LOCUS       NM_003477               2500 bp    mRNA    linear   PRI 11-OCT-2024
DEFINITION  Homo sapiens pyruvate dehydrogenase complex component X (PDHX),
            transcript variant 1, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_003477
VERSION     NM_003477.3
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 2500)
  AUTHORS   Jiang,R., Sun,Y., Li,Y., Tang,X., Hui,B., Ma,S., Zhang,J., Sun,C.,
            Tan,J., Zhou,B., Lei,J. and Jiang,T.
  TITLE     Cuproptosis-related gene PDHX and heat stress-related HSPD1 as
            potential key drivers associated with cell stemness, aberrant
            metabolism and immunosuppression in esophageal carcinoma
  JOURNAL   Int Immunopharmacol 117, 109942 (2023)
   PUBMED   36889194
  REMARK    GeneRIF: Cuproptosis-related gene PDHX and heat stress-related
            HSPD1 as potential key drivers associated with cell stemness,
            aberrant metabolism and immunosuppression in esophageal carcinoma.
REFERENCE   2  (bases 1 to 2500)
  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   3  (bases 1 to 2500)
  AUTHORS   Inoue,J., Kishikawa,M., Tsuda,H., Nakajima,Y., Asakage,T. and
            Inazawa,J.
  TITLE     Identification of PDHX as a metabolic target for esophageal
            squamous cell carcinoma
  JOURNAL   Cancer Sci 112 (7), 2792-2802 (2021)
   PUBMED   33964039
  REMARK    GeneRIF: Identification of PDHX as a metabolic target for
            esophageal squamous cell carcinoma.
REFERENCE   4  (bases 1 to 2500)
  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 2500)
  AUTHORS   Luck,K., Kim,D.K., Lambourne,L., Spirohn,K., Begg,B.E., Bian,W.,
            Brignall,R., Cafarelli,T., Campos-Laborie,F.J., Charloteaux,B.,
            Choi,D., Cote,A.G., Daley,M., Deimling,S., Desbuleux,A., Dricot,A.,
            Gebbia,M., Hardy,M.F., Kishore,N., Knapp,J.J., Kovacs,I.A.,
            Lemmens,I., Mee,M.W., Mellor,J.C., Pollis,C., Pons,C.,
            Richardson,A.D., Schlabach,S., Teeking,B., Yadav,A., Babor,M.,
            Balcha,D., Basha,O., Bowman-Colin,C., Chin,S.F., Choi,S.G.,
            Colabella,C., Coppin,G., D'Amata,C., De Ridder,D., De Rouck,S.,
            Duran-Frigola,M., Ennajdaoui,H., Goebels,F., Goehring,L., Gopal,A.,
            Haddad,G., Hatchi,E., Helmy,M., Jacob,Y., Kassa,Y., Landini,S.,
            Li,R., van Lieshout,N., MacWilliams,A., Markey,D., Paulson,J.N.,
            Rangarajan,S., Rasla,J., Rayhan,A., Rolland,T., San-Miguel,A.,
            Shen,Y., Sheykhkarimli,D., Sheynkman,G.M., Simonovsky,E., Tasan,M.,
            Tejeda,A., Tropepe,V., Twizere,J.C., Wang,Y., Weatheritt,R.J.,
            Weile,J., Xia,Y., Yang,X., Yeger-Lotem,E., Zhong,Q., Aloy,P.,
            Bader,G.D., De Las Rivas,J., Gaudet,S., Hao,T., Rak,J.,
            Tavernier,J., Hill,D.E., Vidal,M., Roth,F.P. and Calderwood,M.A.
  TITLE     A reference map of the human binary protein interactome
  JOURNAL   Nature 580 (7803), 402-408 (2020)
   PUBMED   32296183
REFERENCE   6  (bases 1 to 2500)
  AUTHORS   Geoffroy,V., Fouque,F., Benelli,C., Poggi,F., Saudubray,J.M.,
            Lissens,W., Meirleir,L.D., Marsac,C., Lindsay,J.G. and
            Sanderson,S.J.
  TITLE     Defect in the X-lipoyl-containing component of the pyruvate
            dehydrogenase complex in a patient with neonatal lactic acidemia
  JOURNAL   Pediatrics 97 (2), 267-272 (1996)
   PUBMED   8584393
REFERENCE   7  (bases 1 to 2500)
  AUTHORS   Liu,S., Baker,J.C., Andrews,P.C. and Roche,T.E.
