PLS3_RAT
ID PLS3_RAT Reviewed; 296 AA.
AC Q6QBQ4; Q4V7A3;
DT 24-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 102.
DE RecName: Full=Phospholipid scramblase 3;
DE Short=PL scramblase 3;
DE AltName: Full=Ca(2+)-dependent phospholipid scramblase 3;
GN Name=Plscr3; Synonyms=Pls3;
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].
RC STRAIN=Sprague-Dawley;
RA Chien E.K., Phillippe M., Ji H.;
RT "Phospholipid scramblase 3 expression in pregnant rat myometrium.";
RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [3]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES,
RP SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=29171872; DOI=10.1002/1873-3468.12917;
RA Luevano-Martinez L.A., Kowaltowski A.J.;
RT "Topological characterization of the mitochondrial phospholipid scramblase
RT 3.";
RL FEBS Lett. 591:4056-4066(2017).
CC -!- FUNCTION: Catalyzes calcium-induced ATP-independent rapid bidirectional
CC and non-specific movement of the phospholipids (lipid scrambling or
CC lipid flip-flop) between the inner and outer membrane of the
CC mitochondria (PubMed:29171872). Plays an important role in
CC mitochondrial respiratory function, morphology, and apoptotic response
CC (By similarity). Mediates the translocation of cardiolipin from the
CC mitochondrial inner membrane to outer membrane enhancing t-Bid induced
CC cytochrome c release and apoptosis (By similarity). Enhances TNFSF10-
CC induced apoptosis by regulating the distribution of cardiolipin in the
CC mitochondrial membrane resulting in increased release of apoptogenic
CC factors and consequent amplification of the activity of caspases (By
CC similarity). Regulates cardiolipin de novo biosynthesis and its
CC resynthesis (By similarity). {ECO:0000250|UniProtKB:Q9NRY6,
CC ECO:0000269|PubMed:29171872}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a cardiolipin(in) = a cardiolipin(out); Xref=Rhea:RHEA:38695,
CC ChEBI:CHEBI:62237; Evidence={ECO:0000250|UniProtKB:Q9NRY6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38696;
CC Evidence={ECO:0000250|UniProtKB:Q9NRY6};
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:29171872};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38896;
CC Evidence={ECO:0000305|PubMed:29171872};
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:Q9NRY6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38572;
CC Evidence={ECO:0000250|UniProtKB:Q9NRY6};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:38573;
CC Evidence={ECO:0000250|UniProtKB:Q9NRY6};
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:Q9NRY6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38664;
CC Evidence={ECO:0000250|UniProtKB:Q9NRY6};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-diacyl-sn-glycero-3-phospho-(1'-sn-glycerol)(in) = 1,2-
CC diacyl-sn-glycero-3-phospho-(1'-sn-glycerol)(out);
CC Xref=Rhea:RHEA:39743, ChEBI:CHEBI:64716;
CC Evidence={ECO:0000250|UniProtKB:Q9NRY6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39744;
CC Evidence={ECO:0000250|UniProtKB:Q9NRY6};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:29171872};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9NRY6};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 5.8. Activity decreases at higher pH values.
CC {ECO:0000269|PubMed:29171872};
CC -!- SUBUNIT: Monomer (By similarity). Forms homooligomers upon binding to
CC Ca(2+), Pb(2+) and Hg(2+) ions (By similarity). Interacts with PDCD6 in
CC a calcium-dependent manner (By similarity). Interacts with PRKCD;
CC interaction is enhanced by UV irradiation (By similarity).
CC {ECO:0000250|UniProtKB:Q9NRY6}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:29171872}; Single-pass type II membrane protein
CC {ECO:0000305|PubMed:29171872}. Nucleus {ECO:0000250|UniProtKB:Q9JIZ9}.
CC Note=Palmitoylation regulates its localization to the cell membrane or
CC the nucleus; trafficking to the cell membrane is dependent upon
CC palmitoylation whereas in the absence of palmitoylation, localizes to
CC the nucleus. {ECO:0000250|UniProtKB:Q9JIZ9}.
CC -!- DOMAIN: The Proline-rich domain is required for phospholipid scramblase
CC activity. {ECO:0000250|UniProtKB:O15162}.
CC -!- PTM: Palmitoylation regulates its localization to the cell membrane or
CC the nucleus; trafficking to the cell membrane is dependent upon
CC palmitoylation whereas in the absence of palmitoylation, localizes to
CC the nucleus. {ECO:0000250|UniProtKB:Q9JIZ9}.
