CERS2_MOUSE
ID CERS2_MOUSE Reviewed; 380 AA.
AC Q924Z4; Q3TXC5; Q9DCN6;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Ceramide synthase 2 {ECO:0000303|PubMed:18165233};
DE Short=CerS2 {ECO:0000303|PubMed:18165233};
DE AltName: Full=LAG1 longevity assurance homolog 2 {ECO:0000303|PubMed:15823095};
DE AltName: Full=Sphingosine N-acyltransferase CERS2 {ECO:0000305};
DE EC=2.3.1.24 {ECO:0000269|PubMed:23275342};
DE AltName: Full=Translocating chain-associating membrane protein homolog 3 {ECO:0000303|Ref.1};
DE Short=TRAM homolog 3 {ECO:0000303|Ref.1};
DE AltName: Full=Tumor metastasis-suppressor gene 1 protein {ECO:0000250|UniProtKB:Q96G23};
DE AltName: Full=Very-long-chain ceramide synthase CERS2 {ECO:0000305};
DE EC=2.3.1.297 {ECO:0000269|PubMed:15823095, ECO:0000269|PubMed:18165233, ECO:0000269|PubMed:20110363};
GN Name=Cers2 {ECO:0000303|PubMed:18165233, ECO:0000312|MGI:MGI:1924143};
GN Synonyms=Lass2 {ECO:0000303|PubMed:15823095}, Trh3 {ECO:0000303|Ref.1};
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].
RA Hartmann E.;
RL Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Liver;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary gland;
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 [4]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, GLYCOSYLATION AT ASN-19, TISSUE
RP SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=15823095; DOI=10.1042/bj20050291;
RA Mizutani Y., Kihara A., Igarashi Y.;
RT "Mammalian Lass6 and its related family members regulate synthesis of
RT specific ceramides.";
RL Biochem. J. 390:263-271(2005).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND TISSUE SPECIFICITY.
RX PubMed=18165233; DOI=10.1074/jbc.m707386200;
RA Laviad E.L., Albee L., Pankova-Kholmyansky I., Epstein S., Park H.,
RA Merrill A.H. Jr., Futerman A.H.;
RT "Characterization of ceramide synthase 2: tissue distribution, substrate
RT specificity, and inhibition by sphingosine 1-phosphate.";
RL J. Biol. Chem. 283:5677-5684(2008).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=19801672; DOI=10.1074/jbc.m109.031971;
RA Imgrund S., Hartmann D., Farwanah H., Eckhardt M., Sandhoff R., Degen J.,
RA Gieselmann V., Sandhoff K., Willecke K.;
RT "Adult ceramide synthase 2 (CERS2)-deficient mice exhibit myelin sheath
RT defects, cerebellar degeneration, and hepatocarcinomas.";
RL J. Biol. Chem. 284:33549-33560(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-341; THR-346; SER-348 AND
RP SER-349, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Liver, Lung, Spleen, and
RC 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 [8]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND DISRUPTION PHENOTYPE.
RX PubMed=20110363; DOI=10.1074/jbc.m109.077594;
RA Pewzner-Jung Y., Park H., Laviad E.L., Silva L.C., Lahiri S., Stiban J.,
RA Erez-Roman R., Bruegger B., Sachsenheimer T., Wieland F., Prieto M.,
RA Merrill A.H. Jr., Futerman A.H.;
RT "A critical role for ceramide synthase 2 in liver homeostasis: I.
RT alterations in lipid metabolic pathways.";
RL J. Biol. Chem. 285:10902-10910(2010).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=23275342; DOI=10.1074/jbc.m112.440792;
RA Yamashita-Sugahara Y., Tokuzawa Y., Nakachi Y., Kanesaki-Yatsuka Y.,
RA Matsumoto M., Mizuno Y., Okazaki Y.;
RT "Fam57b (family with sequence similarity 57, member B), a novel peroxisome
RT proliferator-activated receptor gamma target gene that regulates
RT adipogenesis through ceramide synthesis.";
RL J. Biol. Chem. 288:4522-4537(2013).
RN [10]
RP ACETYLATION, AND DEACETYLATION BY SIRT3.
