AKT2_CAEEL
ID AKT2_CAEEL Reviewed; 528 AA.
AC Q9XTG7; O77145;
DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Serine/threonine-protein kinase akt-2;
DE EC=2.7.11.1;
DE AltName: Full=Protein kinase B akt-2;
DE Short=PKB akt-2;
GN Name=akt-2; ORFNames=F28H6.1;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), FUNCTION, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=9716402; DOI=10.1101/gad.12.16.2488;
RA Paradis S., Ruvkun G.;
RT "Caenorhabditis elegans Akt/PKB transduces insulin receptor-like signals
RT from AGE-1 PI3 kinase to the DAF-16 transcription factor.";
RL Genes Dev. 12:2488-2498(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING.
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 [3]
RP FUNCTION.
RX PubMed=10364160; DOI=10.1101/gad.13.11.1438;
RA Paradis S., Ailion M., Toker A., Thomas J.H., Ruvkun G.;
RT "A PDK1 homolog is necessary and sufficient to transduce AGE-1 PI3 kinase
RT signals that regulate diapause in Caenorhabditis elegans.";
RL Genes Dev. 13:1438-1452(1999).
RN [4]
RP FUNCTION.
RX PubMed=11747825; DOI=10.1016/s0960-9822(01)00594-2;
RA Henderson S.T., Johnson T.E.;
RT "daf-16 integrates developmental and environmental inputs to mediate aging
RT in the nematode Caenorhabditis elegans.";
RL Curr. Biol. 11:1975-1980(2001).
RN [5]
RP FUNCTION.
RX PubMed=11381260; DOI=10.1038/88850;
RA Lin K., Hsin H., Libina N., Kenyon C.;
RT "Regulation of the Caenorhabditis elegans longevity protein DAF-16 by
RT insulin/IGF-1 and germline signaling.";
RL Nat. Genet. 28:139-145(2001).
RN [6]
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 [7]
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 [8]
RP FUNCTION, ACTIVITY REGULATION, INTERACTION WITH PDK-1; SGK-1; AKT-1 AND
RP DAF-16, 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 [9]
RP FUNCTION, DOMAIN, AND MUTAGENESIS OF LYS-209.
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).
CC -!- FUNCTION: Acts downstream of PI3 kinase age-1 and kinase pdk-1 in the
CC daf-2/insulin receptor-like transduction pathway (PubMed:9716402,
CC PubMed:10364160, PubMed:11747825, PubMed:11381260, PubMed:18782349,
CC PubMed:15068796). Essential role in regulating developmental arrest at
CC the dauer stage (PubMed:10364160). Phosphorylates Forkhead-related daf-
CC 16 and the longevity-promoting skn-1 transcription factors, which
CC inhibits their entry into the nucleus and antagonizes their functions
CC (PubMed:18358814, PubMed:11747825, PubMed:11381260, PubMed:15068796).
CC Role in immune function and pathogen resistance (PubMed:18782349).
CC Downstream of age-1 and together with akt-2 and sgk-1, promotes cell
CC survival during embryonic development (PubMed:25383666).
CC {ECO:0000269|PubMed:10364160, ECO:0000269|PubMed:11381260,
CC ECO:0000269|PubMed:11747825, ECO:0000269|PubMed:15068796,
CC ECO:0000269|PubMed:18358814, ECO:0000269|PubMed:18782349,
CC ECO:0000269|PubMed:25383666, ECO:0000269|PubMed:9716402}.
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 -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- ACTIVITY REGULATION: Phosphorylated and activated by pdk-1.
CC {ECO:0000269|PubMed:15068796}.
CC -!- SUBUNIT: Interacts with pdk-1, sgk-1, akt-1 and daf-16. Part of a
CC complex containing sgk-1, akt-1 and akt-2.
CC {ECO:0000269|PubMed:15068796}.
