LOCUS       NM_018444               4210 bp    mRNA    linear   PRI 08-OCT-2024
DEFINITION  Homo sapiens pyruvate dehydrogenase phosphatase catalytic subunit 1
            (PDP1), transcript variant 5, mRNA.
ACCESSION   NM_018444
VERSION     NM_018444.4
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 4210)
  AUTHORS   Yuan,M., Zhang,C., Chen,S., Ye,S., Liu,H., Ke,H., Huang,J.,
            Liang,G., Yu,R., Hu,T., Wu,X. and Lan,P.
  TITLE     PDP1 promotes KRAS mutant colorectal cancer progression by serving
            as a scaffold for BRAF and MEK1
  JOURNAL   Cancer Lett 597, 217007 (2024)
   PUBMED   38849010
  REMARK    GeneRIF: PDP1 promotes KRAS mutant colorectal cancer progression by
            serving as a scaffold for BRAF and MEK1.
REFERENCE   2  (bases 1 to 4210)
  AUTHORS   Wang,Y., Dang,H., Qiao,H., Tian,Y. and Guan,Q.
  TITLE     PDP1 promotes the progression of breast cancer through STAT3
            pathway
  JOURNAL   Cell Biochem Funct 42 (3), e3994 (2024)
   PUBMED   38566355
  REMARK    GeneRIF: PDP1 promotes the progression of breast cancer through
            STAT3 pathway.
REFERENCE   3  (bases 1 to 4210)
  AUTHORS   Alshamleh,I., Kurrle,N., Makowka,P., Bhayadia,R., Kumar,R.,
            Susser,S., Seibert,M., Ludig,D., Wolf,S., Koschade,S.E.,
            Stoschek,K., Kreitz,J., Fuhrmann,D.C., Toenges,R., Notaro,M.,
            Comoglio,F., Schuringa,J.J., Berg,T., Brune,B., Krause,D.S.,
            Klusmann,J.H., Oellerich,T., Schnutgen,F., Schwalbe,H. and Serve,H.
  TITLE     PDP1 is a key metabolic gatekeeper and modulator of drug resistance
            in FLT3-ITD-positive acute myeloid leukemia
  JOURNAL   Leukemia 37 (12), 2367-2382 (2023)
   PUBMED   37935978
  REMARK    GeneRIF: PDP1 is a key metabolic gatekeeper and modulator of drug
            resistance in FLT3-ITD-positive acute myeloid leukemia.
REFERENCE   4  (bases 1 to 4210)
  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   5  (bases 1 to 4210)
  AUTHORS   Shi,Y., Wang,Y., Jiang,H., Sun,X., Xu,H., Wei,X., Wei,Y., Xiao,G.,
            Song,Z. and Zhou,F.
  TITLE     Mitochondrial dysfunction induces radioresistance in colorectal
            cancer by activating [Ca2+]m-PDP1-PDH-histone acetylation
            retrograde signaling
  JOURNAL   Cell Death Dis 12 (9), 837 (2021)
   PUBMED   34489398
  REMARK    GeneRIF: Mitochondrial dysfunction induces radioresistance in
            colorectal cancer by activating [Ca(2+)]m-PDP1-PDH-histone
            acetylation retrograde signaling.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 4210)
  AUTHORS   Korotchkina,L.G. and Patel,M.S.
  TITLE     Mutagenesis studies of the phosphorylation sites of recombinant
            human pyruvate dehydrogenase. Site-specific regulation
  JOURNAL   J Biol Chem 270 (24), 14297-14304 (1995)
   PUBMED   7782287
REFERENCE   7  (bases 1 to 4210)
  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   8  (bases 1 to 4210)
  AUTHORS   Ito,M., Kobashi,H., Naito,E., Saijo,T., Takeda,E., Huq,A.H. and
            Kuroda,Y.
  TITLE     Decrease of pyruvate dehydrogenase phosphatase activity in patients
            with congenital lactic acidemia
  JOURNAL   Clin Chim Acta 209 (1-2), 1-7 (1992)
   PUBMED   1327585
  REMARK    GeneRIF: In cultured skin fibroblasts from three patients with
            congenital lactic acidemia due to a defect in activation of the
            pyruvate dehydrogenase complex, the PDP-activity was significantly
            reduced to 50.7%, 64.6% and 63.1% of that of control fibroblasts.
REFERENCE   9  (bases 1 to 4210)
  AUTHORS   Teague,W.M., Pettit,F.H., Wu,T.L., Silberman,S.R. and Reed,L.J.
  TITLE     Purification and properties of pyruvate dehydrogenase phosphatase
            from bovine heart and kidney
  JOURNAL   Biochemistry 21 (22), 5585-5592 (1982)
   PUBMED   6293549
REFERENCE   10 (bases 1 to 4210)
  AUTHORS   Robinson,B.H. and Sherwood,W.G.
