PLS1_HUMAN
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 03-AUG-2022, entry version 206.
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, AND INTERACTION WITH HCV E1 AND E2 PROTEINS (MICROBIAL INFECTION)
RP 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 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 [21]
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 [22]
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 [23]
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 [24]
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 [25]
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 [26]
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 [27]
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 [28]
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 [29]
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 [30]
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). Acts as an attachment
CC receptor for HCV (PubMed:21806988). {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:23590222,
CC ECO:0000269|PubMed:23659204, ECO:0000269|PubMed:24343571,
CC ECO:0000269|PubMed:24648509, ECO:0000269|PubMed:26745724,
CC ECO:0000269|PubMed:27206388, ECO:0000269|PubMed:29748552,
CC ECO:0000269|PubMed:32110987, ECO:0000269|PubMed:8663431,
CC ECO:0000269|PubMed:9218461, ECO:0000269|PubMed:9485382,
CC ECO:0000269|PubMed:9572851}.
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). {ECO:0000250|UniProtKB:Q9JJ00,
CC ECO:0000269|PubMed:11390389, ECO:0000269|PubMed:17567603,
CC ECO:0000269|PubMed:21806988, ECO:0000269|PubMed:22052202,
CC ECO:0000269|PubMed:24648509, ECO:0000269|PubMed:32110987}.
CC -!- SUBUNIT: (Microbial infection) Interacts with hepatitis C virus E1 and
CC E2 glycoproteins. {ECO:0000269|PubMed:21806988}.
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}; Single-pass
CC type II membrane protein {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:24648509}. Cytoplasm {ECO:0000269|PubMed:22052202}.
CC Cytoplasm, perinuclear region {ECO:0000269|PubMed:22052202,
CC ECO:0000269|PubMed:26745724}. Note=Localizes to the perinuclear region
CC in the presence of RELT (PubMed:22052202). Palmitoylation regulates its
CC localization to the cell membrane or the nucleus; trafficking to the
CC cell membrane is dependent upon palmitoylation whereas in the absence
CC of palmitoylation, 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";
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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. [O15162-2]
DR RefSeq; XP_011511206.1; XM_011512904.1. [O15162-1]
DR RefSeq; XP_011511208.1; XM_011512906.2. [O15162-2]
DR RefSeq; XP_011511209.1; XM_011512907.2.
DR RefSeq; XP_016862118.1; XM_017006629.1. [O15162-1]
DR PDB; 1Y2A; X-ray; 2.20 A; P=257-266.
DR PDBsum; 1Y2A; -.
DR AlphaFoldDB; O15162; -.
DR SMR; O15162; -.
DR BioGRID; 111373; 170.
DR IntAct; O15162; 168.
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; O15162; -.
DR PeptideAtlas; O15162; -.
DR PRIDE; O15162; -.
DR ProteomicsDB; 48483; -. [O15162-1]
DR ProteomicsDB; 5105; -.
DR Antibodypedia; 18144; 274 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 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; 1015148at2759; -.
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; 14 hits in 1085 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 202 other tissues.
DR ExpressionAtlas; O15162; baseline and differential.
DR Genevisible; O15162; HS.
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:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
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:UniProtKB.
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; PTHR23248; 1.
DR Pfam; PF03803; Scramblase; 1.
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."
FT /evidence="ECO:0000269|PubMed:12564925,
FT ECO:0000269|PubMed:15611084"
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 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: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
