IPYR2_MOUSE
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 03-AUG-2022, entry version 147.
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, Pancreas,
RC 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 = H(+) + 2 phosphate; 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; 4.
DR IntAct; Q91VM9; 1.
DR MINT; Q91VM9; -.
DR STRING; 10090.ENSMUSP00000029644; -.
DR iPTMnet; Q91VM9; -.
DR PhosphoSitePlus; Q91VM9; -.
DR SwissPalm; Q91VM9; -.
DR REPRODUCTION-2DPAGE; Q91VM9; -.
DR EPD; Q91VM9; -.
DR jPOST; Q91VM9; -.
DR MaxQB; Q91VM9; -.
DR PaxDb; Q91VM9; -.
DR PeptideAtlas; Q91VM9; -.
DR PRIDE; Q91VM9; -.
DR ProteomicsDB; 269324; -. [Q91VM9-1]
DR ProteomicsDB; 269325; -. [Q91VM9-2]
DR Antibodypedia; 26143; 123 antibodies from 21 providers.
DR DNASU; 74776; -.
DR Ensembl; ENSMUST00000029644; ENSMUSP00000029644; ENSMUSG00000028013. [Q91VM9-1]
DR GeneID; 74776; -.
DR KEGG; mmu:74776; -.
DR UCSC; uc008rkm.2; mouse. [Q91VM9-1]
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; HECWKAM; -.
DR OrthoDB; 1398991at2759; -.
DR PhylomeDB; Q91VM9; -.
DR TreeFam; TF300887; -.
DR Reactome; R-MMU-379726; Mitochondrial tRNA aminoacylation.
DR Reactome; R-MMU-71737; Pyrophosphate hydrolysis.
DR BioGRID-ORCS; 74776; 20 hits in 76 CRISPR screens.
DR ChiTaRS; Ppa2; mouse.
DR PRO; PR:Q91VM9; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q91VM9; protein.
DR Bgee; ENSMUSG00000028013; Expressed in right kidney and 254 other tissues.
DR ExpressionAtlas; Q91VM9; baseline and differential.
DR Genevisible; Q91VM9; MM.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0004427; F:inorganic diphosphatase activity; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IBA:GO_Central.
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:MGI.
DR CDD; cd00412; pyrophosphatase; 1.
DR Gene3D; 3.90.80.10; -; 1.
DR InterPro; IPR008162; Pyrophosphatase.
DR InterPro; IPR036649; Pyrophosphatase_sf.
DR PANTHER; PTHR10286; PTHR10286; 1.
DR Pfam; PF00719; Pyrophosphatase; 1.
DR SUPFAM; SSF50324; SSF50324; 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
