CERS4_MOUSE
ID CERS4_MOUSE Reviewed; 393 AA.
AC Q9D6J1; Q8BZA6; Q8C151; Q9CX09;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Ceramide synthase 4 {ECO:0000250|UniProtKB:Q9HA82};
DE Short=CerS4 {ECO:0000250|UniProtKB:Q9HA82};
DE EC=2.3.1.- {ECO:0000269|PubMed:12912983, ECO:0000269|PubMed:15823095};
DE AltName: Full=LAG1 longevity assurance homolog 4 {ECO:0000303|PubMed:15823095};
DE AltName: Full=Sphingosine N-acyltransferase CERS4 {ECO:0000305};
DE EC=2.3.1.24 {ECO:0000269|PubMed:12912983};
DE AltName: Full=Translocating chain-associating membrane protein homolog 1 {ECO:0000303|PubMed:15823095};
DE Short=TRAM homolog 1 {ECO:0000303|PubMed:12912983};
GN Name=Cers4 {ECO:0000312|MGI:MGI:1914510};
GN Synonyms=Lass4 {ECO:0000303|PubMed:15823095},
GN Trh1 {ECO:0000303|PubMed:12912983};
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=Hippocampus, Skin, and Stomach;
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, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, AND
RP PATHWAY.
RX PubMed=12912983; DOI=10.1074/jbc.m307104200;
RA Riebeling C., Allegood J.C., Wang E., Merrill A.H. Jr., Futerman A.H.;
RT "Two mammalian longevity assurance gene (LAG1) family members, trh1 and
RT trh4, regulate dihydroceramide synthesis using different fatty acyl-CoA
RT donors.";
RL J. Biol. Chem. 278:43452-43459(2003).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND PATHWAY.
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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-342; SER-349 AND SER-350, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
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).
CC -!- FUNCTION: Ceramide synthase that catalyzes formation of ceramide from
CC sphinganine and acyl-CoA substrates, with high selectivity toward long
CC and very-long chains (C18:0-C22:0) as acyl donor.
CC {ECO:0000269|PubMed:12912983, ECO:0000269|PubMed:15823095}.
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:12912983,
CC ECO:0000269|PubMed:15823095};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36548;
CC Evidence={ECO:0000269|PubMed:12912983, ECO:0000269|PubMed:15823095};
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:12912983};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36556;
CC Evidence={ECO:0000269|PubMed:12912983};
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 PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36536;
CC Evidence={ECO:0000269|PubMed:15823095};
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 PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33592;
CC Evidence={ECO:0000269|PubMed:15823095};
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 PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33352;
CC Evidence={ECO:0000269|PubMed:15823095};
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:12912983};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23769;
CC Evidence={ECO:0000269|PubMed:12912983};
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:12912983};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36692;
CC Evidence={ECO:0000269|PubMed:12912983};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecasphinganine + octadecanoyl-CoA = CoA + H(+) + N-
CC octadecanoylhexadecasphinganine; Xref=Rhea:RHEA:43044,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57394,
CC ChEBI:CHEBI:71009, ChEBI:CHEBI:82811;
CC Evidence={ECO:0000250|UniProtKB:Q9HA82};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43045;
CC Evidence={ECO:0000250|UniProtKB:Q9HA82};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000269|PubMed:12912983, ECO:0000269|PubMed:15823095}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:12912983}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, with highest levels in
CC skin. {ECO:0000269|PubMed:12912983, ECO:0000269|PubMed:15823095}.
CC -!- DOMAIN: The last loop motif confers selectivity toward stearoyl-CoA
CC (octadecanoyl-CoA; C18:0-CoA) to behenoyl-CoA (docosanoyl-CoA; C22:0-
CC CoA) as acyl donors. {ECO:0000250|UniProtKB:Q9HA82}.
CC -!- PTM: Phosphorylated at the C-terminus by CK2.
CC {ECO:0000250|UniProtKB:Q9HA82}.
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:12912983). {ECO:0000255,
CC ECO:0000269|PubMed:12912983}.
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DR EMBL; AY029531; AAK40299.1; -; mRNA.
DR EMBL; AK013554; BAB28903.1; -; mRNA.
DR EMBL; AK021316; BAB32370.3; -; mRNA.
DR EMBL; AK028937; BAC26202.1; -; mRNA.
DR EMBL; AK028945; BAC26208.1; -; mRNA.
DR EMBL; AK030280; BAC26876.1; -; mRNA.
DR EMBL; BC003946; AAH03946.1; -; mRNA.
DR CCDS; CCDS22086.1; -.
DR RefSeq; NP_080334.3; NM_026058.4.
DR RefSeq; XP_006508924.1; XM_006508861.3.
DR RefSeq; XP_006508925.1; XM_006508862.3.
DR RefSeq; XP_006508926.1; XM_006508863.3.
