Full text data of PPA1
PPA1
(IOPPP, PP)
[Confidence: low (only semi-automatic identification from reviews)]
Inorganic pyrophosphatase; 3.6.1.1 (Pyrophosphate phospho-hydrolase; PPase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Inorganic pyrophosphatase; 3.6.1.1 (Pyrophosphate phospho-hydrolase; PPase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q15181
ID IPYR_HUMAN Reviewed; 289 AA.
AC Q15181; Q2M348; Q5SQT7; Q6P7P4; Q9UQJ5; Q9Y5B1;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 30-MAY-2000, sequence version 2.
DT 22-JAN-2014, entry version 139.
DE RecName: Full=Inorganic pyrophosphatase;
DE EC=3.6.1.1;
DE AltName: Full=Pyrophosphate phospho-hydrolase;
DE Short=PPase;
GN Name=PPA1; Synonyms=IOPPP, PP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Heart;
RX PubMed=10542310; DOI=10.1016/S0167-4781(99)00175-X;
RA Fairchild T.A., Patejunas G.;
RT "Cloning and expression profile of human inorganic pyrophosphatase.";
RL Biochim. Biophys. Acta 1447:133-136(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Saito T., Hattori A., Miyajima N.;
RT "Putative inorganic pyrophosphatase.";
RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Kanni L., Johansson M., Karlsson A.;
RT "Cloning of a human inorganic pyrophosphatase cDNA.";
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Dai F.Y., Yu L., Hu P.R., Xin Y.R., Xu Y.F., Zhao S.Y.;
RT "Cloning and characterization of a novel human cDNA homology to bovine
RT inorganic pyrophosphatase mRNA.";
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Adrenal gland;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H.,
RA Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J.,
RA Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M.,
RA Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal
RT axis and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Lymph, and Uterus;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 5-286.
RA Rumsfeld J., Ziegelbauer K., Spaltmann F.;
RT "Cloning, expression, affinity purification and characterization of
RT polyhistidine-tagged cytosolic Saccharomyces cerevisiae and human
RT inorganic pyrophosphatases for differential screening of compounds for
RT antifungal activity.";
RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP PROTEIN SEQUENCE OF 10-18; 26-41; 58-70; 80-88; 110-128; 140-191;
RP 193-221 AND 239-253, AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 83-196.
RA Lacroix J., Vigneron M., Kedinger C.;
RT "Partial sequence of the human inorganic pyrophosphatase.";
RL Submitted (MAR-1995) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-57 AND LYS-228, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-250, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [16]
RP VARIANT [LARGE SCALE ANALYSIS] ASN-57.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- CATALYTIC ACTIVITY: Diphosphate + H(2)O = 2 phosphate.
CC -!- COFACTOR: Binds 4 magnesium ions per subunit. Other metal ions can
CC support activity, but at a lower rate. Two magnesium ions are
CC required for the activation of the enzyme and are present before
CC substrate binds, two additional magnesium ions form complexes with
CC substrate and product (By similarity).
CC -!- SUBUNIT: Homodimer (By similarity).
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity).
CC -!- TISSUE SPECIFICITY: Expressed ubiquitously.
CC -!- SIMILARITY: Belongs to the PPase family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF154065; AAD34643.1; -; mRNA.
DR EMBL; AB026723; BAA84702.1; -; mRNA.
DR EMBL; AF217186; AAG36780.1; -; mRNA.
DR EMBL; AF092439; AAP97214.1; -; mRNA.
DR EMBL; AF119665; AAF17222.1; -; mRNA.
DR EMBL; AL731540; CAI13692.1; -; Genomic_DNA.
DR EMBL; BC001022; AAH01022.3; -; mRNA.
DR EMBL; BC061581; AAH61581.2; -; mRNA.
DR EMBL; BC105034; AAI05035.1; -; mRNA.
DR EMBL; BC105036; AAI05037.1; -; mRNA.
DR EMBL; BC107882; AAI07883.1; -; mRNA.
DR EMBL; AF108211; AAD24964.1; -; mRNA.
DR EMBL; Z48605; CAA88494.1; -; mRNA.
