ID PLS1_HUMAN Reviewed; 318 AA. AC O15162; B2R8H8; B4DTE8; DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 1. DT 27-MAR-2024, entry version 214. DE RecName: Full=Phospholipid scramblase 1; DE Short=PL scramblase 1; DE AltName: Full=Ca(2+)-dependent phospholipid scramblase 1; DE AltName: Full=Erythrocyte phospholipid scramblase; DE AltName: Full=Mg(2+)-dependent nuclease {ECO:0000303|PubMed:27206388}; DE EC=3.1.-.- {ECO:0000269|PubMed:27206388}; DE AltName: Full=MmTRA1b; GN Name=PLSCR1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 87-118, RP FUNCTION, CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY. RC TISSUE=Erythrocyte; RX PubMed=9218461; DOI=10.1074/jbc.272.29.18240; RA Zhou Q., Zhao J., Stout J.G., Luhm R.A., Wiedmer T., Sims P.J.; RT "Molecular cloning of human plasma membrane phospholipid scramblase. A RT protein mediating transbilayer movement of plasma membrane phospholipids."; RL J. Biol. Chem. 272:18240-18244(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Monocytic leukemia; RX PubMed=9712717; DOI=10.1006/bbrc.1998.9190; RA Kasukabe T., Kobayashi H., Kaneko Y., Okabe-Kado J., Honma Y.; RT "Identity of human normal counterpart (MmTRA1b) of mouse leukemogenesis- RT associated gene (MmTRA1a) product as plasma membrane phospholipid RT scramblase and chromosome mapping of the human MmTRA1b/phospholipid RT scramblase gene."; RL Biochem. Biophys. Res. Commun. 249:449-455(1998). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY. RX PubMed=10930526; DOI=10.1016/s0005-2736(00)00236-4; RA Wiedmer T., Zhou Q., Kwoh D.Y., Sims P.J.; RT "Identification of three new members of the phospholipid scramblase gene RT family."; RL Biochim. Biophys. Acta 1467:244-253(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Kidney, and Placenta; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Colon, and Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP FUNCTION, CATALYTIC ACTIVITY, AND COFACTOR. RC TISSUE=Erythrocyte; RX PubMed=8663431; DOI=10.1074/jbc.271.29.17205; RA Basse F., Stout J.G., Sims P.J., Wiedmer T.; RT "Isolation of an erythrocyte membrane protein that mediates Ca2+-dependent RT transbilayer movement of phospholipid."; RL J. Biol. Chem. 271:17205-17210(1996). RN [9] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, PHOSPHORYLATION AT RP THR-161, AND MUTAGENESIS OF THR-161. RX PubMed=10770950; DOI=10.1074/jbc.m003116200; RA Frasch S.C., Henson P.M., Kailey J.M., Richter D.A., Janes M.S., RA Fadok V.A., Bratton D.L.; RT "Regulation of phospholipid scramblase activity during apoptosis and cell RT activation by protein kinase Cdelta."; RL J. Biol. Chem. 275:23065-23073(2000). RN [10] RP INTERACTION WITH ABL, PHOSPHORYLATION AT TYR-69 AND TYR-74, AND MUTAGENESIS RP OF TYR-69 AND TYR-74. RX PubMed=11390389; DOI=10.1074/jbc.m102505200; RA Sun J., Zhao J., Schwartz M.A., Wang J.Y., Wiedmer T., Sims P.J.; RT "c-Abl tyrosine kinase binds and phosphorylates phospholipid scramblase RT 1."; RL J. Biol. Chem. 276:28984-28990(2001). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, AND PALMITOYLATION. RX PubMed=9572851; DOI=10.1021/bi980218m; RA Zhao J., Zhou Q., Wiedmer T., Sims P.J.; RT "Palmitoylation of phospholipid scramblase is required for normal function RT in promoting Ca2+-activated transbilayer movement of membrane RT phospholipids."; RL Biochemistry 37:6361-6366(1998). RN [12] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ASP-273; ASP-275; PHE-277; RP ILE-279; PHE-281 AND ASP-284. RX PubMed=9485382; DOI=10.1021/bi972625o; RA Zhou Q., Sims P.J., Wiedmer T.; RT "Identity of a conserved motif in phospholipid scramblase that is required RT for Ca2+-accelerated transbilayer movement of membrane phospholipids."; RL Biochemistry 37:2356-2360(1998). RN [13] RP SUBCELLULAR LOCATION, PALMITOYLATION AT CYS-184; CYS-185; CYS-186; CYS-188 RP AND CYS-189, AND MUTAGENESIS OF 184-CYS--CYS-189. RX PubMed=12564925; DOI=10.1021/bi026679w; RA Wiedmer T., Zhao J., Nanjundan M., Sims P.J.; RT "Palmitoylation of phospholipid scramblase 1 controls its distribution RT between nucleus and plasma membrane."; RL Biochemistry 42:1227-1233(2003). RN [14] RP FUNCTION, AND INDUCTION (MICROBIAL INFECTION). RX PubMed=15308695; DOI=10.1128/jvi.78.17.8983-8993.2004; RA Dong B., Zhou Q., Zhao J., Zhou A., Harty R.N., Bose S., Banerjee A., RA Slee R., Guenther J., Williams B.R.G., Wiedmer T., Sims P.J., RA Silverman R.H.; RT "Phospholipid scramblase 1 potentiates the antiviral activity of RT interferon."; RL J. Virol. 