Phospholipid-transporting ATPase IG (ATP11C)
The protein contains 1132 amino acids for an estimated molecular weight of 129477 Da.
Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids, phosphatidylserines (PS) and phosphatidylethanolamines (PE), from the outer to the inner leaflet of the plasma membrane (PubMed:25315773, PubMed:32493773, PubMed:24904167, PubMed:26567335). Major PS-flippase in immune cell subsets. In erythrocyte plasma membrane, it is required to maintain PS in the inner leaflet preventing its exposure on the surface. This asymmetric distribution is critical for the survival of erythrocytes in circulation since externalized PS is a phagocytic signal for erythrocyte clearance by splenic macrophages (PubMed:26944472). Required for B cell differentiation past the pro-B cell stage (By similarity). Seems to mediate PS flipping in pro-B cells (By similarity). May be involved in the transport of cholestatic bile acids (By similarity). (updated: April 7, 2021)
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.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.
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Biological Process
Ion transmembrane transport
Phospholipid translocation
Positive regulation of B cell differentiation
Pre-B cell differentiation
Transmembrane transport
The reference OMIM entry for this protein is 300516
Atpase, class vi, type 11c; atp11c
Atpase iq; atpiq
Atpase ig; atpig
CLONING
By searching for genes near the X-linked hypoparathyroidism locus (HYPX; 307700), followed by cDNA library screening, EST database analysis, and 5-prime RACE, Nesbit et al. (2004) cloned ATP11C. The deduced 1,132-amino acid protein has a calculated molecular mass of 130 kD. By searching EST databases, Nesbit et al. (2004) identified mouse and human ATP11C cDNAs with alternate first exons that encode deduced 1,128-amino acid proteins with apparent molecular masses of 129 kD. The mouse and human proteins share 94.8% amino acid identity. Using RT-PCR, Nesbit et al. (2004) also identified mouse and human ATP11C variants in which alternative splicing of exon 29 results in proteins with different C termini. Northern blot analysis of several human tissues detected a 7.4-kb transcript that was expressed ubiquitously and a minor 7.3-kb transcript that was expressed in some tissues, including liver and pancreas.GENE STRUCTURE
Nesbit et al. (2004) determined that the ATP11C gene contains 31 exons, including the alternate first exons 1a and 1b, and spans more than 211 kb.MAPPING
By genomic sequence analysis, Nesbit et al. (2004) mapped the ATP11C gene to chromosome Xq27.GENE FUNCTION
Using a haploid genetic screen in human cells, Segawa et al. (2014) found that ATP11C and CDC50A (611028) are required for aminophospholipid translocation from the outer to the inner plasma membrane leaflet; that is, they display flippase activity. ATP11C contained caspase recognition sites, and mutations at these sites generated caspase-resistant ATP11C without affecting its flippase activity. Cells expressing caspase-resistant ATP11C did not expose phosphatidylserine during apoptosis and were not engulfed by macrophages, which suggests that inactivation of the flippase activity is required for apoptotic phosphatidylserine exposure. CDC50A-deficient cells displayed phosphatidylserine on their surface and were engulfed by macrophages, indicating that phosphatidylserine is sufficient as an 'eat me' signal. ... More on the omim web site
April 10, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
Nov. 16, 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
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for ATP11C
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 300516 was added.