PPP1R8
Domain
Has a basic N- and C-terminal and an acidic central domain.
The FHA domain mediates interactions with threonine-phosphorylated MELK.
Function
Inhibitor subunit of the major nuclear protein phosphatase-1 (PP-1). It has RNA-binding activity but does not cleave RNA and may target PP-1 to RNA-associated substrates. May also be involved in pre-mRNA splicing. Binds DNA and might act as a transcriptional repressor. Seems to be required for cell proliferation.
Isoform Gamma is a site-specific single-strand endoribonuclease that cleaves single strand RNA 3' to purines and pyrimidines in A+U-rich regions. It generates 5'-phosphate termini at the site of cleavage. This isoform does not inhibit PP-1. May be implicated in mRNA splicing.
Post-translational modifications
May be inactivated by phosphorylation on Ser-199 or Ser-204 (By similarity). Phosphorylated by Lyn in vitro on Tyr-264, and also on Tyr-335 in the presence of RNA.
Tissue Specificity
Ubiquitously expressed, with highest levels in heart and skeletal muscle, followed by brain, placenta, lung, liver and pancreas. Less abundant in kidney. The concentration and ratio between isoforms is cell-type dependent. Isoform Alpha (>90%) and isoform Beta were found in brain, heart and kidney. Isoform Gamma is mainly found in B-cells and T-lymphocytes, and has been found in 293 embryonic kidney cells.
Cellular localization
- Nucleus
- Nucleus speckle
- Primarily, but not exclusively, nuclear.
- Isoform Gamma
- Cytoplasm
- Found mainly in the cytoplasm.
Alternative names
ARD1, NIPP1, PPP1R8, Nuclear inhibitor of protein phosphatase 1, NIPP-1, Protein phosphatase 1 regulatory inhibitor subunit 8