The human homologue of yeast ArgRIII protein is an inositol phosphate multikinase with predominantly nuclear localization.
The function of the transcription regulator ArgRIII in the expression of several genes involved in the metabolism of arginine in yeast has been well studied. It was previously reported that it is also an inositol phosphate multikinase and an important factor of the mRNA export pathway [reviewed by Shears (2000) Bioessays 22, 786-789]. In the present study we report the cloning of a full-length 1248-bp cDNA encoding a human inositol phosphate multikinase (IPMK). This protein has a calculated molecular mass of 47.219 kDa. Functionally important motifs [inositol phosphate-binding site, ATP-binding site, catalytically important SSLL (Ser-Ser-Leu-Leu) domain] are conserved between the human IPMK and yeast ArgRIII. Bacterially expressed protein demonstrated an inositol phosphate multikinase activity similar to that of yeast ArgRIII. Ins(1,4,5)P3 is phosphorylated at positions 3 and 6 up to Ins(1,3,4,5,6)P5. The human IPMK fused with a fluorescent protein tag is localized predominantly in the nucleus when transiently expressed in mammalian cells. A basic cluster in the protein's C-terminus is positively involved in nuclear targeting. These findings are consistent with the concept of a nuclear inositol phosphate signalling and phosphorylation pathway in mammalian cells.
Nalaskowski
Marcus M
MM
Universitaetsklinikum Hamburg-Eppendorf, Institut für Medizinische Biochemie und Molekularbiologie, Abteilung für Zellulaere Signaltransduktion, Martinistrasse 52, 20246 Hamburg, Germany.
Deschermeier
Christina
C
Fanick
Werner
W
Mayr
Georg W
GW
D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology*; D003001:Cloning, Molecular; D017931:DNA Primers; D005656:Fungal Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism*; D007668:Kidney; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry* / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D014162:Transfection
D017931:DNA Primers; D005656:Fungal Proteins; D007295:Inositol Phosphates; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D001120:Arginine; C425775:ARG82 protein, S cerevisiae; D017853:Phosphotransferases (Alcohol Group Acceptor); C434257:inositol polyphosphate multikinase