Serine/threonine-protein phosphatase 6 catalytic subunit (PPP6C)
The protein contains 305 amino acids for an estimated molecular weight of 35144 Da.
Catalytic subunit of protein phosphatase 6 (PP6) (PubMed:17079228, PubMed:29053956). PP6 is a component of a signaling pathway regulating cell cycle progression in response to IL2 receptor stimulation (PubMed:10227379). N-terminal domain restricts G1 to S phase progression in cancer cells, in part through control of cyclin D1 (PubMed:17568194). During mitosis, regulates spindle positioning (PubMed:27335426). Downregulates MAP3K7 kinase activation of the IL1 signaling pathway by dephosphorylation of MAP3K7 (PubMed:17079228). Participates also in the innate immune defense against viruses by desphosphorylating RIG-I/DDX58, an essential step that triggers RIG-I/DDX58-mediated signaling activation (PubMed:29053956). (updated: Feb. 13, 2019)
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.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
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.
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The reference OMIM entry for this protein is 612725
Protein phosphatase 6, catalytic subunit; ppp6c
DESCRIPTION
Reversible phosphorylation of proteins on serine and threonine residues is an important biochemical event that regulates a broad variety of intracellular processes. The phosphorylation state is determined by the well-controlled balance of activities of serine/threonine-specific protein kinases and protein phosphatases. PPP6C is the catalytic subunit of human serine/threonine protein phosphatase-6 (Bastians and Ponstingl, 1996).CLONING
Using a homology-based RT-PCR approach, Bastians and Ponstingl (1996) cloned a cDNA encoding PPP6C. The predicted 305-amino acid protein shares 59%, 56 to 57%, 68%, and 61% identity with PPP4C (602035), isoforms of PPP2A (see 176915 and 176916), S. pombe ppe1, and S. cerevisiae Sit4, respectively. All 42 amino acids that are invariant among serine/threonine PPPs and essential for catalytic activity are present in PPP6C. Northern blot analysis showed that PPP6C was expressed as 3 transcripts of 1.8 kb, 4.2 kb, and 4.7 kb in all 16 human tissues examined. Expression levels were highest in testis, heart, and skeletal muscle and lowest in placenta, lung, and kidney. Immunoblot analysis detected a 35-kD PPP6C protein in lysates from human heart muscle and bull testis.GENE FUNCTION
Bastians and Ponstingl (1996) demonstrated that PPP6C could complement mutations in the S. cerevisiae Sit4 and S. pombe ppe1 genes, indicating that PPP6C is the functional homolog of yeast Sit4 and ppe1. Since Sit4 is required for the G1-to-S transition of the cell cycle, and ppe1 is involved in cell shape control and mitotic division, Bastians and Ponstingl (1996) suggested that PPP6C functions in cell cycle regulation. Using coimmunoprecipitation and protein pull-down assays, Stefansson and Brautigan (2006) showed that epitope-tagged PP6R1 (SAPS1; 610875), PP6R2 (SAPS2; 610877), and PP6R3 (SAPS3; 610879) bound endogenous PPP6C, but not PPP2CA. The SAPS domain of PP6R1 was sufficient for its association with PPP6C. Immunoprecipitates containing PPP6C and PP6R1 or PP6R2 showed phosphatase activity against a test protein, and the activity was inhibited by okadaic acid, a serine/threonine phosphatase inhibitor. Stefansson and Brautigan (2006) found that PPP6C and PP6R1 or PP6R2 associated with I-kappa-B-epsilon (IKBE, or NFKBIE; 604548) in HeLa cells, and knockdown of PP6R1 or PPP6C enhanced degradation of endogenous IKBE in response to TNF-alpha (191160).MAPPING
By fluorescence in situ hybridization followed by fine-mapping on a YAC contig, Bastians et al. (1997) localized the PPP6C gene to chromosome Xq22.3. However, Hartz (2009) mapped the PPP6C gene to chromosome 9q33.3 based on an alignment of the PPP6C sequence submitted by Bastians et al. (1997) (GenBank GENBANK X92972) with the genomic sequence (build 36.1). A sequence highly related to PPP6C maps to chromosome Xq22.3. ... More on the omim web site
Feb. 22, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: 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 612725 was added.