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Protein

Inorganic pyrophosphatase

Gene

PPA1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalytic activityi

Diphosphate + H2O = 2 phosphate.

Cofactori

Mg2+By similarityNote: Binds 4 Mg(2+) ions per subunit. Other metal ions can support activity, but at a lower rate. Two Mg(2+) ions are required for the activation of the enzyme and are present before substrate binds, two additional Mg2+ ions form complexes with substrate and product.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi116 – 1161Magnesium 1By similarity
Metal bindingi121 – 1211Magnesium 1By similarity
Metal bindingi121 – 1211Magnesium 2By similarity
Metal bindingi153 – 1531Magnesium 1By similarity

GO - Molecular functioni

  1. inorganic diphosphatase activity Source: Reactome
  2. magnesium ion binding Source: InterPro

GO - Biological processi

  1. diphosphate metabolic process Source: Reactome
  2. gene expression Source: Reactome
  3. phosphate-containing compound metabolic process Source: ProtInc
  4. tRNA aminoacylation for protein translation Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

Magnesium, Metal-binding

Enzyme and pathway databases

BRENDAi3.6.1.1. 2681.
ReactomeiREACT_15306. Cytosolic tRNA aminoacylation.

Names & Taxonomyi

Protein namesi
Recommended name:
Inorganic pyrophosphatase (EC:3.6.1.1)
Alternative name(s):
Pyrophosphate phospho-hydrolase
Short name:
PPase
Gene namesi
Name:PPA1
Synonyms:IOPPP, PP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:9226. PPA1.

Subcellular locationi

Cytoplasm By similarity

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. cytosol Source: Reactome
  3. extracellular vesicular exosome Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA33550.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed3 Publications
Chaini2 – 289288Inorganic pyrophosphatasePRO_0000137567Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserine3 Publications
Modified residuei57 – 571N6-acetyllysine1 Publication
Modified residuei228 – 2281N6-acetyllysine1 Publication
Modified residuei250 – 2501Phosphoserine1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ15181.
PaxDbiQ15181.
PeptideAtlasiQ15181.
PRIDEiQ15181.

2D gel databases

REPRODUCTION-2DPAGEIPI00015018.

PTM databases

PhosphoSiteiQ15181.

Expressioni

Tissue specificityi

Expressed ubiquitously.1 Publication

Gene expression databases

BgeeiQ15181.
CleanExiHS_PPA1.
ExpressionAtlasiQ15181. baseline and differential.
GenevestigatoriQ15181.

Organism-specific databases

HPAiHPA019878.
HPA020096.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

BioGridi111460. 20 interactions.
IntActiQ15181. 9 interactions.
MINTiMINT-3030968.
STRINGi9606.ENSP00000362329.

Structurei

3D structure databases

ProteinModelPortaliQ15181.
SMRiQ15181. Positions 4-284.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the PPase family.Curated

Phylogenomic databases

eggNOGiCOG0221.
HOGENOMiHOG000195569.
HOVERGENiHBG000491.
InParanoidiQ15181.
KOiK01507.
OMAiWFYYQKN.
OrthoDBiEOG7R2BKH.
PhylomeDBiQ15181.
TreeFamiTF300887.

