PPP2R2B: the B regulatory subunit of PP2A. May modulate substrate selectivity and catalytic activity, and directs the localization of the catalytic enzyme to particular subcellular compartments. PPP2R2B promotes autophagy and oxidative stress induced cell death that is related to apoptosis. The PP2A holoenzyme consists of a common heterodimeric core enzyme composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (subunit A), that associates with a variety of regulatory subunits. Three families of regulatory subunits associate with the core dimmer: B (R2/PR55/B55), B¿ (R5/B56), and B¿ (R3/PR72/PR130/PR59). Five isoforms of the human protein are produced by alternative splicing. Isoform 1 (Bbeta1) localizes within the cytoplasm. Isoform 2 (Bbeta2) localizes to both cytosolic and mitochondrial compartments under basal conditions, relocating to the mitochondrial compartment during apoptosis. Its targeting to the outer mitochondrial membrane (OMM) involves an association with import receptors of the TOM complex and is required to promote proapoptotic activity. The N-terminal 26 residues of isoform 2 constitute a cryptic mitochondrial matrix import signal that is necessary and sufficient for targeting the PP2A holoenzyme to the OMM. The last WD repeat of isoform 2 constitutes a mitochondrial stop-transfer domain that prevents PPP2R2B matrix translocation and signal sequence cleavage. Defects in PPP2R2B are the cause of spinocerebellar ataxia type 12 (SCA12).
Protein type: Motility/polarity/chemotaxis; Apoptosis; Mitochondrial; Protein phosphatase, regulatory subunit
Chromosomal Location of Human Ortholog: 5q32
Cellular Component: mitochondrial outer membrane; protein phosphatase type 2A complex; cytoskeleton; mitochondrion
Molecular Function: protein binding; protein phosphatase type 2A regulator activity
Biological Process: apoptosis; regulation of catalytic activity; signal transduction
Disease: Spinocerebellar Ataxia 12
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