PLS3_HUMAN
ID PLS3_HUMAN Reviewed; 295 AA.
AC Q9NRY6; A8K252; Q567U0; Q8NBW6; Q96F13;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Phospholipid scramblase 3;
DE Short=PL scramblase 3;
DE AltName: Full=Ca(2+)-dependent phospholipid scramblase 3;
GN Name=PLSCR3;
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], AND VARIANT ILE-293.
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], AND VARIANT ILE-293.
RC TISSUE=Placenta, and Thalamus;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ILE-293.
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-293.
RC TISSUE=B-cell, and Placenta;
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 [6]
RP FUNCTION, PHOSPHORYLATION, MUTAGENESIS OF PHE-258, AND INTERACTION WITH
RP PRKCD.
RX PubMed=12649167;
RA Liu J., Chen J., Dai Q., Lee R.M.;
RT "Phospholipid scramblase 3 is the mitochondrial target of protein kinase C
RT delta-induced apoptosis.";
RL Cancer Res. 63:1153-1156(2003).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP PHE-258.
RX PubMed=14573790;
RA Liu J., Dai Q., Chen J., Durrant D., Freeman A., Liu T., Grossman D.,
RA Lee R.M.;
RT "Phospholipid scramblase 3 controls mitochondrial structure, function, and
RT apoptotic response.";
RL Mol. Cancer Res. 1:892-902(2003).
RN [8]
RP FUNCTION, AND MUTAGENESIS OF PHE-258.
RX PubMed=16939411; DOI=10.1042/bj20060373;
RA Van Q., Liu J., Lu B., Feingold K.R., Shi Y., Lee R.M., Hatch G.M.;
RT "Phospholipid scramblase-3 regulates cardiolipin de novo biosynthesis and
RT its resynthesis in growing HeLa cells.";
RL Biochem. J. 401:103-109(2007).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, PHOSPHORYLATION AT THR-21,
RP MUTAGENESIS OF THR-21, AND SUBCELLULAR LOCATION.
RX PubMed=17226776; DOI=10.1002/jcb.21243;
RA He Y., Liu J., Grossman D., Durrant D., Sweatman T., Lothstein L.,
RA Epand R.F., Epand R.M., Lee R.M.;
RT "Phosphorylation of mitochondrial phospholipid scramblase 3 by protein
RT kinase C-delta induces its activation and facilitates mitochondrial
RT targeting of tBid.";
RL J. Cell. Biochem. 101:1210-1221(2007).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF PHE-258.
RX PubMed=18491232; DOI=10.1007/s10495-008-0219-4;
RA Ndebele K., Gona P., Jin T.G., Benhaga N., Chalah A., Degli-Esposti M.,
RA Khosravi-Far R.;
RT "Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)
RT induced mitochondrial pathway to apoptosis and caspase activation is
RT potentiated by phospholipid scramblase-3.";
RL Apoptosis 13:845-856(2008).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND MUTAGENESIS OF PHE-258.
RX PubMed=18358005; DOI=10.1021/bi701962c;
RA Liu J., Epand R.F., Durrant D., Grossman D., Chi N.W., Epand R.M.,
RA Lee R.M.;
RT "Role of phospholipid scramblase 3 in the regulation of tumor necrosis
RT factor-alpha-induced apoptosis.";
RL Biochemistry 47:4518-4529(2008).
RN [12]
RP INTERACTION WITH PDCD6, AND MUTAGENESIS OF PHE-49 AND PHE-52.
RX PubMed=18256029; DOI=10.1074/jbc.m800717200;
RA Shibata H., Suzuki H., Kakiuchi T., Inuzuka T., Yoshida H., Mizuno T.,
RA Maki M.;
RT "Identification of Alix-type and non-Alix-type ALG-2-binding sites in human
RT phospholipid scramblase 3: differential binding to an alternatively spliced
RT isoform and amino acid-substituted mutants.";
RL J. Biol. Chem. 283:9623-9632(2008).
RN [13]
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 [14]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, COFACTOR, AND MUTAGENESIS OF
RP PHE-258.
RX PubMed=29337693; DOI=10.1515/hsz-2017-0309;
RA Palanirajan S.K., Sivagnanam U., Murugan S., Gummadi S.N.;
RT "In vitro reconstitution and biochemical characterization of human
RT phospholipid scramblase 3: phospholipid specificity and metal ion binding
RT studies.";
RL Biol. Chem. 399:361-374(2018).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, COFACTOR, MUTAGENESIS OF PHE-258,
RP AND ACTIVITY REGULATION.
