Serine/threonine-protein phosphatase 6 regulatory subunit 3 (PPP6R3)

The protein contains 873 amino acids for an estimated molecular weight of 97669 Da.

 

Regulatory subunit of protein phosphatase 6 (PP6). May function as a scaffolding PP6 subunit. May have an important role in maintaining immune self-tolerance. (updated: March 4, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. 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.
  3. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  4. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  5. 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.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

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.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology.


Interpro domains
Total structural coverage: 57%
Model score: 0
No model available.

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VariantDescription
dbSNP:rs34009811

The reference OMIM entry for this protein is 610879

Saps domain family, member 3; saps3
Protein phosphatase 6, regulatory subunit 3; pp6r3
Chromosome 11 open reading frame 23; c11orf23
Kiaa1558

DESCRIPTION

Protein phosphatase regulatory subunits, such as SAPS3, modulate the activity of protein phosphatase catalytic subunits by restricting substrate specificity, recruiting substrates, and determining the intracellular localization of the holoenzyme. SAPS3 is a regulatory subunit for the protein phosphatase-6 catalytic subunit (PPP6C; 612725) (Stefansson and Brautigan, 2006).

CLONING

By sequencing clones obtained from a size-fractionated fetal brain cDNA library, Nagase et al. (2000) cloned SAPS3, which they designated KIAA1558. The 3-prime end of the transcript contains several repetitive elements. RT-PCR ELISA detected moderate expression in all adult and fetal tissues and specific brain regions examined. By sequencing the IDDM4 (600319) region of chromosome 11, followed by database analysis, Twells et al. (2001) cloned 2 splice variants of SAPS3, which they called C11ORF23. The variants encode deduced 793- and 791-amino acid proteins, both of which have calculated molecular masses of 89 kD. The first 776 amino acids are identical in the 2 isoforms and include a tandem repeat of ser-thr-asp-ser-glu-glu. Both transcripts have a second putative start methionine that would result in shorter proteins if used. SAPS3 shares significant similarity with yeast Sap190 and Sap185, including conservation of several motifs. Northern blot analysis detected highest expression of 4.9- and 4.1-kb transcripts in skeletal muscle, placenta, heart, pancreas, and testis. Expression was also detected in brain, lung, liver, kidney, spleen, thymus, prostate, small intestine, colon, and leukocytes, but not in ovary. The 4.9-kb transcript predominated in most tissues, but in testis the 4.1-kb transcript was more abundant. By searching databases for sequences similar to yeast Sap155, Sap185, and Sap190, Stefansson and Brautigan (2006) identified multiple splice variants of SAPS3, which they called PP6R3. The variants differ only in their N termini, and all have a central alpha-helical SAPS domain of about 400 amino acids. Northern blot analysis revealed high PP6R3 expression in heart, but little expression in other tissues examined. Western blot analysis of fractionated HeLa and HEK293 cells showed PP6R3 in the cytosolic fraction.

GENE FUNCTION

Using protein pull-down assays, Stefansson and Brautigan (2006) showed that epitope-tagged PP6R3 bound endogenous PPP6C, but not PPP2CA (176915).

GENE STRUCTURE

Twells et al. (2001) determined that the SAPS3 gene contains 22 exons.

MAPPING

By PCR of a human-rodent hybrid panel, Nagase et al. (2000) mapped the SAPS3 gene to chromosome 11. Twells et al. (2001) mapped the SAPS3 gene to chromosome 11q13 by analysis of BAC and PAC clones. ... More on the omim web site

Subscribe to this protein entry history

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 610879 was added.