PLS3_MOUSE
ID PLS3_MOUSE Reviewed; 296 AA.
AC Q9JIZ9;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Phospholipid scramblase 3;
DE Short=PL scramblase 3;
DE AltName: Full=Ca(2+)-dependent phospholipid scramblase 3;
GN Name=Plscr3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo, Skin, and Stomach;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH PRKCD.
RC TISSUE=Brain;
RX PubMed=19428821; DOI=10.1016/j.neuint.2009.01.009;
RA Kowalczyk J.E., Beresewicz M., Gajkowska B., Zablocka B.;
RT "Association of protein kinase C delta and phospholipid scramblase 3 in
RT hippocampal mitochondria correlates with neuronal vulnerability to brain
RT ischemia.";
RL Neurochem. Int. 55:157-163(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, PALMITOYLATION AT CYS-159; CYS-161; CYS-163; CYS-164 AND CYS-166,
RP MUTAGENESIS OF 159-CYS--CYS-166 AND 159-CYS--CYS-161, AND SUBCELLULAR
RP LOCATION.
RX PubMed=21785166; DOI=10.1074/mcp.m110.006007;
RA Merrick B.A., Dhungana S., Williams J.G., Aloor J.J., Peddada S.,
RA Tomer K.B., Fessler M.B.;
RT "Proteomic profiling of S-acylated macrophage proteins identifies a role
RT for palmitoylation in mitochondrial targeting of phospholipid scramblase
RT 3.";
RL Mol. Cell. Proteomics 10:M110.006007-M110.006007(2011).
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 (By similarity). Plays an important role in mitochondrial
CC respiratory function, morphology, and apoptotic response (By
CC 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 (Probable). Enhances TNFSF10-induced
CC 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:0000305|PubMed:21785166}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a cardiolipin(in) = a cardiolipin(out); Xref=Rhea:RHEA:38695,
CC ChEBI:CHEBI:62237; Evidence={ECO:0000305|PubMed:21785166};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38696;
CC Evidence={ECO:0000305|PubMed:21785166};
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:Q9NRY6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38896;
CC Evidence={ECO:0000250|UniProtKB:Q9NRY6};
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:0000250|UniProtKB:Q9NRY6};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9NRY6};
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 (PubMed:19428821).
CC {ECO:0000250|UniProtKB:Q9NRY6, ECO:0000269|PubMed:19428821}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion membrane
CC {ECO:0000269|PubMed:21785166}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q6QBQ4}. Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:Q6QBQ4}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q6QBQ4}. Nucleus {ECO:0000269|PubMed:21785166}.
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:0000269|PubMed:21785166}.
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:0000269|PubMed:21785166}.
CC -!- SIMILARITY: Belongs to the phospholipid scramblase family.
CC {ECO:0000305}.
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DR EMBL; AF159850; AAF89526.1; -; mRNA.
DR EMBL; AK011716; BAB27797.1; -; mRNA.
DR EMBL; AK029154; BAC26329.1; -; mRNA.
DR EMBL; AK075841; BAC35999.1; -; mRNA.
DR EMBL; BC020143; AAH20143.1; -; mRNA.
DR CCDS; CCDS24916.1; -.
DR RefSeq; NP_001161969.1; NM_001168497.1.
DR RefSeq; NP_076053.1; NM_023564.4.
DR RefSeq; XP_006534219.1; XM_006534156.2.
DR RefSeq; XP_006534220.1; XM_006534157.3.
DR AlphaFoldDB; Q9JIZ9; -.
DR STRING; 10090.ENSMUSP00000104272; -.
DR iPTMnet; Q9JIZ9; -.
DR PhosphoSitePlus; Q9JIZ9; -.
DR SwissPalm; Q9JIZ9; -.
DR MaxQB; Q9JIZ9; -.
DR PaxDb; Q9JIZ9; -.
DR PRIDE; Q9JIZ9; -.
DR ProteomicsDB; 289549; -.
DR Antibodypedia; 24083; 166 antibodies from 26 providers.
DR DNASU; 70310; -.
DR Ensembl; ENSMUST00000019605; ENSMUSP00000019605; ENSMUSG00000019461.
DR Ensembl; ENSMUST00000108632; ENSMUSP00000104272; ENSMUSG00000019461.
DR Ensembl; ENSMUST00000108633; ENSMUSP00000104273; ENSMUSG00000019461.
