
RX PubMed=20511718; DOI=10.1159/000315092;
RA Boehmer C., Sopjani M., Klaus F., Lindner R., Laufer J., Jeyaraj S.,
RA Lang F., Palmada M.;
RT "The serum and glucocorticoid inducible kinases SGK1-3 stimulate the
RT neutral amino acid transporter SLC6A19.";
RL Cell. Physiol. Biochem. 25:723-732(2010).
RN [52]
RP PHOSPHORYLATION AT SER-422 BY MTORC2, AND INTERACTION WITH MTORC2.
RX PubMed=20338997; DOI=10.1681/asn.2009111168;
RA Lu M., Wang J., Jones K.T., Ives H.E., Feldman M.E., Yao L.J., Shokat K.M.,
RA Ashrafi K., Pearce D.;
RT "mTOR complex-2 activates ENaC by phosphorylating SGK1.";
RL J. Am. Soc. Nephrol. 21:811-818(2010).
RN [53]
RP FUNCTION.
RX PubMed=20730100; DOI=10.1371/journal.pone.0012163;
RA Wiemuth D., Lott J.S., Ly K., Ke Y., Teesdale-Spittle P., Snyder P.M.,
RA McDonald F.J.;
RT "Interaction of serum- and glucocorticoid regulated kinase 1 (SGK1) with
RT the WW-domains of Nedd4-2 is required for epithelial sodium channel
RT regulation.";
RL PLoS ONE 5:E12163-E12163(2010).
RN [54]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-397, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [55]
RP FUNCTION IN REGULATION OF SLC9A3/NHE3, AND SUBCELLULAR LOCATION.
RX PubMed=21865597; DOI=10.1091/mbc.e11-04-0328;
RA He P., Lee S.J., Lin S., Seidler U., Lang F., Fejes-Toth G.,
RA Naray-Fejes-Toth A., Yun C.C.;
RT "Serum- and glucocorticoid-induced kinase 3 in recycling endosomes mediates
RT acute activation of Na+/H+ exchanger NHE3 by glucocorticoids.";
RL Mol. Biol. Cell 22:3812-3825(2011).
RN [56]
RP REVIEW.
RX PubMed=12649597; DOI=10.1159/000070244;
RA Firestone G.L., Giampaolo J.R., O'Keeffe B.A.;
RT "Stimulus-dependent regulation of serum and glucocorticoid inducible
RT protein kinase (SGK) transcription, subcellular localization and enzymatic
RT activity.";
RL Cell. Physiol. Biochem. 13:1-12(2003).
RN [57]
RP REVIEW.
RX PubMed=16460280; DOI=10.1146/annurev.physiol.68.040104.131654;
RA Loffing J., Flores S.Y., Staub O.;
RT "Sgk kinases and their role in epithelial transport.";
RL Annu. Rev. Physiol. 68:461-490(2006).
RN [58]
RP REVIEW ON FUNCTION.
RX PubMed=20919962; DOI=10.3109/08977194.2010.518616;
RA Bruhn M.A., Pearson R.B., Hannan R.D., Sheppard K.E.;
RT "Second AKT: the rise of SGK in cancer signalling.";
RL Growth Factors 28:394-408(2010).
RN [59]
RP REVIEW ON FUNCTION.
RX PubMed=20530112; DOI=10.1113/jphysiol.2010.190926;
RA Lang F., Strutz-Seebohm N., Seebohm G., Lang U.E.;
RT "Significance of SGK1 in the regulation of neuronal function.";
RL J. Physiol. (Lond.) 588:3349-3354(2010).
RN [60]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 60-431, SUBUNIT, AND DISULFIDE
RP BOND.
RX PubMed=17965184; DOI=10.1110/ps.073161707;
RA Zhao B., Lehr R., Smallwood A.M., Ho T.F., Maley K., Randall T., Head M.S.,
RA Koretke K.K., Schnackenberg C.G.;
RT "Crystal structure of the kinase domain of serum and glucocorticoid-
RT regulated kinase 1 in complex with AMP PNP.";
RL Protein Sci. 16:2761-2769(2007).
