LOCUS       NM_000284               3349 bp    mRNA    linear   PRI 10-OCT-2024
DEFINITION  Homo sapiens pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1),
            transcript variant 1, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_000284
VERSION     NM_000284.4
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 3349)
  AUTHORS   An,S., Yao,Y., Hu,H., Wu,J., Li,J., Li,L., Wu,J., Sun,M., Deng,Z.,
            Zhang,Y., Gong,S., Huang,Q., Chen,Z. and Zeng,Z.
  TITLE     PDHA1 hyperacetylation-mediated lactate overproduction promotes
            sepsis-induced acute kidney injury via Fis1 lactylation
  JOURNAL   Cell Death Dis 14 (7), 457 (2023)
   PUBMED   37479690
  REMARK    GeneRIF: PDHA1 hyperacetylation-mediated lactate overproduction
            promotes sepsis-induced acute kidney injury via Fis1 lactylation.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 3349)
  AUTHORS   Pinho,S.A., Costa,C.F., Deus,C.M., Pinho,S.L.C., Miranda-Santos,I.,
            Afonso,G., Bagshaw,O., Stuart,J.A., Oliveira,P.J. and
            Cunha-Oliveira,T.
  TITLE     Mitochondrial and metabolic remodelling in human skin fibroblasts
            in response to glucose availability
  JOURNAL   FEBS J 289 (17), 5198-5217 (2022)
   PUBMED   35213938
REFERENCE   3  (bases 1 to 3349)
  AUTHORS   Wang,C.H., Lu,W.L., Chiang,S.L., Tsai,T.H., Liu,S.C., Hsieh,C.H.,
            Su,P.H., Huang,C.Y., Tsai,F.J., Lin,Y.J. and Huang,Y.N.
  TITLE     T Cells Mediate Kidney Tubular Injury via Impaired PDHA1 and
            Autophagy in Type 1 Diabetes
  JOURNAL   J Clin Endocrinol Metab 107 (9), 2556-2570 (2022)
   PUBMED   35731579
  REMARK    GeneRIF: T Cells Mediate Kidney Tubular Injury via Impaired PDHA1
            and Autophagy in Type 1 Diabetes.
REFERENCE   4  (bases 1 to 3349)
  AUTHORS   Chevalier,B., Baatallah,N., Najm,M., Castanier,S., Jung,V.,
            Pranke,I., Golec,A., Stoven,V., Marullo,S., Antigny,F.,
            Guerrera,I.C., Sermet-Gaudelus,I., Edelman,A. and Hinzpeter,A.
  TITLE     Differential CFTR-Interactome Proximity Labeling Procedures
            Identify Enrichment in Multiple SLC Transporters
  JOURNAL   Int J Mol Sci 23 (16), 8937 (2022)
   PUBMED   36012204
  REMARK    Publication Status: Online-Only
REFERENCE   5  (bases 1 to 3349)
  AUTHORS   Zhang,Y., Zhao,M., Gao,H., Yu,G., Zhao,Y., Yao,F. and Yang,W.
  TITLE     MAPK signalling-induced phosphorylation and subcellular
            translocation of PDHE1alpha promotes tumour immune evasion
  JOURNAL   Nat Metab 4 (3), 374-388 (2022)
   PUBMED   35315437
  REMARK    GeneRIF: MAPK signalling-induced phosphorylation and subcellular
            translocation of PDHE1alpha promotes tumour immune evasion.
REFERENCE   6  (bases 1 to 3349)
  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   7  (bases 1 to 3349)
  AUTHORS   De Meirleir,L., Lissens,W., Vamos,E. and Liebaers,I.
  TITLE     Pyruvate dehydrogenase (PDH) deficiency caused by a 21-base pair
            insertion mutation in the E1 alpha subunit
  JOURNAL   Hum Genet 88 (6), 649-652 (1992)
   PUBMED   1551669
REFERENCE   8  (bases 1 to 3349)
  AUTHORS   Ito,M., Huq,A.H., Naito,E., Saijo,T., Takeda,E. and Kuroda,Y.
  TITLE     Mutation of E1 alpha gene in a female patient with pyruvate
            dehydrogenase deficiency due to rapid degradation of E1 protein
  JOURNAL   J Inherit Metab Dis 15 (6), 848-856 (1992)
   PUBMED   1338114
REFERENCE   9  (bases 1 to 3349)
  AUTHORS   Dahl,H.H., Brown,G.K., Brown,R.M., Hansen,L.L., Kerr,D.S.,
            Wexler,I.D., Patel,M.S., De Meirleir,L., Lissens,W., Chun,K. et al.
