SGK2_RAT
ID SGK2_RAT Reviewed; 367 AA.
AC Q8R4U9;
DT 22-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 12-DEC-2006, sequence version 2.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Serine/threonine-protein kinase Sgk2;
DE EC=2.7.11.1;
DE AltName: Full=Serum/glucocorticoid-regulated kinase 2;
GN Name=Sgk2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 18-319.
RC STRAIN=Sprague-Dawley; TISSUE=Kidney;
RA Feng Y.X., Huber S.M., Waerntges S., Lang F.;
RT "SGK2 and SGK3 mRNA expression in rat kidney.";
RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION IN THE REGULATION OF SLC1A6/EAAT4.
RX PubMed=15504348; DOI=10.1016/j.bbrc.2004.09.193;
RA Boehmer C., Philippin M., Rajamanickam J., Mack A., Broer S., Palmada M.,
RA Lang F.;
RT "Stimulation of the EAAT4 glutamate transporter by SGK protein kinase
RT isoforms and PKB.";
RL Biochem. Biophys. Res. Commun. 324:1242-1248(2004).
RN [4]
RP FUNCTION IN THE REGULATION OF SLC9A3/NHE3, AND TISSUE SPECIFICITY.
RX PubMed=20926631; DOI=10.1152/ajprenal.00075.2010;
RA Pao A.C., Bhargava A., Di Sole F., Quigley R., Shao X., Wang J., Thomas S.,
RA Zhang J., Shi M., Funder J.W., Moe O.W., Pearce D.;
RT "Expression and role of serum and glucocorticoid-regulated kinase 2 in the
RT regulation of Na+/H+ exchanger 3 in the mammalian kidney.";
RL Am. J. Physiol. 299:F1496-F1506(2010).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Serine/threonine-protein kinase which is involved in the
CC regulation of a wide variety of ion channels, membrane transporters,
CC cell growth, survival and proliferation. Up-regulates Na(+) channels:
CC SCNN1A/ENAC, K(+) channels: KCNA3/Kv1.3, KCNE1 and KCNQ1, amino acid
CC transporter: SLC6A19, glutamate transporter: SLC1A6/EAAT4, glutamate
CC receptors: GRIA1/GLUR1 and GRIK2/GLUR6, Na(+)/H(+) exchanger:
CC SLC9A3/NHE3, and the Na(+)/K(+) ATPase. {ECO:0000269|PubMed:15504348,
CC ECO:0000269|PubMed:20926631}.
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 193) and the other in the C-terminal regulatory region (Ser-356), need
CC to be phosphorylated for its full activation.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in the proximal tubule and thick
CC ascending limb of the loop of Henle (TALH).
CC {ECO:0000269|PubMed:20926631}.
CC -!- PTM: Activated by phosphorylation on Ser-356 by an unknown kinase (may
CC be mTORC2 but not confirmed), transforming it into a substrate for
CC PDPK1 which then phosphorylates it on Thr-193. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; AABR03025367; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF361756; AAL91351.1; -; mRNA.
DR RefSeq; NP_604458.1; NM_134463.1.
DR AlphaFoldDB; Q8R4U9; -.
DR SMR; Q8R4U9; -.
DR STRING; 10116.ENSRNOP00000040718; -.
DR iPTMnet; Q8R4U9; -.
DR PhosphoSitePlus; Q8R4U9; -.
DR PaxDb; Q8R4U9; -.
DR Ensembl; ENSRNOT00000108319; ENSRNOP00000081213; ENSRNOG00000033573.
DR GeneID; 171497; -.
DR KEGG; rno:171497; -.
DR CTD; 10110; -.
DR RGD; 620232; Sgk2.
DR eggNOG; KOG0598; Eukaryota.
DR GeneTree; ENSGT00940000153776; -.
DR InParanoid; Q8R4U9; -.
DR OrthoDB; 614710at2759; -.
DR PhylomeDB; Q8R4U9; -.
DR TreeFam; TF320906; -.
DR Reactome; R-RNO-2672351; Stimuli-sensing channels.
DR PRO; PR:Q8R4U9; -.
DR Proteomes; UP000002494; Chromosome 3.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0015459; F:potassium channel regulator activity; ISS:UniProtKB.
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:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
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 ATP-binding; Cytoplasm; Kinase; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..367
FT /note="Serine/threonine-protein kinase Sgk2"
FT /id="PRO_0000086648"
FT DOMAIN 35..292
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 293..367
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 1..28
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 68..77
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT ACT_SITE 159
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 41..49
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 64
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 193
FT /note="Phosphothreonine; by PDPK1"
FT /evidence="ECO:0000250|UniProtKB:Q9HBY8"
FT MOD_RES 334
FT /note="Phosphoserine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT MOD_RES 356
FT /note="Phosphoserine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT MOD_RES 357
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
SQ SEQUENCE 367 AA; 41361 MW; 49F2231445645B50 CRC64;
MASSPVGVPS PQPSRANGNI NLGPSANPNA RPTDFDFLKV IGKGNYGKVL LAKRKSDGAF
YAVKVLQKKS ILKNKEQSHI MAERNVLLKN VRHPFLVGLR YSFQTPEKLY FVLDYVNGGE
LFFHLQREHR FLEPRARFYT AEVASAIGYL HSLNIIYRDL KPENILLDCQ GHVVLTDFGL
CKECVEPEET TSTFCGTPEY LAPEVLRKEP YDRAVDWWCL GAVLYEMLHG LPPFFNTDVA
QMYENILHQP LQIPGGRTVA ACDLLQGLLH KDQRQRLGSK EDFLDIKNHM FFSPINWDDL
YHKRLTPPFN PNVEGPADLK HFDPEFTQEA VSKSIGCTPD TMSSSSGASS AFLGFSYAQD
DDDILDS