RX PubMed=31769662; DOI=10.1021/acs.chemrestox.9b00406;
RA Palanirajan S.K., Gummadi S.N.;
RT "Heavy-Metals-Mediated Phospholipids Scrambling by Human Phospholipid
RT Scramblase 3: A Probable Role in Mitochondrial Apoptosis.";
RL Chem. Res. Toxicol. 33:553-564(2020).
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:14573790, PubMed:17226776, PubMed:18358005,
CC PubMed:29337693, PubMed:31769662). Plays an important role in
CC mitochondrial respiratory function, morphology, and apoptotic response
CC (PubMed:14573790, PubMed:17226776, PubMed:18358005, PubMed:12649167).
CC Mediates the translocation of cardiolipin from the mitochondrial inner
CC membrane to outer membrane enhancing t-Bid induced cytochrome c release
CC and apoptosis (PubMed:14573790, PubMed:17226776, PubMed:18358005).
CC Enhances TNFSF10-induced apoptosis by regulating the distribution of
CC cardiolipin in the mitochondrial membrane resulting in increased
CC release of apoptogenic factors and consequent amplification of the
CC activity of caspases (PubMed:18491232). Regulates cardiolipin de novo
CC biosynthesis and its resynthesis (PubMed:16939411).
CC {ECO:0000269|PubMed:12649167, ECO:0000269|PubMed:14573790,
CC ECO:0000269|PubMed:16939411, ECO:0000269|PubMed:17226776,
CC ECO:0000269|PubMed:18358005, ECO:0000269|PubMed:18491232,
CC ECO:0000269|PubMed:29337693, ECO:0000269|PubMed:31769662}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a cardiolipin(in) = a cardiolipin(out); Xref=Rhea:RHEA:38695,
CC ChEBI:CHEBI:62237; Evidence={ECO:0000269|PubMed:14573790,
CC ECO:0000305|PubMed:17226776, ECO:0000305|PubMed:18358005};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38696;
CC Evidence={ECO:0000305|PubMed:14573790};
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:29337693,
CC ECO:0000269|PubMed:31769662};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38896;
CC Evidence={ECO:0000305|PubMed:31769662};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:38897;
CC Evidence={ECO:0000305|PubMed:31769662};
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:29337693};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38572;
CC Evidence={ECO:0000305|PubMed:29337693};
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:29337693};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38664;
CC Evidence={ECO:0000305|PubMed:29337693};
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:0000269|PubMed:29337693};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39744;
CC Evidence={ECO:0000305|PubMed:29337693};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:17226776, ECO:0000269|PubMed:18358005,
CC ECO:0000269|PubMed:29337693, ECO:0000269|PubMed:31769662};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:29337693};
CC -!- ACTIVITY REGULATION: Activated by Pb(2+) and Hg(2+) ions.
CC {ECO:0000269|PubMed:31769662}.
CC -!- SUBUNIT: Monomer (PubMed:29337693). Forms homooligomers upon binding to
CC Ca(2+), Pb(2+) and Hg(2+) ions (PubMed:31769662, PubMed:29337693).
CC Interacts with PDCD6 in a calcium-dependent manner (PubMed:18256029).
CC Interacts with PRKCD; interaction is enhanced by UV irradiation
CC (PubMed:12649167). {ECO:0000269|PubMed:12649167,
CC ECO:0000269|PubMed:18256029, ECO:0000269|PubMed:29337693,
CC ECO:0000269|PubMed:31769662}.
