Full text data of PLSCR1
PLSCR1
[Confidence: high (present in two of the MS resources)]
Phospholipid scramblase 1; PL scramblase 1 (Ca(2+)-dependent phospholipid scramblase 1; Erythrocyte phospholipid scramblase; MmTRA1b)
Phospholipid scramblase 1; PL scramblase 1 (Ca(2+)-dependent phospholipid scramblase 1; Erythrocyte phospholipid scramblase; MmTRA1b)
hRBCD
IPI00005181
IPI00005181 Phospholipid scramblase 1 Phospholipid scramblase 1 membrane n/a n/a 1 n/a 1 n/a n/a n/a n/a n/a n/a n/a 2 n/a n/a n/a n/a 3 n/a n/a Type II membrane protein n/a found at its expected molecular weight found at molecular weight
IPI00005181 Phospholipid scramblase 1 Phospholipid scramblase 1 membrane n/a n/a 1 n/a 1 n/a n/a n/a n/a n/a n/a n/a 2 n/a n/a n/a n/a 3 n/a n/a Type II membrane protein n/a found at its expected molecular weight found at molecular weight
UniProt
O15162
ID PLS1_HUMAN Reviewed; 318 AA.
AC O15162; B2R8H8;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JAN-1998, sequence version 1.
DT 22-JAN-2014, entry version 134.
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=MmTRA1b;
GN Name=PLSCR1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 87-118.
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
RT phospholipids.";
RL J. Biol. Chem. 272:18240-18244(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
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
RT leukemogenesis-associated gene (MmTRA1a) product as plasma membrane
RT phospholipid scramblase and chromosome mapping of the human
RT MmTRA1b/phospholipid scramblase gene.";
RL Biochem. Biophys. Res. Commun. 249:449-455(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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
RT gene family.";
RL Biochim. Biophys. Acta 1467:244-253(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP CHARACTERIZATION, AND FUNCTION.
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+-
RT dependent transbilayer movement of phospholipid.";
RL J. Biol. Chem. 271:17205-17210(1996).
RN [8]
RP PHOSPHORYLATION AT THR-161, AND MUTAGENESIS.
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
RT cell activation by protein kinase Cdelta.";
RL J. Biol. Chem. 275:23065-23073(2000).
RN [9]
RP PHOSPHORYLATION AT TYR-69 AND TYR-74, AND MUTAGENESIS.
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
RT scramblase 1.";
RL J. Biol. Chem. 276:28984-28990(2001).
RN [10]
RP 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
RT function in promoting Ca2+-activated transbilayer movement of membrane
RT phospholipids.";
RL Biochemistry 37:6361-6366(1998).
RN [11]
RP MUTAGENESIS.
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
RT required for Ca2+-accelerated transbilayer movement of membrane
RT phospholipids.";
RL Biochemistry 37:2356-2360(1998).
RN [12]
RP SUBCELLULAR LOCATION, PALMITOYLATION, AND MUTAGENESIS OF
RP 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 [13]
RP FUNCTION, AND INDUCTION.
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 [14]
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.,
RA Sims P.J.;
RT "Phospholipid scramblase 1 binds to the promoter region of the
RT inositol 1,4,5-triphosphate receptor type 1 gene to enhance its
RT expression.";
RL J. Biol. Chem. 280:35062-35068(2005).
RN [15]
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.,
RA Buerckstuemmer T., 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 [16]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 257-266 IN COMPLEX WITH MOUSE
RP KPNA2, NUCLEAR LOCALIZATION SIGNAL, AND MUTAGENESIS OF
RP 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
RT localization signal with unique binding site in importin alpha.";
RL J. Biol. Chem. 280:10599-10606(2005).
CC -!- FUNCTION: May mediate accelerated ATP-independent bidirectional
CC transbilayer migration of phospholipids upon binding calcium ions
CC that results in a loss of phospholipid asymmetry in the plasma
CC membrane. May play a central role in the initiation of fibrin clot
CC formation, in the activation of mast cells and in the recognition
CC of apoptotic and injured cells by the reticuloendothelial system.
CC -!- FUNCTION: May play a role in the antiviral response of interferon
CC (IFN) by amplifying and enhancing the IFN response through
CC increased expression of select subset of potent antiviral genes.
CC May contribute to cytokine-regulated cell proliferation and
CC differentiation.
CC -!- COFACTOR: Calcium.
CC -!- SUBUNIT: Interacts with ABL.