RX PubMed=26620563; DOI=10.1074/jbc.m115.668228;
RA Novgorodov S.A., Riley C.L., Keffler J.A., Yu J., Kindy M.S., Macklin W.B.,
RA Lombard D.B., Gudz T.I.;
RT "SIRT3 deacetylates ceramide synthases: Implications for mitochondrial
RT dysfunction and brain injury.";
RL J. Biol. Chem. 291:1957-1973(2016).
RN [11]
RP FUNCTION, AND INTERACTION WITH NDUFS2.
RX PubMed=32279995; DOI=10.1016/j.bbrc.2020.02.166;
RA Yang Y., Yang X., Lin Y., Yang G., Li L.;
RT "LASS2 regulates hepatocyte steatosis by interacting with NDUFS2/OXPHOS
RT related proteins.";
RL Biochem. Biophys. Res. Commun. 526:871-879(2020).
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-long-chain fatty acyl-CoA (chain length C22-C27) (PubMed:15823095,
CC PubMed:18165233, PubMed:20110363, PubMed:23275342). N-acylates
CC sphinganine and sphingosine bases to form dihydroceramides and
CC ceramides in de novo synthesis and salvage pathways, respectively
CC (PubMed:15823095, PubMed:18165233, PubMed:20110363, PubMed:23275342).
CC Plays a non-redundant role in the synthesis of ceramides with very-
CC long-chain fatty acids in kidney, liver and brain. Regulates the
CC abundance of myelin-specific sphingolipids galactosylceramide and
CC sulfatide that affects myelin sheath architecture and motor neuron
CC functions (PubMed:19801672, PubMed:32279995).
CC {ECO:0000269|PubMed:15823095, ECO:0000269|PubMed:18165233,
CC ECO:0000269|PubMed:19801672, ECO:0000269|PubMed:20110363,
CC ECO:0000269|PubMed:23275342, ECO:0000269|PubMed:32279995}.
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:15823095,
CC ECO:0000269|PubMed:18165233, ECO:0000269|PubMed:20110363};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61481;
CC Evidence={ECO:0000269|PubMed:15823095, ECO:0000269|PubMed:18165233,
CC ECO:0000269|PubMed:20110363};
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:15823095,
CC ECO:0000269|PubMed:19801672, ECO:0000269|PubMed:20110363};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36536;
CC Evidence={ECO:0000269|PubMed:15823095, ECO:0000269|PubMed:19801672,
CC ECO:0000269|PubMed:20110363};
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:15823095,
CC ECO:0000269|PubMed:20110363};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33592;
CC Evidence={ECO:0000269|PubMed:15823095, ECO:0000269|PubMed:20110363};
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:15823095,
CC ECO:0000269|PubMed:18165233, ECO:0000269|PubMed:20110363};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33352;
CC Evidence={ECO:0000269|PubMed:15823095, ECO:0000269|PubMed:18165233,
CC ECO:0000269|PubMed:20110363};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(15Z)-tetracosenoyl-CoA + sphinganine = CoA + H(+) + N-(15Z-
CC tetracosenoyl)-sphinganine; Xref=Rhea:RHEA:36667, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57817, ChEBI:CHEBI:74128,
CC ChEBI:CHEBI:74130; Evidence={ECO:0000269|PubMed:19801672};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36668;
CC Evidence={ECO:0000269|PubMed:19801672};
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:0000250|UniProtKB:Q96G23};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36628;
CC Evidence={ECO:0000250|UniProtKB:Q96G23};
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:0000250|UniProtKB:Q96G23};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36620;
CC Evidence={ECO:0000250|UniProtKB:Q96G23};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-hydroxytetracosenoyl-CoA + sphinganine = CoA + H(+) + N-(2-
CC hydroxytetracosenoyl)-sphinganine; Xref=Rhea:RHEA:36767,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57817,
CC ChEBI:CHEBI:74215, ChEBI:CHEBI:74216;
CC Evidence={ECO:0000250|UniProtKB:Q96G23};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36768;
CC Evidence={ECO:0000250|UniProtKB:Q96G23};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=sphinganine + tetracosenoyl-CoA = an N-
CC tetracosenoylsphinganine + CoA + H(+); Xref=Rhea:RHEA:36715,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57817,
CC ChEBI:CHEBI:74146, ChEBI:CHEBI:74160;
CC Evidence={ECO:0000269|PubMed:20110363};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36716;
