PPP2R2B
Domain
The N-terminal 26 residues of isoform 2 constitute a cryptic mitochondrial matrix import signal with critical basic and hydrophobic residues, that is necessary and sufficient for targeting the PP2A holoenzyme to the outer mitochondrial membrane (OMM) and does not affect holoenzyme formation or catalytic activity.
The last WD repeat of isoform 2 constitutes a mitochondrial stop-transfer domain that confers resistance to the unfolding step process required for import and therefore prevents PPP2R2B matrix translocation and signal sequence cleavage.
Function
The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment. Within the PP2A holoenzyme complex, isoform 2 is required to promote proapoptotic activity (By similarity). Isoform 2 regulates neuronal survival through the mitochondrial fission and fusion balance (By similarity).
Involvement in disease
Spinocerebellar ataxia 12
SCA12
Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA12 is an autosomal dominant cerebellar ataxia (ADCA).
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the phosphatase 2A regulatory subunit B family.
Tissue Specificity
Brain.
Cellular localization
- Isoform 1
- Cytoplasm
- Cytoplasm
- Cytoskeleton
- Membrane
- Isoform 2
- Cytoplasm
- Mitochondrion
- Mitochondrion outer membrane
- Under basal conditions, localizes to both cytosolic and mitochondrial compartments. Relocalizes from the cytosolic 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 (By similarity).
Alternative names
Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform, PP2A subunit B isoform B55-beta, PP2A subunit B isoform PR55-beta, PP2A subunit B isoform R2-beta, PP2A subunit B isoform beta, PPP2R2B