DR RefSeq; NP_066952.1; NM_021129.3.
DR UniGene; Hs.437403; -.
DR ProteinModelPortal; Q15181; -.
DR SMR; Q15181; 4-284.
DR IntAct; Q15181; 9.
DR MINT; MINT-3030968; -.
DR STRING; 9606.ENSP00000362329; -.
DR PhosphoSite; Q15181; -.
DR DMDM; 8247940; -.
DR REPRODUCTION-2DPAGE; IPI00015018; -.
DR PaxDb; Q15181; -.
DR PeptideAtlas; Q15181; -.
DR PRIDE; Q15181; -.
DR DNASU; 5464; -.
DR Ensembl; ENST00000373232; ENSP00000362329; ENSG00000180817.
DR GeneID; 5464; -.
DR KEGG; hsa:5464; -.
DR UCSC; uc001jqv.1; human.
DR CTD; 5464; -.
DR GeneCards; GC10M071962; -.
DR H-InvDB; HIX0032502; -.
DR HGNC; HGNC:9226; PPA1.
DR HPA; HPA019878; -.
DR HPA; HPA020096; -.
DR MIM; 179030; gene.
DR neXtProt; NX_Q15181; -.
DR PharmGKB; PA33550; -.
DR eggNOG; COG0221; -.
DR HOGENOM; HOG000195569; -.
DR HOVERGEN; HBG000491; -.
DR InParanoid; Q15181; -.
DR KO; K01507; -.
DR OMA; WFYYQKN; -.
DR OrthoDB; EOG7R2BKH; -.
DR PhylomeDB; Q15181; -.
DR BRENDA; 3.6.1.1; 2681.
DR Reactome; REACT_21259; Pyrophosphate hydrolysis.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; PPA1; human.
DR GenomeRNAi; 5464; -.
DR NextBio; 21148; -.
DR PRO; PR:Q15181; -.
DR ArrayExpress; Q15181; -.
DR Bgee; Q15181; -.
DR CleanEx; HS_PPA1; -.
DR Genevestigator; Q15181; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0004427; F:inorganic diphosphatase activity; EXP:Reactome.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0071344; P:diphosphate metabolic process; TAS:Reactome.
DR GO; GO:0006796; P:phosphate-containing compound metabolic process; TAS:ProtInc.
DR GO; GO:0006418; P:tRNA aminoacylation for protein translation; TAS:Reactome.
DR Gene3D; 3.90.80.10; -; 1.
DR InterPro; IPR008162; Pyrophosphatase.
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; Complete proteome; Cytoplasm; Direct protein sequencing;
KW Hydrolase; Magnesium; Metal-binding; Phosphoprotein; Polymorphism;
KW Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 289 Inorganic pyrophosphatase.
FT /FTId=PRO_0000137567.
FT METAL 116 116 Magnesium 1 (By similarity).
FT METAL 121 121 Magnesium 1 (By similarity).
FT METAL 121 121 Magnesium 2 (By similarity).
FT METAL 153 153 Magnesium 1 (By similarity).
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 57 57 N6-acetyllysine.
FT MOD_RES 228 228 N6-acetyllysine.
FT MOD_RES 250 250 Phosphoserine.
FT VARIANT 57 57 K -> N (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_036358.
FT CONFLICT 12 12 P -> A (in Ref. 8; AAD24964).
FT CONFLICT 84 84 L -> I (in Ref. 10; CAA88494).
FT CONFLICT 96 97 AI -> TL (in Ref. 10; CAA88494).
FT CONFLICT 105 114 GHNDKHTGCC -> HEKDKSTNCF (in Ref. 10;
FT CAA88494).
FT CONFLICT 129 140 VCARGEIIGVKV -> ILSCGEVIHVKI (in Ref. 10;
FT CAA88494).
FT CONFLICT 146 146 M -> L (in Ref. 10; CAA88494).
FT CONFLICT 156 156 V -> L (in Ref. 10; CAA88494).
FT CONFLICT 161 162 VD -> AN (in Ref. 10; CAA88494).
