CERS6_HUMAN
ID CERS6_HUMAN Reviewed; 384 AA.
AC Q6ZMG9; Q32M63; Q8N617;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Ceramide synthase 6 {ECO:0000305};
DE Short=CerS6 {ECO:0000305};
DE AltName: Full=LAG1 longevity assurance homolog 6 {ECO:0000250|UniProtKB:Q8C172};
DE AltName: Full=Sphingoid base N-palmitoyltransferase CERS6 {ECO:0000305};
DE EC=2.3.1.291 {ECO:0000269|PubMed:17977534, ECO:0000269|PubMed:23530041, ECO:0000269|PubMed:26887952, ECO:0000269|PubMed:31916624};
GN Name=CERS6 {ECO:0000312|HGNC:HGNC:23826};
GN Synonyms=LASS6 {ECO:0000250|UniProtKB:Q8C172};
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon mucosa;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 191-384 (ISOFORM 1).
RC TISSUE=Duodenum;
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 GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-18.
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 [5]
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 [6]
RP FUNCTION, AND MUTAGENESIS OF ARG-131.
RX PubMed=17609214; DOI=10.1074/jbc.m703487200;
RA Mesika A., Ben-Dor S., Laviad E.L., Futerman A.H.;
RT "A new functional motif in Hox domain-containing ceramide synthases:
RT identification of a novel region flanking the Hox and TLC domains essential
RT for activity.";
RL J. Biol. Chem. 282:27366-27373(2007).
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 INDUCTION.
RX PubMed=25295788; DOI=10.1016/j.cmet.2014.08.002;
RA Turpin S.M., Nicholls H.T., Willmes D.M., Mourier A., Brodesser S.,
RA Wunderlich C.M., Mauer J., Xu E., Hammerschmidt P., Broenneke H.S.,
RA Trifunovic A., LoSasso G., Wunderlich F.T., Kornfeld J.W., Blueher M.,
RA Kroenke M., Bruening J.C.;
RT "Obesity-induced CerS6-dependent C16:0 ceramide production promotes weight
RT gain and glucose intolerance.";
RL Cell Metab. 20:678-686(2014).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, GLYCOSYLATION, PHOSPHORYLATION,
RP TOPOLOGY, AND MUTAGENESIS OF 341-SER--SER-347.
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 [10]
RP GLYCOSYLATION.
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).
RN [11]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=31916624; DOI=10.1096/fj.201902645r;
RA Jojima K., Edagawa M., Sawai M., Ohno Y., Kihara A.;
RT "Biosynthesis of the anti-lipid-microdomain sphingoid base 4,14-
RT sphingadiene by the ceramide desaturase FADS3.";
RL FASEB J. 34:3318-3335(2020).
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 palmitoyl-CoA (hexadecanoyl-CoA; C16:0-CoA) (PubMed:17977534,
CC PubMed:17609214, PubMed:23530041, PubMed:26887952, PubMed:31916624).
CC Can use other acyl donors, but with less efficiency (By similarity). N-
CC acylates sphinganine and sphingosine bases to form dihydroceramides and
CC ceramides in de novo synthesis and salvage pathways, respectively
CC (PubMed:17977534, PubMed:23530041, PubMed:26887952, PubMed:31916624).
CC Ceramides generated by CERS6 play a role in inflammatory response (By
CC similarity). Acts as a regulator of metabolism and hepatic lipid
CC accumulation (By similarity). Under high fat diet, palmitoyl- (C16:0-)
CC ceramides generated by CERS6 specifically bind the mitochondrial
CC fission factor MFF, thereby promoting mitochondrial fragmentation and
CC contributing to the development of obesity (By similarity).
