Phosphatase Subfamily FCP1

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Phosphatase Classification: Fold HAD: Superfamily HAD: Family FCP: Subfamily FCP1

F-cell production 1 (FCP1) also called TFIIF-stimulated CTD phosphatase 1 (CTDP1), prefers to dephosphorylate pSer2 of heptapeptide repeats at CTD of RNA polymerase II. The molecular function is mainly studied in yeast [1].

Evolution

FCP1 is conserved from yeast to human, usually one copy per genome.

Domain Structure

In additional to the catalytic domain, it has a breast cancer protein-related carboxy-terminal (BRCT) domain and a C-terminal region (FCP1_C) that binds regulatory TFIIF.

The FCP1_C domain is found widely in deuterosomes (from sea urchin to chordates). It is absent from most proteostomes, except some individual organisms. It is present in basal eumetazoan Nematostella. It is probably FCP1_C domain was gained in eumetazoa, but was lost in multiple independent events. See technical notes.

Functions

FCP1 preferentially hydrolyzes Ser2 in CTD repeats in budding yeast [1] and fission yeast [2].

Substrates and Related Kinases

See Phosphorylation of RNA polymerase II C-terminal domain.

Technical notes

FCP1_C domain

In order to find FCP1_C domain phylogenetic distribution among FCP1, we obtained the FCP1 from our internal orthology database, which contains 227 from 183 eukaryotic genomes. We then searched the FCP1_C domain by Pfam web server.

We also searched the FCP1_C domain region of human FCP1 defined by Pfam against NR dataset limiting to metazoa excluding deuterosomes through NCBI BLAST server. We found no hit has E-value lower than 0.1. We did not find FCP1_C in nematostella sequence in NR dataset, because our updated nematostella sequence is different from the one in NR.

References

  1. Kamenski T, Heilmeier S, Meinhart A, and Cramer P. Structure and mechanism of RNA polymerase II CTD phosphatases. Mol Cell. 2004 Aug 13;15(3):399-407. DOI:10.1016/j.molcel.2004.06.035 | PubMed ID:15304220 | HubMed [Kamenski04]
  2. Schwer B, Ghosh A, Sanchez AM, Lima CD, and Shuman S. Genetic and structural analysis of the essential fission yeast RNA polymerase II CTD phosphatase Fcp1. RNA. 2015 Jun;21(6):1135-46. DOI:10.1261/rna.050286.115 | PubMed ID:25883047 | HubMed [Schwer15]
  3. Hsin JP, Xiang K, and Manley JL. Function and control of RNA polymerase II C-terminal domain phosphorylation in vertebrate transcription and RNA processing. Mol Cell Biol. 2014 Jul;34(13):2488-98. DOI:10.1128/MCB.00181-14 | PubMed ID:24752900 | HubMed [hsin2014]
All Medline abstracts: PubMed | HubMed