FT CONFLICT 165 173 DAANYNDIN -> EASKFHDID (in Ref. 10;
FT CAA88494).
FT CONFLICT 177 178 RL -> KF (in Ref. 10; CAA88494).
FT CONFLICT 187 188 VD -> LN (in Ref. 10; CAA88494).
FT CONFLICT 192 192 R -> L (in Ref. 10; CAA88494).
SQ SEQUENCE 289 AA; 32660 MW; E3973C9E6F8CA5CD CRC64;
MSGFSTEERA APFSLEYRVF LKNEKGQYIS PFHDIPIYAD KDVFHMVVEV PRWSNAKMEI
ATKDPLNPIK QDVKKGKLRY VANLFPYKGY IWNYGAIPQT WEDPGHNDKH TGCCGDNDPI
DVCEIGSKVC ARGEIIGVKV LGILAMIDEG ETDWKVIAIN VDDPDAANYN DINDVKRLKP
GYLEATVDWF RRYKVPDGKP ENEFAFNAEF KDKDFAIDII KSTHDHWKAL VTKKTNGKGI
SCMNTTLSES PFKCDPDAAR AIVDALPPPC ESACTVPTDV DKWFHHQKN
//
ID IPYR_HUMAN Reviewed; 289 AA.
AC Q15181; Q2M348; Q5SQT7; Q6P7P4; Q9UQJ5; Q9Y5B1;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 30-MAY-2000, sequence version 2.
DT 22-JAN-2014, entry version 139.
DE RecName: Full=Inorganic pyrophosphatase;
DE EC=3.6.1.1;
DE AltName: Full=Pyrophosphate phospho-hydrolase;
DE Short=PPase;
GN Name=PPA1; Synonyms=IOPPP, PP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Heart;
RX PubMed=10542310; DOI=10.1016/S0167-4781(99)00175-X;
RA Fairchild T.A., Patejunas G.;
RT "Cloning and expression profile of human inorganic pyrophosphatase.";
RL Biochim. Biophys. Acta 1447:133-136(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Saito T., Hattori A., Miyajima N.;
RT "Putative inorganic pyrophosphatase.";
RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Kanni L., Johansson M., Karlsson A.;
RT "Cloning of a human inorganic pyrophosphatase cDNA.";
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Dai F.Y., Yu L., Hu P.R., Xin Y.R., Xu Y.F., Zhao S.Y.;
RT "Cloning and characterization of a novel human cDNA homology to bovine
RT inorganic pyrophosphatase mRNA.";
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Adrenal gland;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H.,
RA Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J.,
RA Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M.,
RA Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal
RT axis and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Lymph, and Uterus;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 5-286.
RA Rumsfeld J., Ziegelbauer K., Spaltmann F.;
RT "Cloning, expression, affinity purification and characterization of
RT polyhistidine-tagged cytosolic Saccharomyces cerevisiae and human
RT inorganic pyrophosphatases for differential screening of compounds for
RT antifungal activity.";
RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP PROTEIN SEQUENCE OF 10-18; 26-41; 58-70; 80-88; 110-128; 140-191;
RP 193-221 AND 239-253, AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 83-196.
RA Lacroix J., Vigneron M., Kedinger C.;
RT "Partial sequence of the human inorganic pyrophosphatase.";
RL Submitted (MAR-1995) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-57 AND LYS-228, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-250, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [16]
RP VARIANT [LARGE SCALE ANALYSIS] ASN-57.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- CATALYTIC ACTIVITY: Diphosphate + H(2)O = 2 phosphate.
CC -!- COFACTOR: Binds 4 magnesium ions per subunit. Other metal ions can
CC support activity, but at a lower rate. Two magnesium ions are
CC required for the activation of the enzyme and are present before
CC substrate binds, two additional magnesium ions form complexes with
CC substrate and product (By similarity).
CC -!- SUBUNIT: Homodimer (By similarity).
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity).
CC -!- TISSUE SPECIFICITY: Expressed ubiquitously.
CC -!- SIMILARITY: Belongs to the PPase family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF154065; AAD34643.1; -; mRNA.
