CERS1_HUMAN
ID CERS1_HUMAN Reviewed; 350 AA.
AC P27544;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Ceramide synthase 1 {ECO:0000303|PubMed:17977534};
DE Short=CerS1 {ECO:0000303|PubMed:17977534};
DE AltName: Full=LAG1 longevity assurance homolog 1 {ECO:0000303|PubMed:9872981};
DE AltName: Full=Longevity assurance gene 1 protein homolog 1 {ECO:0000250|UniProtKB:P27545};
DE AltName: Full=Protein UOG-1 {ECO:0000303|PubMed:2034669};
DE AltName: Full=Sphingoid base N-stearoyltransferase CERS1 {ECO:0000305};
DE EC=2.3.1.299 {ECO:0000269|PubMed:17977534, ECO:0000269|PubMed:23530041, ECO:0000269|PubMed:26887952, ECO:0000269|PubMed:31916624};
GN Name=CERS1 {ECO:0000303|PubMed:17977534, ECO:0000312|HGNC:HGNC:14253};
GN Synonyms=LAG1 {ECO:0000303|PubMed:9872981},
GN LASS1 {ECO:0000250|UniProtKB:P27545}, UOG1 {ECO:0000303|PubMed:2034669};
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] (ISOFORM 1).
RX PubMed=2034669; DOI=10.1073/pnas.88.10.4250;
RA Lee S.-J.;
RT "Expression of growth/differentiation factor 1 in the nervous system:
RT conservation of a bicistronic structure.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:4250-4254(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=9872981; DOI=10.1101/gr.8.12.1259;
RA Jiang J.C., Kirchman P.A., Zagulski M., Hunt J., Jazwinski S.M.;
RT "Homologs of the yeast longevity gene LAG1 in Caenorhabditis elegans and
RT human.";
RL Genome Res. 8:1259-1272(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Hypothalamus;
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 [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=17977534; DOI=10.1016/j.febslet.2007.10.018;
RA Lahiri S., Lee H., Mesicek J., Fuks Z., Haimovitz-Friedman A.,
RA Kolesnick R.N., Futerman A.H.;
RT "Kinetic characterization of mammalian ceramide synthases: determination of
RT K(m) values towards sphinganine.";
RL FEBS Lett. 581:5289-5294(2007).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [7]
RP FUNCTION, AND MUTAGENESIS OF HIS-183.
RX PubMed=22922758; DOI=10.1038/nchembio.1059;
RA Sentelle R.D., Senkal C.E., Jiang W., Ponnusamy S., Gencer S., Selvam S.P.,
RA Ramshesh V.K., Peterson Y.K., Lemasters J.J., Szulc Z.M., Bielawski J.,
RA Ogretmen B.;
RT "Ceramide targets autophagosomes to mitochondria and induces lethal
RT mitophagy.";
RL Nat. Chem. Biol. 8:831-838(2012).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=23530041; DOI=10.1074/jbc.m112.428185;
RA Russo S.B., Tidhar R., Futerman A.H., Cowart L.A.;
RT "Myristate-derived d16:0 sphingolipids constitute a cardiac sphingolipid
RT pool with distinct synthetic routes and functional properties.";
RL J. Biol. Chem. 288:13397-13409(2013).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, PATHWAY, INVOLVEMENT IN EPM8, VARIANT EPM8
RP GLN-183, AND CHARACTERIZATION OF VARIANT EPM8 GLN-183.
RX PubMed=24782409; DOI=10.1002/ana.24170;
RA Vanni N., Fruscione F., Ferlazzo E., Striano P., Robbiano A., Traverso M.,
RA Sander T., Falace A., Gazzerro E., Bramanti P., Bielawski J., Fassio A.,
RA Minetti C., Genton P., Zara F.;
RT "Impairment of ceramide synthesis causes a novel progressive myoclonus
RT epilepsy.";
RL Ann. Neurol. 76:206-212(2014).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=26887952; DOI=10.1074/jbc.m115.695858;
RA Sassa T., Hirayama T., Kihara A.;
RT "Enzyme activities of the ceramide synthases CERS2-6 are regulated by
RT phosphorylation in the C-terminal region.";
RL J. Biol. Chem. 291:7477-7487(2016).
