Phospholipid scramblase 1

Definition:

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. 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. Negatively regulates FcR-mediated phagocytosis in differentiated macrophages. 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. Acts as an attachment receptor for HCV.

References:

[1]. Beihua Dong, et al. Phospholipid scramblase 1 potentiates the antiviral activity of interferon. J Virol. 2004 Sep;78(17):8983-93. [Content Brief]

[2]. Qiaoling Gong, et al. Phospholipid scramblase 1 mediates hepatitis C virus entry into host cells. FEBS Lett. 2011 Sep 2;585(17):2647-52. [Content Brief]

[3]. Hasna Ahyayauch, et al. Pb(II) Induces Scramblase Activation and Ceramide-Domain Generation in Red Blood Cells. Sci Rep. 2018 May 10;8(1):7456. [Content Brief]

[4]. Cecile Herate, et al. Phospholipid Scramblase 1 Modulates FcR-Mediated Phagocytosis in Differentiated Macrophages. PLoS One. 2016 Jan 8;11(1):e0145617. [Content Brief]

[5]. Jessica P Wyles, et al. Nuclear interactions of topoisomerase II alpha and beta with phospholipid scramblase 1. Nucleic Acids Res. 2007;35(12):4076-85. [Content Brief]

[6]. Sarika Rayala, et al. N-terminal proline-rich domain is required for scrambling activity of human phospholipid scramblases. J Biol Chem. 2014 May 9;289(19):13206-18. [Content Brief]

[7]. Ulaganathan Sivagnanam, et al. Identification and characterization of the novel nuclease activity of human phospholipid scramblase 1. BMC Biochem. 2016 May 20;17(1):10. [Content Brief]

[8]. S C Frasch, et al. Regulation of phospholipid scramblase activity during apoptosis and cell activation by protein kinase Cdelta. J Biol Chem. 2000 Jul 28;275(30):23065-73. [Content Brief]

[9]. F Bassé, et al. Isolation of an erythrocyte membrane protein that mediates Ca2+-dependent transbilayer movement of phospholipid. J Biol Chem. 1996 Jul 19;271(29):17205-10. [Content Brief]

[10]. Vincent G Francis, et al. The single C-terminal helix of human phospholipid scramblase 1 is required for membrane insertion and scrambling activity. FEBS J. 2013 Jun;280(12):2855-69. [Content Brief]

[11]. Santosh Kumar Sahu, et al. Over-expression of recombinant human phospholipid scramblase 1 in E. coli and its purification from inclusion bodies. Biotechnol Lett. 2008 Dec;30(12):2131-7. [Content Brief]

[12]. Jizheng Guo, et al. Transient Receptor Potential Canonical 5-Scramblase Signaling Complex Mediates Neuronal Phosphatidylserine Externalization and Apoptosis. Cells. 2020 Feb 26;9(3):547. [Content Brief]

[13]. Q Zhou, et al. Identity of a conserved motif in phospholipid scramblase that is required for Ca2+-accelerated transbilayer movement of membrane phospholipids. Biochemistry. 1998 Feb 24;37(8):2356-60. [Content Brief]

[14]. Q Zhou, et al. Molecular cloning of human plasma membrane phospholipid scramblase. A protein mediating transbilayer movement of plasma membrane phospholipids. J Biol Chem. 1997 Jul 18;272(29):18240-4. [Content Brief]

[15]. J Zhao, et al. Palmitoylation of phospholipid scramblase is required for normal function in promoting Ca2+-activated transbilayer movement of membrane phospholipids. Biochemistry. 1998 May 5;37(18):6361-6. [Content Brief]

[16]. Ashok Kumar Shettihalli, et al. Biochemical evidence for lead and mercury induced transbilayer movement of phospholipids mediated by human phospholipid scramblase 1. Chem Res Toxicol. 2013 Jun 17;26(6):918-25. [Content Brief]

[17]. Lissete Sánchez-Magraner, et al. The C-terminal transmembrane domain of human phospholipid scramblase 1 is essential for the protein flip-flop activity and Ca²⁺-binding. J Membr Biol. 2014 Feb;247(2):155-65. [Content Brief]

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