SGK1_CAEEL
ID SGK1_CAEEL Reviewed; 463 AA.
AC Q2PJ68; Q2PJ69;
DT 22-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2006, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Serine/threonine-protein kinase sgk-1 {ECO:0000250|UniProtKB:O00141, ECO:0000303|PubMed:15068796};
DE EC=2.7.11.1;
DE AltName: Full=Serum- and glucocorticoid-inducible kinase homolog {ECO:0000303|PubMed:15068796};
DE AltName: Full=Serum/glucocorticoid-regulated kinase 1 {ECO:0000250|UniProtKB:O00141};
GN Name=sgk-1 {ECO:0000312|WormBase:W10G6.2b};
GN ORFNames=W10G6.2 {ECO:0000312|WormBase:W10G6.2b};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1] {ECO:0000305, ECO:0000312|EMBL:CAJ55247.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, ACTIVITY REGULATION, INTERACTION WITH PDK-1; AKT-1; AKT-2 AND
RP DAF-16, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=15068796; DOI=10.1016/s1534-5807(04)00095-4;
RA Hertweck M., Goebel C., Baumeister R.;
RT "C. elegans SGK-1 is the critical component in the Akt/PKB kinase complex
RT to control stress response and life span.";
RL Dev. Cell 6:577-588(2004).
RN [3] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18782349; DOI=10.1111/j.1474-9726.2008.00435.x;
RA Evans E.A., Chen W.C., Tan M.-W.;
RT "The DAF-2 insulin-like signaling pathway independently regulates aging and
RT immunity in C. elegans.";
RL Aging Cell 7:879-893(2008).
RN [4] {ECO:0000305}
RP FUNCTION.
RX PubMed=18358814; DOI=10.1016/j.cell.2008.01.030;
RA Tullet J.M., Hertweck M., An J.H., Baker J., Hwang J.Y., Liu S.,
RA Oliveira R.P., Baumeister R., Blackwell T.K.;
RT "Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like
RT signaling in C. elegans.";
RL Cell 132:1025-1038(2008).
RN [5]
RP INTERACTION WITH PPTR-1, AND TISSUE SPECIFICITY.
RX PubMed=19249087; DOI=10.1016/j.cell.2009.01.025;
RA Padmanabhan S., Mukhopadhyay A., Narasimhan S.D., Tesz G., Czech M.P.,
RA Tissenbaum H.A.;
RT "A PP2A regulatory subunit regulates C. elegans insulin/IGF-1 signaling by
RT modulating AKT-1 phosphorylation.";
RL Cell 136:939-951(2009).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19240135; DOI=10.1101/gad.1775409;
RA Soukas A.A., Kane E.A., Carr C.E., Melo J.A., Ruvkun G.;
RT "Rictor/TORC2 regulates fat metabolism, feeding, growth, and life span in
RT Caenorhabditis elegans.";
RL Genes Dev. 23:496-511(2009).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19260765; DOI=10.1371/journal.pbio.1000060;
RA Jones K.T., Greer E.R., Pearce D., Ashrafi K.;
RT "Rictor/TORC2 regulates Caenorhabditis elegans fat storage, body size, and
RT development through sgk-1.";
RL PLoS Biol. 7:60-60(2009).
RN [8]
RP FUNCTION.
RX PubMed=25383666; DOI=10.1038/nsmb.2915;
RA Nakagawa A., Sullivan K.D., Xue D.;
RT "Caspase-activated phosphoinositide binding by CNT-1 promotes apoptosis by
RT inhibiting the AKT pathway.";
RL Nat. Struct. Mol. Biol. 21:1082-1090(2014).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP 286-GLN--VAL-463.
RX PubMed=26115433; DOI=10.1371/journal.pone.0130778;
RA Zhu M., Wu G., Li Y.X., Stevens J.K., Fan C.X., Spang A., Dong M.Q.;
RT "Serum- and Glucocorticoid-Inducible Kinase-1 (SGK-1) Plays a Role in
RT Membrane Trafficking in Caenorhabditis elegans.";
RL PLoS ONE 10:e0130778-e0130778(2015).
RN [10]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF GLU-126.
RX PubMed=27401555; DOI=10.1101/gad.283895.116;
RA Dowen R.H., Breen P.C., Tullius T., Conery A.L., Ruvkun G.;
RT "A microRNA program in the C. elegans hypodermis couples to intestinal
RT mTORC2/PQM-1 signaling to modulate fat transport.";
RL Genes Dev. 30:1515-1528(2016).
RN [11]
RP ERRATUM.
RX PubMed=27631731; DOI=10.1371/journal.pone.0163398;
RA Zhu M., Wu G., Li Y.X., Stevens J.K., Fan C.X., Spang A., Dong M.Q.;
RT "Correction: Serum- and Glucocorticoid-Inducible Kinase-1 (SGK-1) Plays a
RT Role in Membrane Trafficking in Caenorhabditis elegans.";
RL PLoS ONE 11:e0163398-e0163398(2016).