  TITLE     Pyruvate dehydrogenase phosphatase deficiency: a cause of
            congenital chronic lactic acidosis in infancy
  JOURNAL   Pediatr Res 9 (12), 935-939 (1975)
   PUBMED   172850
  REMARK    GeneRIF: In postmortem tissue samples, from male child with
            metabolic acidosis, PDK normally reduced PDH-activity in
            ATP-presence. Addition of Ca++ and Mg++ did not restored
            PDH-activity. The defect was attributed to a markedly reduced
            PDP-activity.
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DB084539.1, BC047619.1,
            AK126862.1 and BX099681.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_018444.3.
            
            Summary: Pyruvate dehydrogenase (E1) is one of the three components
            (E1, E2, and E3) of the large pyruvate dehydrogenase complex.
            Pyruvate dehydrogenase kinases catalyze phosphorylation of serine
            residues of E1 to inactivate the E1 component and inhibit the
            complex. Pyruvate dehydrogenase phosphatases catalyze the
            dephosphorylation and activation of the E1 component to reverse the
            effects of pyruvate dehydrogenase kinases. Pyruvate dehydrogenase
            phosphatase is a heterodimer consisting of catalytic and regulatory
            subunits. Two catalytic subunits have been reported; one is
            predominantly expressed in skeletal muscle and another one is is
            much more abundant in the liver. The catalytic subunit, encoded by
            this gene, is the former, and belongs to the protein phosphatase 2C
            (PP2C) superfamily. Along with the pyruvate dehydrogenase complex
            and pyruvate dehydrogenase kinases, this enzyme is located in the
            mitochondrial matrix. Mutation in this gene causes pyruvate
            dehydrogenase phosphatase deficiency. Multiple alternatively
            spliced transcript variants encoding different isoforms have been
            identified.[provided by RefSeq, Jun 2009].
            
            Transcript Variant: This variant (5) lacks an internal segment,
            compared to variant 2. The difference causes translation initiation
            at a downstream AUG and results in an isoform (3) with a shorter
            N-terminus, compared to isoform 2.
            
            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 :: SRR11853566.26746.1, AK057079.1
                                           [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                 :: ENST00000297598.5/
                                                  ENSP00000297598.4
            RefSeq Select criteria             :: based on conservation,
                                                  expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-496               DB084539.1         69-564
            497-2352            BC047619.1         486-2341
            2353-4208           AK126862.1         2798-4653
            4209-4210           BX099681.1         512-513
FEATURES             Location/Qualifiers
     source          1..4210
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="8"
                     /map="8q22.1"
     gene            1..4210
                     /gene="PDP1"
                     /gene_synonym="PDH; PDP; PDPC; PDPC 1; PPM2A; PPM2C"
                     /note="pyruvate dehydrogenase phosphatase catalytic
                     subunit 1"
                     /db_xref="GeneID:54704"
                     /db_xref="HGNC:HGNC:9279"
                     /db_xref="MIM:605993"
     exon            1..157
                     /gene="PDP1"
                     /gene_synonym="PDH; PDP; PDPC; PDPC 1; PPM2A; PPM2C"
                     /inference="alignment:Splign:2.1.0"
     exon            158..4210
                     /gene="PDP1"
