AAPK2_CAEEL
ID AAPK2_CAEEL Reviewed; 626 AA.
AC Q95ZQ4; Q22068; Q86FL6;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=5'-AMP-activated protein kinase catalytic subunit alpha-2;
DE Short=AMPK subunit alpha-2;
DE EC=2.7.11.1;
GN Name=aak-2 {ECO:0000312|WormBase:T01C8.1b};
GN ORFNames=T01C8.1 {ECO:0000312|WormBase:T01C8.1b};
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:AAR06928.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, ACTIVITY REGULATION,
RP DISRUPTION PHENOTYPE, AND PHOSPHORYLATION AT THR-243.
RX PubMed=15574588; DOI=10.1101/gad.1255404;
RA Apfeld J., O'Connor G., McDonagh T., DiStefano P.S., Curtis R.;
RT "The AMP-activated protein kinase AAK-2 links energy levels and insulin-
RT like signals to lifespan in C. elegans.";
RL Genes Dev. 18:3004-3009(2004).
RN [2]
RP ERRATUM OF PUBMED:15574588.
RA Apfeld J., O'Connor G., McDonagh T., DiStefano P.S., Curtis R.;
RL Genes Dev. 19:188-188(2005).
RN [3]
RP ERRATUM OF PUBMED:15574588.
RA Apfeld J., O'Connor G., McDonagh T., DiStefano P.S., Curtis R.;
RL Genes Dev. 19:411-411(2005).
RN [4]
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 [5]
RP IDENTIFICATION IN AMPK COMPLEX.
RX PubMed=2303451; DOI=10.1016/s0021-9258(19)39766-2;
RA Lu X., Gross R.E., Bagchi S., Rubin C.S.;
RT "Cloning, structure, and expression of the gene for a novel regulatory
RT subunit of cAMP-dependent protein kinase in Caenorhabditis elegans.";
RL J. Biol. Chem. 265:3293-3303(1990).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=18408008; DOI=10.1074/jbc.m709115200;
RA Lee H., Cho J.S., Lambacher N., Lee J., Lee S.J., Lee T.H., Gartner A.,
RA Koo H.S.;
RT "The Caenorhabditis elegans AMP-activated protein kinase AAK-2 is
RT phosphorylated by LKB1 and is required for resistance to oxidative stress
RT and for normal motility and foraging behavior.";
RL J. Biol. Chem. 283:14988-14993(2008).
RN [7]
RP FUNCTION, AND PHOSPHORYLATION AT THR-243.
RX PubMed=20110331; DOI=10.1242/dev.042044;
RA Narbonne P., Hyenne V., Li S., Labbe J.C., Roy R.;
RT "Differential requirements for STRAD in LKB1-dependent functions in C.
RT elegans.";
RL Development 137:661-670(2010).
RN [8]
RP PHOSPHORYLATION AT THR-243.
RX PubMed=24385923; DOI=10.1371/journal.pgen.1004020;
RA Ferguson A.A., Roy S., Kormanik K.N., Kim Y., Dumas K.J., Ritov V.B.,
RA Matern D., Hu P.J., Fisher A.L.;
RT "TATN-1 mutations reveal a novel role for tyrosine as a metabolic signal
RT that influences developmental decisions and longevity in Caenorhabditis
RT elegans.";
RL PLoS Genet. 9:e1004020-e1004020(2013).
RN [9]
RP FUNCTION.
RX PubMed=24431434; DOI=10.1523/jneurosci.2886-13.2014;
RA Hubert T., Wu Z., Chisholm A.D., Jin Y.;
RT "S6 kinase inhibits intrinsic axon regeneration capacity via AMP kinase in
RT Caenorhabditis elegans.";
RL J. Neurosci. 34:758-763(2014).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24763318; DOI=10.1371/journal.pgen.1004273;
RA Possik E., Jalali Z., Nouet Y., Yan M., Gingras M.C., Schmeisser K.,
RA Panaite L., Dupuy F., Kharitidi D., Chotard L., Jones R.G., Hall D.H.,
RA Pause A.;
RT "Folliculin regulates ampk-dependent autophagy and metabolic stress
RT survival.";
RL PLoS Genet. 10:E1004273-E1004273(2014).
RN [11]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26439621; DOI=10.1371/journal.pgen.1005520;
RA Possik E., Ajisebutu A., Manteghi S., Gingras M.C., Vijayaraghavan T.,
RA Flamand M., Coull B., Schmeisser K., Duchaine T., van Steensel M.,
RA Hall D.H., Pause A.;
RT "FLCN and AMPK Confer Resistance to Hyperosmotic Stress via Remodeling of
RT Glycogen Stores.";
RL PLoS Genet. 11:E1005520-E1005520(2015).
RN [12]
RP FUNCTION.
RX PubMed=28128367; DOI=10.1038/ncomms14237;
RA Palamiuc L., Noble T., Witham E., Ratanpal H., Vaughan M., Srinivasan S.;
RT "A tachykinin-like neuroendocrine signalling axis couples central serotonin
RT action and nutrient sensing with peripheral lipid metabolism.";
RL Nat. Commun. 8:14237-14237(2017).