78:8983-8993(2004). RN [15] RP SUBCELLULAR LOCATION, AND DNA-BINDING. RX PubMed=16091359; DOI=10.1074/jbc.m504821200; RA Zhou Q., Ben-Efraim I., Bigcas J.L., Junqueira D., Wiedmer T., Sims P.J.; RT "Phospholipid scramblase 1 binds to the promoter region of the inositol RT 1,4,5-triphosphate receptor type 1 gene to enhance its expression."; RL J. Biol. Chem. 280:35062-35068(2005). RN [16] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH TOP2A AND TOP2B. RX PubMed=17567603; DOI=10.1093/nar/gkm434; RA Wyles J.P., Wu Z., Mirski S.E., Cole S.P.; RT "Nuclear interactions of topoisomerase II alpha and beta with phospholipid RT scramblase 1."; RL Nucleic Acids Res. 35:4076-4085(2007). RN [17] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=18629440; DOI=10.1007/s10529-008-9797-z; RA Sahu S.K., Gopala Krishna A., Gummadi S.N.; RT "Over-expression of recombinant human phospholipid scramblase 1 in E. coli RT and its purification from inclusion bodies."; RL Biotechnol. Lett. 30:2131-2137(2008). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [19] RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HCV E1 AND E2 PROTEINS RP (MICROBIAL INFECTION) AND OCLN. RX PubMed=21806988; DOI=10.1016/j.febslet.2011.07.019; RA Gong Q., Cheng M., Chen H., Liu X., Si Y., Yang Y., Yuan Y., Jin C., RA Yang W., He F., Wang J.; RT "Phospholipid scramblase 1 mediates hepatitis C virus entry into host RT cells."; RL FEBS Lett. 585:2647-2652(2011). RN [20] RP FUNCTION, INTERACTION WITH HUMAN T-CELL LEUKEMIA VIRUS TYPE-1 PROTEIN TAX RP (MICROBIAL INFECTION), AND SUBCELLULAR LOCATION. RX PubMed=22789739; DOI=10.1016/j.virol.2012.06.019; RA Kusano S., Eizuru Y.; RT "Human phospholipid scramblase 1 interacts with and regulates RT transactivation of HTLV-1 Tax."; RL Virology 432:343-352(2012). RN [21] RP INTERACTION WITH RELT; RELL1; RELL2 AND OXSR1, PHOSPHORYLATION, AND RP SUBCELLULAR LOCATION. RX PubMed=22052202; DOI=10.1007/s11010-011-1127-4; RA Cusick J.K., Mustian A., Jacobs A.T., Reyland M.E.; RT "Identification of PLSCR1 as a protein that interacts with RELT family RT members."; RL Mol. Cell. Biochem. 362:55-63(2012). RN [22] RP FUNCTION, INTERACTION WITH HUMAN IMMUNODEFICIENCY VIRUS TYPE-1 PROTEIN TAT RP (MICROBIAL INFECTION), AND SUBCELLULAR LOCATION. RX PubMed=23501106; DOI=10.1016/j.bbrc.2013.02.098; RA Kusano S., Eizuru Y.; RT "Interaction of the phospholipid scramblase 1 with HIV-1 Tat results in the RT repression of Tat-dependent transcription."; RL Biochem. Biophys. Res. Commun. 433:438-444(2013). RN [23] RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND ACTIVITY REGULATION. RX PubMed=23659204; DOI=10.1021/tx400090h; RA Shettihalli A.K., Gummadi S.N.; RT "Biochemical evidence for lead and mercury induced transbilayer movement of RT phospholipids mediated by human phospholipid scramblase 1."; RL Chem. Res. Toxicol. 26:918-925(2013). RN [24] RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBCELLULAR LOCATION, AND RP TRANSMEMBRANE DOMAIN. RX PubMed=23590222; DOI=10.1111/febs.12289; RA Francis V.G., Mohammed A.M., Aradhyam G.K., Gummadi S.N.; RT "The single C-terminal helix of human phospholipid scramblase 1 is required RT for membrane insertion and scrambling activity."; RL FEBS J. 280:2855-2869(2013). RN [25] RP FUNCTION, CATALYTIC ACTIVITY, PROLINE-RICH DOMAIN, SUBCELLULAR LOCATION, RP COFACTOR, AND SUBUNIT. RX PubMed=24648509; DOI=10.1074/jbc.m113.522953; RA Rayala S., Francis V.G., Sivagnanam U., Gummadi S.N.; RT "N-terminal proline-rich domain is required for scrambling activity of RT human phospholipid scramblases."; RL J. Biol. Chem. 289:13206-13218(2014). RN [26] RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND TRANSMEMBRANE DOMAIN. RX PubMed=24343571; DOI=10.1007/s00232-013-9619-7; RA Sanchez-Magraner L., Posada I.M., Andraka N., Contreras F.X., Viguera A.R., RA Guerin D.M., Arrondo J.L., Monaco H.L., Goni F.M.; RT "The C-terminal transmembrane domain of human phospholipid scramblase 1 is RT essential for the protein flip-flop activity and Ca+2-binding."; RL J. Membr. Biol. 247:155-165(2014). RN [27] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [28] RP FUNCTION, AND INTERACTION WITH HEPATITIS B VIRUS PROTEIN HBX (MICROBIAL RP INFECTION). RX PubMed=25365352; DOI=10.1021/pr500943x; RA Yuan Y., Tian C., Gong Q., Shang L., Zhang Y., Jin C., He F., Wang J.; RT "Interactome map reveals phospholipid scramblase 1 as a novel regulator of RT hepatitis B virus x protein."; RL J. Proteome Res. 14:154-163(2015). RN [29] RP FUNCTION AS NUCLEASE, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, AND RP MUTAGENESIS OF HIS-12; HIS-53; HIS-111; HIS-211; HIS-262 AND ASP-275. RX PubMed=27206388; DOI=10.1186/s12858-016-0067-8; RA Sivagnanam U., Narayana Murthy S., Gummadi S.N.; RT "Identification and characterization of the novel nuclease activity of RT human phospholipid scramblase 1."; RL BMC Biochem. 