DR AlphaFoldDB; Q9D6J1; -.
DR BioGRID; 212053; 1.
DR IntAct; Q9D6J1; 1.
DR STRING; 10090.ENSMUSP00000008350; -.
DR SwissLipids; SLP:000000117; -.
DR GlyGen; Q9D6J1; 1 site.
DR iPTMnet; Q9D6J1; -.
DR PhosphoSitePlus; Q9D6J1; -.
DR EPD; Q9D6J1; -.
DR MaxQB; Q9D6J1; -.
DR PaxDb; Q9D6J1; -.
DR PeptideAtlas; Q9D6J1; -.
DR PRIDE; Q9D6J1; -.
DR ProteomicsDB; 281589; -.
DR Antibodypedia; 24821; 295 antibodies from 30 providers.
DR DNASU; 67260; -.
DR Ensembl; ENSMUST00000008350; ENSMUSP00000008350; ENSMUSG00000008206.
DR GeneID; 67260; -.
DR KEGG; mmu:67260; -.
DR UCSC; uc009ktx.2; mouse.
DR CTD; 79603; -.
DR MGI; MGI:1914510; Cers4.
DR VEuPathDB; HostDB:ENSMUSG00000008206; -.
DR eggNOG; KOG1607; Eukaryota.
DR GeneTree; ENSGT01030000234515; -.
DR InParanoid; Q9D6J1; -.
DR OMA; DQGGDCY; -.
DR OrthoDB; 987268at2759; -.
DR PhylomeDB; Q9D6J1; -.
DR TreeFam; TF314319; -.
DR BRENDA; 2.3.1.297; 3474.
DR Reactome; R-MMU-1660661; Sphingolipid de novo biosynthesis.
DR UniPathway; UPA00222; -.
DR BioGRID-ORCS; 67260; 4 hits in 74 CRISPR screens.
DR PRO; PR:Q9D6J1; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q9D6J1; protein.
DR Bgee; ENSMUSG00000008206; Expressed in tail skin and 254 other tissues.
DR ExpressionAtlas; Q9D6J1; baseline and differential.
DR Genevisible; Q9D6J1; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR GO; GO:0016410; F:N-acyltransferase activity; IBA:GO_Central.
DR GO; GO:0050291; F:sphingosine N-acyltransferase activity; IDA:MGI.
DR GO; GO:0046513; P:ceramide biosynthetic process; IDA:MGI.
DR GO; GO:0030148; P:sphingolipid biosynthetic process; IDA:MGI.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR016439; Lag1/Lac1-like.
DR InterPro; IPR006634; TLC-dom.
DR PANTHER; PTHR12560; PTHR12560; 1.
DR Pfam; PF00046; Homeodomain; 1.
DR Pfam; PF03798; TRAM_LAG1_CLN8; 1.
DR PIRSF; PIRSF005225; LAG1_LAC1; 1.
DR SMART; SM00724; TLC; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS50922; TLC; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Glycoprotein; Lipid biosynthesis; Lipid metabolism;
KW Membrane; Phosphoprotein; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..393
FT /note="Ceramide synthase 4"
FT /id="PRO_0000185513"
FT TOPO_DOM 1..31
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q9HA82"
FT TRANSMEM 32..52
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 140..160
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 179..199
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 217..237
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 265..285
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 304..324
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 325..393
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9HA82"
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 341..393
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 291..301
FT /note="Last loop motif"
FT /evidence="ECO:0000250|UniProtKB:Q9HA82"
FT MOD_RES 342
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 349
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 350
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 19
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 19
FT /note="N -> S (in Ref. 2; BAC26208)"
FT /evidence="ECO:0000305"
FT CONFLICT 237
FT /note="L -> M (in Ref. 2; BAB32370)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 393 AA; 46017 MW; B2038F7A128F816F CRC64;
MSFSLSEWLW QETYWLPPNV TWAELEDRDG LVFAHPHHVL AAFPVALVLV AVRIVFERFV
ALPLSRWMGV QDPIRRKIKP NPVLEKYFLR MKQCPEETQM VLLASQCGLT LRQTQRWFRR
RRNQDRPSLS KKFCEACWRF VFYLCSFVGG TSILYHESWL WSPSLCWENY PHQTLNLSLY
WWYLLELGFY LSLLITLPFD VKRKDFKEQV VHHFVAVGLI GFSYSVNLLR IGAVVLLLHD
CSDYLLEGCK ILNYAHFRRG CDALFIMFAL VFFYTRLIFF PTQVIYTSVY DSIKNSGPFF
GYYFFIVLLV MLQILHVYWF CLILRMLYSF LHKGQMTEDI RSDVEEPDSS DDEPVSEGPQ
LKNGMARGSR VAVTNGPRSR AAACLTNGHT RAT