Family and domain databases

Gene3Di3.90.80.10. 1 hit.
InterProiIPR008162. Pyrophosphatase.
[Graphical view]
PANTHERiPTHR10286. PTHR10286. 1 hit.
PfamiPF00719. Pyrophosphatase. 1 hit.
[Graphical view]
SUPFAMiSSF50324. SSF50324. 1 hit.
PROSITEiPS00387. PPASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q15181-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSGFSTEERA APFSLEYRVF LKNEKGQYIS PFHDIPIYAD KDVFHMVVEV
60 70 80 90 100
PRWSNAKMEI ATKDPLNPIK QDVKKGKLRY VANLFPYKGY IWNYGAIPQT
110 120 130 140 150
WEDPGHNDKH TGCCGDNDPI DVCEIGSKVC ARGEIIGVKV LGILAMIDEG
160 170 180 190 200
ETDWKVIAIN VDDPDAANYN DINDVKRLKP GYLEATVDWF RRYKVPDGKP
210 220 230 240 250
ENEFAFNAEF KDKDFAIDII KSTHDHWKAL VTKKTNGKGI SCMNTTLSES
260 270 280
PFKCDPDAAR AIVDALPPPC ESACTVPTDV DKWFHHQKN
Length:289
Mass (Da):32,660
Last modified:May 29, 2000 - v2
Checksum:iE3973C9E6F8CA5CD
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti12 – 121P → A in AAD24964 (Ref. 8) Curated
Sequence conflicti84 – 841L → I in CAA88494 (Ref. 10) Curated
Sequence conflicti96 – 972AI → TL in CAA88494 (Ref. 10) Curated
Sequence conflicti105 – 11410GHNDKHTGCC → HEKDKSTNCF in CAA88494 (Ref. 10) Curated
Sequence conflicti129 – 14012VCARG…IGVKV → ILSCGEVIHVKI in CAA88494 (Ref. 10) CuratedAdd
BLAST
Sequence conflicti146 – 1461M → L in CAA88494 (Ref. 10) Curated
Sequence conflicti156 – 1561V → L in CAA88494 (Ref. 10) Curated
Sequence conflicti161 – 1622VD → AN in CAA88494 (Ref. 10) Curated
Sequence conflicti165 – 1739DAANYNDIN → EASKFHDID in CAA88494 (Ref. 10) Curated
Sequence conflicti177 – 1782RL → KF in CAA88494 (Ref. 10) Curated
Sequence conflicti187 – 1882VD → LN in CAA88494 (Ref. 10) Curated
Sequence conflicti192 – 1921R → L in CAA88494 (Ref. 10) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti57 – 571K → N in a breast cancer sample; somatic mutation. 1 Publication
VAR_036358

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF154065 mRNA. Translation: AAD34643.1.
AB026723 mRNA. Translation: BAA84702.1.
AF217186 mRNA. Translation: AAG36780.1.
AF092439 mRNA. Translation: AAP97214.1.
AF119665 mRNA. Translation: AAF17222.1.
AL731540 Genomic DNA. Translation: CAI13692.1.
BC001022 mRNA. Translation: AAH01022.3.
BC061581 mRNA. Translation: AAH61581.2.
BC105034 mRNA. Translation: AAI05035.1.
BC105036 mRNA. Translation: AAI05037.1.
BC107882 mRNA. Translation: AAI07883.1.
AF108211 mRNA. Translation: AAD24964.1.
Z48605 mRNA. Translation: CAA88494.1.
CCDSiCCDS7299.1.
RefSeqiNP_066952.1. NM_021129.3.
UniGeneiHs.437403.

Genome annotation databases

EnsembliENST00000373232; ENSP00000362329; ENSG00000180817.
GeneIDi5464.
KEGGihsa:5464.
UCSCiuc001jqv.1. human.

Polymorphism databases

DMDMi8247940.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF154065 mRNA. Translation: AAD34643.1.
AB026723 mRNA. Translation: BAA84702.1.
AF217186 mRNA. Translation: AAG36780.1.
AF092439 mRNA. Translation: AAP97214.1.
AF119665 mRNA. Translation: AAF17222.1.
AL731540 Genomic DNA. Translation: CAI13692.1.
BC001022 mRNA. Translation: AAH01022.3.
BC061581 mRNA. Translation: AAH61581.2.
BC105034 mRNA. Translation: AAI05035.1.
BC105036 mRNA. Translation: AAI05037.1.
BC107882 mRNA. Translation: AAI07883.1.
AF108211 mRNA. Translation: AAD24964.1.
Z48605 mRNA. Translation: CAA88494.1.
CCDSiCCDS7299.1.
RefSeqiNP_066952.1. NM_021129.3.
UniGeneiHs.437403.

3D structure databases

ProteinModelPortaliQ15181.
SMRiQ15181. Positions 4-284.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111460. 20 interactions.
IntActiQ15181. 9 interactions.
MINTiMINT-3030968.
STRINGi9606.ENSP00000362329.

PTM databases

PhosphoSiteiQ15181.

Polymorphism databases

DMDMi8247940.

2D gel databases

REPRODUCTION-2DPAGEIPI00015018.