17:10-10(2016). RN [30] RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, AND INDUCTION. RX PubMed=26745724; DOI=10.1371/journal.pone.0145617; RA Herate C., Ramdani G., Grant N.J., Marion S., Gasman S., Niedergang F., RA Benichou S., Bouchet J.; RT "Phospholipid Scramblase 1 Modulates FcR-Mediated Phagocytosis in RT Differentiated Macrophages."; RL PLoS ONE 11:e0145617-e0145617(2016). RN [31] RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION. RX PubMed=29748552; DOI=10.1038/s41598-018-25905-8; RA Ahyayauch H., Garcia-Arribas A.B., Sot J., Gonzalez-Ramirez E.J., RA Busto J.V., Monasterio B.G., Jimenez-Rojo N., Contreras F.X., RA Rendon-Ramirez A., Martin C., Alonso A., Goni F.M.; RT "Pb(II) Induces Scramblase Activation and Ceramide-Domain Generation in Red RT Blood Cells."; RL Sci. Rep. 8:7456-7456(2018). RN [32] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=29352288; DOI=10.1371/journal.ppat.1006851; RA Luo W., Zhang J., Liang L., Wang G., Li Q., Zhu P., Zhou Y., Li J., RA Zhao Y., Sun N., Huang S., Zhou C., Chang Y., Cui P., Chen P., Jiang Y., RA Deng G., Bu Z., Li C., Jiang L., Chen H.; RT "Phospholipid scramblase 1 interacts with influenza A virus NP, impairing RT its nuclear import and thereby suppressing virus replication."; RL PLoS Pathog. 14:e1006851-e1006851(2018). RN [33] RP FUNCTION, AND INTERACTION WITH EPSTEIN-BARR VIRUS BZLF1 (MICROBIAL RP INFECTION). RX PubMed=31434743; DOI=10.1074/jbc.ra119.008193; RA Kusano S., Ikeda M.; RT "Interaction of phospholipid scramblase 1 with the Epstein-Barr virus RT protein BZLF1 represses BZLF1-mediated lytic gene transcription."; RL J. Biol. Chem. 294:15104-15116(2019). RN [34] RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH TRPC5. RX PubMed=32110987; DOI=10.3390/cells9030547; RA Guo J., Li J., Xia L., Wang Y., Zhu J., Du J., Lu Y., Liu G., Yao X., RA Shen B.; RT "Transient Receptor Potential Canonical 5-Scramblase Signaling Complex RT Mediates Neuronal Phosphatidylserine Externalization and Apoptosis."; RL Cells 9:0-0(2020). RN [35] RP FUNCTION, INDUCTION BY TYPE I INTERFERON AND VIRAL INFECTION, AND RP INTERACTION WITH HUMAN CYTOMEGALOVIRUS PROTEINS IE1 AND IE2 (MICROBIAL RP INFECTION). RX PubMed=35138119; DOI=10.1128/spectrum.01342-21; RA Sadanari H., Takemoto M., Ishida T., Otagiri H., Daikoku T., Murayama T., RA Kusano S.; RT "The Interferon-Inducible Human PLSCR1 Protein Is a Restriction Factor of RT Human Cytomegalovirus."; RL Microbiol. Spectr. 10:e0134221-e0134221(2022). RN [36] RP INTERACTION WITH ILDR1, SUBCELLULAR LOCATION, INTERACTION WITH INFLUENZA RP VIRUS NUCLEOPROTEIN NP (MICROBIAL INFECTION), AND FUNCTION. RX PubMed=35595813; DOI=10.1038/s41598-022-12598-3; RA Liu Y., Lin S., Xie Y., Zhao L., Du H., Yang S., Yin B., Li G., Zhao Z., RA Huang Z., Xu Z., Wu J.; RT "ILDR1 promotes influenza A virus replication through binding to PLSCR1."; RL Sci. Rep. 12:8515-8515(2022). RN [37] RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF HIS-262; PHE-281 AND RP 184-CYS--CYS-189. RX PubMed=37438530; DOI=10.1038/s41586-023-06322-y; RA Xu D., Jiang W., Wu L., Gaudet R.G., Park E.S., Su M., Cheppali S.K., RA Cheemarla N.R., Kumar P., Uchil P.D., Grover J.R., Foxman E.F., Brown C.M., RA Stansfeld P.J., Bewersdorf J., Mothes W., Karatekin E., Wilen C.B., RA MacMicking J.D.; RT "PLSCR1 is a cell-autonomous defence factor against SARS-CoV-2 infection."; RL Nature 0:0-0(2023). RN [38] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 257-266 IN COMPLEX WITH MOUSE RP KPNA2, NUCLEAR LOCALIZATION SIGNAL, AND MUTAGENESIS OF 184-CYS--CYS-189. RX PubMed=15611084; DOI=10.1074/jbc.m413194200; RA Chen M.H., Ben-Efraim I., Mitrousis G., Walker-Kopp N., Sims P.J., RA Cingolani G.; RT "Phospholipid scramblase 1 contains a nonclassical nuclear localization RT signal with unique binding site in importin alpha."; RL J. Biol. Chem. 280:10599-10606(2005). CC -!- FUNCTION: Catalyzes calcium-induced ATP-independent rapid bidirectional CC and non-specific movement of phospholipids (lipid scrambling or lipid CC flip-flop) between the inner and outer leaflet of the plasma membrane CC resulting in collapse of the phospholipid asymmetry which leads to CC phosphatidylserine externalization on the cell surface (PubMed:9218461, CC PubMed:8663431, PubMed:10770950, PubMed:9572851, PubMed:9485382, CC PubMed:18629440, PubMed:23590222, PubMed:24648509, PubMed:24343571, CC PubMed:32110987, PubMed:23659204, PubMed:29748552). Mediates calcium- CC dependent phosphatidylserine externalization and apoptosis in neurons CC via its association with TRPC5 (By similarity). Also exhibits CC magnesium-dependent nuclease activity against double-stranded DNA and CC RNA but not single-stranded DNA and can enhance DNA decatenation CC mediated by TOP2A (PubMed:27206388, PubMed:17567603). Negatively CC regulates FcR-mediated phagocytosis in differentiated macrophages