CC -!- INTERACTION:
CC Q9WMX2:- (xeno); NbExp=8; IntAct=EBI-740019, EBI-710918;
CC Q16630:CPSF6; NbExp=2; IntAct=EBI-740019, EBI-358410;
CC P09022:Hoxa1 (xeno); NbExp=3; IntAct=EBI-740019, EBI-3957603;
CC Q8WWR8:NEU4; NbExp=2; IntAct=EBI-740019, EBI-746964;
CC Q16625:OCLN; NbExp=2; IntAct=EBI-740019, EBI-2903088;
CC Q92734:TFG; NbExp=2; IntAct=EBI-740019, EBI-357061;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type II membrane
CC protein. Membrane; Lipid-anchor; Cytoplasmic side. Nucleus.
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
CC detected in brain and skeletal muscle.
CC -!- INDUCTION: By phosphorylation by PKC. Induced by IFNB1/IFN-beta in
CC response to a viral infection.
CC -!- SIMILARITY: Belongs to the phospholipid scramblase family.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Scramblase entry;
CC URL="http://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; AK313377; BAG36175.1; -; mRNA.
DR EMBL; CH471052; EAW78926.1; -; Genomic_DNA.
DR EMBL; BC021100; AAH21100.1; -; mRNA.
DR EMBL; BC032718; AAH32718.1; -; mRNA.
DR PIR; JE0284; JE0284.
DR RefSeq; NP_066928.1; NM_021105.2.
DR RefSeq; XP_005247594.1; XM_005247537.1.
DR UniGene; Hs.130759; -.
DR PDB; 1Y2A; X-ray; 2.20 A; P=257-266.
DR PDBsum; 1Y2A; -.
DR ProteinModelPortal; O15162; -.
DR IntAct; O15162; 105.
DR MINT; MINT-201602; -.
DR STRING; 9606.ENSP00000345494; -.
DR TCDB; 9.A.36.1.1; the ca(2+)-dependent phospholipid scramblase (scramblase) family.
DR PhosphoSite; O15162; -.
DR PaxDb; O15162; -.
DR PRIDE; O15162; -.
DR DNASU; 5359; -.
DR Ensembl; ENST00000342435; ENSP00000345494; ENSG00000188313.
DR GeneID; 5359; -.
DR KEGG; hsa:5359; -.
DR UCSC; uc003evx.4; human.
DR CTD; 5359; -.
DR GeneCards; GC03M146232; -.
DR HGNC; HGNC:9092; PLSCR1.
DR MIM; 604170; gene.
DR neXtProt; NX_O15162; -.
DR PharmGKB; PA33419; -.
DR eggNOG; NOG119855; -.
DR HOGENOM; HOG000237356; -.
DR HOVERGEN; HBG019157; -.
DR InParanoid; O15162; -.
DR OMA; FFESTGS; -.
DR OrthoDB; EOG77T14X; -.
DR PhylomeDB; O15162; -.
DR SignaLink; O15162; -.
DR ChiTaRS; PLSCR1; human.
DR EvolutionaryTrace; O15162; -.
DR GeneWiki; PLSCR1; -.
DR GenomeRNAi; 5359; -.
DR NextBio; 20774; -.
DR PRO; PR:O15162; -.
DR ArrayExpress; O15162; -.
DR Bgee; O15162; -.
DR CleanEx; HS_PLSCR1; -.
DR Genevestigator; O15162; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0005887; C:integral to plasma membrane; IDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0017128; F:phospholipid scramblase activity; IDA:UniProtKB.
DR GO; GO:0001077; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription; IDA:UniProtKB.
DR GO; GO:0017124; F:SH3 domain 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:0045071; P:negative regulation of viral genome replication; IMP:UniProtKB.
DR GO; GO:0006659; P:phosphatidylserine biosynthetic process; ISS:UniProtKB.
DR GO; GO:0030168; P:platelet activation; NAS:UniProtKB.
DR GO; GO:2000373; P:positive regulation of DNA topoisomerase (ATP-hydrolyzing) activity; IDA:UniProtKB.
DR GO; GO:0045089; P:positive regulation of innate immune response; IMP: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 InterPro; IPR005552; Scramblase.
DR PANTHER; PTHR23248; PTHR23248; 1.
DR Pfam; PF03803; Scramblase; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antiviral defense; Calcium; Complete proteome;
KW Direct protein sequencing; DNA-binding; Lipoprotein; Membrane;
KW Nucleus; Palmitate; Phosphoprotein; Polymorphism; Reference proteome;
KW Repeat; SH3-binding; Transmembrane; Transmembrane helix.
FT CHAIN 1 318 Phospholipid scramblase 1.
FT /FTId=PRO_0000100784.
FT TOPO_DOM 1 288 Cytoplasmic.
FT TRANSMEM 289 305 Helical; (Potential).
FT TOPO_DOM 306 318 Extracellular.