CC -!- INTERACTION:
CC Q9XTG7; Q17941: akt-1; NbExp=2; IntAct=EBI-320656, EBI-1770718;
CC Q9XTG7; O16850: daf-16; NbExp=3; IntAct=EBI-320656, EBI-324028;
CC Q9XTG7; Q2PJ68: sgk-1; NbExp=3; IntAct=EBI-320656, EBI-1770776;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a;
CC IsoId=Q9XTG7-1; Sequence=Displayed;
CC Name=b;
CC IsoId=Q9XTG7-2; Sequence=VSP_017047, VSP_017048;
CC -!- TISSUE SPECIFICITY: Expressed in neurons, muscle cells of the pharynx,
CC rectal gland cells, and spermatheca. {ECO:0000269|PubMed:9716402}.
CC -!- DEVELOPMENTAL STAGE: Expressed in late stage embryos and throughout
CC life. {ECO:0000269|PubMed:9716402}.
CC -!- DOMAIN: The PH domain binds to phosphatidylinositol 3,4,5-trisphosphate
CC (PtdIns(3,4,5)P3) resulting in its targeting to the plasma membrane.
CC {ECO:0000269|PubMed:25383666}.
CC -!- DISRUPTION PHENOTYPE: Defective egg-laying and increased resistance to
CC pathogens. Simultaneous knockdown of akt-1 and akt-2 result in dauer
CC formation and a weak extension to life span.
CC {ECO:0000269|PubMed:15068796, ECO:0000269|PubMed:18782349}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. RAC subfamily. {ECO:0000305}.
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DR EMBL; AF072381; AAC62468.1; -; mRNA.
DR EMBL; AL031621; CAA20936.1; -; Genomic_DNA.
DR EMBL; Z92837; CAA20936.1; JOINED; Genomic_DNA.
DR EMBL; AL031621; CAC70087.1; -; Genomic_DNA.
DR EMBL; Z92837; CAC70087.1; JOINED; Genomic_DNA.
DR PIR; T21523; T21523.
DR PIR; T43234; T43234.
DR RefSeq; NP_001024612.1; NM_001029441.3. [Q9XTG7-2]
DR RefSeq; NP_510357.3; NM_077956.5. [Q9XTG7-1]
DR AlphaFoldDB; Q9XTG7; -.
DR SMR; Q9XTG7; -.
DR BioGRID; 46423; 12.
DR ComplexPortal; CPX-1129; Atk-1/Akt-2/Sgk-1 protein kinase complex.
DR DIP; DIP-26368N; -.
DR IntAct; Q9XTG7; 8.
DR STRING; 6239.F28H6.1a; -.
DR iPTMnet; Q9XTG7; -.
DR EPD; Q9XTG7; -.
DR PaxDb; Q9XTG7; -.
DR PeptideAtlas; Q9XTG7; -.
DR EnsemblMetazoa; F28H6.1a.1; F28H6.1a.1; WBGene00000103. [Q9XTG7-1]
DR EnsemblMetazoa; F28H6.1b.1; F28H6.1b.1; WBGene00000103. [Q9XTG7-2]
DR GeneID; 181524; -.
DR KEGG; cel:CELE_F28H6.1; -.
DR UCSC; F28H6.1b; c. elegans. [Q9XTG7-1]
DR CTD; 181524; -.
DR WormBase; F28H6.1a; CE18646; WBGene00000103; akt-2. [Q9XTG7-1]
DR WormBase; F28H6.1b; CE29298; WBGene00000103; akt-2. [Q9XTG7-2]
DR eggNOG; KOG0690; Eukaryota.
DR GeneTree; ENSGT00940000168810; -.
DR HOGENOM; CLU_000288_11_2_1; -.
DR InParanoid; Q9XTG7; -.
DR OMA; PHEREEW; -.
DR OrthoDB; 614710at2759; -.
DR PhylomeDB; Q9XTG7; -.
DR Reactome; R-CEL-1257604; PIP3 activates AKT signaling.
DR Reactome; R-CEL-1474151; Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
DR Reactome; R-CEL-165159; MTOR signalling.
DR Reactome; R-CEL-198323; AKT phosphorylates targets in the cytosol.
DR Reactome; R-CEL-198693; AKT phosphorylates targets in the nucleus.
DR Reactome; R-CEL-199418; Negative regulation of the PI3K/AKT network.
DR Reactome; R-CEL-203615; eNOS activation.
DR Reactome; R-CEL-211163; AKT-mediated inactivation of FOXO1A.
DR Reactome; R-CEL-354192; Integrin signaling.
