LOCUS       NM_005391               1741 bp    mRNA    linear   PRI 10-FEB-2025
DEFINITION  Homo sapiens pyruvate dehydrogenase kinase 3 (PDK3), transcript
            variant 2, mRNA.
ACCESSION   NM_005391
VERSION     NM_005391.5
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 1741)
  AUTHORS   Maciel,V.A.Z., Maximiano-Alves,G., Frezatti,R.S.S., Alves,A.L.M.,
            Andrade,B.M.A., Leal,R.C.C., Tomaselli,P.J., Reilly,M.M. and
            Marques,W.
  TITLE     Unveiling the clinical and electrophysiological profile of CMTX6:
            Insights from two Brazilian families
  JOURNAL   J Peripher Nerv Syst 28 (4), 614-619 (2023)
   PUBMED   37849068
  REMARK    GeneRIF: Unveiling the clinical and electrophysiological profile of
            CMTX6: Insights from two Brazilian families.
REFERENCE   2  (bases 1 to 1741)
  AUTHORS   Narayanan,R.K., Brewer,M.H., Perez-Siles,G., Ellis,M., Ly,C.,
            Burgess,A., Neumann,B., Nicholson,G.A., Vucic,S. and Kennerson,M.L.
  TITLE     Charcot-Marie-tooth disease causing mutation (p.R158H) in pyruvate
            dehydrogenase kinase 3 (PDK3) affects synaptic transmission, ATP
            production and causes neurodegeneration in a CMTX6 C. elegans model
  JOURNAL   Hum Mol Genet 31 (1), 133-145 (2021)
   PUBMED   34387338
  REMARK    GeneRIF: Charcot-Marie-tooth disease causing mutation (p.R158H) in
            pyruvate dehydrogenase kinase 3 (PDK3) affects synaptic
            transmission, ATP production and causes neurodegeneration in a
            CMTX6 C. elegans model.
REFERENCE   3  (bases 1 to 1741)
  AUTHORS   Morgenstern,M., Peikert,C.D., Lubbert,P., Suppanz,I., Klemm,C.,
            Alka,O., Steiert,C., Naumenko,N., Schendzielorz,A., Melchionda,L.,
            Muhlhauser,W.W.D., Knapp,B., Busch,J.D., Stiller,S.B.,
            Dannenmaier,S., Lindau,C., Licheva,M., Eickhorst,C., Galbusera,R.,
            Zerbes,R.M., Ryan,M.T., Kraft,C., Kozjak-Pavlovic,V., Drepper,F.,
            Dennerlein,S., Oeljeklaus,S., Pfanner,N., Wiedemann,N. and
            Warscheid,B.
  TITLE     Quantitative high-confidence human mitochondrial proteome and its
            dynamics in cellular context
  JOURNAL   Cell Metab 33 (12), 2464-2483 (2021)
   PUBMED   34800366
REFERENCE   4  (bases 1 to 1741)
  AUTHORS   Huttlin,E.L., Bruckner,R.J., Navarrete-Perea,J., Cannon,J.R.,
            Baltier,K., Gebreab,F., Gygi,M.P., Thornock,A., Zarraga,G., Tam,S.,
            Szpyt,J., Gassaway,B.M., Panov,A., Parzen,H., Fu,S., Golbazi,A.,
            Maenpaa,E., Stricker,K., Guha Thakurta,S., Zhang,T., Rad,R.,
            Pan,J., Nusinow,D.P., Paulo,J.A., Schweppe,D.K., Vaites,L.P.,
            Harper,J.W. and Gygi,S.P.
  TITLE     Dual proteome-scale networks reveal cell-specific remodeling of the
            human interactome
  JOURNAL   Cell 184 (11), 3022-3040 (2021)
   PUBMED   33961781
REFERENCE   5  (bases 1 to 1741)
  AUTHORS   Korotchkina,L.G. and Patel,M.S.
