SLS4_TRYBB
ID SLS4_TRYBB Reviewed; 365 AA.
AC B3A0M2;
DT 16-NOV-2011, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 1.
DT 03-AUG-2022, entry version 20.
DE RecName: Full=Phosphatidylcholine:ceramide cholinephosphotransferase 4 {ECO:0000303|PubMed:20457606};
DE Short=TbSLS4 {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=Sphingomyelin synthase {ECO:0000303|PubMed:20457606};
DE Short=SM synthase {ECO:0000303|PubMed:20457606};
GN Name=SLS4 {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,
RP SUBCELLULAR LOCATION, 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).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND CATALYTIC ACTIVITY.
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).
CC -!- FUNCTION: Bidirectional lipid cholinephosphotransferase capable of
CC converting inositol phosphorylceramide (IPC) to sphingomyelin (SM) and
CC 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:18699867, ECO:0000269|PubMed:20457606};
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:18699867}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:18699867}.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR AlphaFoldDB; B3A0M2; -.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
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 Golgi apparatus; Kinase; Lipid metabolism; Membrane;
KW Sphingolipid metabolism; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..365
FT /note="Phosphatidylcholine:ceramide
FT cholinephosphotransferase 4"
FT /id="PRO_0000413858"
FT TOPO_DOM 1..44
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 45..65
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 66..92
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 93..113
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 114..165
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 166..186
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 187..229
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 230..250
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 251
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 252..272
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 273..275
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 276..296
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 297..365
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ACT_SITE 228
FT /evidence="ECO:0000250"
FT ACT_SITE 271
FT /evidence="ECO:0000250"
FT ACT_SITE 275
FT /evidence="ECO:0000250"
SQ SEQUENCE 365 AA; 40900 MW; 1C745E790F1FDAD5 CRC64;
MISYPFFSLS PPGLVPPPMA VPPVEMYSGS FWNRMRKPLP LRTQVIRFTV VFVIVSFILA
VALQITHERM PDPKVTKPLP DLGFELLTKV PGMYVLADCC IGFLNILSVF TAFKLYLLHR
HCVGSGEPEL PCNIPGVSRF FLSVWLCKEN CRIELRNIHT IAWIRFITSY ALLLLFRSAV
IVMTSLPAPD DLCQDPPKIE NPVKNVILTV LTAGGGSIHC GDLMYSGHTV ILTLHLMFHW
IYGAMVHWSF RPVVTVVAIF GYYCIVASRF HYTDDVLVAI YLTIATFIAV GHNADGAPWQ
LQLFIRWWPC CGANSREVTE DSQPVMVAFK SEELDEMNGV LEGRQKKHGG VGDGESLMFK
CGAYV
