ID   IPYR2_MOUSE             Reviewed;         330 AA.
AC   Q91VM9; Q3UPK3; Q8BTG5; Q9D1E3;
DT   27-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   02-SEP-2026, entry version 165.
DE   RecName: Full=Inorganic pyrophosphatase 2, mitochondrial {ECO:0000305};
DE            EC=3.6.1.1 {ECO:0000250|UniProtKB:Q9H2U2};
DE   AltName: Full=Pyrophosphate phospho-hydrolase 2;
DE            Short=PPase 2;
DE   Flags: Precursor;
GN   Name=Ppa2;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   STRAIN=C57BL/6J; TISSUE=Embryo, and Spinal cord;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   STRAIN=NMRI; TISSUE=Mammary tumor;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [3]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung,
RC   Pancreas, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [4]
RP   SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-211 AND LYS-254, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA   Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA   Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT   "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT   pathways.";
RL   Mol. Cell 50:919-930(2013).
RN   [5]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-219 AND LYS-256, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA   Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA   Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT   "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT   identifies substrates of SIRT3 in metabolic pathways.";
RL   Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
CC   -!- FUNCTION: Hydrolyzes inorganic pyrophosphate. This activity is
CC       essential for correct regulation of mitochondrial membrane potential,
CC       and mitochondrial organization and function.
CC       {ECO:0000250|UniProtKB:Q9H2U2}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=diphosphate + H2O = 2 phosphate + H(+); Xref=Rhea:RHEA:24576,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC         ChEBI:CHEBI:43474; EC=3.6.1.1;
CC         Evidence={ECO:0000250|UniProtKB:Q9H2U2};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24577;
CC         Evidence={ECO:0000250|UniProtKB:Q9H2U2};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC   -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q9H2U2}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q91VM9-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q91VM9-2; Sequence=VSP_011653, VSP_011654;
CC   -!- SIMILARITY: Belongs to the PPase family. {ECO:0000305}.
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DR   EMBL; AK003660; BAB22922.1; -; mRNA.
DR   EMBL; AK090384; BAC41194.1; -; mRNA.
DR   EMBL; AK143475; BAE25392.1; -; mRNA.
DR   EMBL; BC011417; AAH11417.1; -; mRNA.
DR   CCDS; CCDS17850.1; -. [Q91VM9-1]
DR   RefSeq; NP_001280570.1; NM_001293641.1.
DR   RefSeq; NP_666253.1; NM_146141.2. [Q91VM9-1]
DR   AlphaFoldDB; Q91VM9; -.
DR   SMR; Q91VM9; -.
DR   BioGRID; 217012; 7.
DR   FunCoup; Q91VM9; 2350.
DR   IntAct; Q91VM9; 1.
DR   MINT; Q91VM9; -.
DR   STRING; 10090.ENSMUSP00000029644; -.
DR   GlyGen; Q91VM9; 2 sites, 1 O-linked glycan (1 site).
DR   iPTMnet; Q91VM9; -.
DR   PhosphoSitePlus; Q91VM9; -.
DR   SwissPalm; Q91VM9; -.
DR   REPRODUCTION-2DPAGE; Q91VM9; -.
DR   jPOST; Q91VM9; -.
DR   PaxDb; 10090-ENSMUSP00000029644; -.
DR   PeptideAtlas; Q91VM9; -.
DR   ProteomicsDB; 269324; -. [Q91VM9-1]
DR   ProteomicsDB; 269325; -. [Q91VM9-2]
DR   Pumba; Q91VM9; -.
DR   Antibodypedia; 26143; 129 antibodies from 25 providers.
DR   DNASU; 74776; -.
DR   Ensembl; ENSMUST00000029644.16; ENSMUSP00000029644.10; ENSMUSG00000028013.17. [Q91VM9-1]
DR   GeneID; 74776; -.
DR   KEGG; mmu:74776; -.
DR   UCSC; uc008rkm.2; mouse. [Q91VM9-1]
DR   AGR; MGI:1922026; -.
DR   CTD; 27068; -.
DR   MGI; MGI:1922026; Ppa2.
DR   VEuPathDB; HostDB:ENSMUSG00000028013; -.
DR   eggNOG; KOG1626; Eukaryota.
DR   GeneTree; ENSGT00390000017004; -.