  TITLE     Site specificity of four pyruvate dehydrogenase kinase isoenzymes
            toward the three phosphorylation sites of human pyruvate
            dehydrogenase
  JOURNAL   J Biol Chem 276 (40), 37223-37229 (2001)
   PUBMED   11486000
REFERENCE   6  (bases 1 to 1741)
  AUTHORS   Kolobova,E., Tuganova,A., Boulatnikov,I. and Popov,K.M.
  TITLE     Regulation of pyruvate dehydrogenase activity through
            phosphorylation at multiple sites
  JOURNAL   Biochem J 358 (Pt 1), 69-77 (2001)
   PUBMED   11485553
REFERENCE   7  (bases 1 to 1741)
  AUTHORS   Baker,J.C., Yan,X., Peng,T., Kasten,S. and Roche,T.E.
  TITLE     Marked differences between two isoforms of human pyruvate
            dehydrogenase kinase
  JOURNAL   J Biol Chem 275 (21), 15773-15781 (2000)
   PUBMED   10748134
REFERENCE   8  (bases 1 to 1741)
  AUTHORS   Gudi,R., Bowker-Kinley,M.M., Kedishvili,N.Y., Zhao,Y. and
            Popov,K.M.
  TITLE     Diversity of the pyruvate dehydrogenase kinase gene family in
            humans
  JOURNAL   J Biol Chem 270 (48), 28989-28994 (1995)
   PUBMED   7499431
  REMARK    Erratum:[J Biol Chem 1996 Jan 12;271(2):1250]
REFERENCE   9  (bases 1 to 1741)
  AUTHORS   Ganetzky,R., McCormick,E.M. and Falk,M.J.
  TITLE     Primary Pyruvate Dehydrogenase Complex Deficiency Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   34138529
REFERENCE   10 (bases 1 to 1741)
  AUTHORS   Bird,T.D.
  TITLE     Charcot-Marie-Tooth Hereditary Neuropathy Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301532
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BI549903.1, BC015948.1,
            L42452.1 and AC004656.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Feb 27, 2020 this sequence version replaced NM_005391.4.
            
            Summary: The pyruvate dehydrogenase (PDH) complex is a
            nuclear-encoded mitochondrial multienzyme complex that catalyzes
            the overall conversion of pyruvate to acetyl-CoA and CO(2). It
            provides the primary link between glycolysis and the tricarboxylic
            acid (TCA) cycle, and thus is one of the major enzymes responsible
            for the regulation of glucose metabolism. The enzymatic activity of
            PDH is regulated by a phosphorylation/dephosphorylation cycle, and
            phosphorylation results in inactivation of PDH. The protein encoded
            by this gene is one of the three pyruvate dehydrogenase kinases
            that inhibits the PDH complex by phosphorylation of the E1 alpha
            subunit. This gene is predominantly expressed in the heart and
            skeletal muscles. Alternatively spliced transcript variants
            encoding different isoforms have been found for this gene.
            [provided by RefSeq, Mar 2010].
