CERS4_HUMAN
ID CERS4_HUMAN Reviewed; 394 AA.
AC Q9HA82; D6W665;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Ceramide synthase 4 {ECO:0000303|PubMed:17977534};
DE Short=CerS4 {ECO:0000303|PubMed:17977534};
DE EC=2.3.1.- {ECO:0000269|PubMed:17977534, ECO:0000269|PubMed:23530041, ECO:0000269|PubMed:26887952, ECO:0000269|PubMed:29632068};
DE AltName: Full=LAG1 longevity assurance homolog 4 {ECO:0000250|UniProtKB:Q9D6J1};
DE AltName: Full=Sphingosine N-acyltransferase CERS4 {ECO:0000305};
DE EC=2.3.1.24 {ECO:0000250|UniProtKB:Q9D6J1};
GN Name=CERS4 {ECO:0000303|PubMed:17977534, ECO:0000312|HGNC:HGNC:23747};
GN Synonyms=LASS4 {ECO:0000250|UniProtKB:Q9D6J1};
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], AND VARIANTS VAL-353 AND GLN-379.
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT THR-366.
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS VAL-353 AND GLN-379.
RC TISSUE=Lung;
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 [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, 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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, PHOSPHORYLATION, GLYCOSYLATION,
RP TOPOLOGY, AND MUTAGENESIS OF 342-SER--SER-350.
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 [9]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, GLYCOSYLATION, AND MUTAGENESIS OF
RP 291-GLU--GLY-301.
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 [10]
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 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:17977534, ECO:0000269|PubMed:23530041,
CC ECO:0000269|PubMed:26887952, ECO:0000269|PubMed:29632068,
CC ECO:0000269|PubMed:31916624}.
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:17977534,
CC ECO:0000269|PubMed:23530041, ECO:0000269|PubMed:29632068,
CC ECO:0000269|PubMed:31916624};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36548;
CC Evidence={ECO:0000269|PubMed:17977534, ECO:0000269|PubMed:23530041,
CC ECO:0000269|PubMed:29632068, ECO:0000269|PubMed:31916624};
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:17977534,
CC ECO:0000269|PubMed:26887952};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36556;
CC Evidence={ECO:0000269|PubMed:17977534, ECO:0000269|PubMed:26887952};
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:0000250|UniProtKB:Q9D6J1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36536;
CC Evidence={ECO:0000250|UniProtKB:Q9D6J1};
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:31916624};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33592;
CC Evidence={ECO:0000269|PubMed:31916624};
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:0000250|UniProtKB:Q9D6J1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33352;
CC Evidence={ECO:0000250|UniProtKB:Q9D6J1};
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:0000250|UniProtKB:Q9D6J1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23769;
CC Evidence={ECO:0000250|UniProtKB:Q9D6J1};
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:Q9D6J1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36692;
CC Evidence={ECO:0000250|UniProtKB:Q9D6J1};
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:0000269|PubMed:23530041};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43045;
CC Evidence={ECO:0000269|PubMed:23530041};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.8 uM for sphinganine (with octadecanoyl-CoA as substrate)
CC {ECO:0000269|PubMed:17977534};
CC KM=1.8 uM for sphinganine (with eicosanoyl-CoA as substrate)
CC {ECO:0000269|PubMed:17977534};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000269|PubMed:17977534, ECO:0000269|PubMed:23530041,
CC ECO:0000269|PubMed:26887952, ECO:0000269|PubMed:29632068}.
CC -!- INTERACTION:
CC Q9HA82; Q86Z23: C1QL4; NbExp=3; IntAct=EBI-2622997, EBI-12062109;
