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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
General
DNA-binding protein
protein phosphatase-1 regulatory subunit
RNA-binding protein
Properties
SIZE: entity length = 351 aa
MW = 38 kD
COMPARTMENT: cytoplasm
cell nucleus
MOTIF: domain {1-142}
MOTIF: forkhead-associated (FHA) domain {49-101}
EED interaction {143-224}
MOTIF: nuclear translocation signal {185-209}
PP-1 inhibition {191-200}
Ser phosphorylation site {S199}
PP-1 binding {200-203}
Ser phosphorylation site {S204}
nuclear translocation signal {210-240}
Tyr phosphorylation site {Y264}
EED interaction {310-329}
binding site
SITE: 330-351
FOR-BINDING-OF: ribonucleic acid
MOTIF: domain {331-337}
Tyr phosphorylation site {Y335}
INHIBITS: phosphatase
Database Correlations
OMIM 602636
UniProt Q12972
Pfam PF00498
Entrez Gene 5511
Kegg hsa:5511
ENZYME EC=3.1.4.-
References
UniProt :accession Q12972