  TITLE     Mutations and polymorphisms in the pyruvate dehydrogenase E1 alpha
            gene
  JOURNAL   Hum Mutat 1 (2), 97-102 (1992)
   PUBMED   1301207
  REMARK    Review article
REFERENCE   10 (bases 1 to 3349)
  AUTHORS   Dahl,H.H., Hansen,L.L., Brown,R.M., Danks,D.M., Rogers,J.G. and
            Brown,G.K.
  TITLE     X-linked pyruvate dehydrogenase E1 alpha subunit deficiency in
            heterozygous females: variable manifestation of the same mutation
  JOURNAL   J Inherit Metab Dis 15 (6), 835-847 (1992)
   PUBMED   1293379
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DC361191.1, L13318.1,
            BU170389.1, AL732326.4 and R49470.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 17, 2019 this sequence version replaced NM_000284.3.
            
            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), and
            provides the primary link between glycolysis and the tricarboxylic
            acid (TCA) cycle. The PDH complex is composed of multiple copies of
            three enzymatic components: pyruvate dehydrogenase (E1),
            dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase
            (E3). The E1 enzyme is a heterotetramer of two alpha and two beta
            subunits. This gene encodes the E1 alpha 1 subunit containing the
            E1 active site, and plays a key role in the function of the PDH
            complex. Mutations in this gene are associated with pyruvate
            dehydrogenase E1-alpha deficiency and X-linked Leigh syndrome.
            Alternatively spliced transcript variants encoding different
            isoforms have been found for this gene.[provided by RefSeq, Mar
            2010].
            
            Transcript Variant: This variant (1) represents the predominant
            transcript and encodes 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 :: SRR1803616.267695.1,
                                           SRR1803615.9181.1 [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                 :: ENST00000422285.7/
                                                  ENSP00000394382.2
            RefSeq Select criteria             :: based on conservation,
                                                  expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-551               DC361191.1         35-585
            552-1478            L13318.1           546-1472
            1479-2039           BU170389.1         225-785
            2040-3310           AL732326.4         116837-118107
            3311-3338           R49470.1           19-46               c
            3339-3349           AL732326.4         118136-118146
FEATURES             Location/Qualifiers
     source          1..3349
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="X"
                     /map="Xp22.12"
     gene            1..3349
                     /gene="PDHA1"
                     /gene_synonym="E1alpha; PDHA; PDHAD; PDHCE1A; PHE1A"
                     /note="pyruvate dehydrogenase E1 subunit alpha 1"
                     /db_xref="GeneID:5160"
                     /db_xref="HGNC:HGNC:8806"
                     /db_xref="MIM:300502"
     exon            1..168
                     /gene="PDHA1"
                     /gene_synonym="E1alpha; PDHA; PDHAD; PDHCE1A; PHE1A"
                     /inference="alignment:Splign:2.1.0"
     CDS             112..1284
                     /gene="PDHA1"
                     /gene_synonym="E1alpha; PDHA; PDHAD; PDHCE1A; PHE1A"
                     /EC_number="1.2.4.1"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; pyruvate dehydrogenase E1 component subunit
                     alpha, somatic form, mitochondrial; PDHE1-A type I;
                     pyruvate dehydrogenase alpha 1; pyruvate dehydrogenase
                     (lipoamide) alpha 1; pyruvate dehydrogenase complex,
                     E1-alpha polypeptide 1; pyruvate dehydrogenase E1 alpha 1
                     subunit"
                     /codon_start=1
                     /product="pyruvate dehydrogenase E1 component subunit