FT MOTIF 18 26 SH3-binding 1 (Potential).
FT MOTIF 22 25 WW-binding 1 (Potential).
FT MOTIF 33 36 WW-binding 2 (Potential).
FT MOTIF 42 50 SH3-binding 2 (Potential).
FT MOTIF 84 92 SH3-binding 3 (Potential).
FT MOTIF 257 266 Nuclear localization signal.
FT COMPBIAS 181 189 Cys-rich.
FT MOD_RES 69 69 Phosphotyrosine; by ABL.
FT MOD_RES 74 74 Phosphotyrosine; by ABL.
FT MOD_RES 161 161 Phosphothreonine; by PKC.
FT LIPID 184 184 S-palmitoyl cysteine (Probable).
FT LIPID 185 185 S-palmitoyl cysteine (Probable).
FT LIPID 186 186 S-palmitoyl cysteine (Potential).
FT LIPID 188 188 S-palmitoyl cysteine (Probable).
FT LIPID 189 189 S-palmitoyl cysteine (Probable).
FT VARIANT 262 262 H -> Y (in dbSNP:rs343320).
FT /FTId=VAR_034388.
FT MUTAGEN 69 69 Y->F: Decrease in phosphorylation.
FT MUTAGEN 74 74 Y->F: Decrease in phosphorylation.
FT MUTAGEN 161 161 T->A: No induction by PKC.
FT MUTAGEN 184 189 CCCPCC->AAAPAA: No palmitoylation;
FT constitutively localizes in the nucleus.
FT MUTAGEN 273 273 D->A: Reduces the Ca(2+)-dependent
FT phospholipid scrambling.
FT MUTAGEN 275 275 D->A: Complete inactivation of the
FT Ca(2+)-dependent phospholipid scrambling.
FT MUTAGEN 277 277 F->A: Reduces the Ca(2+)-dependent
FT phospholipid scrambling.
FT MUTAGEN 279 279 I->A: Reduces the Ca(2+)-dependent
FT phospholipid scrambling.
FT MUTAGEN 281 281 F->A: Complete inactivation of the
FT Ca(2+)-dependent phospholipid scrambling.
FT MUTAGEN 284 284 D->A: Reduces the Ca(2+)-dependent
FT phospholipid scrambling.
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
//
ID PLS1_HUMAN Reviewed; 318 AA.
AC O15162; B2R8H8;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JAN-1998, sequence version 1.
DT 22-JAN-2014, entry version 134.
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=MmTRA1b;
GN Name=PLSCR1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 87-118.
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
RT phospholipids.";
RL J. Biol. Chem. 272:18240-18244(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
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
RT leukemogenesis-associated gene (MmTRA1a) product as plasma membrane
RT phospholipid scramblase and chromosome mapping of the human
RT MmTRA1b/phospholipid scramblase gene.";
RL Biochem. Biophys. Res. Commun. 249:449-455(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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
RT gene family.";
RL Biochim. Biophys. Acta 1467:244-253(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP CHARACTERIZATION, AND FUNCTION.
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+-
RT dependent transbilayer movement of phospholipid.";
RL J. Biol. Chem. 271:17205-17210(1996).
RN [8]
RP PHOSPHORYLATION AT THR-161, AND MUTAGENESIS.
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
RT cell activation by protein kinase Cdelta.";
RL J. Biol. Chem. 275:23065-23073(2000).
RN [9]
RP PHOSPHORYLATION AT TYR-69 AND TYR-74, AND MUTAGENESIS.
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
RT scramblase 1.";
RL J. Biol. Chem. 276:28984-28990(2001).
RN [10]
RP 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
RT function in promoting Ca2+-activated transbilayer movement of membrane
RT phospholipids.";
RL Biochemistry 37:6361-6366(1998).
RN [11]
RP MUTAGENESIS.
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
RT required for Ca2+-accelerated transbilayer movement of membrane
RT phospholipids.";
RL Biochemistry 37:2356-2360(1998).
RN [12]
RP SUBCELLULAR LOCATION, PALMITOYLATION, AND MUTAGENESIS OF
RP 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 [13]
RP FUNCTION, AND INDUCTION.
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 [14]
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.,
RA Sims P.J.;
RT "Phospholipid scramblase 1 binds to the promoter region of the
RT inositol 1,4,5-triphosphate receptor type 1 gene to enhance its
RT expression.";
RL J. Biol. Chem. 280:35062-35068(2005).
RN [15]
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.,
RA Buerckstuemmer T., 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 [16]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 257-266 IN COMPLEX WITH MOUSE
RP KPNA2, NUCLEAR LOCALIZATION SIGNAL, AND MUTAGENESIS OF
RP 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
RT localization signal with unique binding site in importin alpha.";
RL J. Biol. Chem. 280:10599-10606(2005).
