ID PDHK2_CAEEL Reviewed; 401 AA.
AC Q02332;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 27-MAR-2024, entry version 161.
DE RecName: Full=Probable [pyruvate dehydrogenase (acetyl-transferring)] kinase, mitochondrial;
DE Short=Pyruvate dehydrogenase kinase;
DE EC=2.7.11.2;
DE Flags: Precursor;
GN Name=pdhk-2; ORFNames=ZK370.5;
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=7906398; DOI=10.1038/368032a0;
RA Wilson R., Ainscough R., Anderson K., Baynes C., Berks M., Bonfield J.,
RA Burton J., Connell M., Copsey T., Cooper J., Coulson A., Craxton M.,
RA Dear S., Du Z., Durbin R., Favello A., Fraser A., Fulton L., Gardner A.,
RA Green P., Hawkins T., Hillier L., Jier M., Johnston L., Jones M.,
RA Kershaw J., Kirsten J., Laisster N., Latreille P., Lightning J., Lloyd C.,
RA Mortimore B., O'Callaghan M., Parsons J., Percy C., Rifken L., Roopra A.,
RA Saunders D., Shownkeen R., Sims M., Smaldon N., Smith A., Smith M.,
RA Sonnhammer E., Staden R., Sulston J., Thierry-Mieg J., Thomas K.,
RA Vaudin M., Vaughan K., Waterston R., Watson A., Weinstock L.,
RA Wilkinson-Sproat J., Wohldman P.;
RT "2.2 Mb of contiguous nucleotide sequence from chromosome III of C.
RT elegans.";
RL Nature 368:32-38(1994).
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] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=36173858; DOI=10.1126/science.abo3191;
RA Bou Sleiman M., Roy S., Gao A.W., Sadler M.C., von Alvensleben G.V.G.,
RA Li H., Sen S., Harrison D.E., Nelson J.F., Strong R., Miller R.A.,
RA Kutalik Z., Williams R.W., Auwerx J.;
RT "Sex- and age-dependent genetics of longevity in a heterogeneous mouse
RT population.";
RL Science 377:eabo3191-eabo3191(2022).
CC -!- FUNCTION: Inhibits the mitochondrial pyruvate dehydrogenase complex by
CC phosphorylation of the E1 alpha subunit, thus contributing to the
CC regulation of glucose metabolism (By similarity). Required for normal
CC lifespan (PubMed:36173858). {ECO:0000250|UniProtKB:Q15118,
CC ECO:0000269|PubMed:36173858}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[pyruvate dehydrogenase E1 alpha subunit] = ADP
CC + H(+) + O-phospho-L-seryl-[pyruvate dehydrogenase E1 alpha subunit];
CC Xref=Rhea:RHEA:23052, Rhea:RHEA-COMP:13689, Rhea:RHEA-COMP:13690,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.2;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000250|UniProtKB:Q15118}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown increases lifespan.
CC {ECO:0000269|PubMed:36173858}.
CC -!- SIMILARITY: Belongs to the PDK/BCKDK protein kinase family.
CC {ECO:0000305}.
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DR EMBL; FO080164; CCD61725.1; -; Genomic_DNA.
DR PIR; S44666; S44666.
DR RefSeq; NP_498928.1; NM_066527.3.
DR AlphaFoldDB; Q02332; -.
DR SMR; Q02332; -.
DR BioGRID; 41429; 9.
DR DIP; DIP-26171N; -.
DR STRING; 6239.ZK370.5.1; -.
DR EPD; Q02332; -.
DR PaxDb; 6239-ZK370-5; -.
DR PeptideAtlas; Q02332; -.
DR EnsemblMetazoa; ZK370.5.1; ZK370.5.1; WBGene00022719.
DR GeneID; 176226; -.
DR KEGG; cel:CELE_ZK370.5; -.
DR AGR; WB:WBGene00022719; -.
