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 27-MAR-2024, entry version 174. 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 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 118. 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 GlyCosmos; Q6ZMG9; 1 site, 4 glycans. DR GlyGen; Q6ZMG9; 2 sites, 4 N-linked glycans (1 site), 1 O-linked glycan (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; 9606-ENSP00000376453; -. DR PeptideAtlas; Q6ZMG9; -. DR Pumba; Q6ZMG9; -. DR Antibodypedia; 33795; 256 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 AGR; HGNC:23826; -. 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; 460400at2759; -. DR PhylomeDB; Q6ZMG9; -. DR TreeFam; TF314319; -. DR BioCyc; MetaCyc:ENSG00000172292-MONOMER; -. 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; 18 hits in 1194 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 212 other cell types or tissues. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IEA:InterPro. 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 Gene3D; 1.10.10.60; Homeodomain-like; 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:SF43; CERAMIDE SYNTHASE 6; 1. DR PANTHER; PTHR12560; LONGEVITY ASSURANCE FACTOR 1 LAG1; 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; Homeodomain-like; 1. DR PROSITE; PS50922; TLC; 1. DR Genevisible; Q6ZMG9; HS. 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 //