            
            Transcript Variant: This variant (2) differs at the 3' end compared
            to variant 1, resulting in a shorter isoform (2) lacking the last 9
            aa from the C-terminus, compared to isoform 1.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: L42452.1, BC015948.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000379162.9/
                                                  ENSP00000368460.4
            RefSeq Select criteria             :: based on conservation,
                                                  expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-421               BI549903.1         65-485
            422-1452            BC015948.1         428-1458
            1453-1665           L42452.1           1305-1517
            1666-1666           AC004656.1         52419-52419
            1667-1741           L42452.1           1518-1592
FEATURES             Location/Qualifiers
     source          1..1741
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="X"
                     /map="Xp22.11"
     gene            1..1741
                     /gene="PDK3"
                     /gene_synonym="CMTX6; GS1-358P8.4"
                     /note="pyruvate dehydrogenase kinase 3"
                     /db_xref="GeneID:5165"
                     /db_xref="HGNC:HGNC:8811"
                     /db_xref="MIM:300906"
     exon            1..276
                     /gene="PDK3"
                     /gene_synonym="CMTX6; GS1-358P8.4"
                     /inference="alignment:Splign:2.1.0"
     CDS             171..1391
                     /gene="PDK3"
                     /gene_synonym="CMTX6; GS1-358P8.4"
                     /EC_number="2.7.11.2"
                     /note="isoform 2 precursor is encoded by transcript
                     variant 2; pyruvate dehydrogenase kinase, isoenzyme 3;
                     pyruvate dehydrogenase, lipoamide, kinase isozyme 3,
                     mitochondrial; [Pyruvate dehydrogenase
                     (acetyl-transferring)] kinase isozyme 3, mitochondrial;
                     pyruvate dehydrogenase kinase, isozyme 3"
                     /codon_start=1
                     /product="pyruvate dehydrogenase kinase, isozyme 3 isoform
                     2 precursor"
                     /protein_id="NP_005382.1"
                     /db_xref="CCDS:CCDS14212.1"
                     /db_xref="GeneID:5165"
                     /db_xref="HGNC:HGNC:8811"
                     /db_xref="MIM:300906"
                     /translation="MRLFRWLLKQPVPKQIERYSRFSPSPLSIKQFLDFGRDNACEKT
                     SYMFLRKELPVRLANTMREVNLLPDNLLNRPSVGLVQSWYMQSFLELLEYENKSPEDP
                     QVLDNFLQVLIKVRNRHNDVVPTMAQGVIEYKEKFGFDPFISTNIQYFLDRFYTNRIS
                     FRMLINQHTLLFGGDTNPVHPKHIGSIDPTCNVADVVKDAYETAKMLCEQYYLVAPEL
                     EVEEFNAKAPDKPIQVVYVPSHLFHMLFELFKNSMRATVELYEDRKEGYPAVKTLVTL
                     GKEDLSIKISDLGGGVPLRKIDRLFNYMYSTAPRPSLEPTRAAPLAGFGYGLPISRLY
                     ARYFQGDLKLYSMEGVGTDAVIYLKALSSESFERLPVFNKSAWRHYKTTPEADDWSNP
                     SSEPRDASKYKAKQ"
     exon            277..418
                     /gene="PDK3"
                     /gene_synonym="CMTX6; GS1-358P8.4"
                     /inference="alignment:Splign:2.1.0"
     exon            419..490
                     /gene="PDK3"
                     /gene_synonym="CMTX6; GS1-358P8.4"
                     /inference="alignment:Splign:2.1.0"
     exon            491..675
                     /gene="PDK3"
                     /gene_synonym="CMTX6; GS1-358P8.4"
                     /inference="alignment:Splign:2.1.0"
     exon            676..765
                     /gene="PDK3"
                     /gene_synonym="CMTX6; GS1-358P8.4"
                     /inference="alignment:Splign:2.1.0"
     exon            766..843
                     /gene="PDK3"