                     alpha, somatic form, mitochondrial isoform 1 precursor"
                     /protein_id="NP_000275.1"
                     /db_xref="CCDS:CCDS14192.1"
                     /db_xref="GeneID:5160"
                     /db_xref="HGNC:HGNC:8806"
                     /db_xref="MIM:300502"
                     /translation="MRKMLAAVSRVLSGASQKPASRVLVASRNFANDATFEIKKCDLH
                     RLEEGPPVTTVLTREDGLKYYRMMQTVRRMELKADQLYKQKIIRGFCHLCDGQEACCV
                     GLEAGINPTDHLITAYRAHGFTFTRGLSVREILAELTGRKGGCAKGKGGSMHMYAKNF
                     YGGNGIVGAQVPLGAGIALACKYNGKDEVCLTLYGDGAANQGQIFEAYNMAALWKLPC
                     IFICENNRYGMGTSVERAAASTDYYKRGDFIPGLRVDGMDILCVREATRFAAAYCRSG
                     KGPILMELQTYRYHGHSMSDPGVSYRTREEIQEVRSKSDPIMLLKDRMVNSNLASVEE
                     LKEIDVEVRKEIEDAAQFATADPEPPLEELGYHIYSSDPPFEVRGANQWIKFKSVS"
     exon            169..228
                     /gene="PDHA1"
                     /gene_synonym="E1alpha; PDHA; PDHAD; PDHCE1A; PHE1A"
                     /inference="alignment:Splign:2.1.0"
     exon            229..402
                     /gene="PDHA1"
                     /gene_synonym="E1alpha; PDHA; PDHAD; PDHCE1A; PHE1A"
                     /inference="alignment:Splign:2.1.0"
     exon            403..529
                     /gene="PDHA1"
                     /gene_synonym="E1alpha; PDHA; PDHAD; PDHCE1A; PHE1A"
                     /inference="alignment:Splign:2.1.0"
     exon            530..621
                     /gene="PDHA1"
                     /gene_synonym="E1alpha; PDHA; PDHAD; PDHCE1A; PHE1A"
                     /inference="alignment:Splign:2.1.0"
     exon            622..714
                     /gene="PDHA1"
                     /gene_synonym="E1alpha; PDHA; PDHAD; PDHCE1A; PHE1A"
                     /inference="alignment:Splign:2.1.0"
     exon            715..870
                     /gene="PDHA1"
                     /gene_synonym="E1alpha; PDHA; PDHAD; PDHCE1A; PHE1A"
                     /inference="alignment:Splign:2.1.0"
     exon            871..942
                     /gene="PDHA1"
                     /gene_synonym="E1alpha; PDHA; PDHAD; PDHCE1A; PHE1A"
                     /inference="alignment:Splign:2.1.0"
     exon            943..1010
                     /gene="PDHA1"
                     /gene_synonym="E1alpha; PDHA; PDHAD; PDHCE1A; PHE1A"
                     /inference="alignment:Splign:2.1.0"
     exon            1011..1119
                     /gene="PDHA1"
                     /gene_synonym="E1alpha; PDHA; PDHAD; PDHCE1A; PHE1A"
                     /inference="alignment:Splign:2.1.0"
     exon            1120..3349
                     /gene="PDHA1"
                     /gene_synonym="E1alpha; PDHA; PDHAD; PDHCE1A; PHE1A"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1453..1458
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PDHA1"
                     /gene_synonym="E1alpha; PDHA; PDHAD; PDHCE1A; PHE1A"
                     /note="hexamer: ATTAAA"
     polyA_site      1486
                     /gene="PDHA1"
                     /gene_synonym="E1alpha; PDHA; PDHAD; PDHCE1A; PHE1A"
                     /note="major polyA site"
     regulatory      3262..3267
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PDHA1"
                     /gene_synonym="E1alpha; PDHA; PDHAD; PDHCE1A; PHE1A"
                     /note="hexamer: CATAAA"
     polyA_site      3282
                     /gene="PDHA1"
                     /gene_synonym="E1alpha; PDHA; PDHAD; PDHCE1A; PHE1A"
     regulatory      3294..3299
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PDHA1"
                     /gene_synonym="E1alpha; PDHA; PDHAD; PDHCE1A; PHE1A"
                     /note="hexamer: AATAAA"
     polyA_site      3316
                     /gene="PDHA1"
                     /gene_synonym="E1alpha; PDHA; PDHAD; PDHCE1A; PHE1A"
ORIGIN      
        1 ggtgcgactg aggcgtggcg tctgctgggg cacctgaagg agacttgggg gcacccgcgt
       61 cgtgcctcct gggttgtgag gagtcgccgc tgccgccact gcctgtgctt catgaggaag
