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 25-MAY-2022, entry version 169. 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}. 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 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; 233 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. 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 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 medial globus pallidus and 152 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 //