The IRBIT domain adds new functions to the AHCY family.
During the past few years, the IRBIT domain has emerged as an important add-on of S-adenosyl-L-homocystein hydrolase (AHCY), thereby creating the new family of AHCY-like proteins. In this review, we discuss the currently available data on this new family of proteins. We describe the IRBIT domain as a unique part of these proteins and give an overview of its regulation via (de)phosphorylation and proteolysis. The second part of this review is focused on the potential functions of the AHCY-like proteins. We propose that the IRBIT domain serves as an anchor for targeting AHCY-like proteins towards cytoplasmic targets. This leads to regulation of (i) intracellular Ca2+ via the inositol 1,4,5-trisphosphate receptor (IP3R), (ii) intracellular pH via the Na+/HCO3 - cotransporters (NBCs); whereas inactivation of the IRBIT domain induces (iii) nuclear translocation and regulation of AHCY activity. Dysfunction of AHCY-like proteins will disturb these three important functions, with various biological implications.
Devogelaere
Benoit
B
Laboratory of Molecular and Cellular Signalling, Department of Molecular Cell Biology, Katholieke Universiteit Leuven, Belgium.
Sammels
Eva
E
De Smedt
Humbert
H
D043383:Adenosylhomocysteinase / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs; D000818:Animals; D047108:Embryonic Development / Q000502:physiology; D006801:Humans; D037181:Lectins, C-Type / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution
C470184:CLECL1 protein, human; D037181:Lectins, C-Type; D008565:Membrane Proteins; D054645:Protein Phosphatase 1; D043383:Adenosylhomocysteinase