CERS3_MOUSE
ID CERS3_MOUSE Reviewed; 383 AA.
AC Q1A3B0; E9PVY9; Q195J4;
DT 18-SEP-2013, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2006, sequence version 1.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=Ceramide synthase 3 {ECO:0000303|PubMed:22038835};
DE Short=CerS3 {ECO:0000303|PubMed:22038835};
DE Short=mCerS3 {ECO:0000303|PubMed:22038835};
DE AltName: Full=Dihydroceramide synthase 3 {ECO:0000305};
DE AltName: Full=LAG1 longevity assurance homolog 3 {ECO:0000303|PubMed:16753040};
DE AltName: Full=Sphingosine N-acyltransferase CERS3 {ECO:0000305};
DE EC=2.3.1.24 {ECO:0000269|PubMed:16753040};
DE AltName: Full=Ultra-long-chain ceramide synthase CERS3 {ECO:0000305};
DE EC=2.3.1.298 {ECO:0000269|PubMed:22038835};
DE AltName: Full=Very-long-chain ceramide synthase CERS3 {ECO:0000305};
DE EC=2.3.1.297 {ECO:0000269|PubMed:16753040, ECO:0000269|PubMed:18541923, ECO:0000269|PubMed:22038835};
GN Name=Cers3 {ECO:0000303|PubMed:22038835, ECO:0000312|MGI:MGI:2681008};
GN Synonyms=Lass3 {ECO:0000303|PubMed:16753040};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, CATALYTIC
RP ACTIVITY, TISSUE SPECIFICITY, AND PATHWAY.
RC TISSUE=Skin;
RX PubMed=16753040; DOI=10.1042/bj20060379;
RA Mizutani Y., Kihara A., Igarashi Y.;
RT "LASS3 (longevity assurance homologue 3) is a mainly testis-specific
RT (dihydro)ceramide synthase with relatively broad substrate specificity.";
RL Biochem. J. 398:531-538(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=18541923; DOI=10.1194/jlr.m800158-jlr200;
RA Mizutani Y., Kihara A., Chiba H., Tojo H., Igarashi Y.;
RT "2-Hydroxy-ceramide synthesis by ceramide synthase family: enzymatic basis
RT for the preference of FA chain length.";
RL J. Lipid Res. 49:2356-2364(2008).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-340, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, DISRUPTION
RP PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=22038835; DOI=10.1093/hmg/ddr494;
RA Jennemann R., Rabionet M., Gorgas K., Epstein S., Dalpke A., Rothermel U.,
RA Bayerle A., van der Hoeven F., Imgrund S., Kirsch J., Nickel W.,
RA Willecke K., Riezman H., Groene H.J., Sandhoff R.;
RT "Loss of ceramide synthase 3 causes lethal skin barrier disruption.";
RL Hum. Mol. Genet. 21:586-608(2012).
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 very- and ultra-long-chain fatty acyl-CoA (chain length greater than
CC C22) (PubMed:16753040, PubMed:18541923, PubMed:22038835). N-acylates
CC sphinganine and sphingosine bases to form dihydroceramides and
CC ceramides in de novo synthesis and salvage pathways, respectively
CC (PubMed:16753040, PubMed:18541923, PubMed:22038835). It is crucial for
CC the synthesis of ultra-long-chain ceramides in the epidermis, to
CC maintain epidermal lipid homeostasis and terminal differentiation
CC (PubMed:22038835). {ECO:0000269|PubMed:16753040,
CC ECO:0000269|PubMed:18541923, ECO:0000269|PubMed:22038835}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a sphingoid base + a very long-chain fatty acyl-CoA = an N-
CC (very-long-chain fatty acyl)-sphingoid base + CoA + H(+);
CC Xref=Rhea:RHEA:61480, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:84410, ChEBI:CHEBI:138261, ChEBI:CHEBI:144712;
CC EC=2.3.1.297; Evidence={ECO:0000269|PubMed:16753040,
CC ECO:0000269|PubMed:18541923, ECO:0000269|PubMed:22038835};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61481;
CC Evidence={ECO:0000269|PubMed:16753040, ECO:0000269|PubMed:18541923,
CC ECO:0000269|PubMed:22038835};
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:16753040};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36536;
CC Evidence={ECO:0000269|PubMed:16753040};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=sphinganine + tetracosanoyl-CoA = CoA + H(+) + N-
CC tetracosanoylsphinganine; Xref=Rhea:RHEA:33591, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:52961, ChEBI:CHEBI:57287, ChEBI:CHEBI:57817,
CC ChEBI:CHEBI:65052; Evidence={ECO:0000269|PubMed:16753040,
CC ECO:0000269|PubMed:22038835};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33592;
CC Evidence={ECO:0000269|PubMed:16753040, ECO:0000269|PubMed:22038835};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexacosanoyl-CoA + sphinganine = CoA + H(+) + N-
CC hexacosanoylsphinganine; Xref=Rhea:RHEA:33351, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:52962, ChEBI:CHEBI:57287, ChEBI:CHEBI:57817,