RN [11]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=31916624; DOI=10.1096/fj.201902645r;
RA Jojima K., Edagawa M., Sawai M., Ohno Y., Kihara A.;
RT "Biosynthesis of the anti-lipid-microdomain sphingoid base 4,14-
RT sphingadiene by the ceramide desaturase FADS3.";
RL FASEB J. 34:3318-3335(2020).
RN [12]
RP VARIANTS EPM8 MET-68 AND 70-TRP--PHE-350 DEL.
RX PubMed=33798445; DOI=10.1016/j.ajhg.2021.03.013;
RA Courage C., Oliver K.L., Park E.J., Cameron J.M., Grabinska K.A., Muona M.,
RA Canafoglia L., Gambardella A., Said E., Afawi Z., Baykan B., Brandt C.,
RA di Bonaventura C., Chew H.B., Criscuolo C., Dibbens L.M., Castellotti B.,
RA Riguzzi P., Labate A., Filla A., Giallonardo A.T., Berecki G.,
RA Jackson C.B., Joensuu T., Damiano J.A., Kivity S., Korczyn A., Palotie A.,
RA Striano P., Uccellini D., Giuliano L., Andermann E., Scheffer I.E.,
RA Michelucci R., Bahlo M., Franceschetti S., Sessa W.C., Berkovic S.F.,
RA Lehesjoki A.E.;
RT "Progressive myoclonus epilepsies-Residual unsolved cases have marked
RT genetic heterogeneity including dolichol-dependent protein glycosylation
RT pathway genes.";
RL Am. J. Hum. Genet. 108:722-738(2021).
CC -!- FUNCTION: Ceramide synthase that catalyzes the transfer of the acyl
CC chain from acyl-CoA to a sphingoid base, with high selectivity toward
CC stearoyl-CoA (octadecanoyl-CoA; C18:0-CoA) (PubMed:17977534,
CC PubMed:23530041, PubMed:26887952, PubMed:31916624). N-acylates
CC sphinganine and sphingosine bases to form dihydroceramides and
CC ceramides in de novo synthesis and salvage pathways, respectively
CC (PubMed:17977534, PubMed:23530041, PubMed:26887952, PubMed:31916624,
CC PubMed:24782409). Plays a predominant role in skeletal muscle in
CC regulating C18 ceramide and dihydroceramide levels with an impact on
CC whole-body glucose metabolism and insulin sensitivity. Protects from
CC diet-induced obesity by suppressing the uptake of glucose in multiple
CC organs in a FGF21-dependent way (By similarity). Generates C18
CC ceramides in the brain, playing a critical role in cerebellar
CC development and Purkinje cell function (By similarity). In response to
CC cellular stress mediates mitophagy, a known defense mechanism against
CC cell transformation and aging. Upon mitochondria fission, generates C18
CC ceramides that anchor lipidated MAP1LC3B/LC3B-II autophagolysosomes to
CC outer mitochondrial membranes to eliminate damaged mitochondria
CC (PubMed:22922758). {ECO:0000250|UniProtKB:P27545,
CC ECO:0000269|PubMed:17977534, ECO:0000269|PubMed:22922758,
CC ECO:0000269|PubMed:23530041, ECO:0000269|PubMed:24782409,
CC ECO:0000269|PubMed:26887952, ECO:0000269|PubMed:31916624}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a sphingoid base + octadecanoyl-CoA = an N-octadecanoyl-
CC sphingoid base + CoA + H(+); Xref=Rhea:RHEA:61476, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57394, ChEBI:CHEBI:84410,
CC ChEBI:CHEBI:144711; EC=2.3.1.299;
CC Evidence={ECO:0000269|PubMed:17977534, ECO:0000269|PubMed:23530041,
CC ECO:0000269|PubMed:26887952, ECO:0000269|PubMed:31916624};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61477;
CC Evidence={ECO:0000269|PubMed:17977534, ECO:0000269|PubMed:23530041,
CC ECO:0000269|PubMed:26887952, ECO:0000269|PubMed:31916624};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=octadecanoyl-CoA + sphinganine = CoA + H(+) + N-
CC (octadecanoyl)-sphinganine; Xref=Rhea:RHEA:36547, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57394, ChEBI:CHEBI:57817,
