SLS3_TRYBB
ID SLS3_TRYBB Reviewed; 329 AA.
AC B3A0M1;
DT 16-NOV-2011, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 1.
DT 03-AUG-2022, entry version 17.
DE RecName: Full=Phosphatidylcholine:ceramide cholinephosphotransferase 3 {ECO:0000303|PubMed:20457606};
DE Short=TbSLS3 {ECO:0000303|PubMed:18699867, ECO:0000303|PubMed:20457606};
DE EC=2.7.8.27 {ECO:0000269|PubMed:20457606};
DE AltName: Full=Ethanolamine-phosphorylceramide synthase {ECO:0000303|PubMed:20457606};
DE Short=EPC synthase {ECO:0000303|PubMed:20457606};
DE AltName: Full=Sphingolipid synthase {ECO:0000303|PubMed:20457606};
DE AltName: Full=Sphingomyelin synthase {ECO:0000303|PubMed:20457606};
DE Short=SM synthase {ECO:0000303|PubMed:20457606};
GN Name=SLS3 {ECO:0000303|PubMed:18699867, ECO:0000303|PubMed:20457606};
OS Trypanosoma brucei brucei.
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Trypanosoma.
OX NCBI_TaxID=5702;
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP MUTAGENESIS OF PHE-252.
RC STRAIN=427 {ECO:0000269|PubMed:20457606};
RX PubMed=20457606; DOI=10.1074/jbc.m110.127662;
RA Sevova E.S., Goren M.A., Schwartz K.J., Hsu F.F., Turk J., Fox B.G.,
RA Bangs J.D.;
RT "Cell-free synthesis and functional characterization of sphingolipid
RT synthases from parasitic trypanosomatid protozoa.";
RL J. Biol. Chem. 285:20580-20587(2010).
RN [2] {ECO:0000305}
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RC STRAIN=427 {ECO:0000269|PubMed:18699867};
RX PubMed=18699867; DOI=10.1111/j.1365-2958.2008.06393.x;
RA Sutterwala S.S., Hsu F.F., Sevova E.S., Schwartz K.J., Zhang K., Key P.,
RA Turk J., Beverley S.M., Bangs J.D.;
RT "Developmentally regulated sphingolipid synthesis in African
RT trypanosomes.";
RL Mol. Microbiol. 70:281-296(2008).
CC -!- FUNCTION: Bidirectional lipid cholinephosphotransferase capable of
CC converting phosphatidylcholine (PC) and ceramide to sphingomyelin (SM)
CC and diacylglycerol (DAG) and vice versa. Direction is dependent on the
CC relative concentrations of DAG and ceramide as phosphocholine
CC acceptors. Directly and specifically recognizes the choline head group
CC on the substrate. Also requires two fatty chains on the choline-P donor
CC molecule in order to be recognized efficiently as a substrate. Does not
CC function strictly as a SM synthase. Essential for viability of the
CC pathogenic bloodstream stage of this human protozoan parasite and,
CC consequently, can be considered as potential drug target.
CC {ECO:0000269|PubMed:18699867, ECO:0000269|PubMed:20457606}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + an N-acylsphing-4-
CC enine = a 1,2-diacyl-sn-glycerol + a sphingomyelin;
CC Xref=Rhea:RHEA:18765, ChEBI:CHEBI:17636, ChEBI:CHEBI:17815,
CC ChEBI:CHEBI:52639, ChEBI:CHEBI:57643; EC=2.7.8.27;
CC Evidence={ECO:0000269|PubMed:20457606};
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- DEVELOPMENTAL STAGE: Expressed in both bloodstream and procyclic stage
CC parasites. {ECO:0000269|PubMed:18699867}.
CC -!- DISRUPTION PHENOTYPE: Elevated ceramide levels and growth arrest; cells
CC were arrested in division but replication of DNA and organelles
CC continued giving rise to cells containing multiple nuclei, kinetoplasts
CC and flagella. {ECO:0000269|PubMed:18699867}.
CC -!- SIMILARITY: Belongs to the sphingomyelin synthase family.
CC {ECO:0000255}.
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DR AlphaFoldDB; B3A0M1; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016301; F:kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0033188; F:sphingomyelin synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0006665; P:sphingolipid metabolic process; IEA:UniProtKB-KW.
DR InterPro; IPR045221; Sphingomyelin_synth-like.
DR InterPro; IPR025749; Sphingomyelin_synth-like_dom.
DR PANTHER; PTHR21290; PTHR21290; 1.
DR Pfam; PF14360; PAP2_C; 1.
PE 1: Evidence at protein level;
KW Kinase; Lipid metabolism; Membrane; Sphingolipid metabolism; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..329
FT /note="Phosphatidylcholine:ceramide
FT cholinephosphotransferase 3"
FT /id="PRO_0000413856"
FT TOPO_DOM 1..26
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 27..47
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 48..74
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 75..95
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 96..147
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 148..168
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 169..211
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 212..232
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 233
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 234..254
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 255..257
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 258..278
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 279..329
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MUTAGEN 252
FT /note="F->S: Enhanced inositol-phosphorylceramide (IPC)
FT synthesis without affecting SM or EPC activity creating a
FT trifunctional enzyme."
FT /evidence="ECO:0000269|PubMed:20457606"
SQ SEQUENCE 329 AA; 37084 MW; 679757DD11F11506 CRC64;
MAVPPVEMYS GSFWNRMRKP LPLRTQVIRF TVVFVIVSFI LAVALQITHE RMPDPKVTKP
LPDLGFELLT KVPGMYVLAD CCIGFLNILS VFTAFKLYLL HRHCVGSGEP ELPCNIPGVS
RFFLSVWLCK ENCRIELRNI HTIAWIRFIT SYALLLLFRS AVIVMTSLPA PDDLCQNPPK
IENPVKNVIL TVLTAGAGSI HCGDLMYSGH TVILTLHLMF HWIYGAMVHW SFRPVVTVVA
IFGYYCIVAS RFHYTDDVLV AIYLTIATFI AVGHNADGAP WQLQLFIRWW PCCGANSREV
TEDSQPVMVA FKSEAAGQSS RKVVDERNH
