プロテインホスファターゼ2、タンパク質脱リン酸化酵素2
- 関
- protein phosphatase 2A
WordNet
- any of a large group of nitrogenous organic compounds that are essential constituents of living cells; consist of polymers of amino acids; essential in the diet of animals for growth and for repair of tissues; can be obtained from meat and eggs and milk and legumes; "a diet high in protein"
- any of a group of enzymes that act as a catalyst in the hydrolysis of organic phosphates
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- 蛋白(たんばく)質
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/07/15 05:48:22」(JST)
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"PP2" redirects here. For the kinase inhibitor, see PP2 (kinase inhibitor). For the movie, see The Pink Panther 2.
| protein phosphatase 2, catalytic subunit, alpha isoform |
| Identifiers |
| Symbol |
PPP2CA |
| Entrez |
5515 |
| HUGO |
9299 |
| OMIM |
176915 |
| RefSeq |
NM_002715 |
| UniProt |
P67775 |
| Other data |
| EC number |
3.1.3.16 |
| Locus |
Chr. 5 q23-q31 |
| protein phosphatase 2, catalytic subunit, beta isozyme |
| Identifiers |
| Symbol |
PPP2CB |
| Entrez |
5516 |
| HUGO |
9300 |
| OMIM |
176916 |
| RefSeq |
NM_001009552 |
| UniProt |
P62714 |
| Other data |
| EC number |
3.1.3.16 |
| Locus |
Chr. 8 p12 |
Protein phosphatase 2 (PP2), also known as PP2A, is an enzyme that in humans is encoded by the PPP2CA gene.[1] 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.
Contents
- 1 Structure and function
- 2 Drug discovery
- 3 References
- 4 Further reading
- 5 External links
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 family (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 eukaryotes 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.
| Function |
Protein |
Description |
Note |
| Structural subunit A |
PPP2R1A |
PP2A 65 kDa regulatory subunit A alpha isoform |
subunit A, PR65-alpha isoform |
| PPP2R1B |
PP2A 65 kDa regulatory subunit A beta isoform |
subunit A, PR65-beta isoform |
| Regulatory subunit B |
PPP2R2B |
PP2A 55 kDa regulatory subunit B beta isoform |
subunit B, B-beta isoform |
| PPP2R2C |
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 |
PP2A 72/130 kDa regulatory subunit B |
subunit B, B''-PR72/PR130 |
| PPP2R3B |
PP2A 48 kDa regulatory subunit B |
subunit B, PR48 isoform |
| PPP2R3C |
PP2A regulatory subunit B'' subunit gamma |
subunit G5PR |
| PPP2R4 |
PP2A regulatory subunit B' |
subunit B', PR53 isoform |
| PPP2R5A |
PP2A 56 kDa regulatory subunit alpha isoform |
subunit B, B' alpha isoform |
| PPP2R5B |
PP2A 56 kDa regulatory subunit beta isoform |
subunit B, B' beta isoform |
| PPP2R5C |
PP2A 56 kDa regulatory subunit gamma isoform |
subunit B, B' gamma isoform |
| PPP2R5D |
PP2A 56 kDa regulatory subunit delta isoform |
subunit B, B' delta isoform |
| PPP2R5E |
PP2A 56 kDa regulatory subunit epsilon isoform |
subunit B, B' epsilon isoform |
| Catalytic subunit C |
PPP2CA |
catalytic subunit alpha isoform |
| PPP2CB |
catalytic subunit beta isoform |
Drug discovery
PP2 has been identified as a potential biological target to discover drugs to treat Parkinsons disease and Alzheimers disease, however as of 2014 it was unclear which isoforms would be most beneficial to target, and also whether activation or inhibition would be most therapeutic.[2][3]
PP2 has also been identified as a tumor suppressor for blood cancers, and as of 2015 programs were underway to identify compounds that could either directly activate it, or that could inhibit other proteins that suppress its activity.[4]
References
- ^ Jones TA, Barker HM, da Cruz e Silva EF, Mayer-Jaekel RE, Hemmings BA, Spurr NK, Sheer D, Cohen PT (1993). "Localization of the genes encoding the catalytic subunits of protein phosphatase 2A to human chromosome bands 5q23→q31 and 8p12→p11.2, respectively". Cytogenet. Cell Genet. 63 (1): 35–41. doi:10.1159/000133497. PMID 8383590.