CC -!- FUNCTION: May mediate accelerated ATP-independent bidirectional
CC transbilayer migration of phospholipids upon binding calcium ions
CC that results in a loss of phospholipid asymmetry in the plasma
CC membrane. May play a central role in the initiation of fibrin clot
CC formation, in the activation of mast cells and in the recognition
CC of apoptotic and injured cells by the reticuloendothelial system.
CC -!- FUNCTION: May play a role in the antiviral response of interferon
CC (IFN) by amplifying and enhancing the IFN response through
CC increased expression of select subset of potent antiviral genes.
CC May contribute to cytokine-regulated cell proliferation and
CC differentiation.
CC -!- COFACTOR: Calcium.
CC -!- SUBUNIT: Interacts with ABL.
CC -!- INTERACTION:
CC Q9WMX2:- (xeno); NbExp=8; IntAct=EBI-740019, EBI-710918;
CC Q16630:CPSF6; NbExp=2; IntAct=EBI-740019, EBI-358410;
CC P09022:Hoxa1 (xeno); NbExp=3; IntAct=EBI-740019, EBI-3957603;
CC Q8WWR8:NEU4; NbExp=2; IntAct=EBI-740019, EBI-746964;
CC Q16625:OCLN; NbExp=2; IntAct=EBI-740019, EBI-2903088;
CC Q92734:TFG; NbExp=2; IntAct=EBI-740019, EBI-357061;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type II membrane
CC protein. Membrane; Lipid-anchor; Cytoplasmic side. Nucleus.
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
CC detected in brain and skeletal muscle.
CC -!- INDUCTION: By phosphorylation by PKC. Induced by IFNB1/IFN-beta in
CC response to a viral infection.
CC -!- SIMILARITY: Belongs to the phospholipid scramblase family.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Scramblase entry;
CC URL="http://en.wikipedia.org/wiki/Scramblase";
CC -----------------------------------------------------------------------
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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; AK313377; BAG36175.1; -; mRNA.
DR EMBL; CH471052; EAW78926.1; -; Genomic_DNA.
DR EMBL; BC021100; AAH21100.1; -; mRNA.
DR EMBL; BC032718; AAH32718.1; -; mRNA.
DR PIR; JE0284; JE0284.
DR RefSeq; NP_066928.1; NM_021105.2.
DR RefSeq; XP_005247594.1; XM_005247537.1.
DR UniGene; Hs.130759; -.
DR PDB; 1Y2A; X-ray; 2.20 A; P=257-266.
DR PDBsum; 1Y2A; -.
DR ProteinModelPortal; O15162; -.
DR IntAct; O15162; 105.
DR MINT; MINT-201602; -.
DR STRING; 9606.ENSP00000345494; -.
DR TCDB; 9.A.36.1.1; the ca(2+)-dependent phospholipid scramblase (scramblase) family.
DR PhosphoSite; O15162; -.
DR PaxDb; O15162; -.
DR PRIDE; O15162; -.
DR DNASU; 5359; -.
DR Ensembl; ENST00000342435; ENSP00000345494; ENSG00000188313.
DR GeneID; 5359; -.
DR KEGG; hsa:5359; -.
DR UCSC; uc003evx.4; human.
DR CTD; 5359; -.
DR GeneCards; GC03M146232; -.
DR HGNC; HGNC:9092; PLSCR1.
DR MIM; 604170; gene.
DR neXtProt; NX_O15162; -.
DR PharmGKB; PA33419; -.
DR eggNOG; NOG119855; -.
DR HOGENOM; HOG000237356; -.
DR HOVERGEN; HBG019157; -.
DR InParanoid; O15162; -.
DR OMA; FFESTGS; -.
DR OrthoDB; EOG77T14X; -.
DR PhylomeDB; O15162; -.
DR SignaLink; O15162; -.
DR ChiTaRS; PLSCR1; human.
DR EvolutionaryTrace; O15162; -.
DR GeneWiki; PLSCR1; -.
DR GenomeRNAi; 5359; -.
DR NextBio; 20774; -.
DR PRO; PR:O15162; -.
DR ArrayExpress; O15162; -.
DR Bgee; O15162; -.
DR CleanEx; HS_PLSCR1; -.
DR Genevestigator; O15162; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0005887; C:integral to plasma membrane; IDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0017128; F:phospholipid scramblase activity; IDA:UniProtKB.
DR GO; GO:0001077; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription; IDA:UniProtKB.
DR GO; GO:0017124; F:SH3 domain 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:0045071; P:negative regulation of viral genome replication; IMP:UniProtKB.