CC -!- SIMILARITY: Belongs to the phospholipid scramblase family.
CC {ECO:0000305}.
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DR EMBL; AY548831; AAS55061.1; -; mRNA.
DR EMBL; BC098055; AAH98055.1; -; mRNA.
DR RefSeq; NP_001012139.1; NM_001012139.2.
DR AlphaFoldDB; Q6QBQ4; -.
DR STRING; 10116.ENSRNOP00000035566; -.
DR PaxDb; Q6QBQ4; -.
DR PRIDE; Q6QBQ4; -.
DR GeneID; 360549; -.
DR KEGG; rno:360549; -.
DR UCSC; RGD:1307016; rat.
DR CTD; 57048; -.
DR RGD; 1307016; Plscr3.
DR VEuPathDB; HostDB:ENSRNOG00000027914; -.
DR eggNOG; KOG0621; Eukaryota.
DR HOGENOM; CLU_053024_1_0_1; -.
DR InParanoid; Q6QBQ4; -.
DR OMA; KAFFGWD; -.
DR OrthoDB; 1015148at2759; -.
DR PhylomeDB; Q6QBQ4; -.
DR TreeFam; TF314939; -.
DR ChiTaRS; Plscr3; rat.
DR PRO; PR:Q6QBQ4; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000027914; Expressed in lung and 19 other tissues.
DR Genevisible; Q6QBQ4; RN.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0048306; F:calcium-dependent protein binding; ISO:RGD.
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:0017128; F:phospholipid scramblase activity; IDA:UniProtKB.
DR GO; GO:0043621; F:protein self-association; ISS:UniProtKB.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; ISO:RGD.
DR GO; GO:0032049; P:cardiolipin biosynthetic process; ISS:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISO:RGD.
DR GO; GO:0042632; P:cholesterol homeostasis; ISO:RGD.
DR GO; GO:0042593; P:glucose homeostasis; ISO:RGD.
DR GO; GO:0017121; P:plasma membrane phospholipid scrambling; IBA:GO_Central.
DR GO; GO:0042981; P:regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0090199; P:regulation of release of cytochrome c from mitochondria; ISS:UniProtKB.
DR InterPro; IPR005552; Scramblase.
DR PANTHER; PTHR23248; PTHR23248; 1.
DR Pfam; PF03803; Scramblase; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Calcium; Lipid transport; Lipoprotein; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Nucleus; Palmitate; Reference proteome;
KW Repeat; SH3-binding; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..296
FT /note="Phospholipid scramblase 3"
FT /id="PRO_0000100791"
FT TOPO_DOM 1..266
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305|PubMed:29171872"
FT TRANSMEM 267..283
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..58
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1..58
FT /note="Proline-rich domain (PRD)"
FT /evidence="ECO:0000250|UniProtKB:O15162"
FT MOTIF 7..15
FT /note="SH3-binding 1"
FT /evidence="ECO:0000255"
FT MOTIF 15..18
FT /note="PPxY motif"
FT /evidence="ECO:0000255"
FT MOTIF 21..27
FT /note="SH3-binding 2"
FT /evidence="ECO:0000255"
FT MOTIF 66..71
FT /note="SH3-binding 3"
FT /evidence="ECO:0000255"
FT COMPBIAS 8..23
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 37..58
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 159
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIZ9"
FT LIPID 161
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIZ9"
FT LIPID 163
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIZ9"
FT LIPID 164
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIZ9"
FT LIPID 166
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIZ9"
SQ SEQUENCE 296 AA; 31646 MW; 9CD3B3B0CAFEADEB CRC64;
MAGYLPPKGY APSPPPPYPV PAGYPEAAAL HPGPGQAPVP TQGPAPAPGF SLFPSPGPVV
PGPPGPFVPL PGVPSGLEFL VQIDQILIHQ KAERVETFLG WETCNRYELR SGTGQQLGQA
AEESNCCARL CCGARRPLRI RLADPGDREV LRLLRPLHCG CSCCPCGLQE MEVQAPPGTT
IGHVLQTWHP FIPKFSILDA DRQPVLRVVG PCCTCGCGTD TNFEVKTKDE SRSVGRISKQ
WGGLLREALT DADDFGLQFP VDLDVRVKAV LLGATFLIDY MFFEKRGGAG PSAITS