                     /gene_synonym="PDH; PDP; PDPC; PDPC 1; PPM2A; PPM2C"
                     /inference="alignment:Splign:2.1.0"
     CDS             202..1815
                     /gene="PDP1"
                     /gene_synonym="PDH; PDP; PDPC; PDPC 1; PPM2A; PPM2C"
                     /EC_number="3.1.3.43"
                     /note="isoform 3 is encoded by transcript variant 5;
                     pyruvate dehydrogenase (Lipoamide)
                     phosphatase-phosphatase; [Pyruvate dehydrogenase
                     [acetyl-transferring]]-phosphatase 1, mitochondrial;
                     protein phosphatase 2C, magnesium-dependent, catalytic
                     subunit; pyruvate dehyrogenase phosphatase catalytic
                     subunit 1; protein phosphatase, Mg2+/Mn2+ dependent 2A"
                     /codon_start=1
                     /product="pyruvate dehyrogenase phosphatase catalytic
                     subunit 1 isoform 3"
                     /protein_id="NP_060914.2"
                     /db_xref="CCDS:CCDS6259.1"
                     /db_xref="GeneID:54704"
                     /db_xref="HGNC:HGNC:9279"
                     /db_xref="MIM:605993"
                     /translation="MPAPTQLFFPLIRNCELSRIYGTACYCHHKHLCCSSSYIPQSRL
                     RYTPHPAYATFCRPKENWWQYTQGRRYASTPQKFYLTPPQVNSILKANEYSFKVPEFD
                     GKNVSSILGFDSNQLPANAPIEDRRSAATCLQTRGMLLGVFDGHAGCACSQAVSERLF
                     YYIAVSLLPHETLLEIENAVESGRALLPILQWHKHPNDYFSKEASKLYFNSLRTYWQE
                     LIDLNTGESTDIDVKEALINAFKRLDNDISLEAQVGDPNSFLNYLVLRVAFSGATACV
                     AHVDGVDLHVANTGDSRAMLGVQEEDGSWSAVTLSNDHNAQNERELERLKLEHPKSEA
                     KSVVKQDRLLGLLMPFRAFGDVKFKWSIDLQKRVIESGPDQLNDNEYTKFIPPNYHTP
                     PYLTAEPEVTYHRLRPQDKFLVLATDGLWETMHRQDVVRIVGEYLTGMHHQQPIAVGG
                     YKVTLGQMHGLLTERRTKMSSVFEDQNAATHLIRHAVGNNEFGTVDHERLSKMLSLPE
                     ELARMYRDDITIIVVQFNSHVVGAYQNQE"
     regulatory      4184..4189
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PDP1"
                     /gene_synonym="PDH; PDP; PDPC; PDPC 1; PPM2A; PPM2C"
                     /note="hexamer: ATTAAA"
     polyA_site      4210
                     /gene="PDP1"
                     /gene_synonym="PDH; PDP; PDPC; PDPC 1; PPM2A; PPM2C"
                     /note="major polyA site"
ORIGIN      
        1 ggcggccccg cacggtaggg gagcagagtg ggcaggccgg gggtgagggc tcgcgctccg
       61 ggagctgcac ggggctgcgt ggaaagagcg ccgagcggtg gcgtcgttgt cgccccctcc
      121 tcgtcgggaa gaatcgtttg gtctcctgcc gtgcccggaa tcccagtcag aagttccagc
      181 ctgccactgt tctctgatgc catgccagca ccaactcaac tgttttttcc tctcatccgt
      241 aactgtgaac tgagcaggat ctatggcact gcatgttact gccaccacaa acatctctgt
      301 tgttcctcat cgtacattcc tcagagtcga ctgagataca cacctcatcc agcatatgct
      361 accttttgca ggccaaagga gaactggtgg cagtacaccc aaggaaggag atatgcttcc
      421 acaccacaga aattttacct cacacctcca caagtcaata gcatccttaa agctaatgaa
      481 tacagtttca aagtgccaga atttgacggc aaaaatgtca gttctatcct tggatttgac
      541 agcaatcagc tgcctgcaaa tgcacccatt gaggaccgga gaagtgcagc aacctgcttg
      601 cagaccagag ggatgctttt gggggttttt gatggccatg caggttgtgc ttgttcccag
      661 gcagtcagtg aaagactctt ttattatatt gctgtctctt tgttacccca tgagactttg
      721 ctagagattg aaaatgcagt ggagagcggc cgggcactgc tacccattct ccagtggcac
      781 aagcacccca atgattactt tagtaaggag gcatccaaat tgtactttaa cagcttgagg
      841 acttactggc aagagcttat agacctcaac actggtgagt cgactgatat tgatgttaag
      901 gaggctctaa ttaatgcctt caagaggctt gataatgaca tctccttgga ggcgcaagtt
      961 ggtgatccta attcttttct caactacctg gtgcttcgag tggcattttc tggagccact
     1021 gcttgtgtgg cccatgtgga tggtgttgac cttcatgtgg ccaatactgg cgatagcaga
     1081 gccatgctgg gtgtgcagga agaggacggc tcatggtcag cagtcacgct gtctaatgac
     1141 cacaatgctc aaaatgaaag agaactagaa cggctgaaat tggaacatcc aaagagtgag