CC (PubMed:26745724). May contribute to cytokine-regulated cell CC proliferation and differentiation (By similarity). May play a role in CC the antiviral response of interferon (IFN) by amplifying and enhancing CC the IFN response through increased expression of select subset of CC potent antiviral genes (PubMed:15308695). Inhibits the functions of CC viral transactivators, including human T-cell leukemia virus (HTLV)-1 CC protein Tax, human immunodeficiency virus (HIV)-1 Tat, human hepatitis CC B virus (HBV) HBx, Epstein-Barr virus (EBV) BZLF1 and human CC cytomegalovirus IE1 and IE2 proteins through direct interactions CC (PubMed:22789739, PubMed:31434743, PubMed:25365352, PubMed:23501106, CC PubMed:35138119). Mediates also the inhibition of influenza virus CC infection by preventing nuclear import of the viral nucleoprotein/NP CC (PubMed:29352288, PubMed:35595813). Plays a crucial role as a defense CC factor against SARS-CoV-2 independently of its scramblase activity by CC directly targeting nascent viral vesicles to prevent virus-membrane CC fusion and the release of viral RNA into the host-cell cytosol CC (PubMed:37438530). {ECO:0000250|UniProtKB:Q9JJ00, CC ECO:0000269|PubMed:10770950, ECO:0000269|PubMed:15308695, CC ECO:0000269|PubMed:17567603, ECO:0000269|PubMed:18629440, CC ECO:0000269|PubMed:21806988, ECO:0000269|PubMed:22789739, CC ECO:0000269|PubMed:23501106, ECO:0000269|PubMed:23590222, CC ECO:0000269|PubMed:23659204, ECO:0000269|PubMed:24343571, CC ECO:0000269|PubMed:24648509, ECO:0000269|PubMed:25365352, CC ECO:0000269|PubMed:26745724, ECO:0000269|PubMed:27206388, CC ECO:0000269|PubMed:29748552, ECO:0000269|PubMed:31434743, CC ECO:0000269|PubMed:32110987, ECO:0000269|PubMed:35138119, CC ECO:0000269|PubMed:37438530, ECO:0000269|PubMed:8663431, CC ECO:0000269|PubMed:9218461, ECO:0000269|PubMed:9485382, CC ECO:0000269|PubMed:9572851}. CC -!- FUNCTION: (Microbial infection) Acts as an attachment receptor for HCV. CC {ECO:0000269|PubMed:21806988}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine(in) = a 1,2-diacyl- CC sn-glycero-3-phosphocholine(out); Xref=Rhea:RHEA:38571, CC ChEBI:CHEBI:57643; Evidence={ECO:0000269|PubMed:10770950, CC ECO:0000269|PubMed:18629440, ECO:0000269|PubMed:23590222, CC ECO:0000269|PubMed:23659204, ECO:0000269|PubMed:24343571, CC ECO:0000269|PubMed:24648509, ECO:0000269|PubMed:8663431, CC ECO:0000269|PubMed:9218461, ECO:0000269|PubMed:9485382, CC ECO:0000269|PubMed:9572851}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38572; CC Evidence={ECO:0000305|PubMed:18629440}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:38573; CC Evidence={ECO:0000305|PubMed:23659204}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(in) = a 1,2- CC diacyl-sn-glycero-3-phosphoethanolamine(out); Xref=Rhea:RHEA:38895, CC ChEBI:CHEBI:64612; Evidence={ECO:0000269|PubMed:18629440}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38896; CC Evidence={ECO:0000305|PubMed:18629440}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-L-serine(in) = a 1,2-diacyl- CC sn-glycero-3-phospho-L-serine(out); Xref=Rhea:RHEA:38663, CC ChEBI:CHEBI:57262; Evidence={ECO:0000269|PubMed:23659204, CC ECO:0000269|PubMed:29748552, ECO:0000305|PubMed:32110987}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38664; CC Evidence={ECO:0000305|PubMed:29748552}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:38665; CC Evidence={ECO:0000305|PubMed:23659204}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000269|PubMed:23590222, ECO:0000269|PubMed:23659204, CC ECO:0000269|PubMed:24343571, ECO:0000269|PubMed:24648509, CC ECO:0000269|PubMed:8663431}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:27206388}; CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:27206388}; CC Note=Magnesium. Can also use zinc with lower efficiency. CC {ECO:0000269|PubMed:27206388}; CC -!- ACTIVITY REGULATION: Activated by Pb(2+) and Hg(2+) ions CC (PubMed:23659204, PubMed:29748552). Phosphorylation at Thr-161 by CC PKC/PKCD increases its phospholipid scramblase activity during both CC cell stimulation and apoptosis (PubMed:10770950). CC {ECO:0000269|PubMed:10770950, ECO:0000269|PubMed:23659204, CC ECO:0000269|PubMed:29748552}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC pH dependence: CC Optimum pH is 8.0-9.0 for nuclease activity. CC {ECO:0000269|PubMed:27206388}; CC Temperature dependence: CC Optimum temperature is 37 degrees Celsius for nuclease activity CC (PubMed:27206388). Activity reduced significantly beyond 45 degrees CC Celsius (PubMed:27206388). {ECO:0000269|PubMed:27206388}; CC -!