DR GO; GO:0006659; P:phosphatidylserine biosynthetic process; ISS:UniProtKB.
DR GO; GO:0030168; P:platelet activation; NAS:UniProtKB.
DR GO; GO:2000373; P:positive regulation of DNA topoisomerase (ATP-hydrolyzing) activity; IDA:UniProtKB.
DR GO; GO:0045089; P:positive regulation of innate immune response; IMP: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 InterPro; IPR005552; Scramblase.
DR PANTHER; PTHR23248; PTHR23248; 1.
DR Pfam; PF03803; Scramblase; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antiviral defense; Calcium; Complete proteome;
KW Direct protein sequencing; DNA-binding; Lipoprotein; Membrane;
KW Nucleus; Palmitate; Phosphoprotein; Polymorphism; Reference proteome;
KW Repeat; SH3-binding; Transmembrane; Transmembrane helix.
FT CHAIN 1 318 Phospholipid scramblase 1.
FT /FTId=PRO_0000100784.
FT TOPO_DOM 1 288 Cytoplasmic.
FT TRANSMEM 289 305 Helical; (Potential).
FT TOPO_DOM 306 318 Extracellular.
FT MOTIF 18 26 SH3-binding 1 (Potential).
FT MOTIF 22 25 WW-binding 1 (Potential).
FT MOTIF 33 36 WW-binding 2 (Potential).
FT MOTIF 42 50 SH3-binding 2 (Potential).
FT MOTIF 84 92 SH3-binding 3 (Potential).
FT MOTIF 257 266 Nuclear localization signal.
FT COMPBIAS 181 189 Cys-rich.
FT MOD_RES 69 69 Phosphotyrosine; by ABL.
FT MOD_RES 74 74 Phosphotyrosine; by ABL.
FT MOD_RES 161 161 Phosphothreonine; by PKC.
FT LIPID 184 184 S-palmitoyl cysteine (Probable).
FT LIPID 185 185 S-palmitoyl cysteine (Probable).
FT LIPID 186 186 S-palmitoyl cysteine (Potential).
FT LIPID 188 188 S-palmitoyl cysteine (Probable).
FT LIPID 189 189 S-palmitoyl cysteine (Probable).
FT VARIANT 262 262 H -> Y (in dbSNP:rs343320).
FT /FTId=VAR_034388.
FT MUTAGEN 69 69 Y->F: Decrease in phosphorylation.
FT MUTAGEN 74 74 Y->F: Decrease in phosphorylation.
FT MUTAGEN 161 161 T->A: No induction by PKC.
FT MUTAGEN 184 189 CCCPCC->AAAPAA: No palmitoylation;
FT constitutively localizes in the nucleus.
FT MUTAGEN 273 273 D->A: Reduces the Ca(2+)-dependent
FT phospholipid scrambling.
FT MUTAGEN 275 275 D->A: Complete inactivation of the
FT Ca(2+)-dependent phospholipid scrambling.
FT MUTAGEN 277 277 F->A: Reduces the Ca(2+)-dependent
FT phospholipid scrambling.
FT MUTAGEN 279 279 I->A: Reduces the Ca(2+)-dependent
FT phospholipid scrambling.
FT MUTAGEN 281 281 F->A: Complete inactivation of the
FT Ca(2+)-dependent phospholipid scrambling.
FT MUTAGEN 284 284 D->A: Reduces the Ca(2+)-dependent
FT phospholipid scrambling.
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
//
MIM
604170
*RECORD*
*FIELD* NO
604170
*FIELD* TI
*604170 PHOSPHOLIPID SCRAMBLASE 1; PLSCR1
;;MM1 CELL-DERIVED TRANSPLANTABILITY-ASSOCIATED GENE 1b, MOUSE, HOMOLOG
read moreOF; MMTRA1B
*FIELD* TX
CLONING
The plasma membrane phospholipids (PLs) are normally asymmetrically
distributed, with phosphatidylcholine (PC) and sphingomyelin located
primarily in the outer leaflet and the aminophospholipids
phosphatidylserine (PS) and phosphatidylethanolamine restricted to the
cytoplasmic leaflet. An increase in intracellular calcium due to cell
activation, cell injury, or apoptosis causes a rapid bidirectional
movement of the plasma membrane PLs between leaflets, resulting in
exposure of PS and phosphatidylethanolamine at the cell surface. This
movement is thought to play a key role in expression of platelet
procoagulant activity and in clearance of injured or apoptotic cells.
Basse et al. (1996) purified PL scramblase, a 37-kD plasma membrane
protein that mediates accelerated transbilayer migration of
phospholipids upon binding calcium ions.
