nuclear inhibitor of protein phosphatase 1; NIPP-1; protein phosphatase 1 regulatory inhibitor subunit 8; includes: activator of RNA decay; ARD-1 (PPP1R8, ARD1, NIPP1)

Function

• inhibitor subunit of the major nuclear protein phosphatase-1 (PP-1)
• RNA-binding activity but does not cleave RNA & may target PP-1 to RNA-associated substrates
• may also be involved in pre-mRNA splicing
• binds DNA & might act as a transcriptional repressor
• seems to be required for cell proliferation
• isoform gamma
  • site-specific single-strand endoribonuclease that cleaves single strand RNA 3' to purines & pyrimidines in A+U-rich regions
  • generates 5'-phosphate termini at the site of cleavage
  • does not inhibit PP-1
  • may be implicated in mRNA splicing
  • may be inactivated by phosphorylation on Ser-199 or Ser-204
  • phosphorylated by Lyn in vitro on Tyr-264, & also on Tyr-335 in the presence of RNA
• interacts with phosphorylated CDC5L, SF3B1 & MELK
• interacts with EED (nucleic acid-stimulated)
• part of a complex consisting of PPP1R8, EED, HDAC2 & PP-1
• part of the spliceosome
• interacts with PPP1CA, PPP1CB & PPP1CC

Cofactor:

• Mg+2
• endoribonuclease function is Mg+2-dependent

Structure

-basic N-terminal & C-terminal & an acidic central domain

• contains 1 FHA domain

Compartment

• nucleus, nuclear speckle
• primarily, but not exclusively, nuclear
• isoform gamma: cytoplasm

Alternative splicing

named isoforms=3; alpha, beta, gamma

Expression

• ubiquitously expressed
• highest levels in heart & skeletal muscle, followed by brain, placenta, lung, liver & pancreas
• less abundant in kidney
• concentration & ratio between isoforms is cell-type dependent
• isoform alpha (>90%) & isoform beta were found in brain, heart & kidney
• isoform gamma is mainly found in B-cells & T-lymphocytes, & has been found in 293 embryonic kidney cells

Notes

• 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

More general terms

• protein phosphatase-1 regulatory subunit
• DNA-binding protein
• RNA-binding protein

Component of

• spliceosome

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=5511
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:5511
• OMIM: https://mirror.omim.org/entry/602636
• UniProt: http://www.uniprot.org/uniprot/Q12972.html