SLS_LEIMA
ID SLS_LEIMA Reviewed; 338 AA.
AC E9AFX2;
DT 16-NOV-2011, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 1.
DT 03-AUG-2022, entry version 47.
DE RecName: Full=Phosphatidylinositol:ceramide inositolphosphotransferase {ECO:0000303|PubMed:20457606};
DE Short=LmjIPCS {ECO:0000303|PubMed:18699867, ECO:0000303|PubMed:20457606};
DE EC=2.7.8.- {ECO:0000269|PubMed:20457606};
DE AltName: Full=Inositol-phosphorylceramide synthase {ECO:0000303|PubMed:20457606};
DE Short=IPC synthase {ECO:0000303|PubMed:20457606};
DE AltName: Full=Sphingolipid synthase {ECO:0000303|PubMed:20457606};
GN Name=IPCS {ECO:0000303|PubMed:18699867, ECO:0000303|PubMed:20457606};
GN ORFNames=LMJF_35_4990;
OS Leishmania major.
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Leishmaniinae; Leishmania.
OX NCBI_TaxID=5664;
RN [1] {ECO:0000312|EMBL:CBZ13127.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MHOM/IL/81/Friedlin;
RX PubMed=16020728; DOI=10.1126/science.1112680;
RA Ivens A.C., Peacock C.S., Worthey E.A., Murphy L., Aggarwal G.,
RA Berriman M., Sisk E., Rajandream M.A., Adlem E., Aert R., Anupama A.,
RA Apostolou Z., Attipoe P., Bason N., Bauser C., Beck A., Beverley S.M.,
RA Bianchettin G., Borzym K., Bothe G., Bruschi C.V., Collins M., Cadag E.,
RA Ciarloni L., Clayton C., Coulson R.M.R., Cronin A., Cruz A.K., Davies R.M.,
RA De Gaudenzi J., Dobson D.E., Duesterhoeft A., Fazelina G., Fosker N.,
RA Frasch A.C., Fraser A., Fuchs M., Gabel C., Goble A., Goffeau A.,
RA Harris D., Hertz-Fowler C., Hilbert H., Horn D., Huang Y., Klages S.,
RA Knights A., Kube M., Larke N., Litvin L., Lord A., Louie T., Marra M.,
RA Masuy D., Matthews K., Michaeli S., Mottram J.C., Mueller-Auer S.,
RA Munden H., Nelson S., Norbertczak H., Oliver K., O'neil S., Pentony M.,
RA Pohl T.M., Price C., Purnelle B., Quail M.A., Rabbinowitsch E.,
RA Reinhardt R., Rieger M., Rinta J., Robben J., Robertson L., Ruiz J.C.,
RA Rutter S., Saunders D., Schaefer M., Schein J., Schwartz D.C., Seeger K.,
RA Seyler A., Sharp S., Shin H., Sivam D., Squares R., Squares S., Tosato V.,
RA Vogt C., Volckaert G., Wambutt R., Warren T., Wedler H., Woodward J.,
RA Zhou S., Zimmermann W., Smith D.F., Blackwell J.M., Stuart K.D.,
RA Barrell B.G., Myler P.J.;
RT "The genome of the kinetoplastid parasite, Leishmania major.";
RL Science 309:436-442(2005).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=MRHO/SU/59/P / LV39 {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 [3] {ECO:0000305}
RP FUNCTION.
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 inositolphosphotransferase capable of
CC converting phosphatidylinositol (PI) and ceramide to inositol-
CC phosphorylceramide (IPC) and diacylglycerol (DAG) and vice versa.
CC Direction is dependent on the relative concentrations of DAG and
CC ceramide as phosphoinositol acceptors. 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 -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the sphingomyelin synthase family.
CC {ECO:0000255}.
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DR EMBL; FR796431; CBZ13127.1; -; Genomic_DNA.
DR RefSeq; XP_003722892.1; XM_003722844.1.
DR AlphaFoldDB; E9AFX2; -.
DR STRING; 5664.LmjF.35.4990; -.
DR EnsemblProtists; CBZ13127; CBZ13127; LMJF_35_4990.
DR GeneID; 12980649; -.
DR KEGG; lma:LMJF_35_4990; -.
DR VEuPathDB; TriTrypDB:LmjF.35.4990; -.
DR VEuPathDB; TriTrypDB:LMJLV39_350057900; -.
DR VEuPathDB; TriTrypDB:LMJSD75_350057200; -.
DR eggNOG; KOG3058; Eukaryota.
DR HOGENOM; CLU_864647_0_0_1; -.
DR InParanoid; E9AFX2; -.
DR OMA; YCILASR; -.
DR BRENDA; 2.7.1.227; 2950.
DR Proteomes; UP000000542; Chromosome 35.
DR GO; GO:0020016; C:ciliary pocket; ISO:GeneDB.
DR GO; GO:0005768; C:endosome; ISO:GeneDB.
DR GO; GO:0005794; C:Golgi apparatus; EXP:GeneDB.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0030173; C:integral component of Golgi membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0047493; F:ceramide cholinephosphotransferase activity; IBA:GO_Central.
DR GO; GO:0016301; F:kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0033188; F:sphingomyelin synthase activity; ISO:GeneDB.
DR GO; GO:0046513; P:ceramide biosynthetic process; IBA:GO_Central.
DR GO; GO:0046335; P:ethanolamine biosynthetic process; ISO:GeneDB.
DR GO; GO:0016310; P:phosphorylation; 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 3: Inferred from homology;
KW Kinase; Lipid metabolism; Membrane; Reference proteome;
KW Sphingolipid metabolism; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..338
FT /note="Phosphatidylinositol:ceramide
FT inositolphosphotransferase"
FT /id="PRO_0000413860"
FT TOPO_DOM 1..36
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 37..57
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 58..87
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 88..108
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 109..116
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 117..137
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 138..152
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 153..173
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 174..189
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 190..210
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 211..222
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 223..243
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 244..338
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ACT_SITE 220
FT /evidence="ECO:0000250"
FT ACT_SITE 264
FT /evidence="ECO:0000250"
FT ACT_SITE 268
FT /evidence="ECO:0000250"
FT CONFLICT 35
FT /note="M -> T (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 116
FT /note="R -> S (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 338 AA; 37644 MW; EDE4EBE152ACEAA8 CRC64;
MTSHVTAHDV GGNEDIGTDH VPWYKQPLPL CTQVMRFILL LLLTVMFLGV AILVANARMP
DPEKVRPLPD LLLESIPKVA LLENGTNVII FLLNATTVVV GFKVFLLERH MNGLPRVTFL
VGVPKIGSFL NRMAFGVLDS GRRPFPLKNV FPIMAIRFLT SYAVVMVFRA FVIMGTSYPA
TDNHCQNPQV IEHPVLNVIL TLVTLGSGAI HCGDLMFSGH TMILSLAFIL AWDYSPFLHP
WAVRVWVSVL LPISYYCILA SRSHYTDDIL VAMYVMIATY KVIDHAETGA PWQMQLLIRW
MPWPGANTIE KWTADEVVVV VQTPAEDSTD ASAALPEH
