| SMART accession number: | SM00156
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| Description: |
Large family of serine/threonine phosphatases, that includes PP1, PP2A and PP2B (calcineurin) family members. |
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| Interpro abstract (IPR006186): |
Protein phosphorylation plays a central role in the regulation of cell functions (PUBMED:2827745), causing the activation or inhibition of many enzymes involved in various biochemical pathways (PUBMED:2176161). Kinases and phosphatases are the enzymes responsible for this, and may themselves be subject to control through the action of hormones and growth factors (PUBMED:2827745). Serine/threonine (S/T) phosphatases (EC 3.1.3.16) catalyse the dephosphorylation of phosphoserine and phosphothreonine residues. In mammalian tissues four different types of PP have been identified and are known as PP1, PP2A, PP2B and PP2C. Except for PP2C, these enzymes are evolutionary related. The catalytic regions of the proteins are well conserved and have a slow mutation rate, suggesting that major changes in these regions are highly detrimental (PUBMED:2827745). Protein phosphatase-1 (PP1) and protein phosphatase-2A (PP2A) have a broad specificity and there are two closely related isoforms of each, alpha and beta. PP2A is a trimeric enzyme that consists of a core composed of a catalytic subunit associated with a 65 kDa regulatory subunit and a third variable subunit. Protein phosphatase-2B (PP2B or calcineurin), a calcium-dependent enzyme whose activity is stimulated by calmodulin, is composed of two subunits the catalytic A-subunit and the calcium-binding B-subunit. The specificity of PP2B is restricted. Other serine/threonine specific protein phosphatases that have been characterised include mammalian phosphatase-X (PP-X), and Drosophila phosphatase-V (PP-V), which are closely related but yet distinct from PP2A; yeast phosphatase PPH3, which is similar to PP2A, but with different enzymatic properties; and Drosophila phosphatase-Y (PP-Y), and yeast phosphatases Z1 and Z2 which are closely related but yet distinct from PP1.
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| GO function: | hydrolase activity (GO:0016787) |
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| Family alignment: |
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Click on the following links for more information.
- Evolution (species in which this domain is found)
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- Literature (relevant references for this domain)
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Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Egloff MP, Cohen PT, Reinemer P, Barford D
- Crystal structure of the catalytic subunit of human protein phosphatase 1 and its complex with tungstate.
- J Mol Biol. 1995; 254: 942-59
- Display abstract
Protein phosphatase 1 (PP1) is a serine/threonine protein phosphatase that is essential in regulating diverse cellular processes. Here we report the crystal structure of the catalytic subunit of human PP1 gamma 1 and its complex with tungstate at 2.5 A resolution. The anomalous scattering from tungstate was used in a multiple wavelength anomalous dispersion experiment to derive crystallographic phase information. The protein adopts a single domain with a novel fold, distinct from that of the protein tyrosine phosphatases. A di-nuclear ion centre consisting of Mn2+ and Fe2+ is situated at the catalytic site that binds the phosphate moiety of the substrate. Proton-induced X-ray emission spectroscopy was used to identify the nature of the ions bound to the enzyme. The structural data indicate that dephosphorylation is catalysed in a single step by a metal-activated water molecule. This contrasts with other phosphatases, including protein tyrosine phosphatases, acid and alkaline phosphatases which form phosphoryl-enzyme intermediates. The structure of PP1 provides insight into the molecular mechanism for substrate recognition, enzyme regulation and inhibition of this enzyme by toxins and tumour promoters and a basis for understanding the expanding family of related phosphatases which include PP2A and PP2B (calcineurin).
- Kinoshita N, Ohkura H, Yanagida M
- Distinct, essential roles of type 1 and 2A protein phosphatases in the control of the fission yeast cell division cycle.
- Cell. 1990; 63: 405-15
- Display abstract
The activities of type 1 protein phosphatase (PP1) and 2A (PP2A) have distinct, essential roles in cell cycle control. Two previously identified PP1 genes (dis2+ and sds21+) and two PP2A genes (ppa1+ and ppa2+), highly homologous to mammalian PP2A, have been isolated from fission yeast. Only double gene disruption of both PP2A genes results in lethality, as is the case for PP1 genes. By fractionating and assaying PPases in wild-type, various deletion, and point mutant strains, the decrease of PP1 or PP2A activity is shown to cause mitotic defects, exhibiting strikingly different cell cycle phenotypes: cold-sensitive mutations in the same amino acid lesion of PP1 and PP2A produce chromosome nondisjunction and premature mitosis, respectively. Consistently, PP1 and PP2A genes cannot be functionally substituted. Although the overall levels of PP1 and PP2A activities do not fluctuate during the cell cycle, subpopulations might be regulated.
- Berndt N et al.
- Isolation and sequence analysis of a cDNA clone encoding a type-1 protein phosphatase catalytic subunit: homology with protein phosphatase 2A.
- FEBS Lett. 1987; 223: 340-6
- Display abstract
A 1.5 kb clone containing the full-length coding sequence of a type-1 protein phosphatase catalytic subunit has been isolated from a rabbit skeletal muscle cDNA library constructed in lambda gt10. The protein sequence deduced from the cDNA contains 311 residues and has a molecular mass of 35.4 kDa. A single mRNA species at 1.6 kb was visualized by Northern blotting. The type-1 protein phosphatase was strikingly homologous to protein phosphatase 2A, 49% of the amino acids between residues 11 and 280 being identical. The first 10 and last 31 residues were dissimilar. Residues 1-101 of the type-1 protein phosphatase also showed 21% sequence identity with a region of mammalian alkaline phosphatases.
