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   12-AUG-2020, entry version 162.
DE   RecName: Full=Ceramide synthase 1 {ECO:0000303|PubMed:17977534};
DE            Short=CerS1 {ECO:0000303|PubMed:17977534};
DE            EC=2.3.1.- {ECO:0000269|PubMed:17977534, ECO:0000269|PubMed:23530041, ECO:0000269|PubMed:26887952};
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};
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, 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   [8]
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   [9]
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).
CC   -!- FUNCTION: Ceramide synthase that catalyzes formation of ceramide from
CC       sphinganine and acyl-CoA substrates, with high selectivity toward
CC       stearoyl-CoA (octadecanoyl-CoA; C18:0-CoA).
CC       {ECO:0000269|PubMed:17977534, ECO:0000269|PubMed:23530041,
CC       ECO:0000269|PubMed:24782409, ECO:0000269|PubMed:26887952}.
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=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   -!- 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
CC       severe form of progressive myoclonic epilepsy characterized by
CC       myoclonus, generalized tonic-clonic seizures and moderate to severe
CC       cognitive impairment. {ECO:0000269|PubMed:24782409}. Note=The disease
CC       is caused by mutations affecting the gene represented in this 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   BioGRID; 115941; 5.
DR   IntAct; P27544; 7.
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; 221 antibodies.
DR   Ensembl; ENST00000429504; ENSP00000389044; ENSG00000223802. [P27544-2]
DR   Ensembl; ENST00000623882; ENSP00000485308; ENSG00000223802. [P27544-1]
DR   GeneID; 10715; -.
DR   KEGG; hsa:10715; -.
DR   UCSC; uc002nki.2; human. [P27544-1]
DR   CTD; 10715; -.
DR   DisGeNET; 10715; -.
DR   EuPathDB; HostDB:ENSG00000223802.7; -.
DR   GeneCards; CERS1; -.
DR   HGNC; HGNC:14253; CERS1.
DR   HPA; ENSG00000223802; Tissue enriched (brain).
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   GeneTree; ENSGT00940000162926; -.
DR   HOGENOM; CLU_028277_0_0_1; -.
DR   InParanoid; P27544; -.
DR   KO; K04710; -.
DR   OMA; HWQMMTH; -.
DR   PhylomeDB; P27544; -.
DR   TreeFam; TF314319; -.
DR   BioCyc; MetaCyc:MONOMER66-34367; -.
DR   BRENDA; 2.3.1.24; 2681.
DR   PathwayCommons; P27544; -.
DR   Reactome; R-HSA-1660661; Sphingolipid de novo biosynthesis.
DR   UniPathway; UPA00222; -.
DR   BioGRID-ORCS; 10715; 38 hits in 850 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 151 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:BHF-UCL.
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:0035690; P:cellular response to drug; 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:0046513; P:ceramide biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0051974; P:negative regulation of telomerase activity; 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 mutation; Endoplasmic reticulum;
KW   Epilepsy; Lipid biosynthesis; Lipid metabolism; Membrane;
KW   Reference proteome; Transferase; Transmembrane; Transmembrane helix.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000244|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:0000244|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         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   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
//