Alternative titles; symbols
HGNC Approved Gene Symbol: PM20D2
Cytogenetic location: 6q15 Genomic coordinates (GRCh38): 6:89,093,940-89,165,565 (from NCBI)
PM20D2 belongs to the M20 family of metalloproteases and preferentially cleaves basic dipeptides derived from beta-alanine and gamma-aminobutyrate (GABA) (Veiga-da-Cunha et al., 2014).
Using in silico analysis to identify the human ortholog of rat Pm20d2, followed by PCR of a human kidney cDNA library, Veiga-da-Cunha et al. (2014) cloned PM20D2. They also cloned mouse Pm20d2. Western blot analysis detected purified rat skeletal muscle Pm20d2 at an apparent molecular mass of 48 kD.
Using mouse Pm20d2 expressed in E. coli or transfected HEK293 cells, Veiga-da-Cunha et al. (2014) showed that Pm20d2 hydrolyzed several basic dipeptides, including beta-alanyl-lysine, beta-alanyl-ornithine, GABA-lysine, and GABA-ornithine, with lower activity against beta-alanyl-arginine and GABA-arginine. It showed virtually no activity against carnosine (beta-alanyl-histidine) or homocarnosine (GABA-histidine). Human and macaque PM20D2 showed the same substrate preference as mouse and rat Pm20d2, but displayed significantly lower rates of hydrolysis than the rodent enzymes. PM20D2 activity in human or macaque muscle and brain was also lower than that measured in rodent muscle and brain. Veiga-da-Cunha et al. (2014) found that rodent carnosine synthase (CARNS1; 613368) was much more promiscuous than primate carnosine synthase and produced a wider range of dipeptides than the primate enzyme. They proposed that PM20D2 might be more important in rodents than in primates, both to prevent accumulation of abnormal dipeptides and to allow accumulation of physiologically relevant carnosine in skeletal muscle and homocarnosine in brain.
Hartz (2014) mapped the PM20D2 gene to chromosome 6q15 based on an alignment of the PM20D2 sequence (GenBank AK127529) with the genomic sequence (GRCh38).
Hartz, P. A. Personal Communication. Baltimore, Md. 7/29/2014.
Veiga-da-Cunha, M., Chevalier, N., Stroobant, V., Vertommen, D., Van Schaftingen, E. Metabolite proofreading in carnosine and homocarnosine synthesis: molecular identification of PM20D2 as beta-alanyl-lysine dipeptidase. J. Biol. Chem. 289: 19726-19736, 2014. [PubMed: 24891507] [Full Text: https://doi.org/10.1074/jbc.M114.576579]