- ^ Braithwaite SP et al. Targeting phosphatases as the next generation of disease modifying therapeutics for Parkinson's disease. Neurochem Int. 2012 Nov;61(6):899-906. doi 10.1016/j.neuint.2012.01.031. PMID 22342821
- ^ Sontag JM, Sontag E. Protein phosphatase 2A dysfunction in Alzheimer's disease. Front Mol Neurosci. 2014 Mar 11;7:16. doi 10.3389/fnmol.2014.00016. eCollection 2014. Review. PMID 24653673 PMC 3949405
- ^ Ciccone M, Calin GA, Perrotti D. From the Biology of PP2A to the PADs for Therapy of Hematologic Malignancies. Front Oncol. 2015 Feb 16;5:21. doi 10.3389/fonc.2015.00021. PMID 25763353 PMC 4329809
Further reading
- Xu Y, Xing Y, Chen Y, Chao Y, Lin Z, Fan E, Yu JW, Strack S, Jeffrey PD, Shi Y (December 2006). "Structure of the protein phosphatase 2A holoenzyme". Cell 127 (6): 1239–51. doi:10.1016/j.cell.2006.11.033. PMID 17174897.
- Xing Y, Xu Y, Chen Y, Jeffrey PD, Chao Y, Lin Z, Li Z, Strack S, Stock JB, Shi Y (October 2006). "Structure of protein phosphatase 2A core enzyme bound to tumor-inducing toxins". Cell 127 (2): 341–53. doi:10.1016/j.cell.2006.09.025. PMID 17055435.
- Ory S, Zhou M, Conrads TP, Veenstra TD, Morrison DK (August 2003). "Protein phosphatase 2A positively regulates Ras signaling by dephosphorylating KSR1 and Raf-1 on critical 14-3-3 binding sites". Curr. Biol. 13 (16): 1356–64. doi:10.1016/S0960-9822(03)00535-9. PMID 12932319.
External links
- PPP2CA protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
|
Hydrolase: esterases (EC 3.1)
|
|
3.1.1: Carboxylic
ester hydrolases |
- Cholinesterase
- Acetylcholinesterase
- Butyrylcholinesterase
- Pectinesterase
- 6-phosphogluconolactonase
- PAF acetylhydrolase
- Lipase
- Bile salt-dependent
- Gastric/Lingual
- Pancreatic
- Lysosomal
- Hormone-sensitive
- Endothelial
- Hepatic
- Lipoprotein
- Monoacylglycerol
- Diacylglycerol
|
|
| 3.1.2: Thioesterase |
- Palmitoyl protein thioesterase
- Ubiquitin carboxy-terminal hydrolase L1
|
|
| 3.1.3: Phosphatase |
- Alkaline phosphatase
- Acid phosphatase (Prostatic)/Tartrate-resistant acid phosphatase/Purple acid phosphatases
- Nucleotidase
- Glucose 6-phosphatase
- Fructose 1,6-bisphosphatase
- Protein phosphatase
- OCRL
- Pyruvate dehydrogenase phosphatase
- Fructose 6-P,2-kinase:fructose 2,6-bisphosphatase
- PTEN
- Phytase
- Inositol-phosphate phosphatase
- Protein phosphatase: Protein tyrosine phosphatase
- Protein serine/threonine phosphatase
- Dual-specificity phosphatase
|
|
| 3.1.4: Phosphodiesterase |
- Autotaxin
- Phospholipase
- Sphingomyelin phosphodiesterase
- PDE1
- PDE2
- PDE3
- PDE4A/PDE4B
- PDE5
- Lecithinase (Clostridium perfringens alpha toxin)
- Cyclic nucleotide phosphodiesterase
|
|
| 3.1.6: Sulfatase |
- arylsulfatase
- Arylsulfatase A
- Arylsulfatase B
- Arylsulfatase E
- Steroid sulfatase
- Galactosamine-6 sulfatase
- Iduronate-2-sulfatase
- N-acetylglucosamine-6-sulfatase
|
|
Nuclease (includes
deoxyribonuclease and
ribonuclease) |
| 3.1.11-16: Exonuclease |
| Exodeoxyribonuclease |
|
|
| Exoribonuclease |
|
|
|
| 3.1.21-31: Endonuclease |
| Endodeoxyribonuclease |
- Deoxyribonuclease I
