LOCUS       NM_176869               1665 bp    mRNA    linear   PRI 09-FEB-2025
DEFINITION  Homo sapiens inorganic pyrophosphatase 2 (PPA2), transcript variant
            1, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_176869 NM_176865
VERSION     NM_176869.3
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 1665)
  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   2  (bases 1 to 1665)
  AUTHORS   Guimier,A., Achleitner,M.T., Moreau de Bellaing,A., Edwards,M., de
            Pontual,L., Mittal,K., Dunn,K.E., Grove,M.E., Tysoe,C.J.,
            Dimartino,C., Cameron,J., Kanthi,A., Shukla,A., van den Broek,F.,
            Chatterjee,D., Alston,C.L., Knowles,C.V., Brett,L., Till,J.A.,
            Homfray,T., French,P., Spentzou,G., Elserafy,N.A., Lichkus,K.S.,
            Sankaran,B.P., Kennedy,H.L., George,P.M., Kidd,A., Wortmann,S.B.,
            Fisk,D.G., Koopmann,T.T., Rafiq,M.A., Merker,J.D., Parikh,S.,
            Ahimaz,P., Weintraub,R.G., Ma,A.S., Turner,C., Ellaway,C.J.,
            Phillips,L.K., Thorburn,D.R., Chung,W.K., Kana,S.L.,
            Faye-Petersen,O.M., Thompson,M.L., Janin,A., McLeod,K., McGowan,R.,
            McFarland,R., Girisha,K.M., Morris-Rosendahl,D.J., Hurst,A.C.E.,
            Turner,C.L.S., Hamilton,R.M., Taylor,R.W., Bajolle,F., Gordon,C.T.,
            Amiel,J., Mayr,J.A. and Doudney,K.
  TITLE     PPA2-associated sudden cardiac death: extending the clinical and
            allelic spectrum in 20 new families
  JOURNAL   Genet Med 23 (12), 2415-2425 (2021)
   PUBMED   34400813
  REMARK    GeneRIF: PPA2-associated sudden cardiac death: extending the
            clinical and allelic spectrum in 20 new families.
            Erratum:[Genet Med. 2022 Apr;24(4):967. doi:
            10.1016/j.gim.2022.02.002.. PMID: 35394429]
REFERENCE   3  (bases 1 to 1665)
  AUTHORS   Hu,F., Huang,Z., Zheng,S., Wu,Q., Chen,Y., Lin,H., Huang,W. and
            Li,L.
  TITLE     Structural and biochemical characterization of inorganic
            pyrophosphatase from Homo sapiens
  JOURNAL   Biochem Biophys Res Commun 533 (4), 1115-1121 (2020)
   PUBMED   33036755
  REMARK    GeneRIF: Structural and biochemical characterization of inorganic
            pyrophosphatase from Homo sapiens.
REFERENCE   4  (bases 1 to 1665)
  AUTHORS   Haenig,C., Atias,N., Taylor,A.K., Mazza,A., Schaefer,M.H., Russ,J.,
            Riechers,S.P., Jain,S., Coughlin,M., Fontaine,J.F., Freibaum,B.D.,
            Brusendorf,L., Zenkner,M., Porras,P., Stroedicke,M., Schnoegl,S.,
            Arnsburg,K., Boeddrich,A., Pigazzini,L., Heutink,P., Taylor,J.P.,
            Kirstein,J., Andrade-Navarro,M.A., Sharan,R. and Wanker,E.E.
  TITLE     Interactome Mapping Provides a Network of Neurodegenerative Disease
            Proteins and Uncovers Widespread Protein Aggregation in Affected
            Brains
  JOURNAL   Cell Rep 32 (7), 108050 (2020)
   PUBMED   32814053
REFERENCE   5  (bases 1 to 1665)
  AUTHORS   Phoon,C.K.L., Halvorsen,M., Goldstein,D.B., Rabin,R., Cecchin,F.,
            Crandall,L. and Devinsky,O.
