PDPK1_CAEEL
ID PDPK1_CAEEL Reviewed; 636 AA.
AC Q9Y1J3; Q9UA36;
DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=3-phosphoinositide-dependent protein kinase 1;
DE EC=2.7.11.1;
DE AltName: Full=Pdk-class protein kinase 1;
GN Name=pdk-1 {ECO:0000312|WormBase:H42K12.1a};
GN ORFNames=H42K12.1 {ECO:0000312|WormBase:H42K12.1a};
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] (ISOFORMS A AND B), MUTAGENESIS OF GLY-297 AND
RP ALA-305, DEVELOPMENTAL STAGE, AND FUNCTION.
RC STRAIN=Bristol N2;
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 [2]
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 [3]
RP FUNCTION, AND INTERACTION WITH SGK-1; AKT-1 AND AKT-2.
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 [4]
RP MUTAGENESIS OF GLY-297.
RX PubMed=16950159; DOI=10.1016/j.neuron.2006.07.024;
RA Tomioka M., Adachi T., Suzuki H., Kunitomo H., Schafer W.R., Iino Y.;
RT "The insulin/PI 3-kinase pathway regulates salt chemotaxis learning in
RT Caenorhabditis elegans.";
RL Neuron 51:613-625(2006).
RN [5]
RP MUTAGENESIS OF GLY-297.
RX PubMed=22069193; DOI=10.1242/dev.069062;
RA Christensen R., de la Torre-Ubieta L., Bonni A., Colon-Ramos D.A.;
RT "A conserved PTEN/FOXO pathway regulates neuronal morphology during C.
RT elegans development.";
RL Development 138:5257-5267(2011).
RN [6]
RP FUNCTION, AND MUTAGENESIS OF TYR-148.
RX PubMed=21980302; DOI=10.1371/journal.pgen.1002299;
RA Mansisidor A.R., Cecere G., Hoersch S., Jensen M.B., Kawli T.,
RA Kennedy L.M., Chavez V., Tan M.W., Lieb J.D., Grishok A.;
RT "A conserved PHD finger protein and endogenous RNAi modulate insulin
RT signaling in Caenorhabditis elegans.";
RL PLoS Genet. 7:E1002299-E1002299(2011).
CC -!- FUNCTION: Involved in the daf-2/insulin receptor-like transduction
CC pathway, which controls longevity and prevents developmental arrest at
CC the dauer stage (PubMed:10364160, PubMed:21980302). Phosphorylates and
CC activates sgk-1, akt-1 and akt-2 (PubMed:15068796).
CC {ECO:0000269|PubMed:10364160, ECO:0000269|PubMed:15068796,
CC ECO:0000269|PubMed:21980302}.
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 -!- SUBUNIT: Interacts directly with sgk-1, akt-1 and akt-2.
CC {ECO:0000269|PubMed:15068796}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:H42K12.1a};
CC IsoId=Q9Y1J3-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:H42K12.1b};
CC IsoId=Q9Y1J3-2; Sequence=VSP_017049, VSP_017050;
CC -!- DEVELOPMENTAL STAGE: Expressed in late stage embryos and throughout
CC life. At L1, expressed in neurons, intestinal cells and hypodermal
CC cells. In adults, expressed in the somatic gonad.
CC {ECO:0000269|PubMed:10364160}.
CC -!- DOMAIN: The PIF-pocket is a small lobe in the catalytic domain required
CC by the enzyme for the binding to the hydrophobic motif of its
CC substrates. It is an allosteric regulatory site that can accommodate
CC small compounds acting as allosteric inhibitors.
CC {ECO:0000250|UniProtKB:O15530}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. PDPK1 subfamily. {ECO:0000305}.
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DR EMBL; AF130406; AAD42307.1; -; mRNA.
DR EMBL; AF130407; AAD42308.1; -; mRNA.
DR EMBL; BX284606; CCD67851.1; -; Genomic_DNA.
DR EMBL; BX284606; CCD67852.1; -; Genomic_DNA.
DR RefSeq; NP_001024742.1; NM_001029571.2. [Q9Y1J3-2]
DR RefSeq; NP_001024743.1; NM_001029572.2. [Q9Y1J3-1]
DR AlphaFoldDB; Q9Y1J3; -.
DR SMR; Q9Y1J3; -.
DR BioGRID; 45427; 5.
DR DIP; DIP-27322N; -.
DR IntAct; Q9Y1J3; 3.
DR STRING; 6239.H42K12.1b; -.
DR iPTMnet; Q9Y1J3; -.
DR EPD; Q9Y1J3; -.
DR PaxDb; Q9Y1J3; -.
DR PeptideAtlas; Q9Y1J3; -.
DR EnsemblMetazoa; H42K12.1a.1; H42K12.1a.1; WBGene00003965. [Q9Y1J3-2]
DR EnsemblMetazoa; H42K12.1b.1; H42K12.1b.1; WBGene00003965. [Q9Y1J3-1]
DR GeneID; 180475; -.
DR KEGG; cel:CELE_H42K12.1; -.
DR UCSC; H42K12.1b; c. elegans. [Q9Y1J3-1]
DR CTD; 180475; -.