CC ChEBI:CHEBI:67033; Evidence={ECO:0000269|PubMed:17977534,
CC ECO:0000269|PubMed:23530041, ECO:0000269|PubMed:26887952};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36548;
CC Evidence={ECO:0000269|PubMed:17977534, ECO:0000269|PubMed:23530041,
CC ECO:0000269|PubMed:26887952};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecasphinganine + octadecanoyl-CoA = CoA + H(+) + N-
CC octadecanoylhexadecasphinganine; Xref=Rhea:RHEA:43044,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57394,
CC ChEBI:CHEBI:71009, ChEBI:CHEBI:82811;
CC Evidence={ECO:0000269|PubMed:23530041};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43045;
CC Evidence={ECO:0000269|PubMed:23530041};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=octadecanoyl-CoA + sphing-4-enine = CoA + H(+) + N-
CC octadecanoylsphing-4-enine; Xref=Rhea:RHEA:36691, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57394, ChEBI:CHEBI:57756,
CC ChEBI:CHEBI:72961; Evidence={ECO:0000269|PubMed:31916624};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36692;
CC Evidence={ECO:0000305|PubMed:31916624};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=heptadecasphing-4-enine + octadecanoyl-CoA = CoA + H(+) + N-
CC octadecanoyl-heptadecasphing-4-enine; Xref=Rhea:RHEA:67596,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57394,
CC ChEBI:CHEBI:74166, ChEBI:CHEBI:172405;
CC Evidence={ECO:0000250|UniProtKB:P27545};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67597;
CC Evidence={ECO:0000250|UniProtKB:P27545};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-hydroxyoctadecanoyl-CoA + sphinganine = CoA + H(+) + N-(2-
CC hydroxyoctadecanoyl)-sphinganine; Xref=Rhea:RHEA:36615,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57817,
CC ChEBI:CHEBI:67034, ChEBI:CHEBI:74116;
CC Evidence={ECO:0000250|UniProtKB:P27545};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36616;
CC Evidence={ECO:0000250|UniProtKB:P27545};
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:0000250|UniProtKB:P27545};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36556;
CC Evidence={ECO:0000250|UniProtKB:P27545};
CC -!- ACTIVITY REGULATION: Inhibited by fumonisin B1.
CC {ECO:0000250|UniProtKB:P27545}.
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000269|PubMed:17977534, ECO:0000269|PubMed:23530041,
CC ECO:0000269|PubMed:26887952}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:24782409}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P27544-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P27544-2; Sequence=VSP_003049;
CC -!- PTM: Acetylated. Deacetylation by SIRT3 increases enzyme activity and
CC promotes mitochondrial ceramide accumulation.
CC {ECO:0000250|UniProtKB:P27545}.
CC -!- DISEASE: Epilepsy, progressive myoclonic 8 (EPM8) [MIM:616230]: A form
CC of progressive myoclonic epilepsy, a clinically and genetically
CC heterogeneous group of disorders defined by the combination of action
CC and reflex myoclonus, other types of epileptic seizures, and
CC progressive neurodegeneration and neurocognitive impairment. EPM8 is an
CC autosomal recessive form characterized by myoclonus, generalized tonic-
CC clonic seizures and moderate to severe cognitive impairment.
CC {ECO:0000269|PubMed:24782409, ECO:0000269|PubMed:33798445}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: This protein is produced by a bicistronic gene which
CC also produces the GDF1 protein from a non-overlapping reading frame.