  TITLE     Sudden unexpected death in asymptomatic infants due to PPA2
            variants
  JOURNAL   Mol Genet Genomic Med 8 (1), e1008 (2020)
   PUBMED   31705601
  REMARK    GeneRIF: Sudden unexpected death in asymptomatic infants due to
            PPA2 variants.
REFERENCE   6  (bases 1 to 1665)
  AUTHORS   Curbo,S., Lagier-Tourenne,C., Carrozzo,R., Palenzuela,L.,
            Lucioli,S., Hirano,M., Santorelli,F., Arenas,J., Karlsson,A. and
            Johansson,M.
  TITLE     Human mitochondrial pyrophosphatase: cDNA cloning and analysis of
            the gene in patients with mtDNA depletion syndromes
  JOURNAL   Genomics 87 (3), 410-416 (2006)
   PUBMED   16300924
  REMARK    GeneRIF: No pathogenic mutations were identified in the PPA2 gene
            in patients with mitochondrial DNA depletion syndromes (MDS).
REFERENCE   7  (bases 1 to 1665)
  AUTHORS   Oh,J.H., Yang,J.O., Hahn,Y., Kim,M.R., Byun,S.S., Jeon,Y.J.,
            Kim,J.M., Song,K.S., Noh,S.M., Kim,S., Yoo,H.S., Kim,Y.S. and
            Kim,N.S.
  TITLE     Transcriptome analysis of human gastric cancer
  JOURNAL   Mamm Genome 16 (12), 942-954 (2005)
   PUBMED   16341674
REFERENCE   8  (bases 1 to 1665)
  AUTHORS   Afjehi-Sadat,L., Krapfenbauer,K., Slavc,I., Fountoulakis,M. and
            Lubec,G.
  TITLE     Hypothetical proteins with putative enzyme activity in human
            amnion, lymphocyte, bronchial epithelial and kidney cell lines
  JOURNAL   Biochim Biophys Acta 1700 (1), 65-74 (2004)
   PUBMED   15210126
REFERENCE   9  (bases 1 to 1665)
  AUTHORS   Gevaert,K., Goethals,M., Martens,L., Van Damme,J., Staes,A.,
            Thomas,G.R. and Vandekerckhove,J.
  TITLE     Exploring proteomes and analyzing protein processing by mass
            spectrometric identification of sorted N-terminal peptides
  JOURNAL   Nat Biotechnol 21 (5), 566-569 (2003)
   PUBMED   12665801
REFERENCE   10 (bases 1 to 1665)
  AUTHORS   Raja,K.B., Smith,G.P. and Peters,T.J.
  TITLE     Subcellular localization and properties of alkaline inorganic
            pyrophosphatase in human polymorphonuclear leucocytes
  JOURNAL   Clin Chim Acta 117 (1), 33-41 (1981)
   PUBMED   6120771
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AF217187.1, BC035569.1,
            AK000466.1 and AI419577.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_176869.2.
            
            Summary: The protein encoded by this gene is localized to the
            mitochondrion, is highly similar to members of the inorganic
            pyrophosphatase (PPase) family, and contains the signature sequence
            essential for the catalytic activity of PPase. PPases catalyze the
            hydrolysis of pyrophosphate to inorganic phosphate, which is
            important for the phosphate metabolism of cells. Alternate
            transcriptional splice variants, encoding different isoforms, have
            been characterized. [provided by RefSeq, Jul 2008].