CC -!- FUNCTION: Acts downstream of PI3 kinase age-1 and kinase pdk-1 in the
CC daf-2/insulin receptor-like transduction pathway (PubMed:15068796).
CC Essential role in regulating development, stress response, and
CC longevity (PubMed:15068796, PubMed:18782349). Phosphorylates Forkhead-
CC related daf-16 and the longevity-promoting skn-1 transcription factors,
CC which inhibits their entry into the nucleus and antagonizes their
CC function (PubMed:18358814). Promotes the cytoplasmic localization of
CC the transcription factor pqm-1 (PubMed:27401555). Plays a role in the
CC intracellular trafficking of proteins such as mig-14 to the cell
CC membrane, and this may be through positively regulating ceramide
CC synthesis (PubMed:26115433). Acts downstream of rict-1 to regulate fat
CC storage, size, development and vitellogenesis (PubMed:19240135,
CC PubMed:19260765, PubMed:27401555). Downstream of age-1 and together
CC with akt-1/2, promotes cell survival during embryonic development
CC (PubMed:25383666). Does not appear to play a role in immune function
CC (PubMed:18782349). {ECO:0000269|PubMed:15068796,
CC ECO:0000269|PubMed:18358814, ECO:0000269|PubMed:18782349,
CC ECO:0000269|PubMed:19240135, ECO:0000269|PubMed:19260765,
CC ECO:0000269|PubMed:25383666, ECO:0000269|PubMed:26115433,
CC ECO:0000269|PubMed:27401555}.
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 Evidence={ECO:0000269|PubMed:15068796};
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; Evidence={ECO:0000269|PubMed:15068796};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:15068796};
CC -!- ACTIVITY REGULATION: Phosphorylated and activated by pdk-1.
CC {ECO:0000269|PubMed:15068796}.
CC -!- SUBUNIT: Interacts with pdk-1, akt-1, akt-2 and daf-16
CC (PubMed:15068796). Part of a complex containing sgk-1, akt-1 and akt-2
CC (PubMed:15068796). Interacts with let-92 phosphatase regulatory subunit
CC pptr-1 (PubMed:19249087). {ECO:0000269|PubMed:15068796,
CC ECO:0000269|PubMed:19249087}.
CC -!- INTERACTION:
CC Q2PJ68; Q17941: akt-1; NbExp=3; IntAct=EBI-1770776, EBI-1770718;
CC Q2PJ68; Q9XTG7: akt-2; NbExp=3; IntAct=EBI-1770776, EBI-320656;
CC Q2PJ68; O16850: daf-16; NbExp=3; IntAct=EBI-1770776, EBI-324028;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15068796,
CC ECO:0000269|PubMed:26115433}. Nucleus {ECO:0000269|PubMed:15068796}.
CC Apical cell membrane {ECO:0000269|PubMed:26115433}. Note=Localized both
CC in the cytoplasm and in the nucleus in neurons, exclusively cytoplasmic
CC in the intestine. Localizes to the apical cell membrane and diffusely
CC throughout the cytoplasm in intestinal cells (PubMed:26115433).
CC {ECO:0000269|PubMed:15068796, ECO:0000269|PubMed:26115433}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=b {ECO:0000312|WormBase:W10G6.2b};
CC IsoId=Q2PJ68-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:W10G6.2a};
CC IsoId=Q2PJ68-2; Sequence=VSP_053156;
CC -!- TISSUE SPECIFICITY: Expressed in late embryos just before hatching. At
CC postembryonic stages, expressed in sensory and motor neurons and in the
CC intestine. Highly expressed in the intestine and head and tail neurons
CC (PubMed:26115433). {ECO:0000269|PubMed:15068796,
CC ECO:0000269|PubMed:19249087, ECO:0000269|PubMed:26115433}.
CC -!- DISRUPTION PHENOTYPE: A mild developmental delay, extended generation
CC time, an extension of life span, defective egg-laying and decreased
CC body size, but increased lipid storage (PubMed:15068796,
CC PubMed:18782349, PubMed:19240135, PubMed:19260765). RNAi-mediated
CC knockdown abolishes expression of the vitellogenin vit-3
CC (PubMed:27401555). {ECO:0000269|PubMed:15068796,
CC ECO:0000269|PubMed:18782349, ECO:0000269|PubMed:19240135,
CC ECO:0000269|PubMed:19260765, ECO:0000269|PubMed:27401555}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. {ECO:0000255}.
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DR EMBL; BX284606; CAJ55246.1; -; Genomic_DNA.
DR EMBL; BX284606; CAJ55247.1; -; Genomic_DNA.
DR RefSeq; NP_001041298.1; NM_001047833.4.
DR RefSeq; NP_001041299.1; NM_001047834.1. [Q2PJ68-1]
DR AlphaFoldDB; Q2PJ68; -.
DR SMR; Q2PJ68; -.
DR BioGRID; 46583; 22.
