Phospholipid scramblase 3 (PLSCR3)
The protein contains 295 amino acids for an estimated molecular weight of 31648 Da.
Catalyzes calcium-induced ATP-independent rapid bidirectional and non-specific movement of the phospholipids (lipid scrambling or lipid flip-flop) between the inner and outer membrane of the mitochondria (PubMed:14573790, PubMed:17226776, PubMed:18358005, PubMed:29337693, PubMed:31769662). Plays an important role in mitochondrial respiratory function, morphology, and apoptotic response (PubMed:14573790, PubMed:17226776, PubMed:18358005, PubMed:12649167). Mediates the translocation of cardiolipin from the mitochondrial inner membrane to outer membrane enhancing t-Bid induced cytochrome c release and apoptosis (PubMed:14573790, PubMed:17226776, PubMed:18358005). Enhances TNFSF10-induced apoptosis by regulating the distribution of cardiolipin in the mitochondrial membrane resulting in increased release of apoptogenic factors and consequent amplification of the activity of caspases (PubMed:18491232). Regulates cardiolipin de novo biosynthesis and its resynthesis (PubMed:16939411). (updated: Aug. 12, 2020)
Protein identification was indicated in the following studies:
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 predicted to be membranous by TOPCONS.
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| Variant | Description |
|---|---|
| dbSNP:rs3744549 |
Biological Process
Apoptotic process
Cardiolipin biosynthetic process
Cellular response to lipopolysaccharide
Cholesterol homeostasis
Glucose homeostasis
Plasma membrane phospholipid scrambling
Regulation of apoptotic process
Regulation of release of cytochrome c from mitochondria
The reference OMIM entry for this protein is 607611
Phospholipid scramblase 3; plscr3
CLONING
Using the sequence of PLSCR1 (604170) as query, Wiedmer et al. (2000) identified an EST containing PLSCR3, and they cloned the full-length cDNA by PCR of an erythroleukemia cell cDNA library. The deduced 295-amino acid protein contains an N-terminal proline-rich region and a C-terminal Ca(2+)-binding domain. The proline-rich region contains several PxxP motifs that mediate binding to proteins containing SH3 and WW domains. PLSCR3 shares 47% identity with PLSCR1, with most of the identity in the C-terminal region. Northern blot analysis revealed a 1.8-kb transcript expressed in most tissues and a 2.1-kb transcript expressed in skeletal muscle. Expression was below the limit of detection in testis, brain, and liver.MAPPING
By genomic sequence analysis, Wiedmer et al. (2000) mapped the PLSCR3 gene to chromosome 17p13.1.ANIMAL MODEL
Wiedmer et al. (2004) investigated mice with a targeted deletion of Plscr3. Plscr3 -/- mice at 2 months of age displayed aberrant accumulation of abdominal fat accompanied by insulin resistance, glucose intolerance, and dyslipidemia when maintained on standard rodent chow. Primary adipocytes and cultured bone marrow-derived macrophages from Plscr3 -/- mice were engorged with neutral lipid, and adipocytes displayed defective responses to exogenous insulin. Compared with wildtype mice, Plscr3 -/- mice had elevated plasma non-high density lipoproteins, cholesterol, triglycerides, nonesterified fatty acids, and leptin, but decreased plasma adiponectin. Wiedmer et al. (2004) suggested that the expression of PLSCR3 may be required for normal adipocyte and/or macrophage maturation or function and that mutations affecting the PLSCR3 gene may contribute to the risk for lipid-related disorders in humans. ... More on the omim web site
Aug. 24, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 607611 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).