- SUBUNIT: Forms homooligomers in the presence of calcium CC (PubMed:24648509). Interacts with ABL (PubMed:11390389). Interacts with CC RELT, RELL1 and RELL2 (PubMed:22052202). Interacts with OXSR1 in the CC presence of RELT (PubMed:22052202). Interacts with TOP2A and TOP2B CC (PubMed:17567603). Interacts with OCLN (PubMed:21806988). Interacts CC with TRPC5 (PubMed:32110987). Interacts with TRPC1 and TRPC4 (By CC similarity). Interacts with ILDR1 (PubMed:35595813). CC {ECO:0000250|UniProtKB:Q9JJ00, ECO:0000269|PubMed:11390389, CC ECO:0000269|PubMed:17567603, ECO:0000269|PubMed:21806988, CC ECO:0000269|PubMed:22052202, ECO:0000269|PubMed:24648509, CC ECO:0000269|PubMed:32110987, ECO:0000269|PubMed:35595813}. CC -!- SUBUNIT: (Microbial infection) Interacts with hepatitis C virus E1 and CC E2 glycoproteins. {ECO:0000269|PubMed:21806988}. CC -!- SUBUNIT: (Microbial infection) Interacts with T-cell leukemia virus CC (HTLV)-1 protein Tax (via N-terminus); this interaction represses Tax CC homodimerization. {ECO:0000269|PubMed:22789739}. CC -!- SUBUNIT: (Microbial infection) Interacts with HIV-1 protein Tat; this CC interaction represses the Tat-dependent transactivation of the HIV-1 CC long terminal repeat (LTR) and reduces the nuclear translocation of CC Tat. {ECO:0000269|PubMed:23501106}. CC -!- SUBUNIT: (Microbial infection) Interacts with hepatitis B virus protein CC HBx; this interaction promotes the proteasomal degradation of HBx. CC {ECO:0000269|PubMed:25365352}. CC -!- SUBUNIT: (Microbial infection) Interacts with human cytomegalovirus CC proteins IE1 and IE2. {ECO:0000269|PubMed:35138119}. CC -!- SUBUNIT: (Microbial infection) Interacts with Epstein Barr virus (EBV) CC lytic switch protein BZLF1; this interaction negatively regulates the CC transcriptional regulatory activity of BZLF1 by preventing the CC formation of the BZLF1-CBP complex. {ECO:0000269|PubMed:31434743}. CC -!- SUBUNIT: (Microbial infection) Interacts with influenza virus CC nucleoprotein NP. {ECO:0000269|PubMed:35595813}. CC -!- INTERACTION: CC O15162; P05067: APP; NbExp=3; IntAct=EBI-740019, EBI-77613; CC O15162; A8KA13: BCL6B; NbExp=3; IntAct=EBI-740019, EBI-10174813; CC O15162; Q8NEC5: CATSPER1; NbExp=3; IntAct=EBI-740019, EBI-744545; CC O15162; Q9H2X0: CHRD; NbExp=3; IntAct=EBI-740019, EBI-947551; CC O15162; Q16630: CPSF6; NbExp=2; IntAct=EBI-740019, EBI-358410; CC O15162; Q9UBR2: CTSZ; NbExp=3; IntAct=EBI-740019, EBI-8636823; CC O15162; Q15038: DAZAP2; NbExp=4; IntAct=EBI-740019, EBI-724310; CC O15162; Q9H4E7: DEF6; NbExp=3; IntAct=EBI-740019, EBI-745369; CC O15162; Q9NQL9: DMRT3; NbExp=3; IntAct=EBI-740019, EBI-9679045; CC O15162; Q92608: DOCK2; NbExp=3; IntAct=EBI-740019, EBI-448771; CC O15162; Q92731: ESR2; NbExp=4; IntAct=EBI-740019, EBI-78505; CC O15162; Q92731-3: ESR2; NbExp=4; IntAct=EBI-740019, EBI-12259414; CC O15162; Q01844: EWSR1; NbExp=4; IntAct=EBI-740019, EBI-739737; CC O15162; O43559: FRS3; NbExp=3; IntAct=EBI-740019, EBI-725515; CC O15162; Q9HBR3: GDPD5; NbExp=3; IntAct=EBI-740019, EBI-10310206; CC O15162; O76003: GLRX3; NbExp=4; IntAct=EBI-740019, EBI-374781; CC O15162; Q9NXX0: ILF3; NbExp=4; IntAct=EBI-740019, EBI-743980; CC O15162; P60412: KRTAP10-11; NbExp=3; IntAct=EBI-740019, EBI-10217483; CC O15162; P60411: KRTAP10-9; NbExp=3; IntAct=EBI-740019, EBI-10172052; CC O15162; Q9BYQ6: KRTAP4-11; NbExp=3; IntAct=EBI-740019, EBI-10302392; CC O15162; Q9BYR5: KRTAP4-2; NbExp=3; IntAct=EBI-740019, EBI-10172511; CC O15162; Q6L8G9: KRTAP5-6; NbExp=3; IntAct=EBI-740019, EBI-10250562; CC O15162; Q9BYQ4: KRTAP9-2; NbExp=3; IntAct=EBI-740019, EBI-1044640; CC O15162; Q5TA82: LCE2D; NbExp=3; IntAct=EBI-740019, EBI-10246750; CC O15162; Q5TA78: LCE4A; NbExp=3; IntAct=EBI-740019, EBI-10246358; CC O15162; Q6DKI2: LGALS9C; NbExp=3; IntAct=EBI-740019, EBI-9088829; CC O15162; Q8WWR8: NEU4; NbExp=2; IntAct=EBI-740019, EBI-746964; CC O15162; Q7Z417: NUFIP2; NbExp=2; IntAct=EBI-740019, EBI-1210753; CC O15162; Q16625: OCLN; NbExp=2; IntAct=EBI-740019, EBI-2903088; CC O15162; Q15077: P2RY6; NbExp=3; IntAct=EBI-740019, EBI-10235794; CC O15162; Q13563: PKD2; NbExp=3; IntAct=EBI-740019, EBI-7813714; CC O15162; Q9NZ81: PRR13; NbExp=3; IntAct=EBI-740019, EBI-740924; CC O15162; P49796: RGS3; NbExp=3; IntAct=EBI-740019, EBI-2107809; CC O15162; Q9BWG6: SCNM1; NbExp=4; IntAct=EBI-740019, EBI-748391; CC O15162; Q92922: SMARCC1; NbExp=3; IntAct=EBI-740019, EBI-355653; CC O15162; Q6RVD6: SPATA8; NbExp=3; IntAct=EBI-740019, EBI-8635958; CC O15162; O75716: STK16; NbExp=3; IntAct=EBI-740019, EBI-749295; CC O15162; Q92734: TFG; NbExp=2; IntAct=EBI-740019, EBI-357061; CC O15162; Q8IWZ5: TRIM42; NbExp=3; IntAct=EBI-740019, EBI-5235829; CC O15162; A5D8V6: VPS37C; NbExp=3; IntAct=EBI-740019, EBI-2559305; CC O15162; Q8TAU3: ZNF417; NbExp=3; IntAct=EBI-740019, EBI-740727; CC O15162; Q96SQ5: ZNF587; NbExp=3; IntAct=EBI-740019, EBI-6427977; CC O15162; A0A0S2Z5X4: ZNF688; NbExp=3; IntAct=EBI-740019, EBI-16429014; CC