CC Evidence={ECO:0000269|PubMed:20110363};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexacosenoyl-CoA + sphinganine = CoA + H(+) + N-
CC hexacosenoylsphinganine; Xref=Rhea:RHEA:36719, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57817, ChEBI:CHEBI:74161,
CC ChEBI:CHEBI:74162; Evidence={ECO:0000250|UniProtKB:Q96G23};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36720;
CC Evidence={ECO:0000250|UniProtKB:Q96G23};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=sphing-4-enine + tetracosanoyl-CoA = CoA + H(+) + N-
CC tetracosanoyl-sphing-4-enine; Xref=Rhea:RHEA:37115,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57756,
CC ChEBI:CHEBI:65052, ChEBI:CHEBI:72965;
CC Evidence={ECO:0000250|UniProtKB:Q96G23};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37116;
CC Evidence={ECO:0000250|UniProtKB:Q96G23};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=sphing-4-enine + tetracosenoyl-CoA = CoA + H(+) + N-
CC (tetracosenoyl)-sphing-4-enine; Xref=Rhea:RHEA:37123,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57756,
CC ChEBI:CHEBI:74146, ChEBI:CHEBI:74457;
CC Evidence={ECO:0000250|UniProtKB:Q96G23};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37124;
CC Evidence={ECO:0000250|UniProtKB:Q96G23};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=heptadecasphing-4-enine + tetracosanoyl-CoA = CoA + H(+) + N-
CC tetracosanoyl-heptadecasphing-4-enine; Xref=Rhea:RHEA:36739,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:65052,
CC ChEBI:CHEBI:74166, ChEBI:CHEBI:74167;
CC Evidence={ECO:0000250|UniProtKB:Q96G23};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36740;
CC Evidence={ECO:0000250|UniProtKB:Q96G23};
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:23275342};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23769;
CC Evidence={ECO:0000269|PubMed:23275342};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecanoyl-CoA + sphing-4-enine = CoA + H(+) + N-
CC hexadecanoylsphing-4-enine; Xref=Rhea:RHEA:36687, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57379, ChEBI:CHEBI:57756,
CC ChEBI:CHEBI:72959; Evidence={ECO:0000269|PubMed:23275342};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36688;
CC Evidence={ECO:0000269|PubMed:23275342};
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:23275342};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36692;
CC Evidence={ECO:0000269|PubMed:23275342};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=eicosanoyl-CoA + sphing-4-enine = CoA + H(+) + N-eicosanoyl-
CC sphing-4-enine; Xref=Rhea:RHEA:45284, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57380, ChEBI:CHEBI:57756,
CC ChEBI:CHEBI:72962; Evidence={ECO:0000269|PubMed:23275342};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45285;
CC Evidence={ECO:0000269|PubMed:23275342};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecanoyl-CoA + sphinganine = CoA + H(+) + N-
CC hexadecanoylsphinganine; Xref=Rhea:RHEA:36539, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57379, ChEBI:CHEBI:57817,
CC ChEBI:CHEBI:67042; Evidence={ECO:0000250|UniProtKB:Q96G23};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36540;
CC Evidence={ECO:0000250|UniProtKB:Q96G23};
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:19801672};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36548;
CC Evidence={ECO:0000269|PubMed:19801672};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoyl-CoA + sphinganine = CoA + H(+) + N-(9Z-
CC octadecenoyl)-sphinganine; Xref=Rhea:RHEA:36575, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57387, ChEBI:CHEBI:57817,
CC ChEBI:CHEBI:74100; Evidence={ECO:0000250|UniProtKB:Q96G23};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36576;
CC Evidence={ECO:0000250|UniProtKB:Q96G23};
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:0000269|PubMed:18165233,
CC ECO:0000269|PubMed:19801672};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36556;
CC Evidence={ECO:0000269|PubMed:18165233, ECO:0000269|PubMed:19801672};
CC -!- ACTIVITY REGULATION: Ceramide synthase activity is inhibited by
CC sphingosine-1-phosphate. {ECO:0000250|UniProtKB:Q96G23}.
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000269|PubMed:15823095, ECO:0000269|PubMed:18165233,
CC ECO:0000269|PubMed:20110363, ECO:0000269|PubMed:23275342}.