- Deoxyribonuclease II
- Deoxyribonuclease IV
- Restriction enzyme
- UvrABC endonuclease
|
|
| Endoribonuclease |
- RNase III
- RNase H
- RNase P
- RNase A
- RNase T1
- RNA-induced silencing complex
|
|
| either deoxy- or ribo- |
- Aspergillus nuclease S1
- Micrococcal nuclease
|
|
|
|
- Biochemistry overview
- Enzymes overview
- By EC number: 1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 10
- 11
- 13
- 14
- 15-18
- 2.1
- 3.1
- 4.1
- 5.1
- 6.1-3
|
|
|
|
|
Intracellular signaling peptides and proteins
|
|
| MAP |
|
|
| Calcium |
- Intracellular calcium-sensing proteins
- Calcineurin
- Ca2+/calmodulin-dependent protein kinase
|
|
| G protein |
| Heterotrimeric |
| cAMP: |
- Heterotrimeric G protein
- Adenylate cyclase
- cAMP
- 3',5'-cyclic-AMP phosphodiesterase
- Protein kinase A
|
|
| cGMP: |
- Guanylate cyclase
- cGMP
- 3',5'-cyclic-GMP phosphodiesterase
- Protein kinase G
|
|
- G beta-gamma complex Gβ
- Gγ
- GNGT1
- GNGT2
- GNG2
- GNG3
- GNG4
- GNG5
- GNG7
- GNG8
- GNG10
- GNG11
- GNG12
- GNG13
- BSCL2
|
|
- G protein-coupled receptor kinase
- AMP-activated protein kinase
|
|
|
| Monomeric |
- ARFs
- Rabs
- Ras
- Rhos
- Arfs
- Ran
- Rhebs
- Raps
- RGKs
|
|
|
| Cyclin |
- Cyclin-dependent kinase inhibitor protein
- Cyclin-dependent kinase
- Cyclin
|
|
| Lipid |
- Phosphoinositide phospholipase C
- Phospholipase C
|
|
| Other protein kinase |
| Serine/threonine: |
- Casein kinase
- eIF-2 kinase
- Glycogen synthase kinase
- GSK1
- GSK2
- GSK-3
- GSK3A
- GSK3B
- IκB kinase
- Interleukin-1 receptor-associated kinase
- Lim kinase
- p21-activated kinases
- Rho-associated protein kinase
- Ribosomal s6 kinase
|
|
| Tyrosine: |
- ZAP70
- Focal adhesion protein-tyrosine kinase
- BTK
|
|
| both |
|
|
|
| Other protein phosphatase |
| Serine/threonine: |
|
|
| Tyrosine: |
- protein tyrosine phosphatase: Receptor-like protein tyrosine phosphatase
- Sh2 domain-containing protein tyrosine phosphatase
|
|
| both: |
- Dual-specificity phosphatase
|
|
|
| Apoptosis |
- see apoptosis signaling pathway
|
|
| GTP-binding protein regulators |
- see GTP-binding protein regulators
|
|
| Other |
- Activating transcription factor 6
- Signal transducing adaptor protein
- I-kappa B protein
- Mucin-4
- Olfactory marker protein
- Phosphatidylethanolamine binding protein
- EDARADD
- PRKCSH
|
|
|
see also deficiencies of intracellular signaling peptides and proteins
|
Index of signal transduction
|
|
| Description |
- Intercellular
- neuropeptides
- growth factors
- cytokines
- hormones
- Cell surface receptors
- ligand-gated
- enzyme-linked
- G protein-coupled
- immunoglobulin superfamily
- integrins
- neuropeptide
- growth factor
- cytokine
- Intracellular
- adaptor proteins
- GTP-binding
- MAP kinase
- Calcium signaling
- Lipid signaling
- Pathways
- hedgehog
- Wnt
- TGF beta
- MAPK ERK
- notch
- JAK-STAT
- apoptosis
- hippo
- TLR
|
|
|
UpToDate Contents
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- 1. 脊髄小脳変性症 the spinocerebellar ataxias
English Journal
- Structural probing of a protein phosphatase 2A network by chemical cross-linking and mass spectrometry.
