CERS2_HUMAN
ID CERS2_HUMAN Reviewed; 380 AA.
AC Q96G23; D3DV06; Q5SZE5; Q9HD96; Q9NW79;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Ceramide synthase 2 {ECO:0000303|PubMed:17977534};
DE Short=CerS2 {ECO:0000303|PubMed:17977534};
DE AltName: Full=LAG1 longevity assurance homolog 2 {ECO:0000303|PubMed:11543633};
DE AltName: Full=SP260 {ECO:0000303|PubMed:11543633};
DE AltName: Full=Sphingosine N-acyltransferase CERS2 {ECO:0000305};
DE EC=2.3.1.24 {ECO:0000269|PubMed:20937905};
DE AltName: Full=Tumor metastasis-suppressor gene 1 protein {ECO:0000303|Ref.8};
DE AltName: Full=Very-long-chain ceramide synthase CERS2 {ECO:0000305};
DE EC=2.3.1.297 {ECO:0000269|PubMed:12869556, ECO:0000269|PubMed:17977534, ECO:0000269|PubMed:18165233, ECO:0000269|PubMed:18541923, ECO:0000269|PubMed:19728861, ECO:0000269|PubMed:20937905, ECO:0000269|PubMed:26887952};
GN Name=CERS2 {ECO:0000303|PubMed:17977534, ECO:0000312|HGNC:HGNC:14076};
GN Synonyms=LASS2 {ECO:0000303|PubMed:11543633}, TMSG1 {ECO:0000303|Ref.8};
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], TISSUE SPECIFICITY, AND INTERACTION WITH
RP ATP6V0C; ASGR1; ASGR2 AND SLC22A1/OCT1.
RC TISSUE=Liver;
RX PubMed=11543633; DOI=10.1006/geno.2001.6614;
RA Pan H., Qin W.-X., Huo K.-K., Wan D.-F., Yu Y., Xu Z.-G., Hu Q.-D.,
RA Gu K.T., Zhou X.-M., Jiang H.-Q., Zhang P.-P., Huang Y., Li Y.-Y.,
RA Gu J.-R.;
RT "Cloning, mapping, and characterization of a human homologue of the yeast
RT longevity assurance gene LAG1.";
RL Genomics 77:58-64(2001).
RN [2]
RP SEQUENCE REVISION.
RA Qin W.-X., Gu J.-R., Wan D.-F., Zhou X.-M., Jiang H.-Q., Zhang P.-P.,
RA Huang Y., Qiu X.-K., Qian L.F., He L.P., Li H.N., Yu Y., Yu J.;
RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Xingfeng C., Yi G.;
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney, and Skin;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 59-380.
RC TISSUE=Embryo;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 151-380.
RC TISSUE=Prostatic carcinoma;
RA Liu Y., Zheng J., Wu B., Fang W.;
RT "Cancer metastasis-related gene.";
RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP CATALYTIC ACTIVITY.
RX PubMed=12869556; DOI=10.1074/jbc.m307554200;
RA Guillas I., Jiang J.C., Vionnet C., Roubaty C., Uldry D., Chuard R.,
RA Wang J., Jazwinski S.M., Conzelmann A.;
RT "Human homologues of LAG1 reconstitute Acyl-CoA-dependent ceramide
RT synthesis in yeast.";
RL J. Biol. Chem. 278:37083-37091(2003).
RN [10]
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=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [11]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-19.
RC TISSUE=Platelet;
RX PubMed=16263699; DOI=10.1074/mcp.m500324-mcp200;
RA Lewandrowski U., Moebius J., Walter U., Sickmann A.;
RT "Elucidation of N-glycosylation sites on human platelet proteins: a
RT glycoproteomic approach.";
RL Mol. Cell. Proteomics 5:226-233(2006).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, 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 [13]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, ACTIVITY REGULATION,
RP PATHWAY, AND MUTAGENESIS OF ARG-230 AND ARG-325.
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 [14]
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 [15]
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=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [17]
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=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment
RT and fractionation of phosphopeptides with strong anion exchange
RT chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [18]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=19728861; DOI=10.1042/bj20090699;
RA Spassieva S.D., Mullen T.D., Townsend D.M., Obeid L.M.;
RT "Disruption of ceramide synthesis by CerS2 down-regulation leads to
RT autophagy and the unfolded protein response.";
RL Biochem. J. 424:273-283(2009).
RN [19]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-19.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [20]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND INTERACTION WITH ELOV1; HSD17B12
RP AND TECR.