RN [61]
RP VARIANTS [LARGE SCALE ANALYSIS] ILE-219 AND VAL-342.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Serine/threonine-protein kinase which is involved in the
CC regulation of a wide variety of ion channels, membrane transporters,
CC cellular enzymes, transcription factors, neuronal excitability, cell
CC growth, proliferation, survival, migration and apoptosis. Plays an
CC important role in cellular stress response. Contributes to regulation
CC of renal Na(+) retention, renal K(+) elimination, salt appetite,
CC gastric acid secretion, intestinal Na(+)/H(+) exchange and nutrient
CC transport, insulin-dependent salt sensitivity of blood pressure, salt
CC sensitivity of peripheral glucose uptake, cardiac repolarization and
CC memory consolidation. Up-regulates Na(+) channels: SCNN1A/ENAC, SCN5A
CC and ASIC1/ACCN2, K(+) channels: KCNJ1/ROMK1, KCNA1-5, KCNQ1-5 and
CC KCNE1, epithelial Ca(2+) channels: TRPV5 and TRPV6, chloride channels:
CC BSND, CLCN2 and CFTR, glutamate transporters: SLC1A3/EAAT1, SLC1A2
CC /EAAT2, SLC1A1/EAAT3, SLC1A6/EAAT4 and SLC1A7/EAAT5, amino acid
CC transporters: SLC1A5/ASCT2, SLC38A1/SN1 and SLC6A19, creatine
CC transporter: SLC6A8, Na(+)/dicarboxylate cotransporter: SLC13A2/NADC1,
CC Na(+)-dependent phosphate cotransporter: SLC34A2/NAPI-2B, glutamate
CC receptor: GRIK2/GLUR6. Up-regulates carriers: SLC9A3/NHE3,
CC SLC12A1/NKCC2, SLC12A3/NCC, SLC5A3/SMIT, SLC2A1/GLUT1, SLC5A1/SGLT1 and
CC SLC15A2/PEPT2. Regulates enzymes: GSK3A/B, PMM2 and Na(+)/K(+) ATPase,
CC and transcription factors: CTNNB1 and nuclear factor NF-kappa-B.
CC Stimulates sodium transport into epithelial cells by enhancing the
CC stability and expression of SCNN1A/ENAC. This is achieved by
CC phosphorylating the NEDD4L ubiquitin E3 ligase, promoting its
CC interaction with 14-3-3 proteins, thereby preventing it from binding to
CC SCNN1A/ENAC and targeting it for degradation. Regulates store-operated
CC Ca(+2) entry (SOCE) by stimulating ORAI1 and STIM1. Regulates
CC KCNJ1/ROMK1 directly via its phosphorylation or indirectly via
CC increased interaction with SLC9A3R2/NHERF2. Phosphorylates MDM2 and
CC activates MDM2-dependent ubiquitination of p53/TP53. Phosphorylates
CC MAPT/TAU and mediates microtubule depolymerization and neurite
CC formation in hippocampal neurons. Phosphorylates SLC2A4/GLUT4 and up-
CC regulates its activity. Phosphorylates APBB1/FE65 and promotes its
CC localization to the nucleus. Phosphorylates MAPK1/ERK2 and activates it
CC by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2.
CC Phosphorylates FBXW7 and plays an inhibitory role in the NOTCH1
CC signaling. Phosphorylates FOXO1 resulting in its relocalization from
CC the nucleus to the cytoplasm. Phosphorylates FOXO3, promoting its exit
CC from the nucleus and interference with FOXO3-dependent transcription.
CC Phosphorylates BRAF and MAP3K3/MEKK3 and inhibits their activity.
CC Phosphorylates SLC9A3/NHE3 in response to dexamethasone, resulting in
CC its activation and increased localization at the cell membrane.
CC Phosphorylates CREB1. Necessary for vascular remodeling during
CC angiogenesis. Sustained high levels and activity may contribute to
CC conditions such as hypertension and diabetic nephropathy. Isoform 2
CC exhibited a greater effect on cell plasma membrane expression of
CC SCNN1A/ENAC and Na(+) transport than isoform 1.
