ID:PP1R8_HUMAN DESCRIPTION: RecName: Full=Nuclear inhibitor of protein phosphatase 1; Short=NIPP-1; AltName: Full=Protein phosphatase 1 regulatory inhibitor subunit 8; Includes: RecName: Full=Activator of RNA decay; EC=3.1.4.-; AltName: Full=ARD-1; 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. FUNCTION: 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. COFACTOR: Magnesium. Endoribonuclease function is magnesium- dependent. SUBUNIT: Interacts with phosphorylated CDC5L, SF3B1 and MELK. Interacts with EED, in a nucleic acid-stimulated manner. Part of a complex consisting of PPP1R8, EED, HDAC2 and PP-1. Part of the spliceosome. Interacts with PPP1CA, PPP1CB and PPP1CC. SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Note=Primarily, but not exclusively, nuclear. SUBCELLULAR LOCATION: Isoform Gamma: Cytoplasm. Note=Found mainly in the cytoplasm. 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. DOMAIN: Has a basic N- and C-terminal and an acidic central domain. DOMAIN: The FHA domain mediates interactions with threonine- phosphorylated MELK (By similarity). PTM: 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. MISCELLANEOUS: A synthetic peptide, NIPP-1(330-351), is able to inhibit PP-1. Phosphorylation of Tyr-335 reduces PP-1 inhibition, whereas phosphorylation of Thr-346 or Ser-348 has no effect. SIMILARITY: Contains 1 FHA domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q12972
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.