The nuclear PP1 interacting protein ZAP3 (ZAP) is a putative nucleoside kinase that complexes with SAM68, CIA, NF110/45, and HNRNP-G

Annegret Ulke-Lemée, Laura Trinkle-Mulcahy, Steve Chaulk, Nina K. Bernstein, Nick Morrice, Mark Glover, Angus I. Lamond, Greg B.G. Moorhead (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    29 Citations (Scopus)


    The targeting of protein kinases and phosphatases is fundamental to their roles as cellular regulators. The type one serine/threonine protein phosphatase (PP1) is enriched in the nucleus, yet few nuclear PP1 targeting subunits have been described and characterized. Here we show that the human protein, ZAP3 (also known as ZAP), is localized to the nucleus, that it is expressed in all mammalian tissues examined, and docks to PP1 through an RVRW motif located in its highly conserved carboxy-terminus. Proteomic analysis of a ZAP3 complex revealed that in addition to binding PP1, ZAP3 complexes with CIA (or nuclear receptor co-activator 5) and the RNA binding proteins hnRNP-G, SAM68 and NF110/45, but loses affinity for SAM68 and hnRNP-G upon digestion of endogenous nucleic acid. Bioinformatics has revealed that the conserved carboxy-terminus is orthologous to T4- and mammalian polynucleotide kinases with residues necessary for kinase activity maintained throughout evolution. Furthermore, the substrate binding pocket of uridine-cytidine kinase (or uridine kinase) has localized sequence similarity with ZAP3, suggesting uridine or cytidine as possible ZAP3 substrates. Most polynucleotide kinases have a phosphohydrolase domain in conjunction with their kinase domain. In ZAP3, although this domain is present, it now appears degenerate and functions to bind PP1 through an RVRW docking site located within the domain.

    Original languageEnglish
    Pages (from-to)1339-1350
    Number of pages12
    JournalBiochimica et Biophysica Acta - Proteins and Proteomics
    Issue number10
    Publication statusPublished - 1 Oct 2007


    • Nucleus
    • Phosphatase
    • Phosphohydrolase
    • Polynucleotide kinase
    • PP1
    • Targeting

    ASJC Scopus subject areas

    • Analytical Chemistry
    • Biophysics
    • Biochemistry
    • Molecular Biology


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