CC {ECO:0000269|PubMed:11154281, ECO:0000269|PubMed:11410590,
CC ECO:0000269|PubMed:11696533, ECO:0000269|PubMed:12397388,
CC ECO:0000269|PubMed:12590200, ECO:0000269|PubMed:12634932,
CC ECO:0000269|PubMed:12650886, ECO:0000269|PubMed:12761204,
CC ECO:0000269|PubMed:12911626, ECO:0000269|PubMed:14623317,
CC ECO:0000269|PubMed:14706641, ECO:0000269|PubMed:15040001,
CC ECO:0000269|PubMed:15044175, ECO:0000269|PubMed:15234985,
CC ECO:0000269|PubMed:15319523, ECO:0000269|PubMed:15496163,
CC ECO:0000269|PubMed:15733869, ECO:0000269|PubMed:15737648,
CC ECO:0000269|PubMed:15845389, ECO:0000269|PubMed:15888551,
CC ECO:0000269|PubMed:16036218, ECO:0000269|PubMed:16443776,
CC ECO:0000269|PubMed:16982696, ECO:0000269|PubMed:17382906,
CC ECO:0000269|PubMed:18005662, ECO:0000269|PubMed:18304449,
CC ECO:0000269|PubMed:18753299, ECO:0000269|PubMed:19447520,
CC ECO:0000269|PubMed:19756449, ECO:0000269|PubMed:20511718,
CC ECO:0000269|PubMed:20730100, ECO:0000269|PubMed:21865597}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- ACTIVITY REGULATION: Two specific sites, one in the kinase domain (Thr-
CC 256) and the other in the C-terminal regulatory region (Ser-422), need
CC to be phosphorylated for its full activation. Phosphorylation at Ser-
CC 397 and Ser-401 are also essential for its activity. Activated by WNK1,
CC WNK2, WNK3 and WNK4.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Forms a trimeric complex with
CC FBXW7 and NOTCH1. Interacts with MAPK3/ERK1, MAPK1/ERK2, MAP2K1/MEK1,
CC MAP2K2/MEK2, NEDD4, NEDD4L, MAPT/TAU, MAPK7, CREB1, SLC9A3R2/NHERF2 and
CC KCNJ1/ROMK1. Associates with the mammalian target of rapamycin complex
CC 2 (mTORC2) via an interaction with MAPKAP1/SIN1.
CC {ECO:0000269|PubMed:11254654, ECO:0000269|PubMed:11696533,
CC ECO:0000269|PubMed:14623317, ECO:0000269|PubMed:15733869,
CC ECO:0000269|PubMed:16982696, ECO:0000269|PubMed:17965184,
CC ECO:0000269|PubMed:19447520, ECO:0000269|PubMed:20338997}.
CC -!- INTERACTION:
CC O00141; O15182: CETN3; NbExp=3; IntAct=EBI-1042854, EBI-712959;
CC O00141; Q969L2: MAL2; NbExp=3; IntAct=EBI-1042854, EBI-944295;
CC O00141; Q9ULP0-2: NDRG4; NbExp=3; IntAct=EBI-1042854, EBI-11978907;
CC O00141; P49815: TSC2; NbExp=4; IntAct=EBI-1042854, EBI-396587;
CC O00141; Q80UE6: Wnk4; Xeno; NbExp=2; IntAct=EBI-1042854, EBI-295378;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Endoplasmic reticulum
CC membrane. Cell membrane. Mitochondrion. Note=The subcellular
CC localization is controlled by the cell cycle, as well as by exposure to
CC specific hormones and environmental stress stimuli. In proliferating
CC cells, it shuttles between the nucleus and cytoplasm in synchrony with
CC the cell cycle, and in serum/growth factor-stimulated cells it resides
CC in the nucleus. In contrast, after exposure to environmental stress or
CC treatment with glucocorticoids, it is detected in the cytoplasm and
CC with certain stress conditions is associated with the mitochondria. In
CC osmoregulation through the epithelial sodium channel, it can be
CC localized to the cytoplasmic surface of the cell membrane. Nuclear,
CC upon phosphorylation.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=O00141-1; Sequence=Displayed;
CC Name=2; Synonyms=Sgk1.1, Sgk1_v2;
CC IsoId=O00141-2; Sequence=VSP_037784;
CC Name=3; Synonyms=Sgk1.2;
CC IsoId=O00141-3; Sequence=VSP_037785;
CC Name=4;
CC IsoId=O00141-4; Sequence=VSP_037786;
CC Name=5;
CC IsoId=O00141-5; Sequence=VSP_037787;
CC -!- TISSUE SPECIFICITY: Expressed in most tissues with highest levels in
CC the pancreas, followed by placenta, kidney and lung. Isoform 2 is
CC strongly expressed in brain and pancreas, weaker in heart, placenta,
CC lung, liver and skeletal muscle. {ECO:0000269|PubMed:10548550,
CC ECO:0000269|PubMed:18753299}.