By searching an EST database with the partial protein sequence of PL
scramblase, Zhou et al. (1997) identified a partial human cDNA. They
used the partial cDNA to screen a human leukemic cell library and
isolated cDNAs corresponding to the entire PL scramblase coding region.
The predicted protein contains 318 amino acids and has a pI of 4.8.
Sequence analysis suggested that PL scramblase is a type II plasma
membrane protein, with a long N-terminal cytoplasmic domain, a
transmembrane region, and a short extracellular tail. The authors noted
that this topology is consistent with the anticipated topology of PL
scramblase in the erythrocyte membrane, where lipid-mobilizing function
is in response to calcium only at the cytoplasmic surface of the
membrane. Using Northern blot analysis, the authors demonstrated that PL
scramblase was expressed as 1.6- and 2.6-kb mRNAs in all tissues and
cell lines tested.
Independently, Kasukabe et al. (1998) identified PL scramblase as the
human homolog of mouse MmTRA1b (Mm1 cell-derived
transplantability-associated gene 1b), the gene encoding a truncated
leukemogenesis-associated cDNA, MmTRA1a. Human and mouse MmTRA1b are 78%
identical. Sequence analysis revealed that the predicted human protein
contains 3 leucine repeats and a proline-rich N-terminal domain with 3
motifs which may act as docking sites for SH3 motifs. Kasukabe et al.
(1998) noted that mouse MmTRA1b was distinct from a putative mouse PL
scramblase homolog identified by Zhou et al. (1998). The mouse protein
described by Zhou et al. (1998) shares 75% and 71% identity with mouse
MmTRA1b and human PL scramblase, respectively.
GENE FUNCTION
Zhou et al. (1997) showed that recombinant PL scramblase exhibited
calcium-dependent PL scramblase activity in vitro. Quantitative
immunoblotting revealed that PL scramblase levels are approximately
10-fold higher in platelets than in erythrocytes, which Zhou et al.
(1997) stated was consistent with the apparent increased enzyme activity
of the platelet plasma membrane.
By yeast 2-hybrid analysis, Kametaka et al. (2003) found that the
cytoplasmic domain of PLSCR1 interacted with BACE1 (604252), a
proteinase responsible for beta-site processing of amyloid precursor
protein (APP; 104760). Mutation analysis indicated that a dileucine
motif in the C-terminal tail of BACE1 was required for BACE1-PLSCR1
interaction. BACE1 and PLSCR1 colocalized in the Golgi area and in
endosomal compartments, and inhibition of intracellular membrane
trafficking showed that both proteins share a common trafficking
pathway. Coimmunoprecipitation analysis identified an endogenous
BACE1-PLSCR1 complex in a human neuroblastoma cell line, and the 2
proteins colocalized in the lipid raft microdomain of the plasma
membrane. A BACE1 mutant lacking the dileucine motif also fractionated
with lipid rafts, but much less stably than wildtype BACE1. Kametaka et
al. (2003) concluded that PLSCR1 is involved in the intracellular
distribution of BACE1 and/or its recruitment into detergent-insoluble
lipid rafts.
GENE STRUCTURE
Wiedmer et al. (2000) determined that the PLSCR1 gene contains 9 exons
and spans about 30 kb. The first exon is untranslated. By deletion
analysis of PLSCR1 promoter-reporter constructs, they found that 97% of
the promoter activity resides between -95 bp in the 5-prime flanking
region to +60 bp of the first exon. This area contains 2 GC boxes, a
CCAAT box, binding sites for several transcriptional activators,
including AP4 (600743), USF (191523), ETS1 (164720), and IRF (see
147575), and an ISRE.
MAPPING
By FISH, Kasukabe et al. (1998) mapped the MmTRA1b/PL scramblase gene to
3q23. By genomic sequence analysis and radiation hybrid analysis,
Wiedmer et al. (2000) determined that the PLSCR1 gene is clustered with
the PLSCR2 (607610) and PLSCR4 (607612) genes on chromosome 3q23.
*FIELD* RF
1. Basse, F.; Stout, J. G.; Sims, P. J.; Wiedmer, T.: Isolation of
an erythrocyte membrane protein that mediates Ca(2+)-dependent transbilayer
movement of phospholipid. J. Biol. Chem. 271: 17205-17210, 1996.
2. Kametaka, S.; Shibata, M.; Moroe, K.; Kanamori, S.; Ohsawa, Y.;
Waguri, S.; Sims, P. J.; Emoto, K.; Umeda, M.; Uchiyama, Y.: Identification
of phospholipid scramblase 1 as a novel interacting molecule with
beta-secretase (beta-site amyloid precursor protein (APP) cleaving
enzyme (BACE). J. Biol. Chem. 278: 15239-15245, 2003.