DR EMBL; AB026723; BAA84702.1; -; mRNA.
DR EMBL; AF217186; AAG36780.1; -; mRNA.
DR EMBL; AF092439; AAP97214.1; -; mRNA.
DR EMBL; AF119665; AAF17222.1; -; mRNA.
DR EMBL; AL731540; CAI13692.1; -; Genomic_DNA.
DR EMBL; BC001022; AAH01022.3; -; mRNA.
DR EMBL; BC061581; AAH61581.2; -; mRNA.
DR EMBL; BC105034; AAI05035.1; -; mRNA.
DR EMBL; BC105036; AAI05037.1; -; mRNA.
DR EMBL; BC107882; AAI07883.1; -; mRNA.
DR EMBL; AF108211; AAD24964.1; -; mRNA.
DR EMBL; Z48605; CAA88494.1; -; mRNA.
DR RefSeq; NP_066952.1; NM_021129.3.
DR UniGene; Hs.437403; -.
DR ProteinModelPortal; Q15181; -.
DR SMR; Q15181; 4-284.
DR IntAct; Q15181; 9.
DR MINT; MINT-3030968; -.
DR STRING; 9606.ENSP00000362329; -.
DR PhosphoSite; Q15181; -.
DR DMDM; 8247940; -.
DR REPRODUCTION-2DPAGE; IPI00015018; -.
DR PaxDb; Q15181; -.
DR PeptideAtlas; Q15181; -.
DR PRIDE; Q15181; -.
DR DNASU; 5464; -.
DR Ensembl; ENST00000373232; ENSP00000362329; ENSG00000180817.
DR GeneID; 5464; -.
DR KEGG; hsa:5464; -.
DR UCSC; uc001jqv.1; human.
DR CTD; 5464; -.
DR GeneCards; GC10M071962; -.
DR H-InvDB; HIX0032502; -.
DR HGNC; HGNC:9226; PPA1.
DR HPA; HPA019878; -.
DR HPA; HPA020096; -.
DR MIM; 179030; gene.
DR neXtProt; NX_Q15181; -.
DR PharmGKB; PA33550; -.
DR eggNOG; COG0221; -.
DR HOGENOM; HOG000195569; -.
DR HOVERGEN; HBG000491; -.
DR InParanoid; Q15181; -.
DR KO; K01507; -.
DR OMA; WFYYQKN; -.
DR OrthoDB; EOG7R2BKH; -.
DR PhylomeDB; Q15181; -.
DR BRENDA; 3.6.1.1; 2681.
DR Reactome; REACT_21259; Pyrophosphate hydrolysis.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; PPA1; human.
DR GenomeRNAi; 5464; -.
DR NextBio; 21148; -.
DR PRO; PR:Q15181; -.
DR ArrayExpress; Q15181; -.
DR Bgee; Q15181; -.
DR CleanEx; HS_PPA1; -.
DR Genevestigator; Q15181; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0004427; F:inorganic diphosphatase activity; EXP:Reactome.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0071344; P:diphosphate metabolic process; TAS:Reactome.
DR GO; GO:0006796; P:phosphate-containing compound metabolic process; TAS:ProtInc.
DR GO; GO:0006418; P:tRNA aminoacylation for protein translation; TAS:Reactome.
DR Gene3D; 3.90.80.10; -; 1.
DR InterPro; IPR008162; Pyrophosphatase.
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; Complete proteome; Cytoplasm; Direct protein sequencing;
KW Hydrolase; Magnesium; Metal-binding; Phosphoprotein; Polymorphism;
KW Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 289 Inorganic pyrophosphatase.
FT /FTId=PRO_0000137567.
FT METAL 116 116 Magnesium 1 (By similarity).
FT METAL 121 121 Magnesium 1 (By similarity).
FT METAL 121 121 Magnesium 2 (By similarity).
FT METAL 153 153 Magnesium 1 (By similarity).
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 57 57 N6-acetyllysine.
FT MOD_RES 228 228 N6-acetyllysine.
FT MOD_RES 250 250 Phosphoserine.
FT VARIANT 57 57 K -> N (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_036358.