CC -!- INDUCTION: Induced by a very large spectrum of stimuli distinct from
CC glucocorticoids and serum. These include aldosterone, cell shrinkage,
CC cell swelling, TGF-beta, ischemic injury of the brain, neuronal
CC excitotoxicity memory consolidation, chronic viral hepatitis, DNA-
CC damaging agents, vitamin D3 psychophysiological stress, iron, glucose,
CC EDN1, CSF2, fibroblast growth factor, platelet-derived growth factor,
CC phorbolesters, follicle-stimulating hormone, sorbitol, heat shock,
CC oxidative stress, UV irradiation, and p53/TP53. Many of these stimuli
CC are highly cell-specific, as is the case, for example for aldosterone,
CC which has been found to stimulate its expression only in cells derived
CC from aldosterone-responsive epithelia. Isoform 2 is not induced by
CC glucocorticoids but by excessive extracellular glucose and by TGFB1, in
CC cultured cells. {ECO:0000269|PubMed:18753299}.
CC -!- DOMAIN: Isoform 2 subcellular localization at the cell membrane and
CC resistance to proteasomal degradation is mediated by the sequences
CC within the first 120 amino acids.
CC -!- PTM: Regulated by phosphorylation. Activated by phosphorylation on Ser-
CC 422 by mTORC2, transforming it into a substrate for PDPK1 which
CC phosphorylates it on Thr-256. Phosphorylation on Ser-397 and Ser-401
CC are also essential for its activity. Phosphorylation on Ser-78 by MAPK7
CC is required for growth factor-induced cell cycle progression.
CC {ECO:0000269|PubMed:10191262, ECO:0000269|PubMed:11096081,
CC ECO:0000269|PubMed:11254654, ECO:0000269|PubMed:18925875,
CC ECO:0000269|PubMed:19068477, ECO:0000269|PubMed:20338997}.
CC -!- PTM: Ubiquitinated by NEDD4L; which promotes proteasomal degradation.
CC Ubiquitinated by SYVN1 at the endoplasmic reticulum; which promotes
CC rapid proteasomal degradation and maintains a high turnover rate in
CC resting cells. Isoform 2 shows enhanced stability.
CC {ECO:0000269|PubMed:15576372}.
CC -!- MISCELLANEOUS: [Isoform 2]: Produced by alternative promoter usage.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: Produced by alternative promoter usage.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 4]: Produced by alternative splicing of isoform
CC 1. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 5]: Produced by alternative promoter usage.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
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DR EMBL; Y10032; CAA71138.1; -; mRNA.
DR EMBL; AJ000512; CAA04146.1; -; Genomic_DNA.
DR EMBL; EU518415; ACD35864.1; -; mRNA.
DR EMBL; FM205707; CAR58095.1; -; mRNA.
DR EMBL; FM205708; CAR58096.1; -; mRNA.
DR EMBL; FM205709; CAR58097.1; -; mRNA.
DR EMBL; FM205710; CAR58098.1; -; mRNA.
DR EMBL; AF153609; AAD41091.1; -; mRNA.
DR EMBL; AK055077; BAG51463.1; -; mRNA.
DR EMBL; AK298688; BAH12848.1; -; mRNA.