3. Kasukabe, T.; Kobayashi, H.; Kaneko, Y.; Okabe-Kado, J.; Honma,
Y.: Identity of human normal counterpart (MmTRA1b) of mouse leukemogenesis-associated
gene (MmTRA1a) product as a plasma membrane phospholipid scramblase
and chromosome mapping of the human MmTRA1b/phospholipid scramblase
gene. Biochem. Biophys. Res. Commun. 249: 449-455, 1998.
4. Wiedmer, T.; Zhou, Q.; Kwoh, D. Y.; Sims, P. J.: Identification
of three new members of the phospholipid scramblase gene family. Biochim.
Biophys. Acta 1467: 244-253, 2000.
5. Zhou, Q.; Sims, P. J.; Wiedmer, T.: Identity of a conserved motif
in phospholipid scramblase that is required for Ca2+-accelerated transbilayer
movement of membrane phospholipids. Biochemistry 37: 2356-2360,
1998.
6. Zhou, Q.; Zhao, J.; Stout, J. G.; Luhm, R. A.; Wiedmer, T.; Sims,
P. J.: Molecular cloning of human plasma membrane phospholipid scramblase:
a protein mediating transbilayer movement of plasma membrane phospholipids. J.
Biol. Chem. 272: 18240-18244, 1997.
*FIELD* CN
Patricia A. Hartz - updated: 11/9/2005
Patricia A. Hartz - updated: 3/7/2003
*FIELD* CD
Rebekah S. Rasooly: 9/14/1999
*FIELD* ED
mgross: 12/02/2005
terry: 11/9/2005
mgross: 3/7/2003
alopez: 9/14/1999
*RECORD*
*FIELD* NO
604170
*FIELD* TI
*604170 PHOSPHOLIPID SCRAMBLASE 1; PLSCR1
;;MM1 CELL-DERIVED TRANSPLANTABILITY-ASSOCIATED GENE 1b, MOUSE, HOMOLOG
read moreOF; MMTRA1B
*FIELD* TX
CLONING
The plasma membrane phospholipids (PLs) are normally asymmetrically
distributed, with phosphatidylcholine (PC) and sphingomyelin located
primarily in the outer leaflet and the aminophospholipids
phosphatidylserine (PS) and phosphatidylethanolamine restricted to the
cytoplasmic leaflet. An increase in intracellular calcium due to cell
activation, cell injury, or apoptosis causes a rapid bidirectional
movement of the plasma membrane PLs between leaflets, resulting in
exposure of PS and phosphatidylethanolamine at the cell surface. This
movement is thought to play a key role in expression of platelet
procoagulant activity and in clearance of injured or apoptotic cells.
Basse et al. (1996) purified PL scramblase, a 37-kD plasma membrane
protein that mediates accelerated transbilayer migration of
phospholipids upon binding calcium ions.
By searching an EST database with the partial protein sequence of PL
scramblase, Zhou et al. (1997) identified a partial human cDNA. They
used the partial cDNA to screen a human leukemic cell library and
isolated cDNAs corresponding to the entire PL scramblase coding region.
The predicted protein contains 318 amino acids and has a pI of 4.8.
Sequence analysis suggested that PL scramblase is a type II plasma
membrane protein, with a long N-terminal cytoplasmic domain, a
transmembrane region, and a short extracellular tail. The authors noted
that this topology is consistent with the anticipated topology of PL
scramblase in the erythrocyte membrane, where lipid-mobilizing function
is in response to calcium only at the cytoplasmic surface of the
membrane. Using Northern blot analysis, the authors demonstrated that PL
scramblase was expressed as 1.6- and 2.6-kb mRNAs in all tissues and
cell lines tested.
Independently, Kasukabe et al. (1998) identified PL scramblase as the
human homolog of mouse MmTRA1b (Mm1 cell-derived
transplantability-associated gene 1b), the gene encoding a truncated
leukemogenesis-associated cDNA, MmTRA1a. Human and mouse MmTRA1b are 78%
identical. Sequence analysis revealed that the predicted human protein
contains 3 leucine repeats and a proline-rich N-terminal domain with 3
motifs which may act as docking sites for SH3 motifs. Kasukabe et al.
(1998) noted that mouse MmTRA1b was distinct from a putative mouse PL
scramblase homolog identified by Zhou et al. (1998). The mouse protein
described by Zhou et al. (1998) shares 75% and 71% identity with mouse
MmTRA1b and human PL scramblase, respectively.