O15162; P09022: Hoxa1; Xeno; NbExp=3; IntAct=EBI-740019, EBI-3957603; CC O15162; Q8ZG77: ompA; Xeno; NbExp=2; IntAct=EBI-740019, EBI-20592302; CC O15162; Q56973: yscB; Xeno; NbExp=2; IntAct=EBI-740019, EBI-20592268; CC O15162; P69974: yscK; Xeno; NbExp=2; IntAct=EBI-740019, EBI-2842860; CC O15162; P61417: yscY; Xeno; NbExp=2; IntAct=EBI-740019, EBI-20592244; CC O15162; Q9WMX2; Xeno; NbExp=8; IntAct=EBI-740019, EBI-710918; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12564925, CC ECO:0000269|PubMed:22052202, ECO:0000269|PubMed:23590222, CC ECO:0000269|PubMed:24648509, ECO:0000269|PubMed:26745724, CC ECO:0000269|PubMed:37438530}; Single-pass type II membrane protein CC {ECO:0000269|PubMed:26745724}. Cell membrane CC {ECO:0000269|PubMed:12564925}; Lipid-anchor CC {ECO:0000305|PubMed:12564925}; Cytoplasmic side. Nucleus CC {ECO:0000269|PubMed:12564925, ECO:0000269|PubMed:16091359, CC ECO:0000269|PubMed:22789739, ECO:0000269|PubMed:23501106, CC ECO:0000269|PubMed:24648509, ECO:0000269|PubMed:35595813}. Cytoplasm CC {ECO:0000269|PubMed:22052202, ECO:0000269|PubMed:22789739, CC ECO:0000269|PubMed:23501106, ECO:0000269|PubMed:29352288, CC ECO:0000269|PubMed:35595813}. Cytoplasm, perinuclear region CC {ECO:0000269|PubMed:22052202, ECO:0000269|PubMed:26745724}. CC Note=Localizes to the perinuclear region in the presence of RELT CC (PubMed:22052202). Palmitoylation regulates its localization to the CC cell membrane or the nucleus; trafficking to the cell membrane is CC dependent upon palmitoylation whereas in the absence of palmitoylation, CC localizes to the nucleus (PubMed:12564925). CC {ECO:0000269|PubMed:12564925, ECO:0000269|PubMed:22052202}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O15162-1; Sequence=Displayed; CC Name=2; CC IsoId=O15162-2; Sequence=VSP_055237, VSP_055238; CC -!- TISSUE SPECIFICITY: Expressed in platelets, erythrocyte membranes, CC lymphocytes, spleen, thymus, prostate, testis, uterus, intestine, CC colon, heart, placenta, lung, liver, kidney and pancreas. Not detected CC in brain and skeletal muscle. {ECO:0000269|PubMed:10930526, CC ECO:0000269|PubMed:9218461}. CC -!- INDUCTION: (Microbial infection) Induced by IFNB1/IFN-beta in response CC to a viral infection. {ECO:0000269|PubMed:15308695}. CC -!- INDUCTION: Up-regulated during PMA-induced differentiation of the CC monocytic cell line THP-1. {ECO:0000269|PubMed:26745724}. CC -!- DOMAIN: The N-terminal proline-rich domain (PRD) is required for CC phospholipid scramblase activity. {ECO:0000269|PubMed:24648509}. CC -!- DOMAIN: The transmembrane domain is essential for membrane insertion, CC phospholipid scramblase activity and proper calcium-binding. CC {ECO:0000269|PubMed:23590222, ECO:0000269|PubMed:24343571}. CC -!- PTM: Phosphorylation at Thr-161 by PKC/PKCD increases its phospholipid CC scramblase activity during both cell stimulation and apoptosis CC (PubMed:10770950). Phosphorylated by OXSR1 in the presence of RELT. CC {ECO:0000269|PubMed:10770950, ECO:0000269|PubMed:22052202}. CC -!- PTM: Palmitoylation is required for its phospholipid scramblase CC activity (PubMed:9572851). Palmitoylation regulates its localization to CC the cell membrane or the nucleus; trafficking to the cell membrane is CC dependent upon palmitoylation whereas in the absence of palmitoylation, CC localizes to the nucleus (PubMed:12564925). CC {ECO:0000269|PubMed:12564925, ECO:0000269|PubMed:9572851}. CC -!- SIMILARITY: Belongs to the phospholipid scramblase family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Scramblase entry; CC URL="https://en.wikipedia.org/wiki/Scramblase"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF098642; AAC99413.1; -; mRNA. DR EMBL; AB006746; BAA32568.1; -; mRNA. DR EMBL; AF224492; AAF80593.1; -; Genomic_DNA. DR EMBL; AK300181; BAG61960.1; -; mRNA. DR EMBL; AC069528; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC116544; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AK313377; BAG36175.1; -; mRNA. DR EMBL; CH471052; EAW78926.1; -; Genomic_DNA. DR EMBL; BC021100; AAH21100.1; -; mRNA. DR EMBL; BC032718; AAH32718.1; -; mRNA. DR CCDS; CCDS3135.1; -. [O15162-1] DR CCDS; CCDS87152.1; -. [O15162-2] DR PIR; JE0284; JE0284. DR RefSeq; NP_066928.1; NM_021105.2. [O15162-1] DR RefSeq; XP_005247595.1; XM_005247538.3. DR RefSeq; XP_011511206.1; XM_011512904.1. DR RefSeq; XP_011511208.1; XM_011512906.2. DR RefSeq; XP_011511209.1; XM_011512907.2. DR RefSeq; XP_016862118.1; XM_017006629.1. DR PDB; 1Y2A; X-ray; 2.20 A; P=257-266. DR PDBsum; 1Y2A; -. DR AlphaFoldDB; O15162; -. DR SMR; O15162; -. DR BioGRID; 111373; 174. DR IntAct; O15162; 167. DR MINT; O15162; -. DR STRING; 9606.ENSP00000345494; -. DR SwissLipids; SLP:000000332; -. DR TCDB; 9.A.36.1.1; the ca(2+)-dependent phospholipid