CC -!- SUBUNIT: Interacts with ATP6V0C, ASGR1, ASGR2 and SLC22A1/OCT1.
CC Interacts with ELOV1, HSD17B12 and TECR (By similarity). Interacts with
CC NDUFS2 (PubMed:32279995). {ECO:0000250|UniProtKB:Q96G23,
CC ECO:0000269|PubMed:32279995}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:15823095}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Broadly expressed, with highest levels in liver and
CC kidney (PubMed:15823095, PubMed:18165233, PubMed:19801672). In brain is
CC detected in neurons, oligodentrocytes, ependymal cells and epithelial
CC cells of the choroid plexus. In kidney is detected in collecting ducts
CC and to a lesser degree in proximal tubules.
CC {ECO:0000269|PubMed:15823095, ECO:0000269|PubMed:18165233,
CC ECO:0000269|PubMed:19801672}.
CC -!- DOMAIN: The last loop motif confers selectivity toward behenoyl-CoA
CC (docosanoyl-CoA; C22:0-CoA) and lignoceroyl-CoA (tetracosanoyl-CoA;
CC C24:0-CoA) as acyl donors. {ECO:0000250|UniProtKB:Q96G23}.
CC -!- PTM: Acetylated (PubMed:26620563). Deacetylation by SIRT3 increases
CC enzyme activity and promotes mitochondrial ceramide accumulation
CC (PubMed:26620563). {ECO:0000269|PubMed:26620563}.
CC -!- PTM: Phosphorylated at the C-terminus by CK2, leading to increase the
CC ceramide synthase activity. {ECO:0000250|UniProtKB:Q96G23}.
CC -!- DISRUPTION PHENOTYPE: Most mice do not survive beyond 16 months
CC (PubMed:20110363). Ceramide and downstream sphingolipids are devoid of
CC very long (C22-C24) acyl chains (PubMed:20110363). Total
CC glycerophospholipid and cholesterol levels are unaltered, while a
CC marked increase in C18:1 and C18:2 fatty acids in
CC phosphatidylethanolamine, concomitant with a reduction in C18:0 and
CC C20:4 fatty acids are observed (PubMed:20110363). Membranes display
CC higher membrane fluidity and show morphological changes
CC (PubMed:20110363). Mutant mice show signs of neurodegeneration
CC characterized by the loss of myelin sheath structure stability and
CC formation of numerous small cysts in the cerebellum. They develop
CC hepatocarcinomas between 7 and 9 months of age.
CC {ECO:0000269|PubMed:19801672, ECO:0000269|PubMed:20110363}.
CC -!- CAUTION: Contains a predicted homeobox domain which is degenerated and
CC lacks residues that are important for DNA-binding. The protein
CC localizes in the endoplasmic reticulum and not in the nucleus, which
CC also argues against homeobox function (PubMed:15823095).
CC {ECO:0000269|PubMed:15823095, ECO:0000305}.
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DR EMBL; AY029532; AAK40300.1; -; mRNA.
DR EMBL; AK050161; BAC34102.1; -; mRNA.
DR EMBL; AK159325; BAE34991.1; -; mRNA.
DR EMBL; BC006847; AAH06847.2; -; mRNA.
DR CCDS; CCDS17612.1; -.
DR RefSeq; NP_001307421.1; NM_001320492.1.
DR RefSeq; NP_084065.1; NM_029789.2.
DR RefSeq; XP_006502323.1; XM_006502260.1.
DR AlphaFoldDB; Q924Z4; -.
DR SMR; Q924Z4; -.
DR BioGRID; 218381; 50.
DR IntAct; Q924Z4; 31.
DR STRING; 10090.ENSMUSP00000015858; -.
DR SwissLipids; SLP:000000116; -.
DR GlyConnect; 2203; 2 N-Linked glycans (1 site).
DR GlyGen; Q924Z4; 1 site, 2 N-linked glycans (1 site).
DR iPTMnet; Q924Z4; -.
DR PhosphoSitePlus; Q924Z4; -.
DR SwissPalm; Q924Z4; -.
DR EPD; Q924Z4; -.
DR jPOST; Q924Z4; -.
DR MaxQB; Q924Z4; -.