GENE FUNCTION
Zhou et al. (1997) showed that recombinant PL scramblase exhibited
calcium-dependent PL scramblase activity in vitro. Quantitative
immunoblotting revealed that PL scramblase levels are approximately
10-fold higher in platelets than in erythrocytes, which Zhou et al.
(1997) stated was consistent with the apparent increased enzyme activity
of the platelet plasma membrane.
By yeast 2-hybrid analysis, Kametaka et al. (2003) found that the
cytoplasmic domain of PLSCR1 interacted with BACE1 (604252), a
proteinase responsible for beta-site processing of amyloid precursor
protein (APP; 104760). Mutation analysis indicated that a dileucine
motif in the C-terminal tail of BACE1 was required for BACE1-PLSCR1
interaction. BACE1 and PLSCR1 colocalized in the Golgi area and in
endosomal compartments, and inhibition of intracellular membrane
trafficking showed that both proteins share a common trafficking
pathway. Coimmunoprecipitation analysis identified an endogenous
BACE1-PLSCR1 complex in a human neuroblastoma cell line, and the 2
proteins colocalized in the lipid raft microdomain of the plasma
membrane. A BACE1 mutant lacking the dileucine motif also fractionated
with lipid rafts, but much less stably than wildtype BACE1. Kametaka et
al. (2003) concluded that PLSCR1 is involved in the intracellular
distribution of BACE1 and/or its recruitment into detergent-insoluble
lipid rafts.
GENE STRUCTURE
Wiedmer et al. (2000) determined that the PLSCR1 gene contains 9 exons
and spans about 30 kb. The first exon is untranslated. By deletion
analysis of PLSCR1 promoter-reporter constructs, they found that 97% of
the promoter activity resides between -95 bp in the 5-prime flanking
region to +60 bp of the first exon. This area contains 2 GC boxes, a
CCAAT box, binding sites for several transcriptional activators,
including AP4 (600743), USF (191523), ETS1 (164720), and IRF (see
147575), and an ISRE.
MAPPING
By FISH, Kasukabe et al. (1998) mapped the MmTRA1b/PL scramblase gene to
3q23. By genomic sequence analysis and radiation hybrid analysis,
Wiedmer et al. (2000) determined that the PLSCR1 gene is clustered with
the PLSCR2 (607610) and PLSCR4 (607612) genes on chromosome 3q23.
*FIELD* RF
1. Basse, F.; Stout, J. G.; Sims, P. J.; Wiedmer, T.: Isolation of
an erythrocyte membrane protein that mediates Ca(2+)-dependent transbilayer
movement of phospholipid. J. Biol. Chem. 271: 17205-17210, 1996.
2. Kametaka, S.; Shibata, M.; Moroe, K.; Kanamori, S.; Ohsawa, Y.;
Waguri, S.; Sims, P. J.; Emoto, K.; Umeda, M.; Uchiyama, Y.: Identification
of phospholipid scramblase 1 as a novel interacting molecule with
beta-secretase (beta-site amyloid precursor protein (APP) cleaving
enzyme (BACE). J. Biol. Chem. 278: 15239-15245, 2003.
3. Kasukabe, T.; Kobayashi, H.; Kaneko, Y.; Okabe-Kado, J.; Honma,
Y.: Identity of human normal counterpart (MmTRA1b) of mouse leukemogenesis-associated
gene (MmTRA1a) product as a plasma membrane phospholipid scramblase
and chromosome mapping of the human MmTRA1b/phospholipid scramblase
gene. Biochem. Biophys. Res. Commun. 249: 449-455, 1998.
4. Wiedmer, T.; Zhou, Q.; Kwoh, D. Y.; Sims, P. J.: Identification
of three new members of the phospholipid scramblase gene family. Biochim.
Biophys. Acta 1467: 244-253, 2000.
5. Zhou, Q.; Sims, P. J.; Wiedmer, T.: Identity of a conserved motif
in phospholipid scramblase that is required for Ca2+-accelerated transbilayer
movement of membrane phospholipids. Biochemistry 37: 2356-2360,
1998.
6. Zhou, Q.; Zhao, J.; Stout, J. G.; Luhm, R. A.; Wiedmer, T.; Sims,
P. J.: Molecular cloning of human plasma membrane phospholipid scramblase:
a protein mediating transbilayer movement of plasma membrane phospholipids. J.
Biol. Chem. 272: 18240-18244, 1997.
*FIELD* CN
Patricia A. Hartz - updated: 11/9/2005
Patricia A. Hartz - updated: 3/7/2003
*FIELD* CD
Rebekah S. Rasooly: 9/14/1999
*FIELD* ED
mgross: 12/02/2005
terry: 11/9/2005
mgross: 3/7/2003
alopez: 9/14/1999