DR   HOGENOM; CLU_040684_0_2_1; -.
DR   InParanoid; Q91VM9; -.
DR   OMA; CASQYNA; -.
DR   OrthoDB; 1608002at2759; -.
DR   PhylomeDB; Q91VM9; -.
DR   Reactome; R-MMU-379726; Mitochondrial tRNA aminoacylation.
DR   Reactome; R-MMU-71737; Pyrophosphate hydrolysis.
DR   BioGRID-ORCS; 74776; 20 hits in 81 CRISPR screens.
DR   PRO; PR:Q91VM9; -.
DR   Proteomes; UP000000589; Chromosome 3.
DR   RNAct; Q91VM9; protein.
DR   Bgee; ENSMUSG00000028013; Expressed in right kidney and 257 other cell types or tissues.
DR   ExpressionAtlas; Q91VM9; baseline and differential.
DR   GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR   GO; GO:0045202; C:synapse; IDA:SynGO.
DR   GO; GO:0004427; F:inorganic diphosphate phosphatase activity; ISS:UniProtKB.
DR   GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR   GO; GO:0004722; F:protein serine/threonine phosphatase activity; IDA:MGI.
DR   GO; GO:0071344; P:diphosphate metabolic process; ISS:UniProtKB.
DR   GO; GO:0006796; P:phosphate-containing compound metabolic process; IBA:GO_Central.
DR   GO; GO:0051881; P:regulation of mitochondrial membrane potential; ISO:GO_Central.
DR   CDD; cd00412; pyrophosphatase; 1.
DR   FunFam; 3.90.80.10:FF:000005; Pyrophosphatase (inorganic) 2; 1.
DR   Gene3D; 3.90.80.10; Inorganic pyrophosphatase; 1.
DR   InterPro; IPR008162; Pyrophosphatase.
DR   InterPro; IPR036649; Pyrophosphatase_sf.
DR   PANTHER; PTHR10286; INORGANIC PYROPHOSPHATASE; 1.
DR   Pfam; PF00719; Pyrophosphatase; 1.
DR   SUPFAM; SSF50324; Inorganic pyrophosphatase; 1.
DR   PROSITE; PS00387; PPASE; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Alternative splicing; Hydrolase; Magnesium; Metal-binding;
KW   Mitochondrion; Reference proteome; Transit peptide.
FT   TRANSIT         1..27
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000250"
FT   CHAIN           28..330
FT                   /note="Inorganic pyrophosphatase 2, mitochondrial"
FT                   /id="PRO_0000025412"
FT   BINDING         159
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         164
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         164
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         196
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         211
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         219
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         254
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         256
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   VAR_SEQ         1..126
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:16141072"
FT                   /id="VSP_011653"
FT   VAR_SEQ         127..170
FT                   /note="IFPHKGYIWNYGALPQTWEDPHLRDKSTDCCGDNDPIDVCEIGS -> MLDA
FT                   DAPQNCQSWEGKDKQIPGPHRPNSQACLVKFQAIETLSQM (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:16141072"
FT                   /id="VSP_011654"
FT   CONFLICT        225..227
FT                   /note="YLE -> HLQ (in Ref. 1; BAC41194)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        254
FT                   /note="K -> T (in Ref. 1; BAC41194)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        321
FT                   /note="Missing (in Ref. 1; BAC41194)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   330 AA;  38115 MW;  8AFD61FA561D7268 CRC64;
     MRALLPLLSV GRGWRVGAAA RPPRRVMSLY RTEELGHPRS QDYRLFFKHV AGHYISPFHD
     IPLKADCKEE HDIPRKKARN DEYENLFNMV VEIPRWTNAK MEIATEEPLN PIKQDIKNGK
     LRYTPNIFPH KGYIWNYGAL PQTWEDPHLR DKSTDCCGDN DPIDVCEIGS KVLSRGDVVH
     VKILGTLALI DQSETDWKII AINVNDPEAE KFHDIDDVKK FKPGYLEATL NWFRLYKVPD
     GKPENKFAFN GEFKNKAFAL DVINSAHERW KEMVMKKCDK GAISCVNVHI CDSPFHCTME
     EARSLVESVP TPSMNKESNV EEEVWHFLRN
//