HYL2_CAEEL
ID HYL2_CAEEL Reviewed; 329 AA.
AC Q7Z139;
DT 06-MAR-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Ceramide synthase hyl-2 {ECO:0000303|PubMed:19372430};
DE Short=HYL-2 {ECO:0000303|PubMed:19372430};
DE EC=2.3.1.24 {ECO:0000305|PubMed:19372430};
GN Name=hyl-2; ORFNames=K02G10.6;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-22, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=Bristol N2;
RX PubMed=17761667; DOI=10.1074/mcp.m600392-mcp200;
RA Kaji H., Kamiie J., Kawakami H., Kido K., Yamauchi Y., Shinkawa T.,
RA Taoka M., Takahashi N., Isobe T.;
RT "Proteomics reveals N-linked glycoprotein diversity in Caenorhabditis
RT elegans and suggests an atypical translocation mechanism for integral
RT membrane proteins.";
RL Mol. Cell. Proteomics 6:2100-2109(2007).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, TISSUE SPECIFICITY, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF 168-HIS-HIS-169.
RX PubMed=19372430; DOI=10.1126/science.1168532;
RA Menuz V., Howell K.S., Gentina S., Epstein S., Riezman I.,
RA Fornallaz-Mulhauser M., Hengartner M.O., Gomez M., Riezman H.,
RA Martinou J.C.;
RT "Protection of C. elegans from anoxia by HYL-2 ceramide synthase.";
RL Science 324:381-384(2009).
CC -!- FUNCTION: Catalyzes the acylation of sphingoid bases to form ceramides.
CC Sphingolipids from Caenorhabditis elegans contain exclusively
CC isosphingoid bases. Exhibits substrate preference for fatty acyl-coA
CC chains containing 20 to 22 carbons. Required for adaptation of the
CC nematode to anoxia. Anoxia tolerance may require one or more of the
CC ceramide species that are either specifically or preferentially
CC synthesized by HYL-2, and seems to be affected by a pathway that is
CC parallel to that involving daf-2. {ECO:0000269|PubMed:19372430}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a fatty acyl-CoA + sphing-4-enine = an N-acylsphing-4-enine +
CC CoA + H(+); Xref=Rhea:RHEA:23768, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:52639, ChEBI:CHEBI:57287, ChEBI:CHEBI:57756,
CC ChEBI:CHEBI:77636; EC=2.3.1.24;
CC Evidence={ECO:0000305|PubMed:19372430};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23769;
CC Evidence={ECO:0000305|PubMed:19372430};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=docosanoyl-CoA + sphinganine = CoA + H(+) + N-
CC docosanoylsphinganine; Xref=Rhea:RHEA:36535, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57817, ChEBI:CHEBI:65059,
CC ChEBI:CHEBI:67021; Evidence={ECO:0000269|PubMed:19372430};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36536;
CC Evidence={ECO:0000269|PubMed:19372430};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=sphinganine + tetradecanoyl-CoA = CoA + H(+) + N-
CC (tetradecanoyl)-sphinganine; Xref=Rhea:RHEA:36571, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57385, ChEBI:CHEBI:57817,
CC ChEBI:CHEBI:67045; Evidence={ECO:0000269|PubMed:19372430};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36572;
CC Evidence={ECO:0000269|PubMed:19372430};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=eicosanoyl-CoA + sphinganine = CoA + H(+) + N-
CC eicosanoylsphinganine; Xref=Rhea:RHEA:36555, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57380, ChEBI:CHEBI:57817,
CC ChEBI:CHEBI:67027; Evidence={ECO:0000305|PubMed:19372430};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36556;
CC Evidence={ECO:0000305|PubMed:19372430};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=15-methylhexadecasphinganine + a fatty acyl-CoA = CoA + H(+) +
CC N-acyl-15-methylhexadecasphinganine; Xref=Rhea:RHEA:34603,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:70829,
CC ChEBI:CHEBI:70845, ChEBI:CHEBI:77636;
CC Evidence={ECO:0000269|PubMed:19372430};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34604;
CC Evidence={ECO:0000269|PubMed:19372430};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000269|PubMed:19372430}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Strong expression in the gut, the posterior bulb of
CC the pharynx, the hypoderm, and unidentified cells of the head and the
CC tail. {ECO:0000269|PubMed:19372430}.