CC ChEBI:CHEBI:64868; Evidence={ECO:0000269|PubMed:22038835};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33352;
CC Evidence={ECO:0000269|PubMed:22038835};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-hydroxydocosanoyl-CoA + sphinganine = CoA + H(+) + N-(2-
CC hydroxydocosanoyl)-sphinganine; Xref=Rhea:RHEA:36619,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57817,
CC ChEBI:CHEBI:67023, ChEBI:CHEBI:74117;
CC Evidence={ECO:0000269|PubMed:18541923};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36620;
CC Evidence={ECO:0000269|PubMed:18541923};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-hydroxytetracosanoyl-CoA + sphinganine = CoA + H(+) + N-(2-
CC hydroxytetracosanoyl)-sphinganine; Xref=Rhea:RHEA:36627,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:52371, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57817, ChEBI:CHEBI:74118;
CC Evidence={ECO:0000269|PubMed:18541923};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36628;
CC Evidence={ECO:0000269|PubMed:18541923};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a sphingoid base + an ultra-long-chain fatty acyl-CoA = an N-
CC (ultra-long-chain-acyl)-sphingoid base + CoA + H(+);
CC Xref=Rhea:RHEA:61492, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:84410, ChEBI:CHEBI:143018, ChEBI:CHEBI:144713;
CC EC=2.3.1.298; Evidence={ECO:0000269|PubMed:22038835};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61493;
CC Evidence={ECO:0000269|PubMed:22038835};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=octacosanoyl-CoA + sphinganine = CoA + H(+) + N-
CC (octacosanoyl)-sphinganine; Xref=Rhea:RHEA:36675, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57817, ChEBI:CHEBI:72019,
CC ChEBI:CHEBI:74141; Evidence={ECO:0000269|PubMed:22038835};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36676;
CC Evidence={ECO:0000269|PubMed:22038835};
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:0000269|PubMed:16753040};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23769;
CC Evidence={ECO:0000269|PubMed:16753040};
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:16753040};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36548;
CC Evidence={ECO:0000269|PubMed:16753040};
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:0000269|PubMed:18541923};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36616;
CC Evidence={ECO:0000269|PubMed:18541923};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000269|PubMed:16753040, ECO:0000269|PubMed:18541923,
CC ECO:0000269|PubMed:22038835}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:22038835}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage; Named isoforms=2;
CC Name=1;
CC IsoId=Q1A3B0-1; Sequence=Displayed;
CC Name=2; Synonyms=LASS3-long {ECO:0000303|PubMed:16753040};
CC IsoId=Q1A3B0-2; Sequence=VSP_047870;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in testis
CC (PubMed:16753040). In skin, present in the upper stratum spinosum and
CC stratum granulosum (at protein level) (PubMed:22038835).
CC {ECO:0000269|PubMed:16753040, ECO:0000269|PubMed:22038835}.
CC -!- DISRUPTION PHENOTYPE: Newborn mice die shortly after birth from
CC transepidermal water loss (PubMed:22038835). Defects are due to a
CC complete loss of ultra long chain (more than C26:0) ceramides
CC (PubMed:22038835). Newborn skin appears unwrinkled, erythematous and
CC sticky (PubMed:22038835). Skin is also prone to C.albicans infection
CC (PubMed:22038835). {ECO:0000269|PubMed:22038835}.
CC -!- CAUTION: Contains a predicted homeobox domain which is degenerated,
CC lacking residues important for DNA-binding. Moreover, the protein
CC localizes in the endoplasmic reticulum and not in the nucleus, which
CC also argues against homeobox function (PubMed:22038835).
CC {ECO:0000269|PubMed:22038835, ECO:0000305}.
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DR EMBL; DQ358087; ABC87758.1; -; mRNA.
DR EMBL; DQ646881; ABG00152.1; -; mRNA.
DR EMBL; AC120791; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS52268.1; -. [Q1A3B0-2]
DR RefSeq; NP_001157673.1; NM_001164201.1. [Q1A3B0-2]
DR RefSeq; XP_011249179.1; XM_011250877.2.
DR AlphaFoldDB; Q1A3B0; -.
DR SMR; Q1A3B0; -.
DR STRING; 10090.ENSMUSP00000069238; -.
DR SwissLipids; SLP:000000260; -.
DR iPTMnet; Q1A3B0; -.
DR PhosphoSitePlus; Q1A3B0; -.