DR ComplexPortal; CPX-1129; Atk-1/Akt-2/Sgk-1 protein kinase complex.
DR IntAct; Q2PJ68; 6.
DR STRING; 6239.W10G6.2b; -.
DR EPD; Q2PJ68; -.
DR PaxDb; Q2PJ68; -.
DR PeptideAtlas; Q2PJ68; -.
DR EnsemblMetazoa; W10G6.2a.1; W10G6.2a.1; WBGene00004789. [Q2PJ68-2]
DR EnsemblMetazoa; W10G6.2a.2; W10G6.2a.2; WBGene00004789. [Q2PJ68-2]
DR EnsemblMetazoa; W10G6.2b.1; W10G6.2b.1; WBGene00004789. [Q2PJ68-1]
DR GeneID; 181697; -.
DR KEGG; cel:CELE_W10G6.2; -.
DR UCSC; W10G6.2a.1; c. elegans.
DR CTD; 181697; -.
DR WormBase; W10G6.2a; CE39527; WBGene00004789; sgk-1. [Q2PJ68-2]
DR WormBase; W10G6.2b; CE39528; WBGene00004789; sgk-1. [Q2PJ68-1]
DR eggNOG; KOG0598; Eukaryota.
DR GeneTree; ENSGT00940000153776; -.
DR InParanoid; Q2PJ68; -.
DR OMA; HFSFQNK; -.
DR OrthoDB; 614710at2759; -.
DR PhylomeDB; Q2PJ68; -.
DR Reactome; R-CEL-2672351; Stimuli-sensing channels.
DR Reactome; R-CEL-6804757; Regulation of TP53 Degradation.
DR Reactome; R-CEL-9031628; NGF-stimulated transcription.
DR SignaLink; Q2PJ68; -.
DR PRO; PR:Q2PJ68; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00004789; Expressed in larva and 4 other tissues.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:1902911; C:protein kinase complex; IPI:ComplexPortal.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IDA:WormBase.
DR GO; GO:0004672; F:protein kinase activity; IDA:WormBase.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:WormBase.
DR GO; GO:0044255; P:cellular lipid metabolic process; IMP:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0048382; P:mesendoderm development; IGI:WormBase.
DR GO; GO:0002119; P:nematode larval development; IMP:WormBase.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:WormBase.
DR GO; GO:1903188; P:positive regulation of vitellogenesis; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:WormBase.
DR GO; GO:0010468; P:regulation of gene expression; IDA:ComplexPortal.
DR GO; GO:1904508; P:regulation of protein localization to basolateral plasma membrane; IMP:WormBase.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR011009; Kinase-like_dom_sf.
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 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 Alternative splicing; ATP-binding; Cell membrane; Cytoplasm;
KW Developmental protein; Kinase; Magnesium; Membrane; Metal-binding;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Stress response; Transferase.
FT CHAIN 1..463
FT /note="Serine/threonine-protein kinase sgk-1"
FT /id="PRO_0000385374"
FT DOMAIN 135..392
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 393..463
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT ACT_SITE 259
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 141..149
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 164
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT VAR_SEQ 1..10
FT /note="Missing (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_053156"
FT MUTAGEN 126
FT /note="E->K: In ft15; suppresses the defect in expression
FT of vit-3 caused by lin-29 mutation."
FT /evidence="ECO:0000269|PubMed:27401555"
FT MUTAGEN 286..463
FT /note="Missing: In mg455; impairs intracellular trafficking
FT of cell membrane receptors. Reduces localization of the
FT cell membrane receptor mig-14 to the basolateral cell
FT membrane and instead mig-14 mis-localizes to late
FT endosomal/early lysosomal structures near the apical cell
FT membrane."
FT /evidence="ECO:0000269|PubMed:26115433"
SQ SEQUENCE 463 AA; 54291 MW; C2006B90F4E9FBCD CRC64;
MGSMYYNESR MVRKDEVTCN VIIGDDKKTV VYALRIGNGP IMQKTFEEYE RFFTTEKDMI
PATIFTAPKK KFLQADSKFY EKRRVWILVI SQHLVDNNLR SEDVRRFFHL ESPDDDENNV
DLGPSERKTA TANDFDYLTT IGKGSFGRVY QVRHKETKKI YAMKILSKEH IRKKNEVKHV
MAERNVLINN FKHPFLVSLH FSFQNKEKLY FVLDHLNGGE LFSHLQREKH FSESRSRFYA
AEIACALGYL HEKNIIYRDL KPENLLLDDK GYLVLTDFGL CKEDMQGSKT TSTFCGTPEY
LAPEIILKKP YDKTVDWWCL GSVLYEMIFG LPPFYSKDHN EMYDKIINQP LRLKHNISVP
CSELITGLLQ KDRSKRLGHR NDFRDIRDHP FFLPVDWDKL LNRELKAPFI PKVKNAMDTS
NISKEFVEIQ IDPSSLAPQQ LAVTHRDHDF ENFTFVDTNR VLV