DR GeneID; 70310; -.
DR KEGG; mmu:70310; -.
DR UCSC; uc007jrz.2; mouse.
DR CTD; 57048; -.
DR MGI; MGI:1917560; Plscr3.
DR VEuPathDB; HostDB:ENSMUSG00000019461; -.
DR eggNOG; KOG0621; Eukaryota.
DR GeneTree; ENSGT00940000161755; -.
DR HOGENOM; CLU_053024_1_0_1; -.
DR InParanoid; Q9JIZ9; -.
DR OMA; KAFFGWD; -.
DR OrthoDB; 1015148at2759; -.
DR PhylomeDB; Q9JIZ9; -.
DR TreeFam; TF314939; -.
DR BioGRID-ORCS; 70310; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Plscr3; mouse.
DR PRO; PR:Q9JIZ9; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q9JIZ9; protein.
DR Bgee; ENSMUSG00000019461; Expressed in lip and 239 other tissues.
DR ExpressionAtlas; Q9JIZ9; baseline and differential.
DR Genevisible; Q9JIZ9; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0048306; F:calcium-dependent protein binding; ISO:MGI.
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; ISS: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; IMP:UniProtKB.
DR GO; GO:0032049; P:cardiolipin biosynthetic process; ISS:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; IMP:MGI.
DR GO; GO:0042593; P:glucose homeostasis; IMP:MGI.
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_0000100790"
FT TOPO_DOM 1..266
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000250|UniProtKB:Q6QBQ4"
FT TRANSMEM 267..283
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..58
FT /note="Proline-rich domain (PRD)"
FT /evidence="ECO:0000250|UniProtKB:O15162"
FT REGION 1..45
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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..45
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 159
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:21785166"
FT LIPID 161
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:21785166"
FT LIPID 163
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:21785166"
FT LIPID 164
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:21785166"
FT LIPID 166
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:21785166"
FT MUTAGEN 159
FT /note="C->A: Complete loss of palmitoylation,
FT mislocalization from mitochondrial membrane to nucleus and
FT reduced apoptotic function; when associated with A-161, A-
FT 163, A-164 and A-166. Partial loss of palmitoylation; when
FT associated with A-161."
FT /evidence="ECO:0000269|PubMed:21785166"
FT MUTAGEN 161
FT /note="C->A: Complete loss of palmitoylation,
FT mislocalization from mitochondrial membrane to nucleus and
FT reduced apoptotic function; when associated with A-159, A-
FT 163, A-164 and A-166. Partial loss of palmitoylation; when
FT associated with A-159."
FT /evidence="ECO:0000269|PubMed:21785166"
FT MUTAGEN 163
FT /note="C->A: Complete loss of palmitoylation,
FT mislocalization from mitochondrial membrane to nucleus and
FT reduced apoptotic function; when associated with A-159, A-
FT 161, A-164 and A-166."
FT /evidence="ECO:0000269|PubMed:21785166"
FT MUTAGEN 164
FT /note="C->A: Complete loss of palmitoylation,
FT mislocalization from mitochondrial membrane and reduced
FT apoptotic function; when associated with A-159, A-161, A-
FT 163 and A-166."
FT /evidence="ECO:0000269|PubMed:21785166"
FT MUTAGEN 166
FT /note="C->A: Complete loss of palmitoylation,
FT mislocalization from mitochondrial membrane to nucleus and
FT reduced apoptotic function; when associated with A-159, A-
FT 161, A-163 and A-164."
FT /evidence="ECO:0000269|PubMed:21785166"
SQ SEQUENCE 296 AA; 31803 MW; B7F31C29758CFB07 CRC64;
MAGYLPPKGY APSPPPPYPV PSGYPEPVAL HPGPGQAPVP TQVPAPAPGF ALFPSPGPVA
PGPPAPFVPL PGVPPGLEFL VQIDQILIHQ KAERVETFLG WETCNMYELR SGTGQQLGQA
AEESNCCARL CCGARRPFRI RLADPGDREV LRLLRPLHCG CSCCPCGLQE MEVQAPPGTT
IGHVLQTWHP FLPKFSILDA DRQPVLRVVG PCWTCGCGTD TNFEVKTKDE SRSVGRISKQ
WGGLLREALT DADDFGLQFP VDLDVKVKAV LLGATFLIDY MFFEKRGGAG PSAITS