DR PaxDb; Q924Z4; -.
DR PeptideAtlas; Q924Z4; -.
DR PRIDE; Q924Z4; -.
DR ProteomicsDB; 281383; -.
DR Antibodypedia; 20302; 234 antibodies from 29 providers.
DR DNASU; 76893; -.
DR Ensembl; ENSMUST00000015858; ENSMUSP00000015858; ENSMUSG00000015714.
DR GeneID; 76893; -.
DR KEGG; mmu:76893; -.
DR UCSC; uc008qjj.1; mouse.
DR CTD; 29956; -.
DR MGI; MGI:1924143; Cers2.
DR VEuPathDB; HostDB:ENSMUSG00000015714; -.
DR eggNOG; KOG1607; Eukaryota.
DR GeneTree; ENSGT01030000234515; -.
DR InParanoid; Q924Z4; -.
DR OMA; CTNCYID; -.
DR OrthoDB; 987268at2759; -.
DR PhylomeDB; Q924Z4; -.
DR TreeFam; TF314319; -.
DR BRENDA; 2.3.1.24; 3474.
DR BRENDA; 2.3.1.297; 3474.
DR Reactome; R-MMU-1660661; Sphingolipid de novo biosynthesis.
DR UniPathway; UPA00222; -.
DR BioGRID-ORCS; 76893; 12 hits in 62 CRISPR screens.
DR ChiTaRS; Cers2; mouse.
DR PRO; PR:Q924Z4; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q924Z4; protein.
DR Bgee; ENSMUSG00000015714; Expressed in right kidney and 263 other tissues.
DR ExpressionAtlas; Q924Z4; baseline and differential.
DR Genevisible; Q924Z4; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS: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; IMP:UniProtKB.
DR GO; GO:0050291; F:sphingosine N-acyltransferase activity; IDA:MGI.
DR GO; GO:0046513; P:ceramide biosynthetic process; IDA:UniProtKB.
DR GO; GO:0048681; P:negative regulation of axon regeneration; ISO:MGI.
DR GO; GO:1900148; P:negative regulation of Schwann cell migration; ISO:MGI.
DR GO; GO:1905045; P:negative regulation of Schwann cell proliferation involved in axon regeneration; ISO:MGI.
DR GO; GO:0019216; P:regulation of lipid metabolic process; IMP:UniProtKB.
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 Acetylation; Endoplasmic reticulum; Glycoprotein; Lipid biosynthesis;
KW Lipid metabolism; Membrane; Phosphoprotein; Reference proteome;
KW Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..380
FT /note="Ceramide synthase 2"
FT /id="PRO_0000185510"
FT TOPO_DOM 1..40
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:15823095"
FT TRANSMEM 41..61
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 140..160
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 175..195
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 209..229
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 264..284
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 304..324
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 325..380
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q96G23"
FT DOMAIN 131..332
FT /note="TLC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00205"
FT REGION 67..128
FT /note="Homeobox-like"
FT /evidence="ECO:0000305"
FT REGION 340..380
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 291..300
FT /note="Last loop motif"
FT /evidence="ECO:0000250|UniProtKB:Q96G23"
FT MOD_RES 341
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 346
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 348
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 349
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 19
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:15823095"
SQ SEQUENCE 380 AA; 45024 MW; B6B5EB5397DB19FD CRC64;
MLQTLYDYFW WERLWLPVNL TWADLEDKDG RVYAKASDLY ITLPLALLFL VIRYFFELYV
ATPLAALLNV KEKTRLRAPP NATLEHFYQT SGKQPKQVEV DLLSRQSGLS GRQVERWFRR
RRNQDRPSLL KKFREASWRF TYYLIAFVAG MAVTVDKPWF YDLRKVWEGY PIQSIIPSQY
WYYMIELSFY WSLLFSIASD VKRKDFKEQI IHHVATIILL CFSWFANYVR AGTLIMALHD
ASDYLLESAK MFNYAGWKNT CNNLFIVFAI VFIITRLVIM PFWILHCTMI YPLELYPAFF
GYYFFNFMMA VLQMLHIFWA YFILRMAHKF ITGKLIEDER SDREETESSE GEETAAGAGA
KSRLLANGHP ILNNNHPKND