            
            Transcript Variant: This variant (1) represents the longest
            transcript, and encodes the longest 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 :: AK000466.1, AF217187.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000341695.10/
                                                  ENSP00000343885.5
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-43                AF217187.1         3-45
            44-1179             BC035569.1         24-1159
            1180-1632           AK000466.1         1196-1648
            1633-1634           AI419577.1         105-106
            1635-1665           AK000466.1         1651-1681
FEATURES             Location/Qualifiers
     source          1..1665
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="4"
                     /map="4q24"
     gene            1..1665
                     /gene="PPA2"
                     /gene_synonym="HSPC124; SCFAI; SCFI; SID6-306"
                     /note="inorganic pyrophosphatase 2"
                     /db_xref="GeneID:27068"
                     /db_xref="HGNC:HGNC:28883"
                     /db_xref="MIM:609988"
     exon            1..169
                     /gene="PPA2"
                     /gene_synonym="HSPC124; SCFAI; SCFI; SID6-306"
                     /inference="alignment:Splign:2.1.0"
     CDS             13..1017
                     /gene="PPA2"
                     /gene_synonym="HSPC124; SCFAI; SCFI; SID6-306"
                     /EC_number="3.6.1.1"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; inorganic pyrophosphatase 2, mitochondrial;
                     PPase 2; pyrophosphatase SID6-306; pyrophosphate
                     phospho-hydrolase 2; pyrophosphatase (inorganic) 2"
                     /codon_start=1
                     /product="inorganic pyrophosphatase 2, mitochondrial
                     isoform 1 precursor"
                     /protein_id="NP_789845.1"
                     /db_xref="CCDS:CCDS3667.1"
                     /db_xref="GeneID:27068"
                     /db_xref="HGNC:HGNC:28883"
                     /db_xref="MIM:609988"
                     /translation="MSALLRLLRTGAPAAACLRLGTSAGTGSRRAMALYHTEERGQPC
                     SQNYRLFFKNVTGHYISPFHDIPLKVNSKEENGIPMKKARNDEYENLFNMIVEIPRWT
                     NAKMEIATKEPMNPIKQYVKDGKLRYVANIFPYKGYIWNYGTLPQTWEDPHEKDKSTN
                     CFGDNDPIDVCEIGSKILSCGEVIHVKILGILALIDEGETDWKLIAINANDPEASKFH
                     DIDDVKKFKPGYLEATLNWFRLYKVPDGKPENQFAFNGEFKNKAFALEVIKSTHQCWK
                     ALLMKKCNGGAINCTNVQISDSPFRCTQEEARSLVESVSSSPNKESNEEEQVWHFLGK
                     "
     exon            170..234
                     /gene="PPA2"
                     /gene_synonym="HSPC124; SCFAI; SCFI; SID6-306"
                     /inference="alignment:Splign:2.1.0"
     exon            235..279
                     /gene="PPA2"
                     /gene_synonym="HSPC124; SCFAI; SCFI; SID6-306"
                     /inference="alignment:Splign:2.1.0"
     exon            280..333
                     /gene="PPA2"
                     /gene_synonym="HSPC124; SCFAI; SCFI; SID6-306"
                     /inference="alignment:Splign:2.1.0"
     exon            334..453
                     /gene="PPA2"
                     /gene_synonym="HSPC124; SCFAI; SCFI; SID6-306"
                     /inference="alignment:Splign:2.1.0"
     exon            454..540
                     /gene="PPA2"
                     /gene_synonym="HSPC124; SCFAI; SCFI; SID6-306"
                     /inference="alignment:Splign:2.1.0"
     exon            541..667
                     /gene="PPA2"
                     /gene_synonym="HSPC124; SCFAI; SCFI; SID6-306"
                     /inference="alignment:Splign:2.1.0"