RX PubMed=20937905; DOI=10.1073/pnas.1005572107;
RA Ohno Y., Suto S., Yamanaka M., Mizutani Y., Mitsutake S., Igarashi Y.,
RA Sassa T., Kihara A.;
RT "ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid
RT synthesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:18439-18444(2010).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-341, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-341; THR-346; SER-348 AND
RP SER-349, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [24]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=22661289; DOI=10.1194/jlr.d025627;
RA Kim H.J., Qiao Q., Toop H.D., Morris J.C., Don A.S.;
RT "A fluorescent assay for ceramide synthase activity.";
RL J. Lipid Res. 53:1701-1707(2012).
RN [25]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=22144673; DOI=10.1074/jbc.m111.280271;
RA Tidhar R., Ben-Dor S., Wang E., Kelly S., Merrill A.H. Jr., Futerman A.H.;
RT "Acyl chain specificity of ceramide synthases is determined within a region
RT of 150 residues in the Tram-Lag-CLN8 (TLC) domain.";
RL J. Biol. Chem. 287:3197-3206(2012).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-349, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [27]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [28]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, BIOPHYSICOCHEMICAL PROPERTIES,
RP PHOSPHORYLATION, GLYCOSYLATION, TOPOLOGY, AND MUTAGENESIS OF
RP 341-SER--SER-349.
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 [29]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, GLYCOSYLATION, AND DOMAIN.
RX PubMed=29632068; DOI=10.1074/jbc.ra118.001936;
RA Tidhar R., Zelnik I.D., Volpert G., Ben-Dor S., Kelly S., Merrill A.H. Jr.,
RA Futerman A.H.;
RT "Eleven residues determine the acyl chain specificity of ceramide
RT synthases.";
RL J. Biol. Chem. 293:9912-9921(2018).
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:17977534,
CC PubMed:18165233, PubMed:18541923, PubMed:19728861, PubMed:20937905,
CC PubMed:22144673, PubMed:22661289, PubMed:26887952, PubMed:29632068). N-
CC acylates sphinganine and sphingosine bases to form dihydroceramides and
CC ceramides in de novo synthesis and salvage pathways, respectively (By
CC similarity) (PubMed:17977534, PubMed:18165233, PubMed:18541923,
CC PubMed:19728861, PubMed:20937905, PubMed:22144673, PubMed:22661289,
CC PubMed:26887952, PubMed:29632068). Plays a non-redundant role in the
CC synthesis of ceramides with very-long-chain fatty acids in kidney,
CC liver and brain. Regulates the abundance of myelin-specific
CC sphingolipids galactosylceramide and sulfatide that affects myelin
CC sheath architecture and motor neuron functions (By similarity).
CC {ECO:0000250|UniProtKB:Q924Z4, ECO:0000269|PubMed:17977534,
CC ECO:0000269|PubMed:18165233, ECO:0000269|PubMed:18541923,
CC ECO:0000269|PubMed:19728861, ECO:0000269|PubMed:20937905,
CC ECO:0000269|PubMed:22144673, ECO:0000269|PubMed:22661289,
CC ECO:0000269|PubMed:26887952, ECO:0000269|PubMed:29632068}.
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:12869556,
CC ECO:0000269|PubMed:17977534, ECO:0000269|PubMed:18165233,
CC ECO:0000269|PubMed:18541923, ECO:0000269|PubMed:19728861,
CC ECO:0000269|PubMed:20937905, ECO:0000269|PubMed:26887952,
CC ECO:0000269|PubMed:29632068};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61481;
CC Evidence={ECO:0000269|PubMed:12869556, ECO:0000269|PubMed:17977534,
CC ECO:0000269|PubMed:18165233, ECO:0000269|PubMed:18541923,
CC ECO:0000269|PubMed:19728861, ECO:0000269|PubMed:20937905,
CC ECO:0000269|PubMed:26887952, ECO:0000269|PubMed:29632068};
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:18165233,
CC ECO:0000269|PubMed:22144673, ECO:0000269|PubMed:29632068};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36536;
CC Evidence={ECO:0000269|PubMed:18165233, ECO:0000269|PubMed:22144673,
CC ECO:0000269|PubMed:29632068};
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:12869556,
CC ECO:0000269|PubMed:17977534, ECO:0000269|PubMed:18165233,
CC ECO:0000269|PubMed:18541923, ECO:0000269|PubMed:29632068};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33592;
CC Evidence={ECO:0000269|PubMed:12869556, ECO:0000269|PubMed:17977534,
CC ECO:0000269|PubMed:18165233, ECO:0000269|PubMed:18541923,
CC ECO:0000269|PubMed:29632068};
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:12869556,
CC ECO:0000269|PubMed:18165233};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33352;
CC Evidence={ECO:0000269|PubMed:12869556, ECO:0000269|PubMed:18165233};
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:18165233,
CC ECO:0000269|PubMed:22661289, ECO:0000269|PubMed:26887952};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36668;
