Serine/threonine-protein phosphatase 5 (PPP5C)
The protein contains 499 amino acids for an estimated molecular weight of 56879 Da.
Serine/threonine-protein phosphatase that dephosphorylates a myriad of proteins involved in different signaling pathways including the kinases CSNK1E, ASK1/MAP3K5, PRKDC and RAF1, the nuclear receptors NR3C1, PPARG, ESR1 and ESR2, SMAD proteins and TAU/MAPT (PubMed:14734805, PubMed:14764652, PubMed:14871926, PubMed:15383005, PubMed:15546861, PubMed:16260606, PubMed:16790549, PubMed:16892053, PubMed:19176521, PubMed:19948726, PubMed:21144835, PubMed:22399290, PubMed:22781750, PubMed:23102700, PubMed:9000529, PubMed:30699359). Implicated in wide ranging cellular processes, including apoptosis, differentiation, DNA damage response, cell survival, regulation of ion channels or circadian rhythms, in response to steroid and thyroid hormones, calcium, fatty acids, TGF-beta as well as oxidative and genotoxic stresses (PubMed:14734805, PubMed:14764652, PubMed:14871926, PubMed:15383005, PubMed:15546861, PubMed:16260606, PubMed:16790549, PubMed:16892053, PubMed:19176521, PubMed:19948726, PubMed:21144835, PubMed:22399290, PubMed:22781750, PubMed:23102700, PubMed:9000529, PubMed:30699359). Participates in the control of DNA damage response mechanisms such as checkpoint activation and DNA damage repair through, for instance, the regulation ATM/ATR-signaling and dephosphorylation of PRKDC and TP53BP1 (PubMed:14871926, PubMed:16260606, PubMed:21144835). Inhibits ASK1/MAP3K5-mediated apoptosis induced by oxidative stress (PubMed:23102700). Plays a positive role in adipogenesis, mainly throug (updated: April 22, 2020)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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Biological Process
Cellular response to cadmium ion
Cellular response to hydrogen peroxide
DNA repair
Double-strand break repair
Histone dephosphorylation
MAPK cascade
Mitotic cell cycle
Mitotic nuclear division
Negative regulation of neuron death
Negative regulation of protein phosphorylation
Peptidyl-serine dephosphorylation
Peptidyl-threonine dephosphorylation
Positive regulation of glucocorticoid receptor signaling pathway
Positive regulation of I-kappaB kinase/NF-kappaB signaling
Protein complex oligomerization
Protein dephosphorylation
Protein heterooligomerization
Response to arachidonic acid
Response to lead ion
Response to morphine
Signal transduction
Transcription, DNA-templated
Cellular Component
Chaperone complex
Cytoplasm
Cytosol
Intracellular membrane-bounded organelle
Membrane
Neuron projection
Neuronal cell body
Nucleoplasm
Nucleus
Perikaryon
Plasma membrane
Protein complex
Protein-containing complex
Proximal dendrite
Molecular Function
ADP binding
ATP binding
G-protein alpha-subunit binding
Hsp90 protein binding
Identical protein binding
Lipid binding
Metal ion binding
Microtubule binding
Obsolete signal transducer activity
Phosphatase activity
Phosphoprotein phosphatase activity
Protein serine phosphatase activity
Protein serine/threonine phosphatase activity
Protein threonine phosphatase activity
Protein-containing complex binding
RNA binding
Tau protein binding
The reference OMIM entry for this protein is 600658
Protein phosphatase 5, catalytic subunit; ppp5c
Pp5
CLONING
A variety of biologic processes, such as cell signaling, transcription, and mitosis, are regulated by reversible protein phosphorylation at serine and threonine residues. The serine/threonine kinases are responsible for phosphorylation and the phosphatases are required for dephosphorylation. A number of protein serine/threonine phosphatases are known and molecular characterization shows that they fall into distinct groups. One family includes the PP1 (see PPP1A, 176875), PP2A, and PP2B (see PPP2B, 114105) genes and their relatives. Chen et al. (1994) described a protein serine/threonine phosphatase, which they designated PP5, that shares similarity to the yeast gene PPT1. The PP5 cDNA was isolated by screening a human teratocarcinoma cDNA library at low stringency with a PP2B probe. By Northern blotting they observed a 2.3-kb mRNA in all tissues they examined. The predicted PP5 protein shares about 35 to 40% identity with other members of the superfamily and the N-terminal domain contains tetratricopeptide-like repeats found in several nuclear regulatory proteins. Recombinant PP5 was able to dephosphorylate serine residues and was shown to be sensitive to the tumor promoter okadaic acid. Antibodies showed that the protein is predominantly found in the nucleus. Yong et al. (1995) reported the isolation of a cDNA from a human fetal brain library by exon amplification from a cosmid contig mapping to a glioma candidate region on chromosome 19q13.3. A nearly full-length cDNA was then obtained that was identical to PPP5C except for 3 additional nucleotides. Xu et al. (1996) cloned the entire coding sequence of the PP5 gene from a human fetal brain cDNA library using a probe generated by a PCR-based cloning approach. The PP5 mRNA was detected in all human tissues examined.GENE FUNCTION
Gentile et al. (2006) identified Pp5 as an effector of Rac (see 602048) GTPase signaling in a rat pituitary cell line. Okadaic acid, a microbial toxin, blocked channel stimulation by thyroid hormone and by Rac, and signaling was restored by expression of a toxin-insensitive Pp5 mutant. Pp5 contains an N-terminal regulatory domain with 3 tetratricopeptide (TRP) repeats that inhibit its activity. Expression of the TRP domain of Pp5 blocked channel stimulation by thyroid hormone, and mutation of the TRP at 2 predicted contact points with Rac-GTP prevented its inhibitory activity. Using yeast 2-hybrid and protein pull-down assays, Kono et al. (2002) found that mouse G5pr (PPP2R3C; 615902) interacted with Ganp DNA primase (MCM3AP; 603294) and with 2 types of catalytic protein phosphatases, Pp2ca (PPP2CA; 176915) and Pp5. G5pr did not interact with Pp2ca and Pp5 simultaneously. Proteins that precipitated with G5pr from mouse spleen lysates showed phosphatase activity that was sensitive to okadaic acid, an inhibitor of both Pp2ca and Pp5. In vitro-phosphorylated Mcm3 (602693) was dephosphorylated by the G5pr complex in the absence of okadaic acid, and dephosphorylation was enhanced by arachidonic acid, a Pp5 activator. Katayama et al. (2014) found that PP5 alone showed little to no phosphatase activity against serine-phosphorylated CRAF (RAF1; 164760), but that it clearly dephosphorylated CRAF in the presence of PPP2R3C. PPP2R3C also stimulated PP5-dependent dephosphorylation of serine-phosphorylated P-glycoprotein (ABCB1; 171050). Knockdown of PP5/PPP2R3C increased P-glycoprotein expression and lowered cell sensitivity to chemotherapeuti ... More on the omim web site
April 25, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 600658 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed