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 27-MAR-2024, entry version 220. 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 ACTIVITY REGULATION, PHOSPHORYLATION AT THR-256 AND SER-422, AND RP MUTAGENESIS OF THR-256 AND 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 ACTIVITY REGULATION, AND 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 ACTIVITY REGULATION, AND PHOSPHORYLATION. RX PubMed=36373794; DOI=10.1242/jcs.260313; RA Saha B., Leite-Dellova D.C.A., Demko J., Soerensen M.V., Takagi E., RA Gleason C.E., Shabbir W., Pearce D.; RT "WNK1 is a chloride-stimulated scaffold that regulates mTORC2 activity and RT ion transport."; RL J. Cell Sci. 135:0-0(2022). RN [57] 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 [58] 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 [59] 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 [60] 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 [61] 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 [62] 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 (PubMed:10191262). CC Phosphorylation at Ser-397 and Ser-401 are also essential for its CC activity (PubMed:19068477). Activated by WNK1, WNK2, WNK3 and WNK4; CC which promote phosphorylation by mTORC2 (PubMed:36373794). CC {ECO:0000269|PubMed:10191262, ECO:0000269|PubMed:19068477, CC ECO:0000269|PubMed:36373794}. 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 (PubMed:10191262, PubMed:11096081, CC PubMed:18925875, PubMed:20338997, PubMed:36373794). Activated by CC phosphorylation on Ser-422 by mTORC2, transforming it into a substrate CC for PDPK1 which phosphorylates it on Thr-256 (PubMed:10191262, CC PubMed:18925875, PubMed:20338997, PubMed:36373794). Phosphorylation on CC Ser-397 and Ser-401 are also essential for its activity CC (PubMed:19068477). Phosphorylation on Ser-78 by MAPK7 is required for CC growth factor-induced cell cycle progression (PubMed:11254654). 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 ECO:0000269|PubMed:36373794}. 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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. 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; 72. 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; 9606-ENSP00000356832; -. DR PeptideAtlas; 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; 1124 antibodies from 47 providers. DR DNASU; 6446; -. DR Ensembl; ENST00000237305.12; 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 AGR; HGNC:10810; -. 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; CWTDMSL; -. DR OrthoDB; 3028764at2759; -. DR PhylomeDB; O00141; -. DR TreeFam; TF320906; -. DR BRENDA; 2.7.11.1; 2681. DR PathwayCommons; O00141; -. DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling. 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; 19 hits in 1198 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 200 other cell types or tissues. DR ExpressionAtlas; O00141; baseline and differential. 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:DNA damage response; 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: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 CDD; cd05602; STKc_SGK1; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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 PANTHER; PTHR24351; RIBOSOMAL PROTEIN S6 KINASE; 1. DR PANTHER; PTHR24351:SF184; SERINE_THREONINE-PROTEIN KINASE SGK1; 1. 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; Protein kinase-like (PK-like); 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. DR Genevisible; O00141; HS. 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 //