PLS1_RAT
ID PLS1_RAT Reviewed; 335 AA.
AC P58195;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 20-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Phospholipid scramblase 1;
DE Short=PL scramblase 1;
DE AltName: Full=Ca(2+)-dependent phospholipid scramblase 1;
DE AltName: Full=Mg(2+)-dependent nuclease {ECO:0000250|UniProtKB:O15162};
DE EC=3.1.-.- {ECO:0000250|UniProtKB:O15162};
GN Name=Plscr1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PHOSPHORYLATION.
RX PubMed=11259432; DOI=10.1074/jbc.m100790200;
RA Pastorelli C., Veiga J., Charles N., Voignier E., Moussu H., Monteiro R.C.,
RA Benhamou M.;
RT "IgE receptor type I-dependent tyrosine phosphorylation of phospholipid
RT scramblase.";
RL J. Biol. Chem. 276:20407-20412(2001).
CC -!- FUNCTION: Catalyzes calcium-induced ATP-independent rapid bidirectional
CC and non-specific distribution of phospholipids (lipid scrambling or
CC lipid flip-flop) between the inner and outer leaflet of the plasma
CC membrane resulting in collapse of the phospholipid asymmetry which
CC leads to phosphatidylserine externalization on the cell surface (By
CC similarity). Mediates calcium-dependent phosphatidylserine
CC externalization and apoptosis in neurons via its association with TRPC5
CC (By similarity). Also exhibits magnesium-dependent nuclease activity
CC against double-stranded DNA and RNA but not single-stranded DNA and can
CC enhance DNA decatenation mediated by TOP2A (By similarity). Negatively
CC regulates FcR-mediated phagocytosis in differentiated macrophages (By
CC similarity). May contribute to cytokine-regulated cell proliferation
CC and differentiation (By similarity). {ECO:0000250|UniProtKB:O15162,
CC ECO:0000250|UniProtKB:Q9JJ00}.
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:0000250|UniProtKB:O15162};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38572;
CC Evidence={ECO:0000250|UniProtKB:O15162};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:38573;
CC Evidence={ECO:0000250|UniProtKB:O15162};
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:0000250|UniProtKB:O15162};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38896;
CC Evidence={ECO:0000250|UniProtKB:O15162};
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:0000250|UniProtKB:O15162};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38664;
CC Evidence={ECO:0000250|UniProtKB:O15162};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:38665;
CC Evidence={ECO:0000250|UniProtKB:O15162};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:O15162};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:O15162};
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:O15162};
CC Note=Magnesium. Can also use zinc with lower efficiency.
CC {ECO:0000250|UniProtKB:O15162};
CC -!- SUBUNIT: Forms homooligomers in the presence of calcium (By
CC similarity). Interacts with ABL (By similarity). Interacts with RELT,
CC RELL1 and RELL2 (By similarity). Interacts with OXSR1 in the presence
CC of RELT (By similarity). Interacts with OCLN, TOP2A and TOP2B (By
CC similarity). Interacts with TRPC1, TRPC4 and TRPC5 (By similarity).
CC {ECO:0000250|UniProtKB:O15162, ECO:0000250|UniProtKB:Q9JJ00}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O15162};
CC Single-pass type II membrane protein {ECO:0000250|UniProtKB:O15162}.
CC Cell membrane {ECO:0000250|UniProtKB:O15162}; Lipid-anchor
CC {ECO:0000250|UniProtKB:O15162}; Cytoplasmic side. Nucleus
CC {ECO:0000250|UniProtKB:O15162}. Cytoplasm
CC {ECO:0000250|UniProtKB:O15162}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:O15162}. Note=Localizes to the perinuclear
CC region in the presence of RELT. 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.
CC {ECO:0000250|UniProtKB:O15162}.
CC -!- DOMAIN: The N-terminal proline-rich domain (PRD) is required for
CC phospholipid scramblase activity. {ECO:0000250|UniProtKB:O15162}.
CC -!- DOMAIN: The transmembrane domain is essential for membrane insertion,
CC phospholipid scramblase activity and proper calcium-binding.
CC {ECO:0000250|UniProtKB:O15162}.
CC -!- PTM: Phosphorylated on tyrosine residues (PubMed:11259432).
CC Phosphorylated by OXSR1 in the presence of RELT (By similarity).
CC Phosphorylation at Thr-178 by PKC/PKCD increases its phospholipid
CC scramblase activity during both cell stimulation and apoptosis (By
CC similarity). {ECO:0000250|UniProtKB:O15162,
CC ECO:0000269|PubMed:11259432}.
CC -!- PTM: Palmitoylation is required for its phospholipid scramblase
CC activity (By similarity). 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 (By similarity).
CC {ECO:0000250|UniProtKB:O15162}.
CC -!- SIMILARITY: Belongs to the phospholipid scramblase family.
CC {ECO:0000305}.
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DR EMBL; AY024347; AAK00575.1; -; mRNA.
DR RefSeq; NP_476542.1; NM_057194.1.
DR RefSeq; XP_006243600.1; XM_006243538.3.
DR AlphaFoldDB; P58195; -.
DR STRING; 10116.ENSRNOP00000053569; -.
DR PaxDb; P58195; -.
DR GeneID; 117540; -.
DR KEGG; rno:117540; -.
DR UCSC; RGD:620521; rat.
DR CTD; 5359; -.
DR RGD; 620521; Plscr1.
DR VEuPathDB; HostDB:ENSRNOG00000008048; -.
DR eggNOG; KOG0621; Eukaryota.
DR HOGENOM; CLU_053024_2_0_1; -.
DR InParanoid; P58195; -.