CC -!- DISRUPTION PHENOTYPE: Animals deficient in HYL-2 show inability to
CC adapt to oxygen deprivation as a result from the loss of ceramide
CC synthase function. {ECO:0000269|PubMed:19372430}.
CC -!- SIMILARITY: Belongs to the sphingosine N-acyltransferase family.
CC {ECO:0000305}.
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DR EMBL; FO081023; CCD68564.1; -; Genomic_DNA.
DR RefSeq; NP_508803.3; NM_076402.6.
DR AlphaFoldDB; Q7Z139; -.
DR STRING; 6239.K02G10.6; -.
DR SwissLipids; SLP:000000003; -.
DR SwissLipids; SLP:000000184; -.
DR SwissLipids; SLP:000000185; -.
DR SwissLipids; SLP:000000195; -.
DR iPTMnet; Q7Z139; -.
DR PaxDb; Q7Z139; -.
DR PeptideAtlas; Q7Z139; -.
DR EnsemblMetazoa; K02G10.6.1; K02G10.6.1; WBGene00002044.
DR GeneID; 180743; -.
DR KEGG; cel:CELE_K02G10.6; -.
DR UCSC; K02G10.6; c. elegans.
DR CTD; 180743; -.
DR WormBase; K02G10.6; CE34329; WBGene00002044; hyl-2.
DR eggNOG; KOG1607; Eukaryota.
DR GeneTree; ENSGT01030000234515; -.
DR HOGENOM; CLU_028277_1_3_1; -.
DR InParanoid; Q7Z139; -.
DR OMA; TDMTERQ; -.
DR OrthoDB; 987268at2759; -.
DR PhylomeDB; Q7Z139; -.
DR Reactome; R-CEL-1660661; Sphingolipid de novo biosynthesis.
DR UniPathway; UPA00222; -.
DR PRO; PR:Q7Z139; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00002044; Expressed in embryo and 3 other tissues.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016410; F:N-acyltransferase activity; IBA:GO_Central.
DR GO; GO:0046513; P:ceramide biosynthetic process; IBA:GO_Central.
DR InterPro; IPR016439; Lag1/Lac1-like.
DR InterPro; IPR006634; TLC-dom.
DR PANTHER; PTHR12560; PTHR12560; 1.
DR Pfam; PF03798; TRAM_LAG1_CLN8; 1.
DR PIRSF; PIRSF005225; LAG1_LAC1; 1.
DR SMART; SM00724; TLC; 1.
DR PROSITE; PS50922; TLC; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Lipid biosynthesis; Lipid metabolism; Membrane;
KW Reference proteome; Sphingolipid metabolism; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..329
FT /note="Ceramide synthase hyl-2"
FT /id="PRO_0000421292"
FT TRANSMEM 41..61
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 95..115
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 134..154
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 162..182
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 187..207
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 221..241
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 270..290
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 86..298
FT /note="TLC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00205"
FT CARBOHYD 22
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17761667"
FT MUTAGEN 168..169
FT /note="HH->QY: In allele hyl-2(gnv1); abrogates ceramide
FT synthase activity and increases sensitivity to anoxia."
FT /evidence="ECO:0000269|PubMed:19372430"
SQ SEQUENCE 329 AA; 39176 MW; 1EC9FF4458A08695 CRC64;
MPWWTDALYW LPRGVSWSDM YNKTTEPGYM YPHYSHLWMT VLTGISLIIY RFVFENYIFV
PLAHFLSRKN PPETRRGTLD REKKYSRMAE CAMRALYYTI SFVCGLYLVL HESHLYDITE
CWRNWPFHPI PNAVAWYYWI QGGFYIALVF GILFLDAKRS DFWQMLVHHF ITLALIGVSW
TMNMVRVGTL ILVSHDAVDI LIDVGKILRY EQFETALTIC FAGVLFVWVA TRLVYYPFWI
IRSVWFDAPA LIQDDYEWLN FDQQPQAPRF IMLLLTALLI LHIFWAYILF KIAYDTIQEG
VVDDVREDFD EQSLVNREKA KQQNKNKDD