DR WormBase; H42K12.1a; CE28739; WBGene00003965; pdk-1. [Q9Y1J3-2]
DR WormBase; H42K12.1b; CE28740; WBGene00003965; pdk-1. [Q9Y1J3-1]
DR eggNOG; KOG0592; Eukaryota.
DR GeneTree; ENSGT00940000155267; -.
DR InParanoid; Q9Y1J3; -.
DR OMA; GYPSIRA; -.
DR OrthoDB; 1157543at2759; -.
DR PhylomeDB; Q9Y1J3; -.
DR SignaLink; Q9Y1J3; -.
DR PRO; PR:Q9Y1J3; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00003965; Expressed in embryo and 4 other tissues.
DR GO; GO:0030424; C:axon; IDA:WormBase.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0043025; C:neuronal cell body; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IMP:WormBase.
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:0071248; P:cellular response to metal ion; IMP:UniProtKB.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; IMP:UniProtKB.
DR GO; GO:0040024; P:dauer larval development; IMP:WormBase.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0007611; P:learning or memory; IMP:WormBase.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IMP:WormBase.
DR GO; GO:0050920; P:regulation of chemotaxis; IMP:WormBase.
DR GO; GO:0008582; P:regulation of synaptic assembly at neuromuscular junction; IGI:UniProtKB.
DR CDD; cd01262; PH_PDK1; 1.
DR CDD; cd05581; STKc_PDK1; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR033931; PDK1-typ_PH.
DR InterPro; IPR039046; PDPK1.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF14593; PH_3; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 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; Coiled coil; Cytoplasm;
KW Developmental protein; Kinase; Nucleotide-binding; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..636
FT /note="3-phosphoinositide-dependent protein kinase 1"
FT /id="PRO_0000086503"
FT DOMAIN 69..364
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..45
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 100..149
FT /note="PIF-pocket"
FT /evidence="ECO:0000250|UniProtKB:O15530"
FT REGION 233..264
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 593..636
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 550..631
FT /evidence="ECO:0000255"
FT COMPBIAS 233..250
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 197
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 79..81
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O15530"
FT BINDING 98
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O15530"
FT BINDING 152..154
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O15530"
FT BINDING 158
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O15530"
FT BINDING 201
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O15530"
FT BINDING 215
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O15530"
FT VAR_SEQ 259..260
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000303|PubMed:10364160"
FT /id="VSP_017049"
FT VAR_SEQ 427..428
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000303|PubMed:10364160"
FT /id="VSP_017050"
FT MUTAGEN 148
FT /note="Y->C: In sa709; increased resistance to oxidative
FT stress induced by paraquat. daf-16 mainly localizes to the
FT nucleus as opposed to the cytoplasm as it does in wild-
FT type."
FT /evidence="ECO:0000269|PubMed:21980302"
FT MUTAGEN 297
FT /note="G->R: In sa680; developmental arrest at dauer stage,
FT extended life span, increased body size, low fertility, and
FT defects in egg-laying and social behavior. Fails to avoid
FT NaCl after exposure to NaCl under starvation conditions.
FT Restores normal AIY interneuron neurite outgrowth in a daf-
FT 18 (mg198) background mutant."
FT /evidence="ECO:0000269|PubMed:10364160,
FT ECO:0000269|PubMed:16950159, ECO:0000269|PubMed:22069193"
FT MUTAGEN 305
FT /note="A->V: In mg142; no obvious phenotype."
FT /evidence="ECO:0000269|PubMed:10364160"
SQ SEQUENCE 636 AA; 71917 MW; 5885237039D80AF2 CRC64;
MEDLTPTNTS LDTTTTNNDT TSDREAAPTT LNLTPTASES ENSLSPVTAE DLIAKSIKEG
CPKRTSNDFM FLQSMGEGAY SQVFRCREVA TDAMFAVKVL QKSYLNRHQK MDAIIREKNI
LTYLSQECGG HPFVTQLYTH FHDQARIYFV IGLVENGDLG ESLCHFGSFD MLTSKFFASE
ILTGLQFLHD NKIVHRDMKP DNVLIQKDGH ILITDFGSAQ AFGGLQLSQE GFTDANQASS
RSSDSGSPPP TRFYSDEEVP EENTARRTTF VGTALYVSPE MLADGDVGPQ TDIWGLGCIL
FQCLAGQPPF RAVNQYHLLK RIQELDFSFP EGFPEEASEI IAKILVRDPS TRITSQELMA
HKFFENVDWV NIANIKPPVL HAYIPATFGE PEYYSNIGPV EPGLDDRALF RLMNLGNDAS
ASQPSTFRPS NVEHRGDPFV SEIAPRANSE AEKNRAARAQ KLEEQRVKNP FHIFTNNSLI
LKQGYLEKKR GLFARRRMFL LTEGPHLLYI DVPNLVLKGE VPWTPCMQVE LKNSGTFFIH
TPNRVYYLFD LEKKADEWCK AINDVRKRYS VTIEKTFNSA MRDGTFGSIY GKKKSRKEMM
REQKALRRKQ EKEEKKALKA EQVSKKLSMQ MDKKSP
