PPP2CB (UniProt P62714) encodes the catalytic subunit beta isoform of protein phosphatase 2A (PP2A-beta, PP2Acbeta). It is the minor catalytic isoform of PP2A, with PPP2CA being the major isoform (~10x more abundant in most tissues). The two share ~97% sequence identity [deep-research-falcon, goguetrubio2020, "~97% sequence similarity/identity reported in multiple authoritative reviews"].
PPP2CB is a metal-dependent serine/threonine phosphoprotein phosphatase (EC 3.1.3.16). It uses a bimetallic Mn2+ active site to hydrolyze phospho-serine and phospho-threonine bonds on protein substrates [PMID:10318862, deep-research-falcon].
The protein functions as the catalytic subunit of the heterotrimeric PP2A holoenzyme complex, consisting of:
- A (scaffold) subunit (PPP2R1A or PPP2R1B)
- C (catalytic) subunit (PPP2CA or PPP2CB)
- B (regulatory) subunit (multiple families: B/B55, B'/B56, B'', B''')
Regulatory B subunits determine substrate specificity and subcellular localization. Combinatorial assembly yields >70-90 distinct PP2A holoenzymes [deep-research-falcon, nasa2020].
PPP2CB is predominantly cytoplasmic and nuclear [deep-research-falcon, baskaran2018, "Cbeta (PPP2CB) is predominantly cytoplasmic and nuclear"]. During prometaphase, localizes to centromeres; during mitosis, found at spindle poles [UniProt subcellular location, PMID:16541025].
PPP2CB is part of the STRIPAK complex [PMID:18782753, "STRIPAK contains the PP2A catalytic (PP2Ac) and scaffolding (PP2A A) subunits, the striatins (PP2A regulatory B''' subunits), the striatin-associated protein Mob3, the novel proteins STRIP1 and STRIP2...PDCD10...and members of the germinal center kinase III family of Ste20 kinases"].
PMID:28159925 shows PPP2CB knockdown in MSCs increases RELA/p65 levels and, in combination with TNFalpha, enhances IL-6, CCL2, and CCL5 transcription. PPP2CB is a direct target of miR-1246. This supports roles in negative regulation of NF-kappaB and TNF-mediated signaling, but the effects are context-dependent (require TNFalpha co-stimulation for pro-inflammatory cytokine changes).
PP2A is the major tau phosphatase in human brain, accounting for ~71% of tau phosphatase activity PMID:16262633. PP2A activity negatively correlates with tau phosphorylation. This supports annotations related to tau binding and neurofibrillary tangle regulation, though these studies used PP2A broadly (not PPP2CB-specific).