FT CONFLICT 12 12 P -> A (in Ref. 8; AAD24964).
FT CONFLICT 84 84 L -> I (in Ref. 10; CAA88494).
FT CONFLICT 96 97 AI -> TL (in Ref. 10; CAA88494).
FT CONFLICT 105 114 GHNDKHTGCC -> HEKDKSTNCF (in Ref. 10;
FT CAA88494).
FT CONFLICT 129 140 VCARGEIIGVKV -> ILSCGEVIHVKI (in Ref. 10;
FT CAA88494).
FT CONFLICT 146 146 M -> L (in Ref. 10; CAA88494).
FT CONFLICT 156 156 V -> L (in Ref. 10; CAA88494).
FT CONFLICT 161 162 VD -> AN (in Ref. 10; CAA88494).
FT CONFLICT 165 173 DAANYNDIN -> EASKFHDID (in Ref. 10;
FT CAA88494).
FT CONFLICT 177 178 RL -> KF (in Ref. 10; CAA88494).
FT CONFLICT 187 188 VD -> LN (in Ref. 10; CAA88494).
FT CONFLICT 192 192 R -> L (in Ref. 10; CAA88494).
SQ SEQUENCE 289 AA; 32660 MW; E3973C9E6F8CA5CD CRC64;
MSGFSTEERA APFSLEYRVF LKNEKGQYIS PFHDIPIYAD KDVFHMVVEV PRWSNAKMEI
ATKDPLNPIK QDVKKGKLRY VANLFPYKGY IWNYGAIPQT WEDPGHNDKH TGCCGDNDPI
DVCEIGSKVC ARGEIIGVKV LGILAMIDEG ETDWKVIAIN VDDPDAANYN DINDVKRLKP
GYLEATVDWF RRYKVPDGKP ENEFAFNAEF KDKDFAIDII KSTHDHWKAL VTKKTNGKGI
SCMNTTLSES PFKCDPDAAR AIVDALPPPC ESACTVPTDV DKWFHHQKN
//
MIM
179030
*RECORD*
*FIELD* NO
179030
*FIELD* TI
*179030 PYROPHOSPHATASE, INORGANIC, 1; PPA1
;;PP
*FIELD* TX
DESCRIPTION
Inorganic pyrophosphates are generated as byproducts of many
read morebiosynthetic reactions, including DNA and RNA synthesis, fatty acid and
amino acid activation, and cyclic nucleotide synthesis. Inorganic
pyrophosphatases (EC 3.6.1.1), such as PPA1, maintain the thermodynamic
favorability of these reactions by catalyzing the hydrolysis of
pyrophosphates into organic phosphates, which are then exported across
the cell membrane (Curbo et al., 2006).
CLONING
Fairchild and Patejunas (1999) cloned PPA1 from a human heart cDNA
library. The deduced 289-amino acid protein has a calculated molecular
mass of 32.7 kD and shares 94% amino acid identity with bovine
pyrophosphatase. Northern blot analysis detected a 1.4-kb PPA1
transcript in all tissues examined. RNA dot blot analysis confirmed
ubiquitous PPA1 expression.
Curbo et al. (2006) found that fluorescence-tagged PPA1 was expressed in
both the cytosol and nucleus of transfected HeLa cells.
GENE FUNCTION
Curbo et al. (2006) found that recombinant PPA1 hydrolyzed pyrophosphate
in vitro. The reaction was dependent on Mg(2+) and inhibited by Ca(2+).
MAPPING
Assignment of the PPA1 gene to chromosome 10 was first reported by Van
Cong et al. (1975) and confirmed by somatic cell hybrid studies in 2
other laboratories (McAlpine et al., 1976; Chern, 1976). From dosage
studies in a patient trisomic for 10pter-10q11.1, Snyder et al. (1984)
showed that PPA1 is not on the short arm; red cell PP levels were
normal.
By radiation hybrid analysis, Fairchild and Patejunas (1999) mapped the
PPA1 gene to chromosome 10q21.3.
MOLECULAR GENETICS
Among 3,000 unrelated persons, Fisher et al. (1974) found no genetically
determined variants of the PP enzyme in red cells.