CC -!- INTERACTION:
CC Q9NRY6; Q9NZN9: AIPL1; NbExp=3; IntAct=EBI-750734, EBI-6557414;
CC Q9NRY6; Q5SWW7: C10orf55; NbExp=3; IntAct=EBI-750734, EBI-12809220;
CC Q9NRY6; Q5BKX5-3: C19orf54; NbExp=3; IntAct=EBI-750734, EBI-11976299;
CC Q9NRY6; Q6P5X5: C22orf39; NbExp=3; IntAct=EBI-750734, EBI-7317823;
CC Q9NRY6; Q8NEC5: CATSPER1; NbExp=8; IntAct=EBI-750734, EBI-744545;
CC Q9NRY6; P27658: COL8A1; NbExp=3; IntAct=EBI-750734, EBI-747133;
CC Q9NRY6; P49639: HOXA1; NbExp=5; IntAct=EBI-750734, EBI-740785;
CC Q9NRY6; Q0VD86: INCA1; NbExp=3; IntAct=EBI-750734, EBI-6509505;
CC Q9NRY6; Q8IUC1: KRTAP11-1; NbExp=3; IntAct=EBI-750734, EBI-1052037;
CC Q9NRY6; Q3LI76: KRTAP15-1; NbExp=3; IntAct=EBI-750734, EBI-11992140;
CC Q9NRY6; Q3LI70: KRTAP19-6; NbExp=3; IntAct=EBI-750734, EBI-12805508;
CC Q9NRY6; Q3SYF9: KRTAP19-7; NbExp=3; IntAct=EBI-750734, EBI-10241353;
CC Q9NRY6; Q9BYR7: KRTAP3-2; NbExp=3; IntAct=EBI-750734, EBI-751260;
CC Q9NRY6; Q9BYR6: KRTAP3-3; NbExp=3; IntAct=EBI-750734, EBI-3957694;
CC Q9NRY6; Q3LI64: KRTAP6-1; NbExp=3; IntAct=EBI-750734, EBI-12111050;
CC Q9NRY6; Q5T751: LCE1C; NbExp=3; IntAct=EBI-750734, EBI-12224199;
CC Q9NRY6; O14633: LCE2B; NbExp=3; IntAct=EBI-750734, EBI-11478468;
CC Q9NRY6; Q5TA78: LCE4A; NbExp=6; IntAct=EBI-750734, EBI-10246358;
CC Q9NRY6; Q5TCM9: LCE5A; NbExp=6; IntAct=EBI-750734, EBI-11955689;
CC Q9NRY6; O60336: MAPKBP1; NbExp=3; IntAct=EBI-750734, EBI-947402;
CC Q9NRY6; P41227: NAA10; NbExp=3; IntAct=EBI-750734, EBI-747693;
CC Q9NRY6; Q96DL1-3: NXPE2; NbExp=3; IntAct=EBI-750734, EBI-12128194;
CC Q9NRY6; O75340: PDCD6; NbExp=9; IntAct=EBI-750734, EBI-352915;
CC Q9NRY6; P78337: PITX1; NbExp=3; IntAct=EBI-750734, EBI-748265;
CC Q9NRY6; Q06455-2: RUNX1T1; NbExp=3; IntAct=EBI-750734, EBI-11984663;
CC Q9NRY6; Q5SY68: S100A7L2; NbExp=3; IntAct=EBI-750734, EBI-12006206;
CC Q9NRY6; P49901: SMCP; NbExp=3; IntAct=EBI-750734, EBI-750494;
CC Q9NRY6; O75716: STK16; NbExp=6; IntAct=EBI-750734, EBI-749295;
CC Q9NRY6; Q96KP6: TNIP3; NbExp=3; IntAct=EBI-750734, EBI-2509913;
CC Q9NRY6; Q63HR2: TNS2; NbExp=3; IntAct=EBI-750734, EBI-949753;
CC Q9NRY6; Q15645: TRIP13; NbExp=7; IntAct=EBI-750734, EBI-358993;
CC Q9NRY6; Q9NZC7-5: WWOX; NbExp=3; IntAct=EBI-750734, EBI-12040603;
CC Q9NRY6; Q15915: ZIC1; NbExp=3; IntAct=EBI-750734, EBI-11963196;
CC -!- SUBCELLULAR LOCATION: Mitochondrion membrane
CC {ECO:0000269|PubMed:14573790, ECO:0000269|PubMed:17226776,
CC ECO:0000269|PubMed:18491232}; 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: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 -!- TISSUE SPECIFICITY: Expressed in heart, placenta, lung, liver, skeletal
CC muscle, kidney, pancreas, spleen, thymus, prostate, uterus, small
CC intestine and peripheral blood lymphocytes. Not detected in testis,
CC brain and liver.
CC -!- DOMAIN: The N-terminal proline-rich domain (PRD) is required for
CC phospholipid scramblase activity. {ECO:0000250|UniProtKB:O15162}.
CC -!- PTM: Phosphorylation at Thr-21 by PKC/PRKCD upon apoptotic stimuli
CC enhances phospholipid scramblase activity.
CC {ECO:0000269|PubMed:17226776, ECO:0000305|PubMed:12649167}.
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; AF159442; AAF91083.1; -; mRNA.
DR EMBL; AK075188; BAC11458.1; -; mRNA.
