PDK3_MOUSE
ID PDK3_MOUSE Reviewed; 415 AA.
AC Q922H2; Q8BTX1;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, mitochondrial;
DE EC=2.7.11.2;
DE AltName: Full=Pyruvate dehydrogenase kinase isoform 3;
DE Flags: Precursor;
GN Name=Pdk3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Tongue;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-278, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
CC -!- FUNCTION: Inhibits pyruvate dehydrogenase activity by phosphorylation
CC of the E1 subunit PDHA1, and thereby regulates glucose metabolism and
CC aerobic respiration. Can also phosphorylate PDHA2. Decreases glucose
CC utilization and increases fat metabolism in response to prolonged
CC fasting, and as adaptation to a high-fat diet. Plays a role in glucose
CC homeostasis and in maintaining normal blood glucose levels in function
CC of nutrient levels and under starvation. Plays a role in the generation
CC of reactive oxygen species (By similarity). {ECO:0000250}.
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 -!- SUBUNIT: Homodimer. Interacts with the pyruvate dehydrogenase complex
CC subunit DLAT, and is part of the multimeric pyruvate dehydrogenase
CC complex that contains multiple copies of pyruvate dehydrogenase (E1),
CC dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide
CC dehydrogenase (DLD, E3) (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the PDK/BCKDK protein kinase family.
CC {ECO:0000305}.
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DR EMBL; AK075879; BAC36024.1; -; mRNA.
DR EMBL; AK075985; BAC36097.1; -; mRNA.
DR EMBL; AK088478; BAC40379.1; -; mRNA.
DR EMBL; BC008126; AAH08126.1; -; mRNA.
DR CCDS; CCDS30275.1; -.
DR RefSeq; NP_663605.1; NM_145630.2.
DR AlphaFoldDB; Q922H2; -.
DR SMR; Q922H2; -.
DR BioGRID; 231815; 8.
DR IntAct; Q922H2; 3.
DR MINT; Q922H2; -.
DR STRING; 10090.ENSMUSP00000036604; -.
DR PhosphoSitePlus; Q922H2; -.
DR EPD; Q922H2; -.
DR jPOST; Q922H2; -.
DR MaxQB; Q922H2; -.
DR PaxDb; Q922H2; -.
DR PRIDE; Q922H2; -.
DR ProteomicsDB; 288083; -.
DR Antibodypedia; 24576; 320 antibodies from 30 providers.
DR DNASU; 236900; -.
DR Ensembl; ENSMUST00000045748; ENSMUSP00000036604; ENSMUSG00000035232.
DR GeneID; 236900; -.
DR KEGG; mmu:236900; -.
DR UCSC; uc009tsx.1; mouse.
DR CTD; 5165; -.
DR MGI; MGI:2384308; Pdk3.
DR VEuPathDB; HostDB:ENSMUSG00000035232; -.
DR eggNOG; KOG0787; Eukaryota.
DR GeneTree; ENSGT01030000234646; -.
DR HOGENOM; CLU_023861_1_1_1; -.
DR InParanoid; Q922H2; -.
DR OMA; ITLNHIG; -.
DR OrthoDB; 1242599at2759; -.
DR PhylomeDB; Q922H2; -.
DR TreeFam; TF314918; -.
DR BRENDA; 2.7.11.2; 3474.
DR Reactome; R-MMU-204174; Regulation of pyruvate dehydrogenase (PDH) complex.
DR Reactome; R-MMU-5362517; Signaling by Retinoic Acid.
DR BioGRID-ORCS; 236900; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Pdk3; mouse.
DR PRO; PR:Q922H2; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q922H2; protein.
DR Bgee; ENSMUSG00000035232; Expressed in spermatid and 270 other tissues.
DR ExpressionAtlas; Q922H2; baseline and differential.
DR Genevisible; Q922H2; MM.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0004672; F:protein kinase activity; ISO:MGI.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0004740; F:pyruvate dehydrogenase (acetyl-transferring) kinase activity; ISS:UniProtKB.
DR GO; GO:0071398; P:cellular response to fatty acid; ISS:UniProtKB.
DR GO; GO:0071333; P:cellular response to glucose stimulus; ISS:UniProtKB.
DR GO; GO:0006006; P:glucose metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0097411; P:hypoxia-inducible factor-1alpha signaling pathway; ISS:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:UniProtKB.
DR GO; GO:0035357; P:peroxisome proliferator activated receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0010510; P:regulation of acetyl-CoA biosynthetic process from pyruvate; ISS:UniProtKB.
DR GO; GO:0010906; P:regulation of glucose metabolic process; ISS:UniProtKB.
DR GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; ISS:UniProtKB.
DR Gene3D; 1.20.140.20; -; 1.
DR Gene3D; 3.30.565.10; -; 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; PTHR11947; 1.
DR Pfam; PF10436; BCDHK_Adom3; 1.
DR Pfam; PF02518; HATPase_c; 1.
DR SMART; SM00387; HATPase_c; 1.
DR SUPFAM; SSF55874; SSF55874; 1.
DR SUPFAM; SSF69012; SSF69012; 1.
DR PROSITE; PS50109; HIS_KIN; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Carbohydrate metabolism; Glucose metabolism; Kinase;
KW Mitochondrion; Nucleotide-binding; Reference proteome; Transferase;
KW Transit peptide.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?..415
FT /note="[Pyruvate dehydrogenase (acetyl-transferring)]
FT kinase isozyme 3, mitochondrial"
FT /id="PRO_0000023444"
FT DOMAIN 131..362
FT /note="Histidine kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00107"
FT REGION 383..415
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 247..254
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 287
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 306..307
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 323..328
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 278
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CONFLICT 21
FT /note="R -> C (in Ref. 1; BAC40379)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 415 AA; 47923 MW; 566497E0F8842822 CRC64;
MRLFYRLLKQ PVPKQIERYS RFSPSPLSIK QFLDFGRDNA CEKTSYMFLR KELPVRLANT
MREVNLLPDN LLNRPSVGLV QSWYMQSFLE LLEYENKSPE DPRVLDNFLN VLINIRNRHN
DVVPTMAQGV IEYKEKFGFD PFISSNIQYF LDRFYTNRIS FRMLINQHTL LFGGDTNPAH
PKHIGSIDPT CNVADVVKDA YETAKMLCEQ YYLVAPELEV EEFNAKAPNK PIQVVYVPSH
LFHMLFELFK NSMRATVELH EDKKEGYPAV KTLVTLGKED LSIKISDLGG GVPLRKIDRL
FNYMYSTAPR PSLEPTRAAP LAGFGYGLPI SRLYARYFQG DLKLYSMEGV GTDAVIYLKA
LSSESFERLP VFNKSAWRHY KTTPEADDWS NPSSEPRDAS KYKAKQDKIK SNRTF