CC -!- FUNCTION: Acts as a sensor that couples lifespan to information about
CC energy levels and insulin-like signals (PubMed:15574588). Role in
CC motility and response to oxidative stress (PubMed:18408008,
CC PubMed:24763318). Involved in the establishment of germline stem cell
CC (GSC) quiescence during dauer development (PubMed:15574588,
CC PubMed:20110331). Plays a role in axon regrowth after axotomy in PLM
CC neurons (PubMed:24431434). Plays a role in the maintenance of glycogen
CC stores which are necessary for resistance to hyperosmotic stress
CC (PubMed:26439621). Plays a role in the regulation of flp-7 secretion
CC from ASI neurons (PubMed:28128367). Keeps the CREB-regulated
CC transcription coactivator 1 homolog crtc-1 inactive which in turn
CC inhibits flp-7 secretion (PubMed:28128367). Following serotonin
CC signaling, derepresses crtc-1 which stimulates flp-7 secretion and
CC subsequent body fat loss (PubMed:28128367).
CC {ECO:0000269|PubMed:15574588, ECO:0000269|PubMed:18408008,
CC ECO:0000269|PubMed:20110331, ECO:0000269|PubMed:24431434,
CC ECO:0000269|PubMed:24763318, ECO:0000269|PubMed:26439621,
CC ECO:0000269|PubMed:28128367}.
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: Activated by phosphorylation.
CC {ECO:0000269|PubMed:15574588}.
CC -!- SUBUNIT: Tetramer, composed of 2 regulatory (R) and 2 catalytic (C)
CC subunits. In the presence of cAMP it dissociates into 2 active
CC monomeric C subunits and an R dimer that binds four cAMP molecules.
CC {ECO:0000269|PubMed:2303451}.
CC -!- INTERACTION:
CC Q95ZQ4; Q9NAH7: aakb-2; NbExp=4; IntAct=EBI-326514, EBI-2417663;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=b {ECO:0000312|WormBase:T01C8.1b};
CC IsoId=Q95ZQ4-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:T01C8.1a};
CC IsoId=Q95ZQ4-2; Sequence=VSP_051941;
CC Name=c {ECO:0000312|WormBase:T01C8.1c};
CC IsoId=Q95ZQ4-3; Sequence=VSP_051940, VSP_051941;
CC -!- TISSUE SPECIFICITY: Expressed in the pharynx, the ventral cord, neurons
CC including the hermaphrodite-specific neuron, body wall muscles, the
CC vulva, the excretory canal, and weakly in the intestine.
CC {ECO:0000269|PubMed:18408008}.
CC -!- PTM: Phosphorylated on Thr-243 in response to oxidative stress and
CC during dauer development (PubMed:24385923). Phosphorylation at Thr-243
CC is increased in response to sodium azide or the AMP analog AICAR (5-
CC amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide)
CC (PubMed:24385923). {ECO:0000269|PubMed:15574588,
CC ECO:0000269|PubMed:20110331, ECO:0000269|PubMed:24385923}.
CC -!- DISRUPTION PHENOTYPE: Shortened life-span (PubMed:15574588,
CC PubMed:18408008). Temperature-dependent hypersensitivity to stress,
CC slow body bending, abnormal modulation of head oscillation
CC (PubMed:15574588, PubMed:18408008). Reduced survival following
CC oxidative stress induced by the superoxide paraquat (PubMed:24763318).
CC Reduced survival as a result of hyperosmotic stress induced by NaCl
CC (PubMed:26439621). Double knockout with aak-1 results in reduced
CC glycogen accumulation (PubMed:26439621). {ECO:0000269|PubMed:15574588,
CC ECO:0000269|PubMed:18408008, ECO:0000269|PubMed:26439621}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. SNF1 subfamily. {ECO:0000305}.
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DR EMBL; AY347273; AAR06928.1; -; mRNA.
DR EMBL; BX284606; CCD68833.1; -; Genomic_DNA.
DR EMBL; BX284606; CCD68834.1; -; Genomic_DNA.
DR EMBL; BX284606; CCD68835.1; -; Genomic_DNA.
DR PIR; T29858; T29858.
DR RefSeq; NP_001024868.1; NM_001029697.3. [Q95ZQ4-3]
DR RefSeq; NP_510710.2; NM_078309.4. [Q95ZQ4-1]
DR RefSeq; NP_510711.2; NM_078310.5. [Q95ZQ4-2]
DR AlphaFoldDB; Q95ZQ4; -.
DR SMR; Q95ZQ4; -.
DR BioGRID; 46610; 22.
DR DIP; DIP-25170N; -.
DR IntAct; Q95ZQ4; 7.
DR STRING; 6239.T01C8.1b; -.
DR iPTMnet; Q95ZQ4; -.
DR EPD; Q95ZQ4; -.