DR EMBL; AK290117; BAF82806.1; -; mRNA.
DR EMBL; CH471108; EAW90200.1; -; Genomic_DNA.
DR EMBL; AC113189; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC011735; AAH11735.1; -; mRNA.
DR EMBL; BC093026; AAH93026.1; -; mRNA.
DR CCDS; CCDS42253.1; -.
DR RefSeq; NP_001188505.1; NM_001201576.1.
DR RefSeq; NP_065093.2; NM_020360.3.
DR AlphaFoldDB; Q9NRY6; -.
DR BioGRID; 121341; 48.
DR IntAct; Q9NRY6; 47.
DR MINT; Q9NRY6; -.
DR STRING; 9606.ENSP00000438547; -.
DR SwissLipids; SLP:000001107; -.
DR TCDB; 9.A.36.1.6; the ca(2+)-dependent phospholipid scramblase (scramblase) family.
DR iPTMnet; Q9NRY6; -.
DR PhosphoSitePlus; Q9NRY6; -.
DR SwissPalm; Q9NRY6; -.
DR BioMuta; PLSCR3; -.
DR DMDM; 296452876; -.
DR EPD; Q9NRY6; -.
DR jPOST; Q9NRY6; -.
DR MassIVE; Q9NRY6; -.
DR MaxQB; Q9NRY6; -.
DR PaxDb; Q9NRY6; -.
DR PeptideAtlas; Q9NRY6; -.
DR PRIDE; Q9NRY6; -.
DR ProteomicsDB; 82444; -.
DR Antibodypedia; 24083; 166 antibodies from 26 providers.
DR DNASU; 57048; -.
DR Ensembl; ENST00000324822.15; ENSP00000316021.11; ENSG00000187838.17.
DR Ensembl; ENST00000574401.5; ENSP00000459019.1; ENSG00000187838.17.
DR Ensembl; ENST00000576201.5; ENSP00000459419.1; ENSG00000187838.17.
DR Ensembl; ENST00000619711.5; ENSP00000483743.2; ENSG00000187838.17.
DR Ensembl; ENST00000639780.1; ENSP00000492083.1; ENSG00000284009.2.
DR Ensembl; ENST00000639874.2; ENSP00000492026.2; ENSG00000284009.2.
DR Ensembl; ENST00000640053.1; ENSP00000491350.1; ENSG00000284009.2.
DR Ensembl; ENST00000640375.1; ENSP00000491393.1; ENSG00000284009.2.
DR GeneID; 57048; -.
DR KEGG; hsa:57048; -.
DR MANE-Select; ENST00000619711.5; ENSP00000483743.2; NM_020360.4; NP_065093.2.
DR UCSC; uc002ggm.3; human.
DR CTD; 57048; -.
DR DisGeNET; 57048; -.
DR GeneCards; PLSCR3; -.
DR HGNC; HGNC:16495; PLSCR3.
DR HPA; ENSG00000187838; Low tissue specificity.
DR MIM; 607611; gene.
DR neXtProt; NX_Q9NRY6; -.
DR OpenTargets; ENSG00000187838; -.
DR PharmGKB; PA33421; -.
DR VEuPathDB; HostDB:ENSG00000187838; -.
DR eggNOG; KOG0621; Eukaryota.
DR GeneTree; ENSGT00940000161755; -.
DR HOGENOM; CLU_053024_1_0_1; -.
DR InParanoid; Q9NRY6; -.
DR OMA; KAFFGWD; -.
DR OrthoDB; 1015148at2759; -.
DR PhylomeDB; Q9NRY6; -.
DR TreeFam; TF314939; -.
DR BRENDA; 7.6.2.1; 2681.
DR PathwayCommons; Q9NRY6; -.
DR SignaLink; Q9NRY6; -.
DR SIGNOR; Q9NRY6; -.
DR BioGRID-ORCS; 57048; 12 hits in 995 CRISPR screens.
DR GeneWiki; PLSCR3; -.
DR GenomeRNAi; 57048; -.
DR Pharos; Q9NRY6; Tbio.
DR PRO; PR:Q9NRY6; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9NRY6; protein.
DR Bgee; ENSG00000187838; Expressed in granulocyte and 94 other tissues.
DR ExpressionAtlas; Q9NRY6; baseline and differential.
DR Genevisible; Q9NRY6; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IMP:UniProtKB.
DR GO; GO:0048306; F:calcium-dependent protein binding; IPI:UniProtKB.