CC Evidence={ECO:0000269|PubMed:18165233, ECO:0000269|PubMed:22661289,
CC ECO:0000269|PubMed:26887952};
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=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-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:0000269|PubMed:18541923};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36768;
CC Evidence={ECO:0000269|PubMed:18541923};
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:18541923};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36716;
CC Evidence={ECO:0000269|PubMed:18541923};
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:0000269|PubMed:18165233};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36720;
CC Evidence={ECO:0000269|PubMed:18165233};
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:0000269|PubMed:20937905};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37116;
CC Evidence={ECO:0000269|PubMed:20937905};
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:0000269|PubMed:20937905};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37124;
CC Evidence={ECO:0000269|PubMed:20937905};
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:0000269|PubMed:19728861};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36740;
CC Evidence={ECO:0000269|PubMed:19728861};
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:20937905};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23769;
CC Evidence={ECO:0000269|PubMed:20937905};
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:0000250|UniProtKB:Q924Z4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36688;
CC Evidence={ECO:0000250|UniProtKB:Q924Z4};
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:0000250|UniProtKB:Q924Z4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36692;
CC Evidence={ECO:0000250|UniProtKB:Q924Z4};
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:0000250|UniProtKB:Q924Z4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45285;
CC Evidence={ECO:0000250|UniProtKB:Q924Z4};
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:0000269|PubMed:12869556};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36540;
CC Evidence={ECO:0000269|PubMed:12869556};
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:0000250|UniProtKB:Q924Z4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36548;
CC Evidence={ECO:0000250|UniProtKB:Q924Z4};
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:0000269|PubMed:12869556};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36576;
CC Evidence={ECO:0000269|PubMed:12869556};
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:12869556,
CC ECO:0000269|PubMed:18165233};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36556;
CC Evidence={ECO:0000269|PubMed:12869556, ECO:0000269|PubMed:18165233};
CC -!- ACTIVITY REGULATION: Ceramide synthase activity is inhibited by
CC sphingosine-1-phosphate. {ECO:0000269|PubMed:18165233}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.8 uM for sphinganine {ECO:0000269|PubMed:17977534};
CC KM=1.07 uM for sphingosine {ECO:0000269|PubMed:26887952};
CC KM=62.9 uM for (15Z)-tetracosenoyl-CoA {ECO:0000269|PubMed:26887952};
CC Vmax=0.51 pmol/min/ug enzyme with sphingosine as substrate
CC {ECO:0000269|PubMed:26887952};
CC Vmax=0.76 pmol/min/ug enzyme with (15Z)-tetracosenoyl-CoA as
CC substrate {ECO:0000269|PubMed:26887952};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000269|PubMed:17977534, ECO:0000269|PubMed:18165233,
CC ECO:0000269|PubMed:18541923, ECO:0000269|PubMed:19728861,
CC ECO:0000269|PubMed:20937905, ECO:0000269|PubMed:22144673,
CC ECO:0000269|PubMed:22661289, ECO:0000269|PubMed:26887952,
CC ECO:0000269|PubMed:29632068}.
CC -!- SUBUNIT: Interacts with ATP6V0C, ASGR1, ASGR2 and SLC22A1/OCT1
CC (PubMed:11543633). Interacts with ELOV1, HSD17B12 and TECR
CC (PubMed:20937905). Interacts with NDUFS2 (By similarity).
CC {ECO:0000250|UniProtKB:Q924Z4, ECO:0000269|PubMed:11543633,
CC ECO:0000269|PubMed:20937905}.
CC -!- INTERACTION:
CC Q96G23; P07306: ASGR1; NbExp=3; IntAct=EBI-1057080, EBI-1172335;
CC Q96G23; P07307: ASGR2; NbExp=3; IntAct=EBI-1057080, EBI-1172636;
CC Q96G23; P27449: ATP6V0C; NbExp=3; IntAct=EBI-1057080, EBI-721179;
CC Q96G23; P07900: HSP90AA1; NbExp=2; IntAct=EBI-1057080, EBI-296047;
CC Q96G23; Q9Y5U9: IER3IP1; NbExp=3; IntAct=EBI-1057080, EBI-725665;
CC Q96G23; Q16236: NFE2L2; NbExp=2; IntAct=EBI-1057080, EBI-2007911;
CC Q96G23; O15245: SLC22A1; NbExp=3; IntAct=EBI-1057080, EBI-1172714;
CC Q96G23; O95070: YIF1A; NbExp=3; IntAct=EBI-1057080, EBI-2799703;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:18165233}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in kidney, liver, brain, heart, placenta
CC and lung. {ECO:0000269|PubMed:11543633}.