     exon            668..795
                     /gene="PPA2"
                     /gene_synonym="HSPC124; SCFAI; SCFI; SID6-306"
                     /inference="alignment:Splign:2.1.0"
     exon            796..881
                     /gene="PPA2"
                     /gene_synonym="HSPC124; SCFAI; SCFI; SID6-306"
                     /inference="alignment:Splign:2.1.0"
     exon            882..951
                     /gene="PPA2"
                     /gene_synonym="HSPC124; SCFAI; SCFI; SID6-306"
                     /inference="alignment:Splign:2.1.0"
     exon            952..988
                     /gene="PPA2"
                     /gene_synonym="HSPC124; SCFAI; SCFI; SID6-306"
                     /inference="alignment:Splign:2.1.0"
     exon            989..1665
                     /gene="PPA2"
                     /gene_synonym="HSPC124; SCFAI; SCFI; SID6-306"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1156..1161
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PPA2"
                     /gene_synonym="HSPC124; SCFAI; SCFI; SID6-306"
                     /note="hexamer: AATAAA"
     polyA_site      1177
                     /gene="PPA2"
                     /gene_synonym="HSPC124; SCFAI; SCFI; SID6-306"
                     /note="major polyA site"
     regulatory      1643..1648
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PPA2"
                     /gene_synonym="HSPC124; SCFAI; SCFI; SID6-306"
                     /note="hexamer: AATAAA"
     polyA_site      1665
                     /gene="PPA2"
                     /gene_synonym="HSPC124; SCFAI; SCFI; SID6-306"
ORIGIN      
        1 gtcattgacg ccatgagcgc gctgctgcgg ctgctgcgca cgggtgcccc agccgctgcg
       61 tgcctgcggt tggggaccag tgcagggacc gggtcgcgcc gtgctatggc cctgtaccac
      121 actgaggagc gcggccagcc ctgctcgcag aattaccgcc tcttctttaa gaatgtaact
      181 ggtcactaca tttccccctt tcatgatatt cctctgaagg tgaactctaa agaggaaaat
      241 ggcattccta tgaagaaagc acgaaatgat gaatatgaga atctgtttaa tatgattgta
      301 gaaatacctc ggtggacaaa tgctaaaatg gagattgcca ccaaggagcc aatgaatccc
      361 attaaacaat atgtaaagga tggaaagcta cgctatgtgg cgaatatctt cccttacaag
      421 ggttatatat ggaattatgg taccctccct cagacttggg aagatcccca tgaaaaagat
      481 aagagcacga actgctttgg agataatgat cctattgatg tttgcgaaat aggctcaaag
      541 attctttctt gtggagaagt tattcatgtg aagatccttg gaattttggc tcttattgat
      601 gaaggtgaaa cagattggaa attaattgct atcaatgcga atgatcctga agcctcaaag
      661 tttcatgata ttgatgatgt taagaagttc aaaccgggtt acctggaagc tactcttaat
      721 tggtttagat tatataaggt accagatgga aaaccagaaa accagtttgc ttttaatgga
      781 gaattcaaaa acaaggcttt tgctcttgaa gttattaaat ccactcatca atgttggaaa
      841 gcattgctta tgaagaagtg taatggagga gctataaatt gcacaaacgt gcagatatct
      901 gatagccctt tccgttgcac tcaagaggaa gcaagatcat tagttgaatc ggtatcatct
      961 tcaccaaata aagaaagtaa tgaagaagag caagtgtggc acttccttgg caagtgattg
     1021 aaacatctga aattctgctg tcaagattcc catctctaag gactccaagt gctagagaca
     1081 agggggtcta tgagcattta ctgacttcct gttaaaactt cattttttca aactttttga
     1141 gctatgcaat atataaataa acagtaagaa ttttaaatta ctctcctttg gacatttatt
     1201 gatataaaaa gaagattttg gccaggcacg gtggctcatg cctgtaattt cagcactttg
     1261 ggaggccgag gtgggcagat cacaaggtca ggagttcaag accagcctgg ccagtatgtt
     1321 gaaaccccat ctctattaaa aatacaaaaa ttagccaggc gtggtggtgc atgcctgtag
     1381 acccagctac tcaggaggct gaggcagaag aactgcttga gcccaggagg cagaggttgc
     1441 agtgagcaga gattgtgcca ctgcactcca gcctaggcga cagagagaga ctccgtctca
     1501 aaaaaaaaaa aaagattttg tttcatttca tagcacaaat ttagaggcat tgagttgacc
     1561 atttctagtt tctatacctg aaggaaccca ttgattttac cagtttttat ttctgtagat
     1621 tggatgtaaa aatcacagat tcaataaatt aataaacttt gtgta
//
