Serine/threonine-protein phosphatase 6 regulatory ankyrin repeat subunit A (ANKRD28)
The protein contains 1053 amino acids for an estimated molecular weight of 112966 Da.
Putative regulatory subunit of protein phosphatase 6 (PP6) that may be involved in the recognition of phosphoprotein substrates. Involved in the PP6-mediated dephosphorylation of NFKBIE opposing its degradation in response to TNF-alpha. Selectively inhibits the phosphatase activity of PPP1C. Targets PPP1C to modulate HNRPK phosphorylation. (updated: Jan. 7, 2015)
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.
- 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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Molecular Function
The reference OMIM entry for this protein is 611122
Ankyrin repeat domain-containing protein 28; ankrd28
Phosphatase interactor targeting k protein; pitk
Kiaa0379
CLONING
By sequencing clones obtained from a size-fractionated human brain cDNA library, Nagase et al. (1997) cloned ANKRD28, which they designated KIAA0379. The deduced 882-amino acid protein shares 30.8% identity with ANKRD3 (605706). RT-PCR analysis detected ubiquitous expression in all human tissues tested. By searching for PP1 (see 176875)-binding proteins in rabbit skeletal muscle, followed by database analysis, Kwiek et al. (2006) identified ANKRD28, which they called PITK. ANKRD28 contains putative PP1-binding motifs at either terminus and 28 successive ankyrin repeats. Western blot analysis of multiple mouse tissues revealed expression of ANKRD28 at similar levels in all tissues tested. In COS-7 cells, immunofluorescence microscopy localized ANKRD28 to subnuclear bodies with exclusion from nucleoli.GENE FUNCTION
By in vitro studies, Kwiek et al. (2006) showed that recombinant ANKRD28 selectively inhibited the phosphorylase activity of PP1C in a dose-dependent manner. Phosphorylation of ser1013 and ser1017, which lie within the putative PP1-binding motif, negatively regulated ANKRD28 binding to PP1C. Immunoprecipitation studies showed that ANKRD28 bound to hnRNP-K (600712). ANKRD28 selectively regulated phosphorylation of hnRNP-K at ser284, an effect that was enhanced in vivo by an S1013A/S1017A double mutant, suggesting that ANKRD28 targets PP1 in a regulated manner to dephosphorylate hnRNP-K selectively at ser284. Microarray analysis found that expression of ANKRD28 resulted in altered expression of 47 genes, including marked induction of MEK5 (MAP2K5; 602520). Expression of only 2 of these genes was altered by the S1013A/S1017A double mutant, indicating the importance of phosphorylation in ANKRD28 function. In addition, the effects of ANKRD28 and S1013A/S1017A double-mutant ANKRD28 could be modulated by coexpression of hnRNP-K.MAPPING
By radiation hybrid analysis, Nagase et al. (1997) mapped the ANKRD28 gene to chromosome 3. Kwiek et al. (2006) noted that the ANKRD28 gene maps to chromosome 3p25.1. ... More on the omim web site
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 611122 was added.