Protein Phosphatase 2
Encyclopedia
Protein phosphatase 2 (PP2), also known as PP2A, is an enzyme
that in humans is encoded by the PPP2CA gene
. The PP2A heterotrimeric protein phosphatase, is a ubiquitous and conserved Serine/Threonine phosphatase with broad substrate specificity and diverse cellular functions. Among the targets of PP2A are proteins of oncogenic signaling cascades, such as Raf
, MEK, and AKT
.
(huntington-elongation-A subunit-TOR), is the scaffold required for the formation of the heterotrimeric complex. When the A subunit binds it alters the enzymatic activity of the catalytic subunit, even if the B subunit is absent. While C and A subunit sequences show remarkable sequence conservation throughout eukaryotes, regulatory B subunits are more heterogeneous and are believed to play key roles in controlling the localization and specific activity of different holoenzymes. Multicellular eukaryote
s express four classes of variable regulatory subunits: B (PR55), B′ (B56 or PR61), B″ (PR72), and B‴ (PR93/PR110), with at least 16 members in these subfamilies. In Addition, accessory proteins and posttranslational modifications (such as methylation) control PP2A subunit associations and activities.
The two catalytic metal ions located at bottom of PP2A's active site have been recently identified as manganese, which had previously been suggested as potential candidates.
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that in humans is encoded by the PPP2CA gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. The PP2A heterotrimeric protein phosphatase, is a ubiquitous and conserved Serine/Threonine phosphatase with broad substrate specificity and diverse cellular functions. Among the targets of PP2A are proteins of oncogenic signaling cascades, such as Raf
C-Raf
RAF proto-oncogene serine/threonine-protein kinase also known as proto-oncogene c-RAF or simply c-Raf is an enzyme that in humans is encoded by the RAF1 gene. The c-Raf protein functions in the MAPK/ERK signal transduction pathway as part of a protein kinase cascade...
, MEK, and AKT
AKT
Akt, also known as Protein Kinase B , is a serine/threonine protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, cell proliferation, apoptosis, transcription and cell migration.-Family members:...
.
Structure and function
PP2A consists of a dimeric core enzyme composed of the structural A and catalytic C subunits, and a regulatory B subunit. When the PP2A catalytic C subunit associates with the A and B subunits several species of holoenzymes are produced with distinct functions and characteristics. The A subunit, a founding member of the HEAT repeat protein familyHeat repeat domain
The HEAT repeat domain is a protein domain found in a number of cytoplasmic proteins including the four that the give rise to the acronym HEAT . HEAT repeats form a rod-like helical structures which are involved in intracellular transport....
(huntington-elongation-A subunit-TOR), is the scaffold required for the formation of the heterotrimeric complex. When the A subunit binds it alters the enzymatic activity of the catalytic subunit, even if the B subunit is absent. While C and A subunit sequences show remarkable sequence conservation throughout eukaryotes, regulatory B subunits are more heterogeneous and are believed to play key roles in controlling the localization and specific activity of different holoenzymes. Multicellular eukaryote
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
s express four classes of variable regulatory subunits: B (PR55), B′ (B56 or PR61), B″ (PR72), and B‴ (PR93/PR110), with at least 16 members in these subfamilies. In Addition, accessory proteins and posttranslational modifications (such as methylation) control PP2A subunit associations and activities.
The two catalytic metal ions located at bottom of PP2A's active site have been recently identified as manganese, which had previously been suggested as potential candidates.