     1201 gccaagagtg tcgtgaaaca ggatcggctg cttggcttgc tgatgccatt tagggcattt
     1261 ggagatgtaa agttcaaatg gagcattgac cttcaaaaga gagtgataga atctggccca
     1321 gaccagttga atgacaatga atataccaag tttattcctc ctaattatca cacacctcct
     1381 tatctcactg ctgagccaga ggtaacttac caccgattaa ggccacagga taagtttctg
     1441 gtgttggcta ctgatgggtt gtgggagact atgcataggc aggatgtggt taggattgtg
     1501 ggtgagtacc taactggcat gcatcaccaa cagccaatag ctgttggtgg ctacaaggtg
     1561 actctgggac agatgcatgg ccttttaaca gaaaggagaa ccaaaatgtc ctcggtattt
     1621 gaggatcaga acgcagcaac ccatctcatt cgccacgctg tgggcaacaa cgagtttggg
     1681 actgttgatc atgagcgcct ctctaaaatg cttagtcttc ctgaagagct tgctcgaatg
     1741 tacagagatg acattacaat cattgtagtt cagttcaatt ctcatgttgt aggggcgtat
     1801 caaaaccaag aatagtgagt ggctctttca ctggcaattc tcaaatgata tacatttaaa
     1861 gggcagattt tttaaaaaga tactactata ataaacattt ccagttggtc attctaagca
     1921 tttacccttt tgatactcta gctagtcagg tactccaaat tgactttgca gcagggtggc
     1981 agggtcagga gagtctggtc ctgcctagct cagatttcat ggcacctgca cttgaagcaa
     2041 gtcacttctt tatcacaggt gtcttgaaac attagcttct tttaccaacc tgagaaaatt
     2101 aggatgacct ggcaaataag atcttgaata ggccaaaagc aagtatcttg ctgtgtgtag
     2161 tctcttggtt aaagtgaaga aacagtactg ttcacacctt tcttcactga gattccagtg
     2221 tacatgagaa catatattta ttgcatgatt ttctagatac acagtctatg cattattcat
     2281 atacatttat tttagcctaa agtggttttc aaatccagtt cttcaagcca taaatgacca
     2341 agatccaagc aatctgaatt tgtttttgtg attatttgac tggaatgctt cttaagtgga
     2401 ataactatac tccgttatcc acccgatttc ctaatgtaat tgaaagattt tctattttgc
     2461 cacacacttg gagacaataa gggtttttag ttttatctac tcttctattg aagttaaaga
     2521 aagaaaaaaa gattttttta tttgtattaa tgaaaagctt tagtttaaaa taaggagatc
     2581 cagaataaaa agaagagact gatctcttca attattgtca tctgtagcca ccagcacatc
     2641 actcttatgt aatccccaaa ggcttggcat gccgtaagtg tgtggtgggt agactgctgc
     2701 cggggaatcg tacttcttat ttagtaatga taagactttt cattattttt ggaattttaa
     2761 agatgacata aataagttta aatatcaatt tggggagtaa ggtttaatat tgccatcggg
     2821 tattgagaca ggaggaagtt tctgtttttc tccatttaga cataggtcaa ttaaaatatt
     2881 tgggtttaaa atgactaaat gctttaaaca tattgtagct taagatatat gtgttaagat
     2941 atatacatga gaaactttaa aaggtaacta ctgtgcatgc ctgatgctta atagaatact
     3001 tagtggcatc aaatgtttgc agcagtctcc ataattatat tcagtccctt ctaatactgt
     3061 atcaatgtaa atgaaataaa tatattcaaa ttggcttttt gatatgcatc aagtggcatt
     3121 ttgttcctgt gtttaatagt gatctgtata cagctgtgca catattgtca tcacttattc
     3181 tagcatcact gttaaggctg tgattatgtt tgatattcac ctggatttta atacaagcca
     3241 atatcagctt cccattgtgt aataacttgg gtgtttagga gtcttttcac attttttggg
     3301 gatatgaact agatgttcaa gaactccttc tggactgtgg atactgaatc agtgtactat
     3361 tggctgcaga atttgtttca attgaaaata gactcaggaa gattgctgct cagaatatca
     3421 tataatgttt attttttgag gtgtttttgt ttttatttgt gtgttttttt ttttttaagt
     3481 cagcttggaa cttttttcct gggtagtatt tgggagaggg aaaggctgta ctatatattt
     3541 atttctaaat gttttgactg ggcatttttc ttttaatgaa atatgtggac tgctctagca
     3601 aaccctattt tcagctacta tttgaatatt cttgaacacc accactgaag agtttcatat
     3661 acaccaaata atgtctcatc tctatagtac agggaatata aaattggttt cctgtggtca
     3721 tgatcaagat agtagtatta ttacacaaga aacttggtct gcagtctgga agcttgtctg
     3781 ctctatagaa atgaaaatgc agcatgaagt tgacattgtg gaaatgaaag taattgggta
     3841 ttagaaatct gaaagtactg tcatctaaaa gcaattgtga ttttattgta attggttgtc
     3901 actgttgtac ggtgtctaga attaaagaat acatgtaaac tttcatggta tttagccttt
     3961 cttaaatttt tttaaaattt aaactttcta acctatgtat tcaacttctg tatttatatt
     4021 taatcagtgg ttcatgttat ataatacacc cttaactagt taaatggaat gttggtatgg
     4081 tacagagtac catattgcta agaaaactgt cttataaaag atgtatatgt gtgaagacat
     4141 gaaagtttaa tgtacagaat ggttggagaa atgcctatgg tgaattaaag cttcatatct
     4201 gctttctgaa
//