CC {ECO:0000250|UniProtKB:Q8C172, ECO:0000269|PubMed:17609214,
CC ECO:0000269|PubMed:17977534, ECO:0000269|PubMed:23530041,
CC ECO:0000269|PubMed:26887952, ECO:0000269|PubMed:31916624}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a sphingoid base + hexadecanoyl-CoA = an N-hexadecanoyl-
CC sphingoid base + CoA + H(+); Xref=Rhea:RHEA:61472, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57379, ChEBI:CHEBI:84410,
CC ChEBI:CHEBI:144703; EC=2.3.1.291;
CC Evidence={ECO:0000269|PubMed:17977534, ECO:0000269|PubMed:23530041,
CC ECO:0000269|PubMed:26887952, ECO:0000269|PubMed:31916624};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61473;
CC Evidence={ECO:0000269|PubMed:17977534, ECO:0000269|PubMed:23530041,
CC ECO:0000269|PubMed:26887952, ECO:0000269|PubMed:31916624};
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:17977534,
CC ECO:0000269|PubMed:23530041, ECO:0000269|PubMed:26887952,
CC ECO:0000269|PubMed:31916624};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36540;
CC Evidence={ECO:0000269|PubMed:17977534, ECO:0000269|PubMed:23530041,
CC ECO:0000269|PubMed:26887952, ECO:0000269|PubMed:31916624};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecanoyl-CoA + hexadecasphinganine = CoA + H(+) + N-
CC hexadecanoylhexadecasphinganine; Xref=Rhea:RHEA:43040,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379,
CC ChEBI:CHEBI:71009, ChEBI:CHEBI:82810;
CC Evidence={ECO:0000269|PubMed:23530041};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43041;
CC Evidence={ECO:0000269|PubMed:23530041};
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:31916624};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36688;
CC Evidence={ECO:0000269|PubMed:31916624};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=sphinganine + tetradecanoyl-CoA = CoA + H(+) + N-
CC (tetradecanoyl)-sphinganine; Xref=Rhea:RHEA:36571, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57385, ChEBI:CHEBI:57817,
CC ChEBI:CHEBI:67045; Evidence={ECO:0000250|UniProtKB:Q8C172};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36572;
CC Evidence={ECO:0000250|UniProtKB:Q8C172};
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:Q8C172};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36548;
CC Evidence={ECO:0000250|UniProtKB:Q8C172};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.0 uM for sphinganine {ECO:0000269|PubMed:17977534};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000269|PubMed:17977534, ECO:0000269|PubMed:23530041,
CC ECO:0000269|PubMed:26887952}.
CC -!- INTERACTION:
CC Q6ZMG9; P30556: AGTR1; NbExp=2; IntAct=EBI-20794243, EBI-6623016;
CC Q6ZMG9; P41146: OPRL1; NbExp=2; IntAct=EBI-20794243, EBI-2624699;
CC Q6ZMG9-2; O75396: SEC22B; NbExp=3; IntAct=EBI-18038706, EBI-1058865;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q8C172}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q8C172}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6ZMG9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6ZMG9-2; Sequence=VSP_045162;
CC -!- INDUCTION: Up-regulated in adipose tissues in obese patients.
CC {ECO:0000269|PubMed:25295788}.
CC -!- PTM: Phosphorylated at the C-terminus by CK2.
CC {ECO:0000269|PubMed:26887952}.
CC -!- PTM: Acetylated. Deacetylation by SIRT3 increases enzyme activity and
CC promotes mitochondrial ceramide accumulation.
CC {ECO:0000250|UniProtKB:Q8C172}.
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 (By similarity).
CC {ECO:0000250|UniProtKB:Q8C172, ECO:0000255}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH30800.2; Type=Erroneous translation; Note=Wrong choice of frame.; Evidence={ECO:0000305};
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DR EMBL; AK172775; BAD18757.1; -; mRNA.
DR EMBL; AC009475; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC019086; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC097453; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC109284; AAI09285.1; -; mRNA.
DR EMBL; BC109285; AAI09286.1; -; mRNA.
DR EMBL; BC030800; AAH30800.2; ALT_SEQ; mRNA.
DR CCDS; CCDS2228.1; -. [Q6ZMG9-1]
DR CCDS; CCDS58734.1; -. [Q6ZMG9-2]
DR RefSeq; NP_001243055.1; NM_001256126.1. [Q6ZMG9-2]
DR RefSeq; NP_982288.1; NM_203463.2. [Q6ZMG9-1]
DR AlphaFoldDB; Q6ZMG9; -.
DR SMR; Q6ZMG9; -.
DR BioGRID; 128987; 107.
DR IntAct; Q6ZMG9; 18.
DR MINT; Q6ZMG9; -.
DR STRING; 9606.ENSP00000376453; -.
DR SwissLipids; SLP:000000700; -.
DR GlyConnect; 1107; 4 N-Linked glycans (1 site).
DR GlyGen; Q6ZMG9; 1 site, 4 N-linked glycans (1 site).
DR iPTMnet; Q6ZMG9; -.
DR PhosphoSitePlus; Q6ZMG9; -.
DR SwissPalm; Q6ZMG9; -.
DR BioMuta; CERS6; -.
DR DMDM; 51316251; -.
DR EPD; Q6ZMG9; -.
DR jPOST; Q6ZMG9; -.
DR MassIVE; Q6ZMG9; -.
DR MaxQB; Q6ZMG9; -.
DR PaxDb; Q6ZMG9; -.
DR PeptideAtlas; Q6ZMG9; -.