  TITLE     Recombinant expression and evaluation of the lipoyl domains of the
            dihydrolipoyl acetyltransferase component of the human pyruvate
            dehydrogenase complex
  JOURNAL   Arch Biochem Biophys 316 (2), 926-940 (1995)
   PUBMED   7864652
REFERENCE   8  (bases 1 to 2500)
  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   9  (bases 1 to 2500)
  AUTHORS   Robinson,B.H., MacKay,N., Petrova-Benedict,R., Ozalp,I., Coskun,T.
            and Stacpoole,P.W.
  TITLE     Defects in the E2 lipoyl transacetylase and the X-lipoyl containing
            component of the pyruvate dehydrogenase complex in patients with
            lactic acidemia
  JOURNAL   J Clin Invest 85 (6), 1821-1824 (1990)
   PUBMED   2112155
REFERENCE   10 (bases 1 to 2500)
  AUTHORS   Cori,C.F.
  TITLE     The glucose-lactic acid cycle and gluconeogenesis
  JOURNAL   Curr Top Cell Regul 18, 377-387 (1981)
   PUBMED   7273846
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC107928.3, BC010389.1,
            AF001437.1 and AA282215.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 17, 2019 this sequence version replaced NM_003477.2.
            
            Summary: The pyruvate dehydrogenase (PDH) complex is located in the
            mitochondrial matrix and catalyzes the conversion of pyruvate to
            acetyl coenzyme A. The PDH complex thereby links glycolysis to
            Krebs cycle. The PDH complex contains three catalytic subunits, E1,
            E2, and E3, two regulatory subunits, E1 kinase and E1 phosphatase,
            and a non-catalytic subunit, E3 binding protein (E3BP). This gene
            encodes the E3 binding protein subunit; also known as component X
            of the pyruvate dehydrogenase complex. This protein tethers E3
            dimers to the E2 core of the PDH complex. Defects in this gene are
            a cause of pyruvate dehydrogenase deficiency which results in
            neurological dysfunction and lactic acidosis in infancy and early
            childhood. This protein is also a minor antigen for
            antimitochondrial antibodies. These autoantibodies are present in
            nearly 95% of patients with the autoimmune liver disease primary
            biliary cirrhosis (PBC). In PBC, activated T lymphocytes attack and
            destroy epithelial cells in the bile duct where this protein is
            abnormally distributed and overexpressed. PBC eventually leads to
            cirrhosis and liver failure. Alternative splicing results in
            multiple transcript variants encoding distinct isoforms.[provided
            by RefSeq, Oct 2009].
            
            Transcript Variant: This variant (1) encodes the longest isoform
            (1).
            
            Sequence Note: Sequence Note: The RefSeq transcript and protein
            were derived from transcript and genomic sequence to make the
            sequence consistent with the reference genome assembly. The genomic
            coordinates used for the transcript record were based on
            alignments.
            
            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 :: U82328.1, SRR1660803.16316.1
                                           [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                 :: ENST00000227868.9/
                                                  ENSP00000227868.4
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-101               AC107928.3         148363-148463
            102-836             BC010389.1         94-828
            837-2344            AF001437.1         807-2314
            2345-2500           AA282215.1         5-160               c
FEATURES             Location/Qualifiers
     source          1..2500
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="11"
                     /map="11p13"
     gene            1..2500
                     /gene="PDHX"
                     /gene_synonym="DLDBP; E3BP; OPDX; PDHXD; PDX1; proX"