- Herzog F, Kahraman A, Boehringer D, Mak R, Bracher A, Walzthoeni T, Leitner A, Beck M, Hartl FU, Ban N, Malmström L, Aebersold R.SourceDepartment of Biology, Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule Zürich, Wolfgang-Pauli Strasse 16, 8093 Zurich, Switzerland.
- Science (New York, N.Y.).Science.2012 Sep 14;337(6100):1348-52.
- The identification of proximate amino acids by chemical cross-linking and mass spectrometry (XL-MS) facilitates the structural analysis of homogeneous protein complexes. We gained distance restraints on a modular interaction network of protein complexes affinity-purified from human cells by applying
- PMID 22984071
- PPP2R2C as a candidate gene of a temperament and character trait-based endophenotype of ADHD.
- Jacob C, Nguyen TT, Weißflog L, Herrmann M, Liedel S, Zamzow K, Jans T, Renner T, Reichert S, Groß-Lesch S, Lesch KP, Reif A.SourceDepartment of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Fuechsleinstrasse 15, 97080, Wuerzburg, Germany, Jacob_C@klinik.uni-wuerzburg.de.
- Attention deficit and hyperactivity disorders.Atten Defic Hyperact Disord.2012 Sep;4(3):145-52. Epub 2012 Jun 5.
- There are several lines of evidence that the 4p16 region is a candidate locus of both attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder. None of the harbored candidate genes of this region were hitherto shown to be associated with ADHD despite promising functionality. One of the m
- PMID 22664926
Japanese Journal
- Local suppression of pro-inflammatory cytokines and the effects in BMP-2-induced bone regeneration.
- Ratanavaraporn Juthamas,Furuya Hiroyuki,Tabata Yasuhiko
- Biomaterials 33(1), 304-316, 2012-01
- … Gelatin hydrogels incorporating mixed immunosuppressive triptolide-micelles and bone morphogenic protein-2 (BMP-2) were prepared. …
- NAID 120003674150
- Functional characterization of the regulators of calcineurin in Candida glabrata
- Miyazaki Taiga,Izumikawa Koichi,Nagayoshi Yohsuke,Saijo Tomomi,Yamauchi Shunsuke,Morinaga Yoshitomo,Seki Masafumi,Kakeya Hiroshi,Yamamoto Yoshihiro,Yanagihara Katsunori,Miyazaki Yoshitsugu,Kohno Shigeru
- FEMS Yeast Research 11(8), 621-630, 2011-12
- … The serine-threonine-specific protein phosphatase calcineurin is a key mediator of various stress responses in fungi. …
- NAID 120003751871
Related Links
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★リンクテーブル★
[★]
- 英
- protein phosphatase 2
- 関
- タンパク質脱リン酸化酵素2、プロテインホスファターゼ2A
[★]
- 英
- protein phosphatase 2
- 関
- プロテインホスファターゼ2
[★]
- 関
- PP2A、protein phosphatase 2
[★]
プロテインホスファターゼ2B
- 関
- calcineurin、PP2B
[★]
ホスファターゼ、フォスファターゼ、脱リン酸化酵素、脱リン酸酵素
- 関
- phosphohydrolase、phosphoric monoester hydrolase
[★]
蛋白質ホスファターゼ