      121 atgctcgccg ccgtctcccg cgtgctgtct ggcgcttctc agaagccggc aagcagagtg
      181 ctggtagcat cccgtaattt tgcaaatgat gctacatttg aaattaagaa atgtgacctt
      241 caccggctgg aagaaggccc tcctgtcaca acagtgctca ccagggagga tgggctcaaa
      301 tactacagga tgatgcagac tgtacgccga atggagttga aagcagatca gctgtataaa
      361 cagaaaatta ttcgtggttt ctgtcacttg tgtgatggtc aggaagcttg ctgtgtgggc
      421 ctggaggccg gcatcaaccc cacagaccat ctcatcacag cctaccgggc tcacggcttt
      481 actttcaccc ggggcctttc cgtccgagaa attctcgcag agcttacagg acgaaaagga
      541 ggttgtgcta aagggaaagg aggatcgatg cacatgtatg ccaagaactt ctacgggggc
      601 aatggcatcg tgggagcgca ggtgcccctg ggcgctggga ttgctctagc ctgtaagtat
      661 aatggaaaag atgaggtctg cctgacttta tatggcgatg gtgctgctaa ccagggccag
      721 atattcgaag cttacaacat ggcagctttg tggaaattac cttgtatttt catctgtgag
      781 aataatcgct atggaatggg aacgtctgtt gagagagcgg cagccagcac tgattactac
      841 aagagaggcg atttcattcc tgggctgaga gtggatggaa tggatatcct gtgcgtccga
      901 gaggcaacaa ggtttgctgc tgcctattgt agatctggga aggggcccat cctgatggag
      961 ctgcagactt accgttacca cggacacagt atgagtgacc ctggagtcag ttaccgtaca
     1021 cgagaagaaa ttcaggaagt aagaagtaag agtgacccta ttatgcttct caaggacagg
     1081 atggtgaaca gcaatcttgc cagtgtggaa gaactaaagg aaattgatgt ggaagtgagg
     1141 aaggagattg aggatgctgc ccagtttgcc acggccgatc ctgagccacc tttggaagag
     1201 ctgggctacc acatctactc cagcgaccca ccttttgaag ttcgtggtgc caatcagtgg
     1261 atcaagttta agtcagtcag ttaaggggag gagaaggaga ggttatacct tcagggggct
     1321 accagacagt gttctcaact tggttaagga ggaagaaaac ccagtcaatg aaattcaatg
     1381 aaattcttgg aaacttccat taagtgtgta gattgagcag gtagtaattg catgcagttt
     1441 gtacattagt gcattaaaag atgaattatt gagtgcttaa agattatttt tgacttaaaa
     1501 tagtatactt tgaacaaata ctctaattat gaaaaggaag aacaattcct tgtatgcctg
     1561 tttcccctgc ccccagccac ctttttggga ggagaccatt atggcggggc ccctcacagc
     1621 attctaccaa ccatagcacc caccccgagc agcgctggtg ctgcagcctg ttcgcgctga
     1681 ccatttctct acaagataca atatttatta tcaggcaaga ggacagttcc attttaaaat
     1741 aagacttttg taatcattcc aattttgtaa tcatttcaaa ggccacataa cttagttttc
     1801 tctacttaca cattcagtat aaatatgaag ctattttctg ttcatatcaa acattaacta
     1861 caaggcacat tcgtatcagt tttgtgtttc tcaaattgaa gtaccatacc agttctgagg
     1921 cagtgtccca gcttccatgt ttgttaaata ccccttgttt gtttcaccat tccagcaagt
     1981 gctgaagggt gtactttttt tgagacaggg tcgggctctg ttgcccaggc tggagtgcag
     2041 tggtgtgatc atggctcact gcagcctcca cacctcctgg gctcaagcaa tcctcccacc
     2101 tcagcctcct gcatagctgg gactacaagt gaatttccta atattccggg aggtcaaaac
     2161 caaggctcac tgttttcaca atacacacag ttctatgttt ataaataaca ggtttcaaaa
     2221 gaaactcagg acagtattta aaacaagttc ttaaactatt aattgaacaa tggcattttt
     2281 aaatatgtaa acacagcgga attcgtgtat acactaacag aagctttaac aaaacatgta
     2341 gcgtggtggg acactctgcc acagcttagc tgattggtat caagccttgt ctttggtttc
     2401 tgaggcctcc tgagcccttc tgtactggga gaccgcactc cagagtctgc agaggagacc
     2461 acccctggga aacaaacaca gctgtcttca gagtcagtgc ttcaagccaa cagagcttaa
     2521 aactgcagtc cctaatttaa aaacctaatg aaaataaaaa cattctcctc acatatggag
     2581 gtgacgctcg tgtcccagca gtagtaggac atggccttag aggtacgtac ctgcagagag
     2641 ctggctattt caaatgactc gggaacaaga aggcaggctg cagtttaaag aagggggtgg
     2701 gtccagcgtg caggcacgct tgccatgtgc ctccacccac tcccagccag gcattaatgg
     2761 caggagattg gccagctctt ctctgtcaca ttcctatttc tgacttctgc ctggctttca
     2821 gtttctgccc caccttggct ttttcccagc ttgaacctaa tagaactcca gagtttgggg
     2881 ggaggcccag ccctttgttt tctgctcttg aagcatattc acacataaaa agttgtattc
     2941 tcttatacaa actgttttga ggctcttacc gtagtcgaag gtatcttaga tcttccttag
     3001 tgatctcatt aagaatatcc gaaagtgtat aaccctcttc aacaatctga aacaaagatc
     3061 agatccttaa gagctgagca gctgtgtaac aacagcataa gaatttcttt gttgtaaatt
     3121 taccttttca attgtctttg catcagctcc ttgcagccgc aaccagtcta taagctcttt
     3181 atctgttctc tgcccgtagg ggcctgctgg gttctctgta atacctgtaa cgattggcaa
     3241 tttgttatat attagtctaa ccataaaact cttcaaaagt aaccagttgg attaataaat
     3301 gattccagaa tgtaaatgtg atgtgaaaaa gagatgaatt aaccctgta
//