*FIELD* SA
Fisher et al. (1974); Snyder et al. (1984)
*FIELD* RF
1. Chern, C. J.: Localization of the structural genes for hexokinase-1
and inorganic pyrophosphatase on region (pter-q24) of human chromosome
10. Cytogenet. Cell Genet. 17: 338-342, 1976.
2. Curbo, S.; Lagier-Tourenne, C.; Carrozzo, R.; Palenzuela, L.; Lucioli,
S.; Hirano, M.; Santorelli, F.; Arenas, J.; Karlsson, A.; Johansson,
M.: Human mitochondrial pyrophosphatase: cDNA cloning and analysis
of the gene in patients with mtDNA depletion syndromes. Genomics 87:
410-416, 2006.
3. Fairchild, T. A.; Patejunas, G.: Cloning and expression profile
of human inorganic pyrophosphatase. Biochim. Biophys. Acta 1447:
133-136, 1999.
4. Fisher, R.; Putt, W.; Harris, H.: Further studies on erythrocyte
inorganic pyrophosphatase: an examination of different mammalian species
and human-Chinese hamster hybrid cells. Ann. Hum. Genet. 38: 171-177,
1974.
5. Fisher, R. A.; Turner, B. M.; Dorkin, H. L.; Harris, H.: Studies
on human erythrocyte inorganic pyrophosphatase. Ann. Hum. Genet. 37:
341-353, 1974.
6. McAlpine, P. J.; Mohandas, T.; Ray, M.; Wang, H.; Hamerton, J.
L.: Assignment of the inorganic pyrophosphatase gene locus (PP) to
chromosome 10 in man. Cytogenet. Cell Genet. 16: 201-203, 1976.
7. Snyder, F. F.; Hoo, J. J.; Shearer, J. E.; Heikkila, E. M.; Rudd,
N. L.; Lin, C. C.: Gene dosage studies of inorganic pyrophosphatase
(PP) and hexokinase (HK1) on human chromosome 10. (Abstract) Cytogenet.
Cell Genet. 37: 588 only, 1984.
8. Snyder, F. F.; Lin, C. C.; Rudd, N. L.; Shearer, J. E.; Heikkila,
E. M.; Hoo, J. J.: A de novo case of trisomy 10p: gene dosage studies
of hexokinase, inorganic pyrophosphatase and adenosine kinase. Hum.
Genet. 67: 187-189, 1984.
9. Van Cong, N.; Rebourcet, R.; Weil, D.; Pangalos, C.; Frezal, J.
: Localisation d'un locus de structure de la pyrophosphatase inorganique
'erythrocytaire' sur le chromosome 10 chez l'homme par la methode
d'hypridation cellulaire homme-hamster. Comp. Rend. Acad. Sci. (Paris) 281:
435-438, 1975.
*FIELD* CN
Patricia A. Hartz - updated: 3/21/2006
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
mgross: 03/22/2006
mgross: 3/21/2006
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/27/1989
marie: 3/25/1988
reenie: 6/2/1986
*RECORD*
*FIELD* NO
179030
*FIELD* TI
*179030 PYROPHOSPHATASE, INORGANIC, 1; PPA1
;;PP
*FIELD* TX
DESCRIPTION
Inorganic pyrophosphates are generated as byproducts of many
read morebiosynthetic reactions, including DNA and RNA synthesis, fatty acid and
amino acid activation, and cyclic nucleotide synthesis. Inorganic
pyrophosphatases (EC 3.6.1.1), such as PPA1, maintain the thermodynamic
favorability of these reactions by catalyzing the hydrolysis of
pyrophosphates into organic phosphates, which are then exported across
the cell membrane (Curbo et al., 2006).
CLONING
Fairchild and Patejunas (1999) cloned PPA1 from a human heart cDNA
library. The deduced 289-amino acid protein has a calculated molecular
mass of 32.7 kD and shares 94% amino acid identity with bovine
pyrophosphatase. Northern blot analysis detected a 1.4-kb PPA1
transcript in all tissues examined. RNA dot blot analysis confirmed
ubiquitous PPA1 expression.
