2',5'-phosphodiesterase 12 (PDE12)

The protein contains 609 amino acids for an estimated molecular weight of 67352 Da.

 

Enzyme that cleaves 2',5'-phosphodiester bond linking adenosines of the 5'-triphosphorylated oligoadenylates, triphosphorylated oligoadenylates referred as 2-5A modulates the 2-5A system. Degrades triphosphorylated 2-5A to produce AMP and ATP (PubMed:26055709). Also cleaves 3',5'-phosphodiester bond of oligoadenylates (PubMed:21666256, PubMed:30389976, PubMed:26055709). Plays a role as a negative regulator of the 2-5A system that is one of the major pathways for antiviral and antitumor functions induced by interferons (IFNs). Suppression of this enzyme increases cellular 2-5A levels and decreases viral replication in cultured small-airway epithelial cells and Hela cells (PubMed:26055709). (updated: June 5, 2019)

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.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

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.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

Interpro domains
Total structural coverage: 0%
Model score: 0
MODL_I-TASSER-3.0

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VariantDescription
dbSNP:rs2241988

The reference OMIM entry for this protein is 616519

Phosphodiesterase 12; pde12
Pde, 2-prime

DESCRIPTION

PDE12 degrades 2-prime,5-prime-oligoadenylate (2-5A), a second messenger involved in the antiviral action of interferon (IFN; see 147660) that is synthesized by OAS enzymes (see 164350) (Wood et al., 2015).

CLONING

Kubota et al. (2004) purified Pde12, which they called 2-prime-PDE, from bovine liver. By EST database analysis and RT-PCR of human liver RNA, they obtained full-length human PDE12. The predicted 609-amino acid protein has a calculated molecular mass of 67 kD and contains a potential endonuclease/exonuclease/phosphatase domain. It shares 88% amino acid identity with the mouse ortholog. Northern blot and RT-PCR analyses revealed ubiquitous expression of a 4.0-kb transcript in human tissues and cell lines.

GENE FUNCTION

Kubota et al. (2004) showed that recombinant human PDE12 degraded 2-5A. Overexpression of PDE12 reduced antitumor cytotoxicity by IFN, and suppression of PDE12 via small interfering RNA or an inhibitor resulted in reduced viral replication. Kubota et al. (2004) concluded that PDE12 is a key enzyme in the 2-5A system. Rorbach et al. (2011) found that increased PDE12 expression in human mitochondria resulted in alteration of mitochondrial RNA expression accompanied by altered poly(A) tail length and severe inhibition of mitochondrial protein synthesis. They concluded that PDE12 removes mitochondrial RNA poly(A) tails and controls translation in human mitochondria. Wood et al. (2015) found that HeLa cells lacking PDE12 had increased 2-5A levels in response to IFN and poly(I-C) and showed increased resistance to viral pathogens.

GENE STRUCTURE

Kubota et al. (2004) determined that the PDE12 gene contains 3 exons.

MAPPING

By genomic sequence analysis, Kubota et al. (2004) mapped the PDE12 gene to chromosome 3q21.2. ... More on the omim web site

Subscribe to this protein entry history

June 6, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

May 11, 2019: Protein entry updated
Automatic update: model status changed

Jan. 21, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

Nov. 16, 2018: Protein entry updated
Automatic update: model status changed

Feb. 6, 2018: Protein entry updated
Automatic update: OMIM entry 616519 was added.

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