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. The PP2A-PPP2R5C holoenzyme may specifically dephosphorylate and activate TP53 and play a role in DNA damage-induced inhibition of cell proliferation. PP2A-PPP2R5C may also regulate the ERK signaling pathway through ERK dephosphorylation. Ref.12 Ref.14
Subunit structure: PP2A consists of a common heterodimeric core enzyme, composed of PPP2CA a 36 kDa catalytic subunit (subunit C) and PPP2R1A a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Interacts with PPP2CA AND PPP2R1A; the interaction is direct. Interacts with SGOL1; the interaction is direct. Isoform 1 and isoform 2 interact with TP53 (phosphorylated at Ser-15 by ATM); increased upon DNA damage it drives PP2A-mediated dephosphorylation of TP53 at Thr-55. Interacts with IER3 and/or ERK kinases; regulates ERK dephosphorylation. Ref.11 Ref.12 Ref.13 Ref.14 Ref.15
Subcellular location: Nucleus. Chromosome › centromere Ref.9 Ref.11.
Tissue specificity: Highest levels in heart, skeletal muscle and brain. Lower levels in pancreas, kidney, lung and placenta. Very low levels in liver.
Induction: Up-regulated upon DNA damage. Ref.14
Post-translational modification: Isoform Gamma-3 is phosphorylated on serine residues. Isoform Gamma-1 phosphorylation by ERK2 is IER3-dependent and inhibits ERK dephosphorylation by PP2A-PPP2R5C. Ref.9 Ref.12
Sequence similarities: Belongs to the phosphatase 2A regulatory subunit B56 family.
Sequence caution: The sequence AAC50387.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.The sequence BAG63760.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.
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