DR EMBL; AL355881; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL135839; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z84486; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW47991.1; -; Genomic_DNA.
DR EMBL; CH471051; EAW47992.1; -; Genomic_DNA.
DR EMBL; CH471051; EAW47993.1; -; Genomic_DNA.
DR EMBL; BC001263; AAH01263.1; -; mRNA.
DR CCDS; CCDS47476.1; -. [O00141-2]
DR CCDS; CCDS47477.1; -. [O00141-5]
DR CCDS; CCDS47478.1; -. [O00141-3]
DR CCDS; CCDS5170.1; -. [O00141-1]
DR RefSeq; NP_001137148.1; NM_001143676.1. [O00141-2]
DR RefSeq; NP_001137149.1; NM_001143677.1. [O00141-5]
DR RefSeq; NP_001137150.1; NM_001143678.1. [O00141-3]
DR RefSeq; NP_001278924.1; NM_001291995.1.
DR RefSeq; NP_005618.2; NM_005627.3. [O00141-1]
DR RefSeq; XP_011534373.1; XM_011536071.1. [O00141-2]
DR PDB; 2R5T; X-ray; 1.90 A; A=60-431.
DR PDB; 3HDM; X-ray; 2.60 A; A=60-431.
DR PDB; 3HDN; X-ray; 3.10 A; A=60-431.
DR PDB; 7PUE; X-ray; 2.51 A; A=60-431.
DR PDBsum; 2R5T; -.
DR PDBsum; 3HDM; -.
DR PDBsum; 3HDN; -.
DR PDBsum; 7PUE; -.
DR AlphaFoldDB; O00141; -.
DR SMR; O00141; -.
DR BioGRID; 112344; 68.
DR CORUM; O00141; -.
DR DIP; DIP-42464N; -.
DR ELM; O00141; -.
DR IntAct; O00141; 21.
DR MINT; O00141; -.
DR STRING; 9606.ENSP00000356832; -.
DR BindingDB; O00141; -.
DR ChEMBL; CHEMBL2343; -.
DR DrugBank; DB08191; 4-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid.
DR DrugBank; DB07837; [4-(5-naphthalen-2-yl-1H-pyrrolo[2,3-b]pyridin-3-yl)phenyl]acetic acid.
DR DrugBank; DB03247; Flavin mononucleotide.
DR GuidetoPHARMACOLOGY; 1534; -.
DR iPTMnet; O00141; -.
DR PhosphoSitePlus; O00141; -.
DR BioMuta; SGK1; -.
DR EPD; O00141; -.
DR jPOST; O00141; -.
DR MassIVE; O00141; -.
DR MaxQB; O00141; -.
DR PaxDb; O00141; -.
DR PeptideAtlas; O00141; -.
DR PRIDE; O00141; -.
DR ProteomicsDB; 47726; -. [O00141-1]
DR ProteomicsDB; 47727; -. [O00141-2]
DR ProteomicsDB; 47728; -. [O00141-3]
DR ProteomicsDB; 47729; -. [O00141-4]
DR ProteomicsDB; 47730; -. [O00141-5]
DR ABCD; O00141; 1 sequenced antibody.
DR Antibodypedia; 19734; 919 antibodies from 47 providers.
DR DNASU; 6446; -.
DR Ensembl; ENST00000237305.11; ENSP00000237305.7; ENSG00000118515.12. [O00141-1]
DR Ensembl; ENST00000367857.9; ENSP00000356831.5; ENSG00000118515.12. [O00141-4]
DR Ensembl; ENST00000367858.10; ENSP00000356832.5; ENSG00000118515.12. [O00141-2]
DR Ensembl; ENST00000413996.7; ENSP00000396242.3; ENSG00000118515.12. [O00141-3]
DR Ensembl; ENST00000528577.5; ENSP00000434450.1; ENSG00000118515.12. [O00141-5]
DR GeneID; 6446; -.
DR KEGG; hsa:6446; -.
DR MANE-Select; ENST00000367858.10; ENSP00000356832.5; NM_001143676.3; NP_001137148.1. [O00141-2]
DR UCSC; uc003qen.5; human. [O00141-1]
DR CTD; 6446; -.