DR WormBase; ZK370.5; CE00397; WBGene00022719; pdhk-2.
DR eggNOG; KOG0787; Eukaryota.
DR GeneTree; ENSGT01030000234646; -.
DR HOGENOM; CLU_023861_1_0_1; -.
DR InParanoid; Q02332; -.
DR OMA; SKMVSNW; -.
DR OrthoDB; 3058550at2759; -.
DR PhylomeDB; Q02332; -.
DR Reactome; R-CEL-204174; Regulation of pyruvate dehydrogenase (PDH) complex.
DR Reactome; R-CEL-5362517; Signaling by Retinoic Acid.
DR PRO; PR:Q02332; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00022719; Expressed in germ line (C elegans) and 4 other cell types or tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:WormBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004740; F:pyruvate dehydrogenase (acetyl-transferring) kinase activity; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0010906; P:regulation of glucose metabolic process; IBA:GO_Central.
DR CDD; cd16929; HATPase_PDK-like; 1.
DR Gene3D; 1.20.140.20; Alpha-ketoacid/pyruvate dehydrogenase kinase, N-terminal domain; 1.
DR Gene3D; 3.30.565.10; Histidine kinase-like ATPase, C-terminal domain; 1.
DR InterPro; IPR036784; AK/P_DHK_N_sf.
DR InterPro; IPR018955; BCDHK/PDK_N.
DR InterPro; IPR039028; BCKD/PDK.
DR InterPro; IPR003594; HATPase_C.
DR InterPro; IPR036890; HATPase_C_sf.
DR InterPro; IPR005467; His_kinase_dom.
DR PANTHER; PTHR11947:SF3; [PYRUVATE DEHYDROGENASE (ACETYL-TRANSFERRING)] KINASE, MITOCHONDRIAL; 1.
DR PANTHER; PTHR11947; PYRUVATE DEHYDROGENASE KINASE; 1.
DR Pfam; PF10436; BCDHK_Adom3; 1.
DR Pfam; PF02518; HATPase_c; 1.
DR SMART; SM00387; HATPase_c; 1.
DR SUPFAM; SSF69012; alpha-ketoacid dehydrogenase kinase, N-terminal domain; 1.
DR SUPFAM; SSF55874; ATPase domain of HSP90 chaperone/DNA topoisomerase II/histidine kinase; 1.
DR PROSITE; PS50109; HIS_KIN; 1.
PE 3: Inferred from homology;
KW ATP-binding; Kinase; Mitochondrion; Nucleotide-binding; Reference proteome;
KW Transferase; Transit peptide.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?..401
FT /note="Probable [pyruvate dehydrogenase (acetyl-
FT transferring)] kinase, mitochondrial"
FT /id="PRO_0000023450"
FT DOMAIN 131..360
FT /note="Histidine kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00107"
FT BINDING 247..254
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 286
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 305..306
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 321..326
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
SQ SEQUENCE 401 AA; 45282 MW; 00754E7999BACC12 CRC64;
MRFSRKLLGP FVGSLAKKLD YYSQFQPSSL TIQQYLDFGR IGTSANSYTF LKNELLVRLA
NIMQEFTLLP PKLLQMPSSK MVSNWYAESF EDLLLFEASD SSPEQVARFN DQLTVVLKRH
AHVVETMAEG LIELRESDGV DIASEKGIQY FLDRFYINRI SIRMLQNQHL VVFGNVLPES
PRHVGCIDPA CDVESVVYDA FENARFLCDR YYLTSPSMKL EMHNAVEKGK PISIVAVPSH
LYHMMFELFK NAMRATVEYH GVDDDLPDIK VYVVKGQEDL SIKICDRGGG VSRTILERLY
NYMYSTAPPP PRDGTQAPLA GYGYGLPLSR LYARYFLGDL FLVSMEGHGT DACIYLKAVP
VEASEVLPIY STSSRRNLTM GPQVADWSHH VPGQGNRPAQ S
//
