Inorganic pyrophosphatase 2, mitochondrial (PPA2)

The protein contains 334 amino acids for an estimated molecular weight of 37920 Da.

 

Hydrolyzes inorganic pyrophosphate (PubMed:27523597). This activity is essential for correct regulation of mitochondrial membrane potential, and mitochondrial organization and function (PubMed:27523598). (updated: Dec. 20, 2017)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 85%
Model score: 50

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VariantDescription
dbSNP:rs13787
SCFI; loss of function in regulation of mitochondrial membrane potential
SCFI
SCFI
SCFI
SCFI
SCFI and SCFAI
SCFAI
SCFI

The reference OMIM entry for this protein is 609988

Pyrophosphatase, inorganic, 2; ppa2

DESCRIPTION

Inorganic pyrophosphates are generated as byproducts of many biosynthetic 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 PPA2, 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

By searching databases using PPA1 (179030) as query, Curbo et al. (2006) identified PPA2. The deduced 334-amino acid protein has a calculated molecular mass of 38 kD. PPA2 shares about 60% amino acid identity with PPA1, and it has a 31-amino acid N-terminal extension not found in PPA1 that functions as a mitochondrial import signal. Northern blot analysis detected a 1.4-kb PPA2 transcript in all 12 tissues examined, with highest levels in heart, skeletal muscle, kidney, and liver. Fluorescence-tagged PPA2 localized with a mitochondrial marker in transfected HeLa cells.

GENE FUNCTION

Curbo et al. (2006) found that recombinant PPA2 hydrolyzed pyrophosphate in vitro. The reaction was dependent on Mg(2+) and inhibited by Ca(2+).

GENE STRUCTURE

Curbo et al. (2006) determined that the PPA2 gene contains 12 exons and spans about 100 kb.

MAPPING

By genomic sequence analysis, Curbo et al. (2006) mapped the PPA2 gene to chromosome 4q25. ... More on the omim web site

Subscribe to this protein entry history

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 609988 was added.