Curbo et al. (2006) found that fluorescence-tagged PPA1 was expressed in
both the cytosol and nucleus of transfected HeLa cells.
GENE FUNCTION
Curbo et al. (2006) found that recombinant PPA1 hydrolyzed pyrophosphate
in vitro. The reaction was dependent on Mg(2+) and inhibited by Ca(2+).
MAPPING
Assignment of the PPA1 gene to chromosome 10 was first reported by Van
Cong et al. (1975) and confirmed by somatic cell hybrid studies in 2
other laboratories (McAlpine et al., 1976; Chern, 1976). From dosage
studies in a patient trisomic for 10pter-10q11.1, Snyder et al. (1984)
showed that PPA1 is not on the short arm; red cell PP levels were
normal.
By radiation hybrid analysis, Fairchild and Patejunas (1999) mapped the
PPA1 gene to chromosome 10q21.3.
MOLECULAR GENETICS
Among 3,000 unrelated persons, Fisher et al. (1974) found no genetically
determined variants of the PP enzyme in red cells.
*FIELD* SA
Fisher et al. (1974); Snyder et al. (1984)
*FIELD* RF
1. Chern, C. J.: Localization of the structural genes for hexokinase-1
and inorganic pyrophosphatase on region (pter-q24) of human chromosome
10. Cytogenet. Cell Genet. 17: 338-342, 1976.
2. Curbo, S.; Lagier-Tourenne, C.; Carrozzo, R.; Palenzuela, L.; Lucioli,
S.; Hirano, M.; Santorelli, F.; Arenas, J.; Karlsson, A.; Johansson,
M.: Human mitochondrial pyrophosphatase: cDNA cloning and analysis
of the gene in patients with mtDNA depletion syndromes. Genomics 87:
410-416, 2006.
3. Fairchild, T. A.; Patejunas, G.: Cloning and expression profile
of human inorganic pyrophosphatase. Biochim. Biophys. Acta 1447:
133-136, 1999.
4. Fisher, R.; Putt, W.; Harris, H.: Further studies on erythrocyte
inorganic pyrophosphatase: an examination of different mammalian species
and human-Chinese hamster hybrid cells. Ann. Hum. Genet. 38: 171-177,
1974.
5. Fisher, R. A.; Turner, B. M.; Dorkin, H. L.; Harris, H.: Studies
on human erythrocyte inorganic pyrophosphatase. Ann. Hum. Genet. 37:
341-353, 1974.
6. McAlpine, P. J.; Mohandas, T.; Ray, M.; Wang, H.; Hamerton, J.
L.: Assignment of the inorganic pyrophosphatase gene locus (PP) to
chromosome 10 in man. Cytogenet. Cell Genet. 16: 201-203, 1976.
7. Snyder, F. F.; Hoo, J. J.; Shearer, J. E.; Heikkila, E. M.; Rudd,
N. L.; Lin, C. C.: Gene dosage studies of inorganic pyrophosphatase
(PP) and hexokinase (HK1) on human chromosome 10. (Abstract) Cytogenet.
Cell Genet. 37: 588 only, 1984.
8. Snyder, F. F.; Lin, C. C.; Rudd, N. L.; Shearer, J. E.; Heikkila,
E. M.; Hoo, J. J.: A de novo case of trisomy 10p: gene dosage studies
of hexokinase, inorganic pyrophosphatase and adenosine kinase. Hum.
Genet. 67: 187-189, 1984.
9. Van Cong, N.; Rebourcet, R.; Weil, D.; Pangalos, C.; Frezal, J.
: Localisation d'un locus de structure de la pyrophosphatase inorganique
'erythrocytaire' sur le chromosome 10 chez l'homme par la methode
d'hypridation cellulaire homme-hamster. Comp. Rend. Acad. Sci. (Paris) 281:
435-438, 1975.
*FIELD* CN
Patricia A. Hartz - updated: 3/21/2006
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
mgross: 03/22/2006
mgross: 3/21/2006
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/27/1989
marie: 3/25/1988
reenie: 6/2/1986