- Green DD, Yang SI, Mumby MC
- Molecular cloning and sequence analysis of the catalytic subunit of bovine type 2A protein phosphatase.
- Proc Natl Acad Sci U S A. 1987; 84: 4880-4
- Display abstract
We have isolated a cDNA clone corresponding to the Mr 38,000 catalytic subunit of bovine type 2A protein phosphatase. The cDNA was isolated from a bovine adrenal gland cDNA library through the use of oligonucleotide probes whose sequences were based on partial amino acid sequence obtained from cyanogen bromide fragments of the purified cardiac enzyme. The entire 1724-base-pair cDNA has been sequenced and found to contain an open reading frame coding for a protein of 325 amino acids having a calculated molecular weight of 37,320. The deduced amino acid sequence contains the experimentally determined sequences of five different cyanogen bromide peptides. Transfection of COS-m6 cells with the cloned cDNA resulted in transient expression of a protein that could be detected by immunoblot analysis with a monoclonal antibody directed against the purified cardiac protein phosphatase. The expressed protein had the same apparent molecular weight as the purified enzyme when analyzed by NaDodSO4/polyacrylamide gel electrophoresis, suggesting that this clone contains the entire coding region of the phosphatase mRNA. The cloned cDNA hybridizes to a mRNA of 2.0 kilobases in bovine heart and adrenal gland. Under conditions of reduced stringency, the cDNA also hybridizes to a mRNA species of 1.2 kilobases in cardiac tissue.
- Metabolism (metabolic pathways involving proteins which contain this domain)
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Click the image to view the interactive version of the map in iPath | This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with PP2Ac domain which could be assigned to a KEGG orthologous group, and not all proteins containing PP2Ac domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%. |
- Structure (3D structures containing this domain)
3D Structures of PP2Ac domains in PDB
| PDB code | Main view | Title | | 1aui |  | Human calcineurin heterodimer |
| 1fjm |  | Protein serine/threonine phosphatase-1 (alpha isoform, type i) complexed with microcystin-lr toxin |
| 1g5b |  | Bacteriophage lambda ser/thr protein phosphatase |
| 1it6 |  | Crystal structure of the complex between calyculin a and the catalytic subunit of protein phosphatase 1 |
| 1jk7 |  | Crystal structure of the tumor-promoter okadaic acid bound to protein phosphatase-1 |
| 1m63 |  | Crystal structure of calcineurin-cyclophilin-cyclosporin shows common but distinct recognition of immunophilin-drug complexes |
| 1mf8 |  | Crystal structure of human calcineurin complexed with cyclosporin a and human cyclophilin |
| 1s70 |  | Complex between protein ser/thr phosphatase-1 (delta) and the myosin phosphatase targeting subunit 1 (mypt1) |
| 1s95 |  | Structure of serine/threonine protein phosphatase 5 |
| 1tco |  | Ternary complex of a calcineurin a fragment, calcineurin b, fkbp12 and the immunosuppressant drug fk506 (tacrolimus) |
| 1u32 |  | Crystal structure of a protein phosphatase-1: calcineurin hybrid bound to okadaic acid |
| 1v73 |  | Crystal structure of cold-active protein-tyrosine phosphatase of a psychrophile shewanella sp. |
| 1wao |  | Pp5 structure |
| 2bcd |  | X-ray crystal structure of protein phosphatase-1 with the marine toxin motuporin bound |
| 2bdx |  | X-ray crystal structure of dihydromicrocystin-la bound to protein phosphatase-1 |
| 2iae |  | Crystal structure of a protein phosphatase 2a (pp2a) holoenzyme. |
| 2ie3 |  | Structure of the protein phosphatase 2a core enzyme bound to tumor-inducing toxins |
| 2ie4 |  | Structure of the protein phosphatase 2a core enzyme bound to okadaic acid |
| 2jog |  | Structure of the calcineurin-nfat complex |
| 2npp |  | Structure of the protein phosphatase 2a holoenzyme |
| 2nyl |  | Crystal structure of protein phosphatase 2a (pp2a) holoenzyme with the catalytic subunit carboxyl terminus truncated |
| 2nym |  | Crystal structure of protein phosphatase 2a (pp2a) with c- terminus truncated catalytic subunit |
| 2o8a |  | Rat pp1cgamma complexed with mouse inhibitor-2 |
| 2o8g |  | Rat pp1c gamma complexed with mouse inhibitor-2 |
| 2p6b |  | Crystal structure of human calcineurin in complex with pvivit peptide |
| 2z72 |  | New structure of cold-active protein tyrosine phosphatase at 1.1 angstrom |
| 2zbm |  | Crystal structure of i115m mutant cold-active protein tyrosine phosphatase |
| 3c5w |  | Complex between pp2a-specific methylesterase pme-1 and pp2a core enzyme |
| 3dw8 |  | |
| 3e7a |  | |
| 3e7b |  | |
| 3fga |  | |
| 3h60 |  | |
| 3h61 |  | |
| 3h62 |  | |
| 3h63 |  | |
| 3h64 |  | |
| 3h66 |  | |
| 3h67 |  | |
| 3h68 |  | |
| 3h69 |  | |
| 3icf |  | |
| 3k7v |  | |
| 3k7w |  | |
- Links (links to other resources describing this domain)
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