DR PRIDE; Q6ZMG9; -.
DR Antibodypedia; 33795; 235 antibodies from 26 providers.
DR DNASU; 253782; -.
DR Ensembl; ENST00000305747.11; ENSP00000306579.6; ENSG00000172292.15. [Q6ZMG9-1]
DR Ensembl; ENST00000392687.4; ENSP00000376453.4; ENSG00000172292.15. [Q6ZMG9-2]
DR GeneID; 253782; -.
DR KEGG; hsa:253782; -.
DR MANE-Select; ENST00000305747.11; ENSP00000306579.6; NM_203463.3; NP_982288.1.
DR UCSC; uc002ueb.3; human. [Q6ZMG9-1]
DR CTD; 253782; -.
DR DisGeNET; 253782; -.
DR GeneCards; CERS6; -.
DR HGNC; HGNC:23826; CERS6.
DR HPA; ENSG00000172292; Low tissue specificity.
DR MIM; 615336; gene.
DR neXtProt; NX_Q6ZMG9; -.
DR OpenTargets; ENSG00000172292; -.
DR PharmGKB; PA134925480; -.
DR VEuPathDB; HostDB:ENSG00000172292; -.
DR eggNOG; KOG1607; Eukaryota.
DR GeneTree; ENSGT01030000234515; -.
DR HOGENOM; CLU_028277_1_2_1; -.
DR InParanoid; Q6ZMG9; -.
DR OMA; YLIGAPY; -.
DR OrthoDB; 987268at2759; -.
DR PhylomeDB; Q6ZMG9; -.
DR TreeFam; TF314319; -.
DR BioCyc; MetaCyc:ENSG00000172292-MON; -.
DR BRENDA; 2.3.1.24; 2681.
DR PathwayCommons; Q6ZMG9; -.
DR Reactome; R-HSA-1660661; Sphingolipid de novo biosynthesis.
DR SignaLink; Q6ZMG9; -.
DR UniPathway; UPA00222; -.
DR BioGRID-ORCS; 253782; 15 hits in 1105 CRISPR screens.
DR ChiTaRS; CERS6; human.
DR GenomeRNAi; 253782; -.
DR Pharos; Q6ZMG9; Tbio.
DR PRO; PR:Q6ZMG9; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q6ZMG9; protein.
DR Bgee; ENSG00000172292; Expressed in hair follicle and 210 other tissues.
DR Genevisible; Q6ZMG9; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
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:0006954; P:inflammatory response; IEA:UniProtKB-KW.
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; Alternative splicing; Endoplasmic reticulum; Glycoprotein;
KW Inflammatory response; Lipid biosynthesis; Lipid metabolism; Membrane;
KW Phosphoprotein; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..384
FT /note="Ceramide synthase 6"
FT /id="PRO_0000185516"
FT TOPO_DOM 1..34
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:29632068"
FT TRANSMEM 35..55
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 178..198
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 303..323
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 324..384
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:26887952"
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 338..384
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 357..384
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 18
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT VAR_SEQ 334
FT /note="K -> KAGKWNPLH (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_045162"
FT MUTAGEN 131
FT /note="R->A: Abolished ceramide synthase activity."
FT /evidence="ECO:0000269|PubMed:17609214"
FT MUTAGEN 131
FT /note="R->K: Does not affect ceramide synthase activity."
FT /evidence="ECO:0000269|PubMed:17609214"
FT MUTAGEN 341..347
FT /note="SDIESSS->ADIEAAA: Decreased phosphorylation."
FT /evidence="ECO:0000269|PubMed:26887952"
SQ SEQUENCE 384 AA; 44890 MW; B3C400D6317D9E5E CRC64;
MAGILAWFWN ERFWLPHNVT WADLKNTEEA TFPQAEDLYL AFPLAFCIFM VRLIFERFVA
KPCAIALNIQ ANGPQIAPPN AILEKVFTAI TKHPDEKRLE GLSKQLDWDV RSIQRWFRQR
RNQEKPSTLT RFCESMWRFS FYLYVFTYGV RFLKKTPWLW NTRHCWYNYP YQPLTTDLHY
YYILELSFYW SLMFSQFTDI KRKDFGIMFL HHLVSIFLIT FSYVNNMARV GTLVLCLHDS
ADALLEAAKM ANYAKFQKMC DLLFVMFAVV FITTRLGIFP LWVLNTTLFE SWEIVGPYPS
WWVFNLLLLL VQGLNCFWSY LIVKIACKAV SRGKVSKDDR SDIESSSDEE DSEPPGKNPH
TATTTNGTSG TNGYLLTGSC SMDD