| Function | Protein | Description | Note |
|---|---|---|---|
| Structural subunit A | PPP2R1A PPP2R1A Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform is an enzyme that in humans is encoded by the PPP2R1A gene. In the plant Arabidopsis thaliana a similar enzyme is encoded by the RCN1 gene .- Function :... |
PP2A 65 kDa regulatory subunit A alpha isoform | subunit A, PR65-alpha isoform |
| PPP2R1B PPP2R1B Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform is an enzyme that in humans is encoded by the PPP2R1B gene.-Interactions:... |
PP2A 65 kDa regulatory subunit A beta isoform | subunit A, PR65-beta isoform | |
| Regulatory subunit B | PPP2R2B PPP2R2B Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform is an enzyme that in humans is encoded by the PPP2R2B gene.-External Links:* -Further reading:... |
PP2A 55 kDa regulatory subunit B beta isoform | subunit B, B-beta isoform |
| PPP2R2C PPP2R2C Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform is an enzyme that in humans is encoded by the PPP2R2C gene.-Further reading:... |
PP2A 55 kDa regulatory subunit B gamma isoform | subunit B, B-gamma isoform | |
| PPP2R2D | PP2A 55 kDa regulatory subunit B delta isoform | subunit B, B-delta isoform | |
| PPP2R3A PPP2R3A Serine/threonine-protein phosphatase 2A regulatory subunit B subunit alpha is an enzyme that in humans is encoded by the PPP2R3A gene.-Interactions:PPP2R3A has been shown to interact with CDC6 and PPP2R4.-Further reading:... |
PP2A 72/130 kDa regulatory subunit B | subunit B, B |
|
| PPP2R3B PPP2R3B Serine/threonine-protein phosphatase 2A regulatory subunit B subunit beta is an enzyme that in humans is encoded by the PPP2R3B gene.-Interactions:PPP2R3B has been shown to interact with PPP2R1B, PPP2R1A, CDC6 and PPP2CA.-Further reading:... |
PP2A 48 kDa regulatory subunit B | subunit B, PR48 isoform | |
| PPP2R3C PPP2R3C Serine/threonine-protein phosphatase 2A regulatory subunit B subunit gamma is an enzyme that in humans is encoded by the PPP2R3C gene.-Further reading:... |
PP2A regulatory subunit B |
subunit G5PR | |
| PPP2R4 PPP2R4 Serine/threonine-protein phosphatase 2A regulatory subunit B is an enzyme that in humans is encoded by the PPP2R4 gene.-Interactions:PPP2R4 has been shown to interact with PPP2R3A, CCNG1 and Janus kinase 2.-Further reading:... |
PP2A regulatory subunit B' | subunit B', PR53 isoform | |
| PPP2R5A PPP2R5A Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform is an enzyme that in humans is encoded by the PPP2R5A gene.-Interactions:PPP2R5A has been shown to interact with PPP2R1B, PPP2R1A, CTLA-4, AXIN1 and PPP2CA.... |
PP2A 56 kDa regulatory subunit alpha isoform | subunit B, B' alpha isoform | |
| PPP2R5B PPP2R5B Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform is an enzyme that in humans is encoded by the PPP2R5B gene.-Interactions:PPP2R5B has been shown to interact with PPP2R1B and PPP2CA.-Further reading:... |
PP2A 56 kDa regulatory subunit beta isoform | subunit B, B' beta isoform | |
| PPP2R5C PPP2R5C Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform is an enzyme that in humans is encoded by the PPP2R5C gene.-Interactions:PPP2R5C has been shown to interact with PPP2R1B and PPP2CA.-Further reading:... |
PP2A 56 kDa regulatory subunit gamma isoform | subunit B, B' gamma isoform | |
| PPP2R5D PPP2R5D Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform is an enzyme that in humans is encoded by the PPP2R5D gene.-Interactions:PPP2R5D has been shown to interact with PPP2R1B, liprin-alpha-1, HAND2 and PPP2CA.... |
PP2A 56 kDa regulatory subunit delta isoform | subunit B, B' delta isoform | |
| PPP2R5E PPP2R5E Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform is an enzyme that in humans is encoded by the PPP2R5E gene.-Interactions:PPP2R5E has been shown to interact with PPP2R1B and PPP2CA.-Further reading:... |
PP2A 56 kDa regulatory subunit epsilon isoform | subunit B, B' epsilon isoform | |
| Catalytic subunit C | PPP2CA PPP2CA Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform is an enzyme that in humans is encoded by the PPP2CA gene.-Interactions:... |
catalytic subunit alpha isoform | |
| PPP2CB PPP2CB Serine/threonine-protein phosphatase 2A catalytic subunit beta isoform is an enzyme that in humans is encoded by the PPP2CB gene.-Interactions:PPP2CB has been shown to interact with TLX1, PPP2R1B and PPP2R1A.-Further reading:... |
catalytic subunit beta isoform | ||