scramblase (scramblase) family. DR GlyGen; O15162; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O15162; -. DR PhosphoSitePlus; O15162; -. DR SwissPalm; O15162; -. DR BioMuta; PLSCR1; -. DR EPD; O15162; -. DR jPOST; O15162; -. DR MassIVE; O15162; -. DR MaxQB; O15162; -. DR PaxDb; 9606-ENSP00000345494; -. DR PeptideAtlas; O15162; -. DR ProteomicsDB; 48483; -. [O15162-1] DR ProteomicsDB; 5105; -. DR Pumba; O15162; -. DR Antibodypedia; 18144; 301 antibodies from 34 providers. DR DNASU; 5359; -. DR Ensembl; ENST00000342435.9; ENSP00000345494.4; ENSG00000188313.13. [O15162-1] DR Ensembl; ENST00000448787.6; ENSP00000411675.2; ENSG00000188313.13. [O15162-2] DR GeneID; 5359; -. DR KEGG; hsa:5359; -. DR MANE-Select; ENST00000342435.9; ENSP00000345494.4; NM_021105.3; NP_066928.1. DR UCSC; uc003evx.5; human. [O15162-1] DR AGR; HGNC:9092; -. DR CTD; 5359; -. DR DisGeNET; 5359; -. DR GeneCards; PLSCR1; -. DR HGNC; HGNC:9092; PLSCR1. DR HPA; ENSG00000188313; Low tissue specificity. DR MIM; 604170; gene. DR neXtProt; NX_O15162; -. DR OpenTargets; ENSG00000188313; -. DR PharmGKB; PA33419; -. DR VEuPathDB; HostDB:ENSG00000188313; -. DR eggNOG; KOG0621; Eukaryota. DR GeneTree; ENSGT00940000154435; -. DR InParanoid; O15162; -. DR OMA; QNWHLWR; -. DR OrthoDB; 4390at2759; -. DR PhylomeDB; O15162; -. DR TreeFam; TF314939; -. DR BRENDA; 7.6.2.1; 2681. DR PathwayCommons; O15162; -. DR SignaLink; O15162; -. DR SIGNOR; O15162; -. DR BioGRID-ORCS; 5359; 20 hits in 1170 CRISPR screens. DR ChiTaRS; PLSCR1; human. DR EvolutionaryTrace; O15162; -. DR GeneWiki; PLSCR1; -. DR GenomeRNAi; 5359; -. DR Pharos; O15162; Tbio. DR PRO; PR:O15162; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; O15162; Protein. DR Bgee; ENSG00000188313; Expressed in palpebral conjunctiva and 204 other cell types or tissues. DR ExpressionAtlas; O15162; baseline and differential. DR GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB. DR GO; GO:0042609; F:CD4 receptor binding; IPI:UniProtKB. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:UniProtKB. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0005154; F:epidermal growth factor receptor binding; IPI:UniProtKB. DR GO; GO:0032791; F:lead ion binding; IDA:UniProtKB. DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB. DR GO; GO:0045340; F:mercury ion binding; IDA:UniProtKB. DR GO; GO:0004518; F:nuclease activity; IMP:UniProtKB. DR GO; GO:0017128; F:phospholipid scramblase activity; IDA:UniProtKB. DR GO; GO:0017124; F:SH3 domain binding; IDA:UniProtKB. DR GO; GO:0001618; F:virus receptor activity; IMP:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0006953; P:acute-phase response; ISS:UniProtKB. DR GO; GO:0006915; P:apoptotic process; IDA:UniProtKB. DR GO; GO:0051607; P:defense response to virus; IMP:UniProtKB. DR GO; GO:0050765; P:negative regulation of phagocytosis; IMP:UniProtKB. DR GO; GO:0045071; P:negative regulation of viral genome replication; IMP:UniProtKB. DR GO; GO:0006659; P:phosphatidylserine biosynthetic process; ISS:UniProtKB. DR GO; GO:0070782; P:phosphatidylserine exposure on apoptotic cell surface; IMP:UniProtKB. DR GO; GO:0017121; P:plasma membrane phospholipid scrambling; IDA:UniProtKB. DR GO; GO:0030168; P:platelet activation; NAS:UniProtKB. DR GO; GO:1905820; P:positive regulation of chromosome separation; IDA:UniProtKB. DR GO; GO:2000373; P:positive regulation of DNA topoisomerase (ATP-hydrolyzing) activity; IDA:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB. DR GO; GO:0045089; P:positive regulation of innate immune response; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0060368; P:regulation of Fc receptor mediated stimulatory signaling pathway; ISS:UniProtKB. DR GO; GO:0033003; P:regulation of mast cell activation; ISS:UniProtKB. DR GO; GO:0035456; P:response to interferon-beta; IMP:UniProtKB. DR GO; GO:0010288; P:response to lead ion; IDA:UniProtKB. DR IDEAL; IID00006; -. DR InterPro; IPR005552; Scramblase. DR PANTHER; PTHR23248:SF38; PHOSPHOLIPID SCRAMBLASE 1; 1. DR PANTHER; PTHR23248; PHOSPHOLIPID SCRAMBLASE-RELATED; 1. DR Pfam; PF03803; Scramblase; 1. DR Genevisible; O15162; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Antiviral defense; Calcium; KW Cell membrane; Cytoplasm; Direct protein sequencing; DNA-binding; KW Host cell receptor for virus entry; Host-virus interaction; Hydrolase; KW Lipid transport; Lipoprotein; Magnesium; Membrane; Nuclease; Nucleus; KW Palmitate; Phosphoprotein; Receptor; Reference proteome; Repeat; KW SH3-binding; Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..318 FT /note="Phospholipid scramblase 1" FT /id="PRO_0000100784" FT TOPO_DOM 1..288 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:26745724" FT TRANSMEM 289..305 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:23590222" FT