                     /note="pyruvate dehydrogenase complex component X"
                     /db_xref="GeneID:8050"
                     /db_xref="HGNC:HGNC:21350"
                     /db_xref="MIM:608769"
     exon            1..198
                     /gene="PDHX"
                     /gene_synonym="DLDBP; E3BP; OPDX; PDHXD; PDX1; proX"
                     /inference="alignment:Splign:2.1.0"
     CDS             39..1544
                     /gene="PDHX"
                     /gene_synonym="DLDBP; E3BP; OPDX; PDHXD; PDX1; proX"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; pyruvate dehydrogenase protein X component,
                     mitochondrial; dihydrolipoamide dehydrogenase-binding
                     protein of pyruvate dehydrogenase complex; pyruvate
                     dehydrogenase complex, E3-binding protein subunit;
                     pyruvate dehydrogenase complex, lipoyl-containing
                     component X; lipoyl-containing pyruvate dehydrogenase
                     complex component X"
                     /codon_start=1
                     /product="pyruvate dehydrogenase protein X component,
                     mitochondrial isoform 1 precursor"
                     /protein_id="NP_003468.2"
                     /db_xref="CCDS:CCDS7896.1"
                     /db_xref="GeneID:8050"
                     /db_xref="HGNC:HGNC:21350"
                     /db_xref="MIM:608769"
                     /translation="MAASWRLGCDPRLLRYLVGFPGRRSVGLVKGALGWSVSRGANWR
                     WFHSTQWLRGDPIKILMPSLSPTMEEGNIVKWLKKEGEAVSAGDALCEIETDKAVVTL
                     DASDDGILAKIVVEEGSKNIRLGSLIGLIVEEGEDWKHVEIPKDVGPPPPVSKPSEPR
                     PSPEPQISIPVKKEHIPGTLRFRLSPAARNILEKHSLDASQGTATGPRGIFTKEDALK
                     LVQLKQTGKITESRPTPAPTATPTAPSPLQATAGPSYPRPVIPPVSTPGQPNAVGTFT
                     EIPASNIRRVIAKRLTESKSTVPHAYATADCDLGAVLKVRQDLVKDDIKVSVNDFIIK
                     AAAVTLKQMPDVNVSWDGEGPKQLPFIDISVAVATDKGLLTPIIKDAAAKGIQEIADS
                     VKALSKKARDGKLLPEEYQGGSFSISNLGMFGIDEFTAVINPPQACILAVGRFRPVLK
                     LTEDEEGNAKLQQRQLITVTMSSDSRVVDDELATRFLKSFKANLENPIRLA"
     exon            199..279
                     /gene="PDHX"
                     /gene_synonym="DLDBP; E3BP; OPDX; PDHXD; PDX1; proX"
                     /inference="alignment:Splign:2.1.0"
     exon            280..380
                     /gene="PDHX"
                     /gene_synonym="DLDBP; E3BP; OPDX; PDHXD; PDX1; proX"
                     /inference="alignment:Splign:2.1.0"
     exon            381..580
                     /gene="PDHX"
                     /gene_synonym="DLDBP; E3BP; OPDX; PDHXD; PDX1; proX"
                     /inference="alignment:Splign:2.1.0"
     exon            581..679
                     /gene="PDHX"
                     /gene_synonym="DLDBP; E3BP; OPDX; PDHXD; PDX1; proX"
                     /inference="alignment:Splign:2.1.0"
     exon            680..854
                     /gene="PDHX"
                     /gene_synonym="DLDBP; E3BP; OPDX; PDHXD; PDX1; proX"
                     /inference="alignment:Splign:2.1.0"
     exon            855..1002
                     /gene="PDHX"
                     /gene_synonym="DLDBP; E3BP; OPDX; PDHXD; PDX1; proX"
                     /inference="alignment:Splign:2.1.0"
     exon            1003..1061
                     /gene="PDHX"
                     /gene_synonym="DLDBP; E3BP; OPDX; PDHXD; PDX1; proX"
                     /inference="alignment:Splign:2.1.0"
     exon            1062..1220
                     /gene="PDHX"
                     /gene_synonym="DLDBP; E3BP; OPDX; PDHXD; PDX1; proX"
                     /inference="alignment:Splign:2.1.0"
     exon            1221..1285
                     /gene="PDHX"
                     /gene_synonym="DLDBP; E3BP; OPDX; PDHXD; PDX1; proX"
                     /inference="alignment:Splign:2.1.0"
     exon            1286..2500
                     /gene="PDHX"