DR PRO; PR:P58195; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Bgee; ENSRNOG00000008048; Expressed in adult mammalian kidney and 18 other tissues.
DR ExpressionAtlas; P58195; baseline and differential.
DR Genevisible; P58195; RN.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0042609; F:CD4 receptor binding; ISS: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; ISS:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; ISS:UniProtKB.
DR GO; GO:0032791; F:lead ion binding; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0045340; F:mercury ion binding; ISS:UniProtKB.
DR GO; GO:0004518; F:nuclease activity; ISS:UniProtKB.
DR GO; GO:0017128; F:phospholipid scramblase activity; ISS:UniProtKB.
DR GO; GO:0017124; F:SH3 domain binding; ISS:UniProtKB.
DR GO; GO:0001618; F:virus receptor activity; ISO:RGD.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0006953; P:acute-phase response; ISO:RGD.
DR GO; GO:0006915; P:apoptotic process; ISS:UniProtKB.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; ISO:RGD.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISO:RGD.
DR GO; GO:0051607; P:defense response to virus; ISS:UniProtKB.
DR GO; GO:0006955; P:immune response; IMP:RGD.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0030099; P:myeloid cell differentiation; ISO:RGD.
DR GO; GO:0050765; P:negative regulation of phagocytosis; ISS:UniProtKB.
DR GO; GO:0032091; P:negative regulation of protein binding; ISO:RGD.
DR GO; GO:0045071; P:negative regulation of viral genome replication; ISS:UniProtKB.
DR GO; GO:0006659; P:phosphatidylserine biosynthetic process; ISO:RGD.
DR GO; GO:0070782; P:phosphatidylserine exposure on apoptotic cell surface; ISS:UniProtKB.
DR GO; GO:0015914; P:phospholipid transport; TAS:RGD.
DR GO; GO:0017121; P:plasma membrane phospholipid scrambling; IMP:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR GO; GO:1905820; P:positive regulation of chromosome separation; ISS:UniProtKB.
DR GO; GO:2000373; P:positive regulation of DNA topoisomerase (ATP-hydrolyzing) activity; ISS:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0045089; P:positive regulation of innate immune response; ISS:UniProtKB.
DR GO; GO:1902231; P:positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0060368; P:regulation of Fc receptor mediated stimulatory signaling pathway; IMP:UniProtKB.
DR GO; GO:0033003; P:regulation of mast cell activation; IMP:UniProtKB.
DR GO; GO:0035455; P:response to interferon-alpha; ISO:RGD.
DR GO; GO:0035456; P:response to interferon-beta; ISO:RGD.
DR GO; GO:0010288; P:response to lead ion; ISO:RGD.
DR InterPro; IPR005552; Scramblase.
DR PANTHER; PTHR23248; PTHR23248; 1.
DR Pfam; PF03803; Scramblase; 1.
PE 1: Evidence at protein level;
KW Calcium; Cell membrane; Cytoplasm; DNA-binding; Hydrolase; Lipid transport;
KW Lipoprotein; Membrane; Nuclease; Nucleus; Palmitate; Phosphoprotein;
KW Reference proteome; Repeat; SH3-binding; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..335
FT /note="Phospholipid scramblase 1"
FT /id="PRO_0000100786"
FT TOPO_DOM 1..305
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O15162"
FT TRANSMEM 306..322
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 323..335
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O15162"
FT REPEAT 23..29
FT /note="1"
FT REPEAT 30..36
FT /note="2"
FT REPEAT 37..43
FT /note="3"
FT REPEAT 44..50
FT /note="4"
FT REPEAT 51..57
FT /note="5"
FT REPEAT 58..64
FT /note="6"
FT REPEAT 65..71
FT /note="7; approximate"
FT REGION 1..102
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1..101
FT /note="Proline-rich domain (PRD)"
FT /evidence="ECO:0000250|UniProtKB:O15162"
FT REGION 23..71
FT /note="7 X 7 AA tandem repeats of Q-G-P-Y-[AP]-G-P"
FT MOTIF 64..72
FT /note="SH3-binding 1"
FT /evidence="ECO:0000255"
FT MOTIF 101..109
FT /note="SH3-binding 2"
FT /evidence="ECO:0000255"
FT MOTIF 274..283
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:O15162"
FT COMPBIAS 27..73
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 91
FT /note="Phosphotyrosine; by ABL"
FT /evidence="ECO:0000250|UniProtKB:O15162"
FT MOD_RES 178
FT /note="Phosphothreonine; by PKC/PRKCD"
FT /evidence="ECO:0000250|UniProtKB:O15162"
FT LIPID 201
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:O15162"
FT LIPID 202
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:O15162"
FT LIPID 205
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:O15162"
FT LIPID 206
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:O15162"
SQ SEQUENCE 335 AA; 36711 MW; 7A674DDE7F2759EB CRC64;
MEKHGPPEHA AYPIPQADYQ GSQGPYPGPQ GPYPGPQGPY AGPQGPYPGP QGPYAGPQGP
YPGPQPGYPV PPGSYAGGDP SGFPVQHQPA YNHPGGPGGT PWMQAPPPPL DCPPGLEYLT
QIDQILVHQQ IELLEVLTGF ETNNKYEIKN SLGQRVYFAV EDTDCCTRNC CGASRPFTLR
ILDNMGREVM TLERPLRCSS CCFPCCLQEI EIQAPPGVPV GYVIQTWHPC LPKFTLQNEK
RQDVLKVVGP CVVCSCCSDI DFELKSLDEE SVVGKISKQW SGFVREAFTD ADNFGIQFPL
DLDVKMKAVM LGACFLIDFM FFERTGNEEQ RSGVW