TOPO_DOM 306..318 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:26745724" FT REGION 1..84 FT /note="Proline-rich domain (PRD)" FT /evidence="ECO:0000269|PubMed:24648509" FT REGION 1..64 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 99..290 FT /note="Interaction with hepatitis C virus E2 glycoprotein" FT /evidence="ECO:0000269|PubMed:21806988" FT MOTIF 18..26 FT /note="SH3-binding 1" FT /evidence="ECO:0000255" FT MOTIF 22..25 FT /note="PPXY motif 1" FT /evidence="ECO:0000255" FT MOTIF 33..36 FT /note="PPXY motif 2" FT /evidence="ECO:0000255" FT MOTIF 42..50 FT /note="SH3-binding 2" FT /evidence="ECO:0000255" FT MOTIF 84..92 FT /note="SH3-binding 3" FT /evidence="ECO:0000255" FT MOTIF 257..266 FT /note="Nuclear localization signal" FT /evidence="ECO:0000269|PubMed:15611084" FT COMPBIAS 40..64 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 69 FT /note="Phosphotyrosine; by ABL" FT /evidence="ECO:0000269|PubMed:11390389" FT MOD_RES 74 FT /note="Phosphotyrosine; by ABL" FT /evidence="ECO:0000269|PubMed:11390389" FT MOD_RES 161 FT /note="Phosphothreonine; by PKC/PRKCD" FT /evidence="ECO:0000269|PubMed:10770950" FT LIPID 184 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000305|PubMed:12564925" FT LIPID 185 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000305|PubMed:12564925" FT LIPID 186 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000305|PubMed:12564925" FT LIPID 188 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000305|PubMed:12564925" FT LIPID 189 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000305|PubMed:12564925" FT VAR_SEQ 1..23 FT /note="MDKQNSQMNASHPETNLPVGYPP -> MLLTRKQTCQLGILLSIHRQHSK FT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055237" FT VAR_SEQ 24..104 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055238" FT VARIANT 262 FT /note="H -> Y (in dbSNP:rs343320)" FT /id="VAR_034388" FT MUTAGEN 12 FT /note="H->A: 60% reduction in nuclease activity; when FT associated with A-53; A-111; A-211 and A-262." FT /evidence="ECO:0000269|PubMed:27206388" FT MUTAGEN 53 FT /note="H->A: 60% reduction in nuclease activity; when FT associated with A-12; A-111; A-211 and A-262." FT /evidence="ECO:0000269|PubMed:27206388" FT MUTAGEN 69 FT /note="Y->F: Decrease in phosphorylation." FT /evidence="ECO:0000269|PubMed:11390389" FT MUTAGEN 74 FT /note="Y->F: Decrease in phosphorylation." FT /evidence="ECO:0000269|PubMed:11390389" FT MUTAGEN 111 FT /note="H->A: 60% reduction in nuclease activity; when FT associated with A-12; A-53; A-211 and A-262." FT /evidence="ECO:0000269|PubMed:27206388" FT MUTAGEN 161 FT /note="T->A: No induction by PKC/PRKCD." FT /evidence="ECO:0000269|PubMed:10770950" FT MUTAGEN 184..189 FT /note="CCCPCC->AAAPAA: No palmitoylation; constitutively FT localizes in the nucleus. Loss of protection against FT SARS-CoV-2-containing vesicles." FT /evidence="ECO:0000269|PubMed:12564925, FT ECO:0000269|PubMed:15611084, ECO:0000269|PubMed:37438530" FT MUTAGEN 211 FT /note="H->A: 60% reduction in nuclease activity; when FT associated with A-12; A-53; A-111 and A-262." FT /evidence="ECO:0000269|PubMed:27206388" FT MUTAGEN 262 FT /note="H->A: 60% reduction in nuclease activity; when FT associated with A-12; A-53; A-111 and A-211." FT /evidence="ECO:0000269|PubMed:27206388" FT MUTAGEN 262 FT /note="H->Y: Significantly impaired anti-SARS-CoV-2 FT activity." FT /evidence="ECO:0000269|PubMed:37438530" FT MUTAGEN 273 FT /note="D->A: Reduces the Ca(2+)-dependent phospholipid FT scrambling." FT /evidence="ECO:0000269|PubMed:9485382" FT MUTAGEN 275 FT /note="D->A: Complete inactivation of the Ca(2+)-dependent FT phospholipid scrambling. No effect on its nuclease FT activity." FT /evidence="ECO:0000269|PubMed:27206388, FT ECO:0000269|PubMed:9485382" FT MUTAGEN 277 FT /note="F->A: Reduces the Ca(2+)-dependent phospholipid FT scrambling." FT /evidence="ECO:0000269|PubMed:9485382" FT MUTAGEN 279 FT /note="I->A: Reduces the Ca(2+)-dependent phospholipid FT scrambling." FT /evidence="ECO:0000269|PubMed:9485382" FT MUTAGEN 281 FT /note="F->A: Complete inactivation of the Ca(2+)-dependent FT phospholipid scrambling." FT /evidence="ECO:0000269|PubMed:37438530, FT ECO:0000269|PubMed:9485382" FT MUTAGEN 284 FT /note="D->A: Reduces the Ca(2+)-dependent phospholipid FT scrambling." FT /evidence="ECO:0000269|PubMed:9485382" SQ SEQUENCE 318 AA; 35049 MW; 9860744DEC40616E CRC64; MDKQNSQMNA SHPETNLPVG YPPQYPPTAF QGPPGYSGYP GPQVSYPPPP AGHSGPGPAG FPVPNQPVYN QPVYNQPVGA AGVPWMPAPQ PPLNCPPGLE YLSQIDQILI HQQIELLEVL TGFETNNKYE IKNSFGQRVY FAAEDTDCCT RNCCGPSRPF TLRIIDNMGQ EVITLERPLR CSSCCCPCCL QEIEIQAPPG VPIGYVIQTW HPCLPKFTIQ NEKREDVLKI SGPCVVCSCC GDVDFEIKSL DEQCVVGKIS KHWTGILREA FTDADNFGIQ FPLDLDVKMK AVMIGACFLI DFMFFESTGS QEQKSGVW //