CC {ECO:0000269|PubMed:2034669}.
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DR EMBL; M62302; AAA58500.1; -; mRNA.
DR EMBL; AF105009; AAD16892.1; -; Genomic_DNA.
DR EMBL; AF105005; AAD16892.1; JOINED; Genomic_DNA.
DR EMBL; AF105006; AAD16892.1; JOINED; Genomic_DNA.
DR EMBL; AF105007; AAD16892.1; JOINED; Genomic_DNA.
DR EMBL; AF105008; AAD16892.1; JOINED; Genomic_DNA.
DR EMBL; AC005197; AAC24611.1; -; Genomic_DNA.
DR EMBL; AC003972; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC022450; AAH22450.1; -; mRNA.
DR CCDS; CCDS46020.1; -. [P27544-1]
DR CCDS; CCDS46021.1; -. [P27544-2]
DR PIR; D39364; D39364.
DR RefSeq; NP_067090.1; NM_021267.4. [P27544-1]
DR RefSeq; NP_937850.1; NM_198207.2. [P27544-2]
DR AlphaFoldDB; P27544; -.
DR SMR; P27544; -.
DR BioGRID; 115941; 22.
DR IntAct; P27544; 9.
DR MINT; P27544; -.
DR SwissLipids; SLP:000000698; -.
DR iPTMnet; P27544; -.
DR PhosphoSitePlus; P27544; -.
DR SwissPalm; P27544; -.
DR BioMuta; CERS1; -.
DR DMDM; 137046; -.
DR EPD; P27544; -.
DR jPOST; P27544; -.
DR MassIVE; P27544; -.
DR MaxQB; P27544; -.
DR PaxDb; P27544; -.
DR PeptideAtlas; P27544; -.
DR PRIDE; P27544; -.
DR ProteomicsDB; 54401; -. [P27544-1]
DR ProteomicsDB; 54402; -. [P27544-2]
DR Antibodypedia; 28219; 236 antibodies from 30 providers.
DR DNASU; 10715; -.
DR Ensembl; ENST00000429504.6; ENSP00000389044.1; ENSG00000223802.9. [P27544-2]
DR Ensembl; ENST00000623882.4; ENSP00000485308.1; ENSG00000223802.9. [P27544-1]
DR GeneID; 10715; -.
DR KEGG; hsa:10715; -.
DR MANE-Select; ENST00000623882.4; ENSP00000485308.1; NM_021267.5; NP_067090.1.
DR UCSC; uc002nki.2; human. [P27544-1]
DR CTD; 10715; -.
DR DisGeNET; 10715; -.
DR GeneCards; CERS1; -.
DR HGNC; HGNC:14253; CERS1.
DR HPA; ENSG00000223802; Group enriched (brain, choroid plexus).
DR MalaCards; CERS1; -.
DR MIM; 606919; gene.
DR MIM; 616230; phenotype.
DR neXtProt; NX_P27544; -.
DR OpenTargets; ENSG00000223802; -.
DR Orphanet; 424027; Progressive myoclonic epilepsy type 8.
DR PharmGKB; PA30299; -.
DR VEuPathDB; HostDB:ENSG00000223802; -.
DR GeneTree; ENSGT01030000234515; -.
DR HOGENOM; CLU_028277_0_0_1; -.
DR InParanoid; P27544; -.
DR OMA; FFCAFLW; -.
DR PhylomeDB; P27544; -.
DR TreeFam; TF314319; -.
DR BioCyc; MetaCyc:MON66-34367; -.
DR BRENDA; 2.3.1.299; 2681.
DR PathwayCommons; P27544; -.
DR Reactome; R-HSA-1660661; Sphingolipid de novo biosynthesis.
DR SignaLink; P27544; -.
DR UniPathway; UPA00222; -.
DR BioGRID-ORCS; 10715; 52 hits in 1019 CRISPR screens.
DR ChiTaRS; CERS1; human.
DR GeneWiki; LASS1; -.