                     /gene_synonym="DLDBP; E3BP; OPDX; PDHXD; PDX1; proX"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2319..2324
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PDHX"
                     /gene_synonym="DLDBP; E3BP; OPDX; PDHXD; PDX1; proX"
                     /note="hexamer: AATAAA"
     polyA_site      2344
                     /gene="PDHX"
                     /gene_synonym="DLDBP; E3BP; OPDX; PDHXD; PDX1; proX"
                     /note="major polyA site"
     regulatory      2477..2482
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PDHX"
                     /gene_synonym="DLDBP; E3BP; OPDX; PDHXD; PDX1; proX"
                     /note="hexamer: AATAAA"
     polyA_site      2500
                     /gene="PDHX"
                     /gene_synonym="DLDBP; E3BP; OPDX; PDHXD; PDX1; proX"
ORIGIN      
        1 aggctgtgct gcgggcagcc agtgagaagg ccgtcaagat ggcggcctcc tggaggctgg
       61 gctgtgatcc gcggctgctg cgttatcttg tgggcttccc cggccgccga agcgtagggc
      121 tggtgaaggg ggctcttggg tggtctgtaa gccgcggagc taattggaga tggtttcaca
      181 gcacgcagtg gcttcggggt gatcccatta agatactaat gccatcactg tctcctacaa
      241 tggaagaagg aaacattgtg aaatggctga aaaaggaagg tgaagcggtg agtgctggag
      301 atgcattatg tgaaattgag actgacaaag ctgtggttac cttagatgca agtgatgatg
      361 gaatcttggc caaaatcgtg gttgaagaag gaagtaaaaa tatacggcta ggttcactaa
      421 ttggtttgat agtagaagaa ggagaagatt ggaaacatgt tgaaattccc aaagacgtag
      481 gtcctccacc accagtttca aaaccttcag agcctcgccc ctcaccagaa ccacagattt
      541 ccatccctgt caagaaggaa cacatacccg ggacactacg gttccgttta agtccagctg
      601 cccgcaatat tctggaaaaa cactcactgg atgctagcca gggcacagcc actggccctc
      661 gggggatatt cactaaagag gatgctctca aacttgtcca gttgaaacaa acgggcaaga
      721 ttaccgagtc cagaccaact ccagccccca cagccactcc cacagcacct tcgcccctac
      781 aggccacagc tggaccatct tatccccggc ctgtgatccc accagtatca actcctggac
      841 aacccaatgc agtgggcaca ttcactgaaa tccccgccag caatattcga agagttattg
      901 ccaagagatt aactgaatct aaaagtactg tacctcatgc atatgctact gctgactgtg
      961 accttggagc tgttttaaaa gttaggcaag atctggtcaa agatgacatt aaagtatcag
     1021 taaatgattt tatcatcaag gcagcagctg ttacccttaa acaaatgcca gatgttaatg
     1081 taagctggga tggagagggc ccaaagcaac tgccatttat tgacatttca gtggctgtgg
     1141 caacagataa aggcttactt actccaatca taaaagatgc tgctgctaaa ggtatccagg
     1201 aaattgctga ctctgtaaag gctctatcaa agaaagcaag agatggaaaa ttgttgcctg
     1261 aagaatacca aggaggatct tttagtattt ccaacttggg gatgtttggc atcgacgaat
     1321 ttactgcagt gattaaccct cctcaggcct gcattttggc ggttgggagg ttccgacctg
     1381 tgctgaagct cactgaggat gaagagggaa atgccaaact gcagcagcgc cagctcataa
     1441 cagtcacaat gtcaagtgac agtcgagtgg ttgatgacga actggcaacc aggtttctta
     1501 aaagttttaa agcaaaccta gagaatccta tccgacttgc ctagtcctca aagataagaa
     1561 gttggtgttc agcttagttg attcagtagt tgttaccaag aaacatatgt tataggaaaa
     1621 caacttggta tttaagtatg aagtggatga aatgtttatt tatttaaggt gaaagcattt
     1681 gacccagggt gtcttcatct tcaatttggg tttaatgtta tagaaataaa tgatgataaa
     1741 ctctaactaa taaaggaaag agaatatttg gttactcaga tccattttta acctctggtg
     1801 ctgtataaag ggaatattaa actagatgta aatcaaagta tatgtttggc tcatttgagc
     1861 attttggaat atttgagaat gtatgataca tgtaaaatta aaaaaactat tagaactgta
     1921 ccataattat gttgaaggta gaagtgatct tcaaagagat ggccattaac ttagcagtgg
     1981 gacctcactt ttacaagcac tgctctagat atacttgaag aatttaatag gtacagaagt
     2041 ttattctgga taataaataa ataaggatca cactgtatta ggggttatgg caacattatt
     2101 gaatttttta tgtacataaa gccatatgtt tagggtggtt tctatctgtc ttgtttttca
     2161 cttatataac actgtgaact tctaaagcaa gaggataaaa gaagcatgaa tgaaaagaat
     2221 gacatttcaa aaaaatggtt caatgaaaaa ctatagctaa aatatgtaaa cctttctagg
     2281 taaaccgctt gccttcatct tgagtcggaa tatatttaaa taaattgtgt tatctcttgc
     2341 caaacatttt gttagtgttt atttaaaaac aaaatgttgt ttcttaatgc atttaaatca
     2401 gttttgtatt gtgcagtaaa atgtgagaaa atataaacat ttctattgta ttttaaatgt
     2461 taaaacacaa aagttcaata aaccttgaag ttgattagta
//
