Alternative titles; symbols
HGNC Approved Gene Symbol: PPP1CC
Cytogenetic location: 12q24.11 Genomic coordinates (GRCh38): 12:110,708,376-110,742,891 (from NCBI)
Norman and Mott (1994) isolated from human skeletal muscle a human homolog of rat cDNA for liver protein phosphatase 1, gamma subunit. The nucleotide sequence contained a 957-nucleotide open reading frame encoding an amino acid sequence identical to that encoded by the rat liver cDNA. Northern blot analysis showed that PPP1G-specific mRNA is expressed in human heart, brain, placenta, lung, liver, skeletal muscle, kidney, and pancreas.
Hrabchak and Varmuza (2004) reviewed previous research showing that mouse Ppp1cc is alternatively spliced to form gamma-1 and gamma-2 isoforms, the latter of which is predominantly expressed in mouse testis. By immunohistochemical analysis, Hrabchak and Varmuza (2004) showed that the gamma-2 isoform was expressed during all stages of mouse spermatogenesis, with stronger expression in germ cells and Sertoli cells and weaker expression in spermatogonia and along the basement membrane of seminiferous epithelium. Immunofluorescence experiments in COS-1 monkey kidney cells demonstrated that gamma-2 localized uniformly throughout cytoplasm and to nucleoli within nucleus. Coexpression with the gamma-2 repressor Spz1 caused both proteins to colocalize in nucleus.
Using fluorescence imaging of HeLa cells, Trinkle-Mulcahy et al. (2006) showed that both PP1-alpha (PPP1CA; 176875) and -gamma localized in the cytoplasm and nucleus throughout G1, S, and G2 phases. However, nuclear PP1-alpha was mainly in a diffuse pool and largely excluded from nucleoli, whereas nuclear PP1-gamma showed strong accumulation within nucleoli. PP1-alpha and -gamma also differed in their dynamic distribution during cell division. Both PP1-alpha and -gamma localized to kinetochores in metaphase, but PP1-alpha appeared to be predominantly excluded from other chromatin regions at this stage, in contrast with PP1-gamma. In addition, accumulation of PP1-gamma on chromatin increased dramatically at anaphase.
By analysis of genomic DNA from human/hamster somatic hybrid cell lines, Norman and Mott (1994) localized the PPP1G gene to chromosome 12. (The PPP1A gene (more appropriately symbolized PPP1CA) is located on chromosome 11; see 176875. The PPP1CB gene (600590) is located on 2p23.) By fluorescence in situ hybridization, Saadat et al. (1996) demonstrated that the PPP1CC gene maps to human 12q24.1-q24.2, rat 7q22, and mouse 10C.
Using a combination of proteomics, cytology, and functional analysis in C. elegans, Chu et al. (2006) reduced 1,099 proteins copurified with spermatogenic chromatin to 132 proteins for functional analysis. This strategy to find fertility factors conserved from C. elegans to mammals achieved its goal: of mouse gene knockouts corresponding to nematode proteins, 37% (7 of 19) cause male sterility. This list includes PPP1CC, H2AX (601772), SON (182465), TOP1 (126420), DDX4 (605281), DBY (400010), and CENPC (117141).
Using a gene trap-based system to create knockin mouse embryonic stem cells, followed by tandem affinity purification, MacLeod and Varmuza (2012) identified significant protein-protein interactions of Ppp1cc with 9 Pp1-interacting proteins and 2 additional proteins, Ddost (602202) and Atp5c1 (108729). Sedimentation and Western blot analyses confirmed interaction of the testis-specific Ppp1cc2 isoform with Ddost. Confocal microscopy demonstrated localization of Ddost at the nuclear envelope in mouse spermatogenic cells.
Hrabchak and Varmuza (2004) reviewed previous research showing that Ppp1cc is negatively regulated by Staufen (STAU1; 601716), neurabin I (PPP1R9A; 602468), and the skeletal muscle glycogen-targeting subunit GM (PPP1R3A; 600917).
MacLeod and Varmuza (2012) noted that homozygous deletion of Ppp1cc results in failure of spermatogenesis in mice.
Chu, D. S., Liu, H., Nix, P., Wu, T. F., Ralston, E. J., Yates, J. R., III, Meyer, B. J. Sperm chromatin proteomics identifies evolutionarily conserved fertility factors. Nature 443: 101-105, 2006. [PubMed: 16943775] [Full Text: https://doi.org/10.1038/nature05050]
Hrabchak, C., Varmuza, S. Identification of the spermatogenic zip protein Spz1 as a putative protein phosphatase-1 (PP1) regulatory protein that specifically binds the PP1c-gamma-2 splice variant in mouse testis. J. Biol. Chem. 279: 37079-37086, 2004. [PubMed: 15226296] [Full Text: https://doi.org/10.1074/jbc.M403710200]
MacLeod, G., Varmuza, S. Tandem affinity purification in transgenic mouse embryonic stem cells identifies DDOST as a novel PPP1CC2 interacting protein. Biochemistry 51: 9678-9688, 2012. [PubMed: 23140390] [Full Text: https://doi.org/10.1021/bi3010158]
Norman, S. A., Mott, D. M. Molecular cloning and chromosomal localization of a human skeletal muscle PP-1-gamma-1 cDNA. Mammalian Genome 5: 41-45, 1994. [PubMed: 8111128] [Full Text: https://doi.org/10.1007/BF00360567]
Saadat, M., Nomoto, K., Mizuno, Y., Kikuchi, K., Yoshida, M. C. Assignment of the gene encoding type 1-gamma protein phosphatase catalytic subunit (PPP1CC) on human, rat, and mouse chromosomes. Jpn. J. Hum. Genet. 41: 159-165, 1996. [PubMed: 8914631] [Full Text: https://doi.org/10.1007/BF01892623]
Trinkle-Mulcahy, L., Andersen, J., Lam, Y. W., Moorhead, G., Mann, M., Lamond, A. I. Repo-Man recruits PP1-gamma to chromatin and is essential for cell viability. J. Cell Biol. 172: 679-692, 2006. [PubMed: 16492807] [Full Text: https://doi.org/10.1083/jcb.200508154]