DR GO; GO:0032791; F:lead ion binding; IMP:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IMP:UniProtKB.
DR GO; GO:0045340; F:mercury ion binding; IMP:UniProtKB.
DR GO; GO:0017128; F:phospholipid scramblase activity; IMP:UniProtKB.
DR GO; GO:0043621; F:protein self-association; IDA: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; IMP:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0042632; P:cholesterol homeostasis; IEA:Ensembl.
DR GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl.
DR GO; GO:0017121; P:plasma membrane phospholipid scrambling; IBA:GO_Central.
DR GO; GO:0042981; P:regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0090199; P:regulation of release of cytochrome c from mitochondria; IMP: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; Phosphoprotein;
KW Reference proteome; Repeat; SH3-binding; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..295
FT /note="Phospholipid scramblase 3"
FT /id="PRO_0000100789"
FT TOPO_DOM 1..265
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000250|UniProtKB:Q6QBQ4"
FT TRANSMEM 266..282
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..57
FT /note="Proline-rich domain (PRD)"
FT /evidence="ECO:0000250|UniProtKB:O15162"
FT REGION 1..40
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 65..70
FT /note="SH3-binding 3"
FT /evidence="ECO:0000255"
FT COMPBIAS 8..40
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 21
FT /note="Phosphothreonine; by PKC/PRKCD"
FT /evidence="ECO:0000269|PubMed:17226776"
FT LIPID 158
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIZ9"
FT LIPID 160
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIZ9"
FT LIPID 162
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 165
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIZ9"
FT VARIANT 293
FT /note="V -> I (in dbSNP:rs3744549)"
FT /evidence="ECO:0000269|PubMed:10930526,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|Ref.4"
FT /id="VAR_015568"
FT MUTAGEN 21
FT /note="T->A: Fails to enhance apoptosis mediated by PRKCD
FT activators."
FT /evidence="ECO:0000269|PubMed:17226776"
FT MUTAGEN 21
FT /note="T->D: Promotes apoptosis, more potent in lipid
FT flippase activity."
FT /evidence="ECO:0000269|PubMed:17226776"
FT MUTAGEN 49
FT /note="F->A: Reduces interaction with PDCD6. Abolishes
FT interaction with PDCD6; when associated with A-52."
FT /evidence="ECO:0000269|PubMed:18256029"
FT MUTAGEN 49
FT /note="F->W: No effect on the interaction with PDCD6."
FT /evidence="ECO:0000269|PubMed:18256029"
FT MUTAGEN 49
FT /note="F->Y,L: Reduces interaction with PDCD6."
FT /evidence="ECO:0000269|PubMed:18256029"
FT MUTAGEN 52
FT /note="F->A: Abolishes interaction with PDCD6; when
FT associated with A-49."
FT /evidence="ECO:0000269|PubMed:18256029"
FT MUTAGEN 258
FT /note="F->V: Reduced phospholipid scramblase activity.
FT Reduced calcium and magnesium-binding. Diminished apoptotic
FT responsiveness. Defective mitochondrial structure and
FT oxidative function. Reduced binding affinity for Pb(2+) and
FT Hg(2+) ions. Increased cardiolipin biosynthesis from
FT glycerol and decreased cardiolipin resynthesis from
FT linoleic acid."
FT /evidence="ECO:0000269|PubMed:12649167,
FT ECO:0000269|PubMed:14573790, ECO:0000269|PubMed:16939411,
FT ECO:0000269|PubMed:18358005, ECO:0000269|PubMed:18491232,
FT ECO:0000269|PubMed:29337693, ECO:0000269|PubMed:31769662"
FT CONFLICT 149
FT /note="V -> L (in Ref. 5; AAH11735)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 295 AA; 31648 MW; B53AAA8166E6D99E CRC64;
MAGYLPPKGY APSPPPPYPV TPGYPEPALH PGPGQAPVPA QVPAPAPGFA LFPSPGPVAL
GSAAPFLPLP GVPSGLEFLV QIDQILIHQK AERVETFLGW ETCNRYELRS GAGQPLGQAA
EESNCCARLC CGARRPLRVR LADPGDREVL RLLRPLHCGC SCCPCGLQEM EVQAPPGTTI
GHVLQTWHPF LPKFSIQDAD RQTVLRVVGP CWTCGCGTDT NFEVKTRDES RSVGRISKQW
GGLVREALTD ADDFGLQFPL DLDVRVKAVL LGATFLIDYM FFEKRGGAGP SAVTS