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:0000269|PubMed:29632068}.
CC -!- PTM: Acetylated. Deacetylation by SIRT3 increases enzyme activity and
CC promotes mitochondrial ceramide accumulation.
CC {ECO:0000250|UniProtKB:Q924Z4}.
CC -!- PTM: Phosphorylated at the C-terminus by CK2, leading to increase the
CC ceramide synthase activity. {ECO:0000269|PubMed:26887952}.
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:18165233).
CC {ECO:0000269|PubMed:18165233, ECO:0000305}.
CC -!- CAUTION: Some prediction bioinformatics tools predict the presence of a
CC homeobox domain (By similarity). However, the domain is degenerate and
CC residues that are important for DNA-binding are absent (By similarity).
CC Moreover, the protein localizes in the endoplasmic reticulum and not in
CC the nucleus, strongly suggesting that it does not constitute a
CC canonical homeobox domain (PubMed:18165233). {ECO:0000255,
CC ECO:0000269|PubMed:18165233}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA91505.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF177338; AAG17982.2; -; mRNA.
DR EMBL; AY091458; AAM12028.1; -; mRNA.
DR EMBL; AL590133; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW53497.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW53498.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW53499.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW53502.1; -; Genomic_DNA.
DR EMBL; BC001357; AAH01357.2; -; mRNA.
DR EMBL; BC010032; AAH10032.1; -; mRNA.
DR EMBL; AK001105; BAA91505.1; ALT_INIT; mRNA.
DR EMBL; AF189062; AAF01058.4; -; mRNA.
DR CCDS; CCDS973.1; -.
DR RefSeq; NP_071358.1; NM_022075.4.
DR RefSeq; NP_859530.1; NM_181746.3.
DR RefSeq; XP_011507754.1; XM_011509452.2.
DR AlphaFoldDB; Q96G23; -.
DR BioGRID; 118992; 231.
DR IntAct; Q96G23; 44.
DR MINT; Q96G23; -.
DR STRING; 9606.ENSP00000271688; -.
DR SwissLipids; SLP:000000256; -.
DR GlyConnect; 1105; 15 N-Linked glycans (1 site).
DR GlyGen; Q96G23; 3 sites, 15 N-linked glycans (1 site), 1 O-linked glycan (2 sites).
DR iPTMnet; Q96G23; -.
DR PhosphoSitePlus; Q96G23; -.
DR SwissPalm; Q96G23; -.
DR BioMuta; CERS2; -.
DR DMDM; 51316514; -.
DR EPD; Q96G23; -.
DR jPOST; Q96G23; -.
DR MassIVE; Q96G23; -.
DR MaxQB; Q96G23; -.
DR PaxDb; Q96G23; -.
DR PeptideAtlas; Q96G23; -.
DR PRIDE; Q96G23; -.
DR ProteomicsDB; 76584; -.
DR Antibodypedia; 20302; 234 antibodies from 29 providers.
DR DNASU; 29956; -.
DR Ensembl; ENST00000271688.10; ENSP00000271688.6; ENSG00000143418.20.
DR Ensembl; ENST00000368954.10; ENSP00000357950.5; ENSG00000143418.20.
DR GeneID; 29956; -.
DR KEGG; hsa:29956; -.
DR MANE-Select; ENST00000368954.10; ENSP00000357950.5; NM_022075.5; NP_071358.1.
DR UCSC; uc001evy.3; human.
DR CTD; 29956; -.
DR DisGeNET; 29956; -.
DR GeneCards; CERS2; -.
DR HGNC; HGNC:14076; CERS2.
DR HPA; ENSG00000143418; Tissue enhanced (liver).
DR MIM; 606920; gene.
DR neXtProt; NX_Q96G23; -.
DR OpenTargets; ENSG00000143418; -.
DR PharmGKB; PA30300; -.
DR VEuPathDB; HostDB:ENSG00000143418; -.
DR eggNOG; KOG1607; Eukaryota.
DR GeneTree; ENSGT01030000234515; -.
DR InParanoid; Q96G23; -.
DR OMA; CTNCYID; -.