DR DisGeNET; 6446; -.
DR GeneCards; SGK1; -.
DR HGNC; HGNC:10810; SGK1.
DR HPA; ENSG00000118515; Tissue enhanced (parathyroid).
DR MIM; 602958; gene.
DR neXtProt; NX_O00141; -.
DR OpenTargets; ENSG00000118515; -.
DR PharmGKB; PA162403013; -.
DR VEuPathDB; HostDB:ENSG00000118515; -.
DR eggNOG; KOG0598; Eukaryota.
DR GeneTree; ENSGT00940000155726; -.
DR HOGENOM; CLU_000288_63_5_1; -.
DR InParanoid; O00141; -.
DR OMA; HICITDF; -.
DR OrthoDB; 614710at2759; -.
DR PhylomeDB; O00141; -.
DR TreeFam; TF320906; -.
DR BRENDA; 2.7.11.1; 2681.
DR PathwayCommons; O00141; -.
DR Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR Reactome; R-HSA-6804757; Regulation of TP53 Degradation.
DR Reactome; R-HSA-8986944; Transcriptional Regulation by MECP2.
DR Reactome; R-HSA-9031628; NGF-stimulated transcription.
DR SignaLink; O00141; -.
DR SIGNOR; O00141; -.
DR BioGRID-ORCS; 6446; 17 hits in 1119 CRISPR screens.
DR ChiTaRS; SGK1; human.
DR EvolutionaryTrace; O00141; -.
DR GeneWiki; SGK; -.
DR GenomeRNAi; 6446; -.
DR Pharos; O00141; Tchem.
DR PRO; PR:O00141; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; O00141; protein.
DR Bgee; ENSG00000118515; Expressed in palpebral conjunctiva and 198 other tissues.
DR ExpressionAtlas; O00141; baseline and differential.
DR Genevisible; O00141; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005246; F:calcium channel regulator activity; TAS:UniProtKB.
DR GO; GO:0017081; F:chloride channel regulator activity; TAS:UniProtKB.
DR GO; GO:0015459; F:potassium channel regulator activity; IBA:GO_Central.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IDA:MGI.
DR GO; GO:0017080; F:sodium channel regulator activity; TAS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:1904045; P:cellular response to aldosterone; IEA:Ensembl.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0007616; P:long-term memory; TAS:UniProtKB.
DR GO; GO:0048812; P:neuron projection morphogenesis; IBA:GO_Central.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0032411; P:positive regulation of transporter activity; TAS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc.
DR GO; GO:0042981; P:regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:0008217; P:regulation of blood pressure; TAS:UniProtKB.
DR GO; GO:0050790; P:regulation of catalytic activity; TAS:UniProtKB.
DR GO; GO:0001558; P:regulation of cell growth; TAS:UniProtKB.
DR GO; GO:0030334; P:regulation of cell migration; TAS:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; TAS:UniProtKB.
DR GO; GO:0051090; P:regulation of DNA-binding transcription factor activity; TAS:UniProtKB.
DR GO; GO:0060453; P:regulation of gastric acid secretion; TAS:UniProtKB.
DR GO; GO:1901796; P:regulation of signal transduction by p53 class mediator; TAS:Reactome.
DR GO; GO:0070294; P:renal sodium ion absorption; TAS:UniProtKB.
DR GO; GO:0006814; P:sodium ion transport; TAS:ProtInc.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative promoter usage; Alternative splicing; Apoptosis;
KW ATP-binding; Cell membrane; Cytoplasm; Disulfide bond;
KW Endoplasmic reticulum; Kinase; Membrane; Mitochondrion; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Stress response; Transferase;
KW Ubl conjugation.