                     /gene_synonym="CMTX6; GS1-358P8.4"
                     /inference="alignment:Splign:2.1.0"
     exon            844..920
                     /gene="PDK3"
                     /gene_synonym="CMTX6; GS1-358P8.4"
                     /inference="alignment:Splign:2.1.0"
     exon            921..1022
                     /gene="PDK3"
                     /gene_synonym="CMTX6; GS1-358P8.4"
                     /inference="alignment:Splign:2.1.0"
     exon            1023..1133
                     /gene="PDK3"
                     /gene_synonym="CMTX6; GS1-358P8.4"
                     /inference="alignment:Splign:2.1.0"
     exon            1134..1247
                     /gene="PDK3"
                     /gene_synonym="CMTX6; GS1-358P8.4"
                     /inference="alignment:Splign:2.1.0"
     exon            1248..1741
                     /gene="PDK3"
                     /gene_synonym="CMTX6; GS1-358P8.4"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1434..1439
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PDK3"
                     /gene_synonym="CMTX6; GS1-358P8.4"
                     /note="hexamer: AATAAA"
     polyA_site      1464
                     /gene="PDK3"
                     /gene_synonym="CMTX6; GS1-358P8.4"
                     /note="major polyA site"
     regulatory      1717..1722
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PDK3"
                     /gene_synonym="CMTX6; GS1-358P8.4"
                     /note="hexamer: AATAAA"
     polyA_site      1741
                     /gene="PDK3"
                     /gene_synonym="CMTX6; GS1-358P8.4"
ORIGIN      
        1 gctgtcctgg agctgctgct gctgctgcgg cggctgcacc ggcggcgccg aggccgagat
       61 cgaggccggg gtgcgcgctt cgcaaacgtg ccctatccgt gcggcttggc tgcgccagcc
      121 cttgcggcca cccgggcgtc taggcgggtc tgtgcgccgc ccgggcgagg atgcggctgt
      181 tccggtggct gctgaagcag ccggtgccca agcagatcga gcgctactcg cgcttttcgc
      241 cgtcgccgct ctccatcaaa caattcctgg acttcgggag agataatgca tgtgagaaaa
      301 cttcatatat gtttctacga aaggaacttc ctgtgcggct ggctaacaca atgagagaag
      361 ttaatcttct gccggataat ttacttaacc gcccttcagt gggattggtt cagagttggt
      421 atatgcagag ttttcttgaa cttttagaat atgaaaataa gagccctgag gatccacagg
      481 tcttggataa ctttctacaa gttctgatta aagtcagaaa tagacacaat gatgtggttc
      541 ctacaatggc acaaggagtg attgaataca aggagaagtt tgggtttgat cctttcatta
      601 gcactaacat ccaatatttt ctggatcggt tttataccaa ccgcatctct ttccgcatgc
      661 ttattaatca gcacacactt ctgtttgggg gtgacactaa tcctgttcat cctaaacaca
      721 taggaagtat cgatcccacc tgtaacgtgg cggatgtggt gaaagatgca tatgaaacag
      781 ccaagatgct gtgtgaacag tattacctgg tagctccaga gctggaagtt gaagaattca
      841 atgccaaagc gccagacaaa cctattcagg tggtttatgt gccctcacat ctgtttcata
      901 tgctatttga gttgttcaag aactcaatga gagcgacagt tgaactctat gaagacagaa
      961 aagagggcta ccctgctgtt aaaaccctcg ttactttggg taaagaagac ttatccatta
     1021 agatcagtga cctaggtggt ggtgtcccac ttcgaaaaat agatcgtctt tttaactaca
     1081 tgtattctac tgctcctaga cccagcctgg agcctaccag agctgcccct ttggctggat
     1141 ttggttatgg tttgccaatt tcccgtctgt atgctagata ttttcaagga gatctgaaac
     1201 tgtattccat ggaaggagtg ggtactgatg ctgtcattta tttgaaggct ctttcaagtg
     1261 agtcatttga gagacttcca gtttttaata agtccgcatg gcgccattac aagaccacgc
     1321 ctgaagccga tgattggagc aatcccagca gtgaacccag ggatgcttca aaatacaaag
     1381 caaaacagta atataccacc ttgatttcca ttacaaagta tctgatttgt ctgaataaag
     1441 gtgtcccact cactgttcca ggaattcttg cagtgtagag gtattcacaa cagcaagcag
     1501 ggatttggcc tgccatcaat tttatttaaa aagcaattaa gtttgcagtt tgtcctcata
     1561 aacgttgtag gttgaaactg aaaaataagt taaaatgatc aatcaagata aaaggtgatc
     1621 tatccatcca atggaatatt atttggcctt aaaaaggaag gacattctga tatgtgctgc
     1681 aacatgggtg aatcttgaag tcattatgct aagtgaaata aaccagacat aaaaggacaa
     1741 a
//