DR GenomeRNAi; 10715; -.
DR Pharos; P27544; Tbio.
DR PRO; PR:P27544; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P27544; protein.
DR Bgee; ENSG00000223802; Expressed in C1 segment of cervical spinal cord and 135 other tissues.
DR ExpressionAtlas; P27544; baseline and differential.
DR Genevisible; P27544; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISS:HGNC.
DR GO; GO:0016020; C:membrane; TAS:UniProtKB.
DR GO; GO:0016410; F:N-acyltransferase activity; IBA:GO_Central.
DR GO; GO:0050291; F:sphingosine N-acyltransferase activity; IDA:UniProtKB.
DR GO; GO:0072721; P:cellular response to dithiothreitol; IDA:UniProtKB.
DR GO; GO:0036146; P:cellular response to mycotoxin; IDA:UniProtKB.
DR GO; GO:0071492; P:cellular response to UV-A; IDA:UniProtKB.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IDA:UniProtKB.
DR GO; GO:0046513; P:ceramide biosynthetic process; IDA:UniProtKB.
DR GO; GO:0051974; P:negative regulation of telomerase activity; IDA:UniProtKB.
DR GO; GO:1901526; P:positive regulation of mitophagy; IDA:UniProtKB.
DR GO; GO:0030148; P:sphingolipid biosynthetic process; IDA:UniProtKB.
DR InterPro; IPR015615; TGF-beta-rel.
DR InterPro; IPR006634; TLC-dom.
DR PANTHER; PTHR11848; PTHR11848; 1.
DR Pfam; PF03798; TRAM_LAG1_CLN8; 1.
DR SMART; SM00724; TLC; 1.
DR PROSITE; PS50922; TLC; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Disease variant; Endoplasmic reticulum;
KW Epilepsy; Lipid biosynthesis; Lipid metabolism; Membrane;
KW Neurodegeneration; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22223895"
FT CHAIN 2..350
FT /note="Ceramide synthase 1"
FT /id="PRO_0000185507"
FT TRANSMEM 53..73
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 103..123
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 148..168
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 176..196
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 239..259
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 287..307
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 97..311
FT /note="TLC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00205"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22223895"
FT VAR_SEQ 338..350
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_003049"
FT VARIANT 68
FT /note="L -> M (in EPM8; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:33798445"
FT /id="VAR_085037"
FT VARIANT 70..350
FT /note="Missing (in EPM8)"
FT /evidence="ECO:0000269|PubMed:33798445"
FT /id="VAR_085038"
FT VARIANT 183
FT /note="H -> Q (in EPM8; expressed and localized properly to
FT the ER; impaired ceramide synthase activity;
FT dbSNP:rs200024180)"
FT /evidence="ECO:0000269|PubMed:24782409"
FT /id="VAR_073336"
FT MUTAGEN 183
FT /note="H->A: Loss of ceramide synthase activity."
FT /evidence="ECO:0000269|PubMed:22922758"
FT CONFLICT 111
FT /note="G -> C (in Ref. 4; AAH22450)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 350 AA; 39536 MW; F102C12C47DB4162 CRC64;
MAAAGPAAGP TGPEPMPSYA QLVQRGWGSA LAAARGCTDC GWGLARRGLA EHAHLAPPEL
LLLALGALGW TALRSAATAR LFRPLAKRCC LQPRDAAKMP ESAWKFLFYL GSWSYSAYLL
FGTDYPFFHD PPSVFYDWTP GMAVPRDIAA AYLLQGSFYG HSIYATLYMD TWRKDSVVML
LHHVVTLILI VSSYAFRYHN VGILVLFLHD ISDVQLEFTK LNIYFKSRGG SYHRLHALAA
DLGCLSFGFS WFWFRLYWFP LKVLYATSHC SLRTVPDIPF YFFFNALLLL LTLMNLYWFL
YIVAFAAKVL TGQVHELKDL REYDTAEAQS LKPSKAEKPL RNGLVKDKRF