DR Reactome; R-CEL-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-CEL-389513; CTLA4 inhibitory signaling.
DR Reactome; R-CEL-392451; G beta:gamma signalling through PI3Kgamma.
DR Reactome; R-CEL-450385; Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA.
DR Reactome; R-CEL-450604; KSRP (KHSRP) binds and destabilizes mRNA.
DR Reactome; R-CEL-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-CEL-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-CEL-69202; Cyclin E associated events during G1/S transition.
DR Reactome; R-CEL-69656; Cyclin A:Cdk2-associated events at S phase entry.
DR Reactome; R-CEL-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR Reactome; R-CEL-8948751; Regulation of PTEN stability and activity.
DR Reactome; R-CEL-9009391; Extra-nuclear estrogen signaling.
DR Reactome; R-CEL-9604323; Negative regulation of NOTCH4 signaling.
DR Reactome; R-CEL-9607240; FLT3 Signaling.
DR Reactome; R-CEL-9614399; Regulation of localization of FOXO transcription factors.
DR Reactome; R-CEL-9634638; Estrogen-dependent nuclear events downstream of ESR-membrane signaling.
DR Reactome; R-CEL-9755511; KEAP1-NFE2L2 pathway.
DR SignaLink; Q9XTG7; -.
DR PRO; PR:Q9XTG7; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00000103; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
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:0008340; P:determination of adult lifespan; IMP:WormBase.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IMP:WormBase.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:WormBase.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:WormBase.
DR GO; GO:0006468; P:protein phosphorylation; IDA:WormBase.
DR GO; GO:0010468; P:regulation of gene expression; IDA:ComplexPortal.
DR GO; GO:0008582; P:regulation of synaptic assembly at neuromuscular junction; IGI:UniProtKB.
DR CDD; cd01241; PH_PKB; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR039026; PH_PKB.
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; PF00169; PH; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR SMART; SM00233; PH; 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; PS50003; PH_DOMAIN; 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; Developmental protein; Immunity;
KW Innate immunity; Kinase; Magnesium; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..528
FT /note="Serine/threonine-protein kinase akt-2"
FT /id="PRO_0000085616"
FT DOMAIN 12..115
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 180..437
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 438..515
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 121..153
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 303
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 186..194
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 209
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT VAR_SEQ 470..483
FT /note="EFTSMPVQLTPPRR -> VRYVSILLKVSEAI (in isoform b)"
FT /evidence="ECO:0000303|PubMed:9716402"
FT /id="VSP_017047"
FT VAR_SEQ 484..528
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000303|PubMed:9716402"
FT /id="VSP_017048"
FT MUTAGEN 209
FT /note="K->M: Probable loss of kinase activity. Increased
FT apoptosis during embryonic development in an akt-1 tm399
FT mutant background."
FT /evidence="ECO:0000269|PubMed:25383666"
SQ SEQUENCE 528 AA; 61058 MW; 9750E8F0AE4F6AE7 CRC64;
MSTENAHLQK EDIVIESWLH KKGEHIRNWR PRYFILFRDG TLLGFRSKPK EDQPLPEPLN
NFMIRDAATV CLDKPRPNMF IVRCLQWTTV IERTFYADSA DFRQMWIEAI QAVSSHNRLK
ENAGNTSMQE EDTNGNPSGE SDVNMDATST RSDNDFESTV MNIDEPEEVP RKNTVTMDDF
DFLKVLGQGT FGKVILCREK SSDKLYAIKI IRKEMVVDRS EVAHTLTENR VLYACVHPFL
TLLKYSFQAQ YHICFVMEFA NGGELFTHLQ RCKTFSEART RFYGSEIILA LGYLHHRNIV
YRDMKLENLL LDRDGHIKIT DFGLCKEEIK YGDKTSTFCG TPEYLAPEVI EDIDYDRSVD
WWGVGVVMYE MMCGRLPFSA KENGKLFELI TTCDLKFPNR LSPEAVTLLS GLLERVPAKR
LGAGPDDARE VSRAEFFKDV DWEATLRKEV EPPFKPNVMS ETDTSFFDRE FTSMPVQLTP
PRRGEELPTV DEEEELQANF IQFASYYVSG SLERSYDTNR SADKYEIR