Proteomic databases

MaxQBiQ15181.
PaxDbiQ15181.
PeptideAtlasiQ15181.
PRIDEiQ15181.

Protocols and materials databases

DNASUi5464.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000373232; ENSP00000362329; ENSG00000180817.
GeneIDi5464.
KEGGihsa:5464.
UCSCiuc001jqv.1. human.

Organism-specific databases

CTDi5464.
GeneCardsiGC10M071962.
H-InvDBHIX0032502.
HGNCiHGNC:9226. PPA1.
HPAiHPA019878.
HPA020096.
MIMi179030. gene.
neXtProtiNX_Q15181.
PharmGKBiPA33550.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0221.
HOGENOMiHOG000195569.
HOVERGENiHBG000491.
InParanoidiQ15181.
KOiK01507.
OMAiWFYYQKN.
OrthoDBiEOG7R2BKH.
PhylomeDBiQ15181.
TreeFamiTF300887.

Enzyme and pathway databases

BRENDAi3.6.1.1. 2681.
ReactomeiREACT_15306. Cytosolic tRNA aminoacylation.

Miscellaneous databases

ChiTaRSiPPA1. human.
GenomeRNAii5464.
NextBioi21148.
PROiQ15181.
SOURCEiSearch...

Gene expression databases

BgeeiQ15181.
CleanExiHS_PPA1.
ExpressionAtlasiQ15181. baseline and differential.
GenevestigatoriQ15181.

Family and domain databases

Gene3Di3.90.80.10. 1 hit.
InterProiIPR008162. Pyrophosphatase.
[Graphical view]
PANTHERiPTHR10286. PTHR10286. 1 hit.
PfamiPF00719. Pyrophosphatase. 1 hit.
[Graphical view]
SUPFAMiSSF50324. SSF50324. 1 hit.
PROSITEiPS00387. PPASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and expression profile of human inorganic pyrophosphatase."
    Fairchild T.A., Patejunas G.
    Biochim. Biophys. Acta 1447:133-136(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
    Tissue: Heart.
  2. "Putative inorganic pyrophosphatase."
    Saito T., Hattori A., Miyajima N.
    Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Brain.
  3. "Cloning of a human inorganic pyrophosphatase cDNA."
    Kanni L., Johansson M., Karlsson A.
    Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  4. "Cloning and characterization of a novel human cDNA homology to bovine inorganic pyrophosphatase mRNA."
    Dai F.Y., Yu L., Hu P.R., Xin Y.R., Xu Y.F., Zhao S.Y.
    Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Adrenal gland.
  6. "The DNA sequence and comparative analysis of human chromosome 10."
    Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J.
    , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
    Nature 429:375-381(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain, Lymph and Uterus.
  8. "Cloning, expression, affinity purification and characterization of polyhistidine-tagged cytosolic Saccharomyces cerevisiae and human inorganic pyrophosphatases for differential screening of compounds for antifungal activity."
    Rumsfeld J., Ziegelbauer K., Spaltmann F.
    Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 5-286.
  9. Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.
    Submitted (NOV-2008) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 10-18; 26-41; 58-70; 80-88; 110-128; 140-191; 193-221 AND 239-253, IDENTIFICATION BY MASS SPECTROMETRY.
    Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
  10. "Partial sequence of the human inorganic pyrophosphatase."
    Lacroix J., Vigneron M., Kedinger C.
    Submitted (FEB-1995) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 83-196.
  11. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
    Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
    Anal. Chem. 81:4493-4501(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
  12. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
    Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
    Science 325:834-840(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-57 AND LYS-228, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  13. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
    Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
    Sci. Signal. 3:RA3-RA3(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-250, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  14. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  15. "Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
    Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
    Mol. Cell. Proteomics 11:M111.015131-M111.015131(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
  16. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
  17. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  18. Cited for: VARIANT [LARGE SCALE ANALYSIS] ASN-57.

Entry informationi

Entry nameiIPYR_HUMAN
AccessioniPrimary (citable) accession number: Q15181
Secondary accession number(s): Q2M348
, Q5SQT7, Q6P7P4, Q9UQJ5, Q9Y5B1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 31, 1997
Last sequence update: May 29, 2000
Last modified: March 3, 2015
This is version 150 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.