UniProt functional annotation for Q12972



	UniProt functional annotation for Q12972

UniProt code: Q12972.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Note=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. {ECO:0000269|PubMed:10827081, ECO:0000269|PubMed:11739654, ECO:0000269|PubMed:12105215, ECO:0000269|PubMed:12788942, ECO:0000269|PubMed:14699119, ECO:0000269|PubMed:20516061}.

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. {ECO:0000269|PubMed:10103062, ECO:0000269|PubMed:7499293}.

Domain: Has a basic N- and C-terminal and an acidic central domain.

Domain: The FHA domain mediates interactions with threonine- phosphorylated MELK. {ECO:0000250}.

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. {ECO:0000250, ECO:0000269|PubMed:11104670}.

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.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Note=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. {ECO:0000269\|PubMed:10827081, ECO:0000269\|PubMed:11739654, ECO:0000269\|PubMed:12105215, ECO:0000269\|PubMed:12788942, ECO:0000269\|PubMed:14699119, ECO:0000269\|PubMed:20516061}.
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. {ECO:0000269\|PubMed:10103062, ECO:0000269\|PubMed:7499293}.
Domain:		Has a basic N- and C-terminal and an acidic central domain.
Domain:		The FHA domain mediates interactions with threonine- phosphorylated MELK. {ECO:0000250}.
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. {ECO:0000250, ECO:0000269\|PubMed:11104670}.
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.