PLSCR1

PLSCR1 (Phospholipid Scramblase 1) is a protein coding gene. Diseases associated with PLSCR1 include Scott Syndrome. Among its related pathways are EGF/EGFR Signaling Pathway. Gene Ontology annotations related to this gene include calcium ion binding and transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding. An important paralog of the gene is PLSCR2.

Full Name

PLSCR1

Function

Catalyzes calcium-induced ATP-independent rapid bidirectional and non-specific movement of phospholipids (lipid scrambling or lipid flip-flop) between the inner and outer leaflet of the plasma membrane resulting in collapse of the phospholipid asymmetry which leads to phosphatidylserine externalization on the cell surface (PubMed:9218461, PubMed:8663431, PubMed:10770950, PubMed:9572851, PubMed:9485382, PubMed:18629440, PubMed:23590222, PubMed:24648509, PubMed:24343571, PubMed:32110987, PubMed:23659204, PubMed:29748552).
Mediates calcium-dependent phosphatidylserine externalization and apoptosis in neurons via its association with TRPC5 (By similarity).
Also exhibits magnesium-dependent nuclease activity against double-stranded DNA and RNA but not single-stranded DNA and can enhance DNA decatenation mediated by TOP2A (PubMed:27206388, PubMed:17567603).
Negatively regulates FcR-mediated phagocytosis in differentiated macrophages (PubMed:26745724).
May contribute to cytokine-regulated cell proliferation and differentiation (By similarity).
May play a role in the antiviral response of interferon (IFN) by amplifying and enhancing the IFN response through increased expression of select subset of potent antiviral genes (PubMed:15308695).
Acts as an attachment receptor for HCV (PubMed:21806988).

Biological Process

Acute-phase responseISS:UniProtKB
Apoptotic processManual Assertion Based On ExperimentIDA:UniProtKB
Defense response to virusManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of phagocytosisManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of viral genome replicationManual Assertion Based On ExperimentIMP:UniProtKB
Phosphatidylserine biosynthetic processISS:UniProtKB
Phosphatidylserine exposure on apoptotic cell surfaceManual Assertion Based On ExperimentIMP:UniProtKB
Plasma membrane phospholipid scramblingManual Assertion Based On ExperimentIDA:UniProtKB
Platelet activation1 PublicationNAS:UniProtKB
Positive regulation of chromosome separationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of DNA topoisomerase (ATP-hydrolyzing) activityManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of gene expressionManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of innate immune responseManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of Fc receptor mediated stimulatory signaling pathwayISS:UniProtKB
Regulation of mast cell activationISS:UniProtKB
Response to interferon-betaManual Assertion Based On ExperimentIMP:UniProtKB
Response to lead ionManual Assertion Based On ExperimentIDA:UniProtKB

Cellular Location

Cell membrane
Nucleus
Cytoplasm
Cytoplasm, perinuclear region
Localizes to the perinuclear region in the presence of RELT (PubMed:22052202).
Palmitoylation regulates its localization to the cell membrane or the nucleus; trafficking to the cell membrane is dependent upon palmitoylation whereas in the absence of palmitoylation, localizes to the nucleus (PubMed:12564925).

Topology

Cytoplasmic: 1-288
Helical: 289-305
Extracellular: 306-318

PTM

Phosphorylation at Thr-161 by PKC/PKCD increases its phospholipid scramblase activity during both cell stimulation and apoptosis (PubMed:10770950).
Phosphorylated by OXSR1 in the presence of RELT
Palmitoylation is required for its phospholipid scramblase activity (PubMed:9572851).
Palmitoylation regulates its localization to the cell membrane or the nucleus; trafficking to the cell membrane is dependent upon palmitoylation whereas in the absence of palmitoylation, localizes to the nucleus (PubMed:12564925).