Phospholipid-transporting ATPase ABCA7 (ABCA7)
The protein contains 2146 amino acids for an estimated molecular weight of 234350 Da.
Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981). Transports preferentially phosphatidylserine over phosphatidylcholine (PubMed:24097981). Plays a role in lipid homeostasis and macrophage-mediated phagocytosis (PubMed:14592415, PubMed:12917409, PubMed:12925201, PubMed:14570867). Binds APOA1 and may function in apolipoprotein-mediated phospholipid efflux from cells (PubMed:12917409, PubMed:14570867, PubMed:14592415). May also mediate cholesterol efflux (PubMed:14570867). May regulate cellular ceramide homeostasis during keratinocyte differentiation (PubMed:12925201). Involved in lipid raft organization and CD1D localization on thymocytes and antigen-presenting cells, which plays an important role in natural killer T-cell development and activation (By similarity). Plays a role in phagocytosis of apoptotic cells by macrophages (By similarity). Macrophage phagocytosis is stimulated by APOA1 or APOA2, probably by stabilization of ABCA7 (By similarity). Also involved in phagocytic clearance of amyloid-beta by microglia cells and macrophages (By similarity). Further limits amyloid-beta production by playing a role in the regulation of amyloid-beta A4 precursor protein (APP) endocytosis and/or processing (PubMed:26260791). Amyloid-beta is the main component of amyloid plaques found in the brains of Alzheimer patients (PubMed:26260791). (updated: July 3, 2019)
Protein identification was indicated in the following studies:
- 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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No binding partner found
Biological Process
Amyloid-beta clearance by cellular catabolic process
Amyloid-beta formation
Apolipoprotein A-I-mediated signaling pathway
Cholesterol efflux
High-density lipoprotein particle assembly
Lipid transport
Memory
Negative regulation of amyloid precursor protein biosynthetic process
Negative regulation of amyloid-beta formation
Negative regulation of endocytosis
Negative regulation of MAPK cascade
Negative regulation of PERK-mediated unfolded protein response
Peptide cross-linking
Phagocytosis
Phospholipid efflux
Phospholipid translocation
Plasma membrane raft organization
Positive regulation of amyloid-beta clearance
Positive regulation of cholesterol efflux
Positive regulation of engulfment of apoptotic cell
Positive regulation of ERK1 and ERK2 cascade
Positive regulation of phagocytosis
Positive regulation of phospholipid efflux
Positive regulation of protein localization to cell surface
Protein localization to nucleus
Regulation of amyloid precursor protein catabolic process
Regulation of lipid metabolic process
Transmembrane transport
Visual learning
The reference OMIM entry for this protein is 605414
Atp-binding cassette, subfamily a, member 7; abca7
Abcx
Sjogren syndrome antigen ss-n
For background information on the ATP-binding cassette (ABC) family of transporter proteins, see ABCA4 (601691).
CLONING
By RT-PCR and screening of differentiated monocytes, Kaminski et al. (2000) obtained a cDNA encoding ABCA7. The deduced 2,146-amino acid protein contains 2 highly conserved ATP-binding cassettes with Walker A and B motifs and signature sequences. ABCA7 shares closest homology with ABC subfamily A members. Northern dot blot analysis demonstrated predominant expression in myelolymphatic tissues. Flow cytometric analysis of permeabilized leukocytes revealed greatest expression in monocytes, followed by granulocytes and lymphocytes. Broccardo et al. (2001) cloned human and mouse ABCA7 cDNAs and determined that the deduced proteins share 79% sequence identity. Northern blot analysis showed that mouse Abca7 is widely expressed both during embryogenesis and in adult tissues; the highest level of transcription is detectable in the spleen and hematopoietic tissues. The same pattern of expression was found in human tissues, with a strong signal also detected in fetal liver. Tanaka et al. (2001) observed identity between residues 195 and 352 of ABCA7 and a Sjogren syndrome autoantigen. They determined that ABCA7 encodes the autoantigen SS-N.GENE FUNCTION
By RT-PCR and Western blot analysis of differentiated monocytes, Kaminski et al. (2000) found increased expression of ABCA7 after addition of low density lipoprotein and decreased expression after deloading of macrophages with high density lipoprotein. Therefore, ABCA7, like ABCA1 (600046) and ABCG1 (603076), exhibits a regulatory response to cholesterol influx and efflux.GENE STRUCTURE
Kaminski et al. (2000) determined that the ABCA7 gene contains 46 exons and spans about 32 kb. Analysis of the promoter region revealed binding sites for transcription factors with roles in hematopoiesis and cholesterol metabolism. They also determined that the terminal exon of ABCA7 is separated from the 5-prime end of the coding region of the minor histocompatibility antigen HA-1 (601155) by about 1.7 kb.MAPPING
Kaminski et al. (2000) identified ABCA7 in tandem with HA-1, which shares sequence identity with a BAC clone mapped to chromosome 19p13.3. By FISH and radiation hybrid analysis, Broccardo et al. (2001) mapped the human ABCA7 gene to chromosome 19p13.3 and the mouse counterpart to a region of syntenic homology on chromosome 10. ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 605414 was added.
July 4, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Jan. 21, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).