Preferentially catalyzes the dephosphorylation of 'Ser-5' within the tandem 7 residue repeats in the C-terminal domain (CTD) of the largest RNA polymerase II subunit POLR2A. Negatively regulates RNA polymerase II transcription, possibly by controlling the transition from initiation/capping to processive transcript elongation. Recruited by REST to neuronal genes that contain RE-1 elements, leading to neuronal gene silencing in non-neuronal cells. (updated: April 1, 2015)
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
No sequence conservation computed yet.
Total structural coverage: 82%
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The reference OMIM entry for this protein is 605323
C-terminal domain of rna polymerase ii polypeptide a, small phosphatase of, 1; ctdsp1
Ctd small phosphatase 1
Small ctd phosphatase 1; scp1
Nuclear lim interactor-interacting factor; nliif
CLONING
While sequencing genomic DNA surrounding the NRAMP1 gene (
600266) on chromosome 2q34, Marquet et al. (2000) identified a novel gene, which they termed nuclear LIM interactor-interacting factor (NLIIF) by analogy to its closest ortholog, chicken NLI-interacting factor. It encodes a deduced 261-amino acid protein that contains putative regulatory elements including consensus binding sequences for Sp1 (
189906), AP2 (see
107580), NF-kappa-B (see
164011), and PU1 (
165170). Analysis of the predicted amino acid sequence suggested to the authors that NLIIF is a cytoplasmic protein that may be translocated to the nucleus. Northern blot analysis revealed ubiquitous expression of a 2.6-kb NLIIF mRNA in all tissues tested, with highest expression in spleen, lung, and placenta. A second mRNA of approximately 7 kb was expressed only in placenta. By EST database analysis, Yeo et al. (2003) identified a CTDSP1 splice variant encoding a deduced 214-amino acid protein. This isoform has an N-terminal truncation but retains the complete CTD phosphatase domain. The phosphatase domain of CTDSP1 shares more than 90% homology with the phosphatase domains of CTDSP2 (
608711) and CTDSPL (
608592), and about 20% homology with the phosphatase domain of CTDP1 (
604927). Immunofluorescence microscopy localized endogenous CTDSP1 in the nucleus of COS-7 cells.
GENE FUNCTION
Using the synthetic substrate para-nitrophenylphosphate in an in vitro phosphatase assay, Yeo et al. (2003) determined that both the 261-amino acid and the 214-amino acid CTDSP1 splice variants had phosphatase activity. The pH optimum was near 5, and the activity was Mg(2+) dependent and resistant to the phosphatase inhibitors okadaic acid and microcystin. By mutating critical asp residues, Yeo et al. (2003) determined that CTDSP1 is a class 2C phosphatase with activity dependent on the conserved DxD motif. They also found that the shorter isoform preferentially dephosphorylated ser5 within the C-terminal domain of the large subunit of RNA polymerase II (POLR2A;
180660), and activity was stimulated by the RAP74 (GTF2F1;
189968) subunit of general transcription factor IIF. Expression of CTDSP1 inhibited activated transcription from several promoter-reporter gene constructs, but expression of a mutant lacking phosphatase activity enhanced transcription. Neuronal gene transcription is repressed in nonneuronal cells by the repressor element-1 (RE1)-silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF;
600571) complex. To understand how this silencing is achieved, Yeo et al. (2005) examined CTDSP1, CTDSP2, and CTDSPL, the small CTD phosphatases (SCP), whose expression is restricted to nonneuronal tissues. Yeo et al. (2005) showed that REST/NRSF recruits SCPs to neuronal genes that contain RE1 elements, leading to neuronal gene silencing in nonneuronal cells. Phosphatase-inactive forms of SCP interfere with REST/NRSF function and promote neuronal differentiation of P19 stem cells. Likewise, small interfering RNA directed to the single Drosophila SCP unmasks neuronal gene expression in S2 cells. Thus, Yeo et al. (2005) concluded that SCP activity is an evolutionarily conserved transcriptional regulator that acts globally to silence neuronal genes.
GENE STRUCTURE
Marquet et al. (2000) determined that the NLIIF gene contains 7 exons that vary in size from 57 to 1,644 bp. Chang et al. (2008) found that intron 4 of CTDSP1 contains the microRNA MIRN ...
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Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 605323 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed