Alternative titles; symbols
HGNC Approved Gene Symbol: PPP1R3C
Cytogenetic location: 10q23.32 Genomic coordinates (GRCh38): 10:91,628,442-91,633,071 (from NCBI)
Protein phosphatase-1 (PP1; see 176875) participates in the regulation of a wide variety of cellular functions by reversible protein phosphorylation. The ability of PP1 to regulate diverse functions resides in its capacity to interact with a variety of regulatory subunits that may target PP1 to specific subcellular locations, modulate its substrate specificity, and allow its activity to be responsive to extracellular signals. Several targeting subunits of PP1 have been identified, including PPP1R5, the glycogen-binding subunits PPP1R3 (600917) and PPP1R4, and the nuclear inhibitor of PP1 (PPP1R8; 602636) (summary by Doherty et al., 1996).
Doherty et al. (1996) identified the novel PP1 binding subunit PPP1R5 from a human gallbladder cDNA library, by searching an EST database for sequences related to the rat liver glycogen-binding subunit PPP1R4. Overlapping assemblies of ESTs resulted in an estimated mRNA of at least 2.5 kb. Because there was more than one potential initiation codon, the complete open reading frame predicted a protein of 36.4 kD and 317 amino acids, or 35.6 kD and 312 amino acids. The protein contained a motif involved in the binding of PPP1R3 and PPP1R4 to PP1 and a region homologous to a postulated glycogen-binding site in PPP1R3. The amino acid sequence of the PPP1R5 protein showed 42% identity and 51% similarity to rat liver PPP1R4. Whereas rat PPP1R4 appears to be a liver-specific protein, the PPP1R5 protein was identified in cDNA libraries from several adult tissues and cells. Doherty et al. (1996) detected a 36-kD PPP1R5 protein on immunoblot of rat liver and skeletal muscle extracts using an antibody to a PPP1R5 fusion protein. Doherty et al. (1996) demonstrated that PPP1R5 binds to PP1, inhibits the phosphorylase phosphatase activity of PP1, and, unlike PPP1R4, is not regulated by phosphorylase a.
Fernandez-Sanchez et al. (2003) showed that full-length laforin (EPM2A; 607566) interacted with PPP1R5. However, a minimal central region of PPP1R5 (amino acids 116 to 238), including the binding sites for glycogen and for glycogen synthase (GYS1; 138570), was sufficient to interact with laforin. Point mutagenesis of the PPP1R5 glycogen synthase-binding site completely blocked interaction with laforin. Fernandez-Sanchez et al. (2003) identified an EPM2A missense mutation found in Lafora disease (254780) patients that had no effect on the phosphatase or glycogen-binding activities of laforin but disrupted laforin interaction with PPP1R5, suggesting that binding to PPP1R5 may be critical for laforin function.
Doherty et al. (1996) found that the extreme 3-prime region of the assembled PPP1R5 cDNA overlapped 2 sequence tagged sites (WI-11129, TIGR-A004S47) that had been localized to human chromosome 10q23-q24, placing PPP1R5 in this region.
Stumpf (2023) mapped the PPP1R3C gene to chromosome 10q23.32 based on an alignment of the PPP1R3C sequence (GenBank BC012625) with the genomic sequence (GRCh38).
Doherty, M. J., Young, P. R., Cohen, P. T. W. Amino acid sequence of a novel protein phosphatase 1 binding protein (R5) which is related to the liver- and muscle-specific glycogen binding subunits of protein phosphatase 1. FEBS Lett. 399: 339-343, 1996. [PubMed: 8985175] [Full Text: https://doi.org/10.1016/s0014-5793(96)01357-9]
Fernandez-Sanchez, M. E., Criado-Garcia, O., Heath, K. E., Garcia-Fojeda, B., Medrano-Fernandez, I., Gomez-Garre, P., Sanz, P., Serratosa, J. M., Rodriguez de Cordoba, S. Laforin, the dual-phosphatase responsible for Lafora disease, interacts with R5 (PTG), a regulatory subunit of protein phosphatase-1 that enhances glycogen accumulation. Hum. Molec. Genet. 12: 3161-3171, 2003. [PubMed: 14532330] [Full Text: https://doi.org/10.1093/hmg/ddg340]
Stumpf, A. M. Personal Communication. Baltimore, Md. 10/25/2023.