FT CHAIN 1..431
FT /note="Serine/threonine-protein kinase Sgk1"
FT /id="PRO_0000086642"
FT DOMAIN 98..355
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 356..431
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 1..60
FT /note="Necessary for localization to the mitochondria"
FT REGION 66..92
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 131..141
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:12631736"
FT ACT_SITE 222
FT /note="Proton acceptor"
FT BINDING 104..112
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 127
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT MOD_RES 74
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 78
FT /note="Phosphoserine; by MAPK7"
FT /evidence="ECO:0000269|PubMed:11254654"
FT MOD_RES 256
FT /note="Phosphothreonine; by PDPK1"
FT /evidence="ECO:0000269|PubMed:10191262"
FT MOD_RES 369
FT /note="Phosphothreonine; by PKA"
FT /evidence="ECO:0000269|PubMed:11096081"
FT MOD_RES 397
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19068477,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 401
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19068477,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195"
FT MOD_RES 422
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:10191262,
FT ECO:0000269|PubMed:18925875, ECO:0000269|PubMed:20338997"
FT DISULFID 193
FT /note="Interchain (with C-258)"
FT /evidence="ECO:0000269|PubMed:17965184"
FT DISULFID 258
FT /note="Interchain (with C-193)"
FT /evidence="ECO:0000269|PubMed:17965184"
FT VAR_SEQ 1..25
FT /note="MTVKTEAAKGTLTYSRMRGMVAILI -> MVNKDMNGFPVKKCSAFQFFKKR
FT VRRWIKSPMVSVDKHQSPSLKYTGSSMVHIPPGEPDFESSLCQTCLGEHAFQRGVLPQE
FT NESCSWETQSGCEVREPCNHANILTKPDPRTFWTNDDP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:18753299, ECO:0000303|Ref.4"
FT /id="VSP_037784"
FT VAR_SEQ 1..25
FT /note="MTVKTEAAKGTLTYSRMRGMVAILI -> MGEMQGALARARLESLLRPRHKK
FT RAEAQKRSESFLLSGL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.4"
FT /id="VSP_037785"
FT VAR_SEQ 1..25
FT /note="MTVKTEAAKGTLTYSRMRGMVAILI -> MKPSKRFFISPPSST (in
FT isoform 4)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_037786"
FT VAR_SEQ 1..25
FT /note="MTVKTEAAKGTLTYSRMRGMVAILI -> MSSQSSSLSEACSREAYSSHNWA
FT LPPASRSNPQPAYPWATRRMKEEAIKPPLK (in isoform 5)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_037787"
FT VARIANT 219
FT /note="V -> I (in dbSNP:rs34133418)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041071"
FT VARIANT 342
FT /note="A -> V (in dbSNP:rs55932330)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041072"
FT MUTAGEN 127
FT /note="K->M: Abolishes enzymatic activity."
FT /evidence="ECO:0000269|PubMed:11696533,
FT ECO:0000269|PubMed:12911626, ECO:0000269|PubMed:15040001"
FT MUTAGEN 256
FT /note="T->A: Low activity."
FT /evidence="ECO:0000269|PubMed:10191262"
FT MUTAGEN 256
FT /note="T->D: Low activity."
FT /evidence="ECO:0000269|PubMed:10191262"
FT MUTAGEN 256
FT /note="T->E: Low activity."
FT /evidence="ECO:0000269|PubMed:10191262"
FT MUTAGEN 298
FT /note="Y->A: Abolishes interaction with NEDD4 and NEDD4L."
FT /evidence="ECO:0000269|PubMed:11696533"
FT MUTAGEN 422
FT /note="S->A: Low activity."
FT /evidence="ECO:0000269|PubMed:10191262,
FT ECO:0000269|PubMed:11696533, ECO:0000269|PubMed:12911626,
FT ECO:0000269|PubMed:15040001"
FT MUTAGEN 422
FT /note="S->D: 10-fold activation."