DR PaxDb; Q95ZQ4; -.
DR PeptideAtlas; Q95ZQ4; -.
DR EnsemblMetazoa; T01C8.1a.1; T01C8.1a.1; WBGene00020142. [Q95ZQ4-2]
DR EnsemblMetazoa; T01C8.1b.1; T01C8.1b.1; WBGene00020142. [Q95ZQ4-1]
DR EnsemblMetazoa; T01C8.1c.1; T01C8.1c.1; WBGene00020142. [Q95ZQ4-3]
DR GeneID; 181727; -.
DR KEGG; cel:CELE_T01C8.1; -.
DR UCSC; T01C8.1c.1; c. elegans. [Q95ZQ4-1]
DR CTD; 181727; -.
DR WormBase; T01C8.1a; CE31222; WBGene00020142; aak-2. [Q95ZQ4-2]
DR WormBase; T01C8.1b; CE31223; WBGene00020142; aak-2. [Q95ZQ4-1]
DR WormBase; T01C8.1c; CE07458; WBGene00020142; aak-2. [Q95ZQ4-3]
DR eggNOG; KOG0583; Eukaryota.
DR GeneTree; ENSGT00940000167424; -.
DR InParanoid; Q95ZQ4; -.
DR OMA; KALNYEW; -.
DR OrthoDB; 1127668at2759; -.
DR PhylomeDB; Q95ZQ4; -.
DR Reactome; R-CEL-1632852; Macroautophagy.
DR Reactome; R-CEL-163680; AMPK inhibits chREBP transcriptional activation activity.
DR Reactome; R-CEL-200425; Carnitine metabolism.
DR Reactome; R-CEL-380972; Energy dependent regulation of mTOR by LKB1-AMPK.
DR Reactome; R-CEL-5628897; TP53 Regulates Metabolic Genes.
DR PRO; PR:Q95ZQ4; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00020142; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR GO; GO:0030424; C:axon; IDA:WormBase.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0043025; C:neuronal cell body; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0004679; F:AMP-activated protein kinase activity; IDA:WormBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
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:0008340; P:determination of adult lifespan; IMP:WormBase.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0050709; P:negative regulation of protein secretion; IMP:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:WormBase.
DR GO; GO:0061066; P:positive regulation of dauer larval development; IGI:WormBase.
DR GO; GO:0050714; P:positive regulation of protein secretion; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR InterPro; IPR032270; AMPK_C.
DR InterPro; IPR028375; KA1/Ssp2_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; PF16579; AdenylateSensor; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF103243; SSF103243; 1.
DR SUPFAM; SSF56112; SSF56112; 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; Kinase; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Stress response; Transferase.
FT CHAIN 1..626
FT /note="5'-AMP-activated protein kinase catalytic subunit
FT alpha-2"
FT /id="PRO_0000085599"
FT DOMAIN 87..339
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..77
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 541..568
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..21
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 22..40
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 60..77
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 541..555
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 210
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 93..101
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 116
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 243
FT /note="Phosphothreonine; by par-4"
FT /evidence="ECO:0000269|PubMed:15574588,
FT ECO:0000269|PubMed:20110331, ECO:0000269|PubMed:24385923"
FT VAR_SEQ 1..62
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_051940"
FT VAR_SEQ 370..371
FT /note="Missing (in isoform a and isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_051941"
SQ SEQUENCE 626 AA; 70443 MW; D1401DB1286D8624 CRC64;
MFSHQDRDRD RKEDGGGDGT EMKSKSRSQP SGLNRVKNLS RKLSAKSRKE RKDRDSTDNS
SKMSSPGGET STKQQQELKA QIKIGHYILK ETLGVGTFGK VKVGIHETTQ YKVAVKILNR
QKIKSLDVVG KIRREIQNLS LFRHPHIIRL YQVISTPSDI FMIMEHVSGG ELFDYIVKHG
RLKTAEARRF FQQIISGVDY CHRHMVVHRD LKPENLLLDE QNNVKIADFG LSNIMTDGDF
LRTSCGSPNY AAPEVISGKL YAGPEVDVWS CGVILYALLC GTLPFDDEHV PSLFRKIKSG
VFPTPDFLER PIVNLLHHML CVDPMKRATI KDVIAHEWFQ KDLPNYLFPP INESEASIVD
IEAVREVTEF QRYHVAEEEV TSALLGDDPH HHLSIAYNLI VDNKRIADET AKLSIEEFYQ
VTPNKGPGPV HRHPERIAAS VSSKITPTLD NTEASGANRN KRAKWHLGIR SQSRPEDIMF
EVFRAMKQLD MEWKVLNPYH VIVRRKPDAP AADPPKMSLQ LYQVDQRSYL LDFKSLADEE
SGSASASSSR HASMSMPQKP AGIRGTRTSS MPQAMSMEAS IEKMEVHDFS DMSCDVTPPP
SPGGAKLSQT MQFFEICAAL IGTLAR