DR OrthoDB; 987268at2759; -.
DR PhylomeDB; Q96G23; -.
DR TreeFam; TF314319; -.
DR BioCyc; MetaCyc:ENSG00000143418-MON; -.
DR BRENDA; 2.3.1.24; 2681.
DR BRENDA; 2.3.1.297; 2681.
DR PathwayCommons; Q96G23; -.
DR Reactome; R-HSA-1660661; Sphingolipid de novo biosynthesis.
DR SignaLink; Q96G23; -.
DR UniPathway; UPA00222; -.
DR BioGRID-ORCS; 29956; 104 hits in 1108 CRISPR screens.
DR ChiTaRS; CERS2; human.
DR GeneWiki; LASS2; -.
DR GenomeRNAi; 29956; -.
DR Pharos; Q96G23; Tbio.
DR PRO; PR:Q96G23; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q96G23; protein.
DR Bgee; ENSG00000143418; Expressed in right adrenal gland cortex and 198 other tissues.
DR ExpressionAtlas; Q96G23; baseline and differential.
DR Genevisible; Q96G23; 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:0016020; C:membrane; HDA:UniProtKB.
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:0048681; P:negative regulation of axon regeneration; ISS:BHF-UCL.
DR GO; GO:1900148; P:negative regulation of Schwann cell migration; ISS:BHF-UCL.
DR GO; GO:1905045; P:negative regulation of Schwann cell proliferation involved in axon regeneration; ISS:BHF-UCL.
DR GO; GO:0019216; P:regulation of lipid metabolic process; ISS:UniProtKB.
DR GO; GO:0030148; P:sphingolipid biosynthetic process; TAS:Reactome.
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_0000185509"
FT TOPO_DOM 1..40
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:16263699,
FT ECO:0000305|PubMed:19159218"
FT TRANSMEM 41..61
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 140..160
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 181..201
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:0000305|PubMed:26887952"
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 338..380
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 291..300
FT /note="Last loop motif"
FT /evidence="ECO:0000269|PubMed:29632068"
FT MOD_RES 341
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18088087, ECO:0007744|PubMed:18318008,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT MOD_RES 346
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18088087, ECO:0007744|PubMed:18318008,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 348
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18088087, ECO:0007744|PubMed:18318008,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 349
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18088087, ECO:0007744|PubMed:18318008,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT CARBOHYD 19
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16263699,
FT ECO:0000269|PubMed:19159218"
FT VARIANT 115
FT /note="E -> A (in dbSNP:rs267738)"
FT /id="VAR_052325"
FT MUTAGEN 230
FT /note="R->A: Abolished inhibition by sphingosine-1-
FT phosphate; when associated with A-325."
FT /evidence="ECO:0000269|PubMed:18165233"
FT MUTAGEN 325
FT /note="R->A: Abolished inhibition by sphingosine-1-
FT phosphate; when associated with A-230."
FT /evidence="ECO:0000269|PubMed:18165233"
FT MUTAGEN 341..349
FT /note="SDREETESS->ADREEAEAA: Strongly decreased
FT phosphorylation leading to reduced ceramide synthase
FT activity."
FT /evidence="ECO:0000269|PubMed:26887952"
FT CONFLICT 154
FT /note="I -> T (in Ref. 8; AAF01058)"
FT /evidence="ECO:0000305"
FT CONFLICT 345
FT /note="E -> V (in Ref. 8; AAF01058)"
FT /evidence="ECO:0000305"
FT CONFLICT 353
FT /note="E -> K (in Ref. 8; AAF01058)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 380 AA; 44876 MW; C8CEAF6AAD0B4577 CRC64;
MLQTLYDYFW WERLWLPVNL TWADLEDRDG RVYAKASDLY ITLPLALLFL IVRYFFELYV
ATPLAALLNI KEKTRLRAPP NATLEHFYLT SGKQPKQVEV ELLSRQSGLS GRQVERWFRR
RRNQDRPSLL KKFREASWRF TFYLIAFIAG MAVIVDKPWF YDMKKVWEGY PIQSTIPSQY
WYYMIELSFY WSLLFSIASD VKRKDFKEQI IHHVATIILI SFSWFANYIR AGTLIMALHD
SSDYLLESAK MFNYAGWKNT CNNIFIVFAI VFIITRLVIL PFWILHCTLV YPLELYPAFF
GYYFFNSMMG VLQLLHIFWA YLILRMAHKF ITGKLVEDER SDREETESSE GEEAAAGGGA
KSRPLANGHP ILNNNHRKND
