SGK3_RAT
ID SGK3_RAT Reviewed; 496 AA.
AC Q8R4V0;
DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT 12-DEC-2006, sequence version 2.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=Serine/threonine-protein kinase Sgk3;
DE EC=2.7.11.1;
DE AltName: Full=Cytokine-independent survival kinase;
DE AltName: Full=Serum/glucocorticoid-regulated kinase 3;
DE AltName: Full=Serum/glucocorticoid-regulated kinase-like;
GN Name=Sgk3; Synonyms=Cisk, Sgkl;
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 20-279.
RC STRAIN=Sprague-Dawley;
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).
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, proliferation, survival and migration. Up-regulates Na(+)
CC channels: SCNN1A/ENAC and SCN5A, K(+) channels: KCNA3/KV1.3, KCNE1,
CC KCNQ1 and KCNH2/HERG, epithelial Ca(2+) channels: TRPV5 and TRPV6,
CC chloride channel: BSND, creatine transporter: SLC6A8,
CC Na(+)/dicarboxylate cotransporter: SLC13A2/NADC1, Na(+)-dependent
CC phosphate cotransporter: SLC34A2/NAPI-2B, amino acid transporters:
CC SLC1A5/ASCT2 and SLC6A19, glutamate transporters: SLC1A3/EAAT1,
CC SLC1A6/EAAT4 and SLC1A7/EAAT5, glutamate receptors: GRIA1/GLUR1 and
CC GRIK2/GLUR6, Na(+)/H(+) exchanger: SLC9A3/NHE3, and the Na(+)/K(+)
CC ATPase. Plays a role in the regulation of renal tubular phosphate
CC transport and bone density. Phosphorylates NEDD4L and GSK3B. Positively
CC regulates ER transcription activity through phosphorylation of FLII.
CC Negatively regulates the function of ITCH/AIP4 via its phosphorylation
CC and thereby prevents CXCR4 from being efficiently sorted to lysosomes
CC (By similarity). {ECO:0000250, ECO:0000269|PubMed:15504348}.
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 320) and the other in the C-terminal regulatory region (Ser-486), need
CC to be phosphorylated for its full activation.
CC -!- SUBUNIT: Interacts with GSK3B and FLII. Interacts with PDPK1 in a
CC phosphorylation-dependent manner. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle {ECO:0000250}. Early endosome
CC {ECO:0000250}. Recycling endosome {ECO:0000250}. Note=Endosomal
CC localization is a prerequisite for complete kinase activity. It is
CC essential for its colocalization with the kinase responsible for
CC phosphorylating Ser-486 thus allowing PDPK1 phosphorylation of Thr-320
CC resulting in complete activation of SGK3. Localized in vesicle-like
CC structures and in the early endosome. Colocalizes with SLC9A3/NHE3 in
CC the recycling endosomes (By similarity). {ECO:0000250}.
CC -!- PTM: Activated by phosphorylation on Ser-486 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-320. {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; AABR03002244; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF361755; AAL91350.1; -; mRNA.
DR AlphaFoldDB; Q8R4V0; -.
DR SMR; Q8R4V0; -.
DR STRING; 10116.ENSRNOP00000064540; -.
DR iPTMnet; Q8R4V0; -.
DR PhosphoSitePlus; Q8R4V0; -.
DR PaxDb; Q8R4V0; -.
DR PRIDE; Q8R4V0; -.
DR RGD; 620242; Sgk3.
DR eggNOG; KOG0598; Eukaryota.
DR eggNOG; KOG2101; Eukaryota.
DR InParanoid; Q8R4V0; -.
DR PhylomeDB; Q8R4V0; -.
DR Reactome; R-RNO-2672351; Stimuli-sensing channels.
DR PRO; PR:Q8R4V0; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0055037; C:recycling endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0035091; F:phosphatidylinositol binding; IEA:InterPro.
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; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; ISO:RGD.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR CDD; cd06870; PX_CISK; 1.
DR CDD; cd05604; STKc_SGK3; 1.
DR Gene3D; 3.30.1520.10; -; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR037900; CISK_PX.
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; IPR001683; PX_dom.
DR InterPro; IPR036871; PX_dom_sf.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR037709; SGK3_dom.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR Pfam; PF00787; PX; 1.
DR SMART; SM00312; PX; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF64268; SSF64268; 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 PROSITE; PS50195; PX; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cytoplasmic vesicle; Endosome; Kinase; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..496
FT /note="Serine/threonine-protein kinase Sgk3"
FT /id="PRO_0000263053"
FT DOMAIN 12..124
FT /note="PX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00147"
FT DOMAIN 162..464
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 420..496
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 121..157
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 195..205
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 124..140
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 286
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 168..176
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 191
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 126
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ERE3"
FT MOD_RES 129
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ERE3"
FT MOD_RES 320
FT /note="Phosphothreonine; by PDPK1"
FT /evidence="ECO:0000250|UniProtKB:Q96BR1"
FT MOD_RES 486
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96BR1"
SQ SEQUENCE 496 AA; 57171 MW; 4D3B4F2E74078A47 CRC64;
MQRDCTMDYK ESCPSVSIPS SDEHREKKKR FTVYKVLVSV GRSEWFVFRR YAEFDKLYNS
LKKQFPAMAL KIPAKRIFGD NFDPDFIKQR RAGLNEFIQN LVRYPELYNH PDVRAFLQMD
SPRHQSDPSE DEDERSTPKP HSTSRNINLG PTGNPHAKPS DFDFLKVIGK GSFGKVLLAK
RKLDGKFYAV KVLQKKIVLN RKEQKHIMAE RNVLLKNVKH PFLVGLHYSF QTTEKLYFVL
DFVNGGELFF HLQRERSFPE PRARFYAAEI ASALGYLHSI KIVYRDLKPE NILLDSMGHV
VLTDFGLCKE GIAISDTTTT FCGTPEYLAP EVIRKQPYDR TVDWWCLGAV LYEMLYGLPP
FYCRDVAEMY DNILHKPLNL RPGVSLTAWS ILEELLEKNR QNRLGAKEDF LEIQNHPFFE
SLSWTDLVQK KIPPPFNPNV AGPDDIRNFD AVFTEETVPY SVCVSSDYSI VNASVLEADD
AFVGFSYAPP SEDLFL