FT /evidence="ECO:0000269|PubMed:10191262,
FT ECO:0000269|PubMed:11696533, ECO:0000269|PubMed:12911626,
FT ECO:0000269|PubMed:15040001"
FT CONFLICT 62
FT /note="Q -> E (in Ref. 4; CAR58097)"
FT /evidence="ECO:0000305"
FT CONFLICT 152
FT /note="K -> R (in Ref. 4; CAR58096)"
FT /evidence="ECO:0000305"
FT CONFLICT 196
FT /note="E -> G (in Ref. 4; CAR58095)"
FT /evidence="ECO:0000305"
FT CONFLICT 228
FT /note="I -> V (in Ref. 6; BAH12848)"
FT /evidence="ECO:0000305"
FT CONFLICT 371
FT /note="P -> R (in Ref. 4; CAR58097)"
FT /evidence="ECO:0000305"
FT CONFLICT 381
FT /note="D -> E (in Ref. 1; CAA71138 and 2; CAA04146)"
FT /evidence="ECO:0000305"
FT HELIX 95..97
FT /evidence="ECO:0007829|PDB:2R5T"
FT STRAND 98..105
FT /evidence="ECO:0007829|PDB:2R5T"
FT STRAND 111..117
FT /evidence="ECO:0007829|PDB:2R5T"
FT TURN 118..120
FT /evidence="ECO:0007829|PDB:2R5T"
FT STRAND 123..130
FT /evidence="ECO:0007829|PDB:2R5T"
FT HELIX 131..133
FT /evidence="ECO:0007829|PDB:2R5T"
FT STRAND 162..167
FT /evidence="ECO:0007829|PDB:2R5T"
FT STRAND 169..177
FT /evidence="ECO:0007829|PDB:2R5T"
FT HELIX 184..191
FT /evidence="ECO:0007829|PDB:2R5T"
FT HELIX 196..215
FT /evidence="ECO:0007829|PDB:2R5T"
FT HELIX 225..227
FT /evidence="ECO:0007829|PDB:2R5T"
FT STRAND 228..230
FT /evidence="ECO:0007829|PDB:2R5T"
FT STRAND 232..234
FT /evidence="ECO:0007829|PDB:3HDN"
FT STRAND 236..238
FT /evidence="ECO:0007829|PDB:2R5T"
FT HELIX 245..247
FT /evidence="ECO:0007829|PDB:2R5T"
FT STRAND 256..258
FT /evidence="ECO:0007829|PDB:2R5T"
FT HELIX 266..269
FT /evidence="ECO:0007829|PDB:2R5T"
FT HELIX 277..292
FT /evidence="ECO:0007829|PDB:2R5T"
FT HELIX 302..311
FT /evidence="ECO:0007829|PDB:2R5T"
FT STRAND 318..320
FT /evidence="ECO:0007829|PDB:2R5T"
FT HELIX 322..331
FT /evidence="ECO:0007829|PDB:2R5T"
FT HELIX 336..338
FT /evidence="ECO:0007829|PDB:2R5T"
FT TURN 340..345
FT /evidence="ECO:0007829|PDB:2R5T"
FT HELIX 346..350
FT /evidence="ECO:0007829|PDB:2R5T"
FT HELIX 353..355
FT /evidence="ECO:0007829|PDB:2R5T"
FT HELIX 360..364
FT /evidence="ECO:0007829|PDB:2R5T"
SQ SEQUENCE 431 AA; 48942 MW; F3697C63AB1F499D CRC64;
MTVKTEAAKG TLTYSRMRGM VAILIAFMKQ RRMGLNDFIQ KIANNSYACK HPEVQSILKI
SQPQEPELMN ANPSPPPSPS QQINLGPSSN PHAKPSDFHF LKVIGKGSFG KVLLARHKAE
EVFYAVKVLQ KKAILKKKEE KHIMSERNVL LKNVKHPFLV GLHFSFQTAD KLYFVLDYIN
GGELFYHLQR ERCFLEPRAR FYAAEIASAL GYLHSLNIVY RDLKPENILL DSQGHIVLTD
FGLCKENIEH NSTTSTFCGT PEYLAPEVLH KQPYDRTVDW WCLGAVLYEM LYGLPPFYSR
NTAEMYDNIL NKPLQLKPNI TNSARHLLEG LLQKDRTKRL GAKDDFMEIK SHVFFSLINW
DDLINKKITP PFNPNVSGPN DLRHFDPEFT EEPVPNSIGK SPDSVLVTAS VKEAAEAFLG
FSYAPPTDSF L