DR PaxDb; Q1A3B0; -.
DR PRIDE; Q1A3B0; -.
DR ProteomicsDB; 280075; -. [Q1A3B0-1]
DR ProteomicsDB; 280076; -. [Q1A3B0-2]
DR Antibodypedia; 1805; 157 antibodies from 30 providers.
DR Ensembl; ENSMUST00000066475; ENSMUSP00000069238; ENSMUSG00000030510. [Q1A3B0-2]
DR Ensembl; ENSMUST00000208521; ENSMUSP00000146745; ENSMUSG00000030510. [Q1A3B0-1]
DR GeneID; 545975; -.
DR KEGG; mmu:545975; -.
DR UCSC; uc009hhv.2; mouse. [Q1A3B0-2]
DR CTD; 204219; -.
DR MGI; MGI:2681008; Cers3.
DR VEuPathDB; HostDB:ENSMUSG00000030510; -.
DR eggNOG; KOG1607; Eukaryota.
DR GeneTree; ENSGT01030000234515; -.
DR HOGENOM; CLU_028277_1_1_1; -.
DR OMA; DRPCRMK; -.
DR OrthoDB; 987268at2759; -.
DR PhylomeDB; Q1A3B0; -.
DR TreeFam; TF314319; -.
DR BRENDA; 2.3.1.297; 3474.
DR BRENDA; 2.3.1.298; 3474.
DR Reactome; R-MMU-1660661; Sphingolipid de novo biosynthesis.
DR UniPathway; UPA00222; -.
DR BioGRID-ORCS; 545975; 1 hit in 76 CRISPR screens.
DR ChiTaRS; Cers3; mouse.
DR PRO; PR:Q1A3B0; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q1A3B0; protein.
DR Bgee; ENSMUSG00000030510; Expressed in spermatocyte and 65 other tissues.
DR Genevisible; Q1A3B0; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
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:0046513; P:ceramide biosynthetic process; IDA:UniProtKB.
DR GO; GO:0070268; P:cornification; IMP:UniProtKB.
DR GO; GO:0008544; P:epidermis development; IMP:UniProtKB.
DR GO; GO:0030216; P:keratinocyte differentiation; ISO:MGI.
DR GO; GO:0030148; P:sphingolipid biosynthetic process; IDA:MGI.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR016439; Lag1/Lac1-like.
DR InterPro; IPR006634; TLC-dom.
DR PANTHER; PTHR12560; PTHR12560; 1.
DR Pfam; PF00046; Homeodomain; 1.
DR Pfam; PF03798; TRAM_LAG1_CLN8; 1.
DR PIRSF; PIRSF005225; LAG1_LAC1; 1.
DR SMART; SM00724; TLC; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS50922; TLC; 1.
PE 1: Evidence at protein level;
KW Alternative promoter usage; Endoplasmic reticulum; Lipid biosynthesis;
KW Lipid metabolism; Membrane; Phosphoprotein; Reference proteome;
KW Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..383
FT /note="Ceramide synthase 3"
FT /id="PRO_0000423433"
FT TRANSMEM 32..52
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 139..159
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 174..194
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 205..225
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 263..283
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 302..322
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 323..383
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8IU89"
FT DOMAIN 130..331
FT /note="TLC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00205"
FT REGION 66..127
FT /note="Homeobox-like"
FT /evidence="ECO:0000305"
FT REGION 340..383
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 340..356
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 340
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1
FT /note="M -> MRCVALENKAAWNGKPLQLLPTGEEYPVQTGALGRRM (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:16753040"
FT /id="VSP_047870"
FT CONFLICT Q1A3B0-2:6
FT /note="L -> H (in Ref. 1; ABG00152)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 383 AA; 46081 MW; 98C178A298EBDDEF CRC64;
MFQTFRKWFW SERYWLPPTI KWSDLEDHDG LVFVKASHLY ITIPYAFLLM VVRYFFEKFV
ATPLANALGI KKTQHKIKPN AILENFFKHS TSKPSHTDIY GLAKKCNLTE RQVERWLRIR
QKQNKPCRLQ KFQESCWRFT FYLLITMAGA VFLYDKPWAY DLWEVWNDYP RQPLLPSQYW
YYILEMSFYW SLVFSLSTDI KRKDFLAHVI HHLAAISLMS FSWCANYIRS GTLVMFIHDI
SDIWLESAKM FSYAGWKQTC NTLFFIFTVV FFISRFIIFP FWILYCTLIL PLHYLEPFFS
YIFLNLQLMI LQGLHVYWGY FILKMLNRCI FTQNVQDVRS DNEEEEEEEE EEEAESTKGK
ETEYLKNGLG TNRHLIANGQ HGR