CC Q9HA82; Q8NHW4: CCL4L2; NbExp=3; IntAct=EBI-2622997, EBI-10271156;
CC Q9HA82; Q8NC01: CLEC1A; NbExp=3; IntAct=EBI-2622997, EBI-11996768;
CC Q9HA82; P29400-2: COL4A5; NbExp=3; IntAct=EBI-2622997, EBI-12211159;
CC Q9HA82; Q4LDR2: CTXN3; NbExp=3; IntAct=EBI-2622997, EBI-12019274;
CC Q9HA82; P00387: CYB5R3; NbExp=3; IntAct=EBI-2622997, EBI-1046040;
CC Q9HA82; P50402: EMD; NbExp=3; IntAct=EBI-2622997, EBI-489887;
CC Q9HA82; Q969F0: FATE1; NbExp=3; IntAct=EBI-2622997, EBI-743099;
CC Q9HA82; Q9H0Q3: FXYD6; NbExp=3; IntAct=EBI-2622997, EBI-713304;
CC Q9HA82; Q8TDV0: GPR151; NbExp=3; IntAct=EBI-2622997, EBI-11955647;
CC Q9HA82; Q9Y5U9: IER3IP1; NbExp=3; IntAct=EBI-2622997, EBI-725665;
CC Q9HA82; P24593: IGFBP5; NbExp=3; IntAct=EBI-2622997, EBI-720480;
CC Q9HA82; P11215: ITGAM; NbExp=3; IntAct=EBI-2622997, EBI-2568251;
CC Q9HA82; Q8N5M9: JAGN1; NbExp=3; IntAct=EBI-2622997, EBI-10266796;
CC Q9HA82; Q8TAF8: LHFPL5; NbExp=3; IntAct=EBI-2622997, EBI-2820517;
CC Q9HA82; P11836: MS4A1; NbExp=3; IntAct=EBI-2622997, EBI-2808234;
CC Q9HA82; Q9UHE5: NAT8; NbExp=3; IntAct=EBI-2622997, EBI-2863634;
CC Q9HA82; Q99519: NEU1; NbExp=3; IntAct=EBI-2622997, EBI-721517;
CC Q9HA82; Q04941: PLP2; NbExp=3; IntAct=EBI-2622997, EBI-608347;
CC Q9HA82; P54315: PNLIPRP1; NbExp=3; IntAct=EBI-2622997, EBI-8652812;
CC Q9HA82; P43378: PTPN9; NbExp=3; IntAct=EBI-2622997, EBI-742898;
CC Q9HA82; Q8TAC9: SCAMP5; NbExp=3; IntAct=EBI-2622997, EBI-2695784;
CC Q9HA82; O00767: SCD; NbExp=3; IntAct=EBI-2622997, EBI-2684237;
CC Q9HA82; O75920: SERF1B; NbExp=3; IntAct=EBI-2622997, EBI-2115181;
CC Q9HA82; Q8N6R1: SERP2; NbExp=3; IntAct=EBI-2622997, EBI-749270;
CC Q9HA82; Q9UKG4: SLC13A4; NbExp=3; IntAct=EBI-2622997, EBI-12808018;
CC Q9HA82; P78382: SLC35A1; NbExp=3; IntAct=EBI-2622997, EBI-12870360;
CC Q9HA82; Q8N357: SLC35F6; NbExp=3; IntAct=EBI-2622997, EBI-713484;
CC Q9HA82; P30825: SLC7A1; NbExp=3; IntAct=EBI-2622997, EBI-4289564;
CC Q9HA82; P58511: SMIM11; NbExp=3; IntAct=EBI-2622997, EBI-1051936;
CC Q9HA82; O15400: STX7; NbExp=3; IntAct=EBI-2622997, EBI-3221827;
CC Q9HA82; Q9UNK0: STX8; NbExp=3; IntAct=EBI-2622997, EBI-727240;
CC Q9HA82; Q9Y6I9: TEX264; NbExp=3; IntAct=EBI-2622997, EBI-10329860;
CC Q9HA82; Q96HP8: TMEM176A; NbExp=3; IntAct=EBI-2622997, EBI-2800645;
CC Q9HA82; Q8TBM7: TMEM254; NbExp=3; IntAct=EBI-2622997, EBI-11956809;
CC Q9HA82; A0PK05: TMEM72; NbExp=3; IntAct=EBI-2622997, EBI-12878352;
CC Q9HA82; Q96B49: TOMM6; NbExp=3; IntAct=EBI-2622997, EBI-10826510;
CC Q9HA82; Q5TGU0: TSPO2; NbExp=3; IntAct=EBI-2622997, EBI-12195249;
CC Q9HA82; O75841: UPK1B; NbExp=3; IntAct=EBI-2622997, EBI-12237619;
CC Q9HA82; P63027: VAMP2; NbExp=3; IntAct=EBI-2622997, EBI-520113;
CC Q9HA82; Q96FB2; NbExp=3; IntAct=EBI-2622997, EBI-2857623;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9D6J1}; Multi-pass membrane protein
CC {ECO:0000255}.
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:0000269|PubMed:29632068}.
CC -!- PTM: Phosphorylated at the C-terminus by CK2.
CC {ECO:0000269|PubMed:26887952}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:26887952,
CC ECO:0000269|PubMed:29632068}.
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 {ECO:0000255}.
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DR EMBL; AK022151; BAB13972.1; -; mRNA.
DR EMBL; AC022146; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471139; EAW68940.1; -; Genomic_DNA.
DR EMBL; CH471139; EAW68941.1; -; Genomic_DNA.
DR EMBL; CH471139; EAW68942.1; -; Genomic_DNA.
DR EMBL; CH471139; EAW68945.1; -; Genomic_DNA.
DR EMBL; BC009828; AAH09828.1; -; mRNA.
DR CCDS; CCDS12197.1; -.
DR RefSeq; NP_078828.2; NM_024552.2.
DR RefSeq; XP_011526592.1; XM_011528290.2.
DR RefSeq; XP_011526593.1; XM_011528291.2.
DR RefSeq; XP_011526594.1; XM_011528292.2.
DR RefSeq; XP_011526595.1; XM_011528293.2.
DR RefSeq; XP_011526596.1; XM_011528294.2.
DR RefSeq; XP_011526597.1; XM_011528295.2.
DR RefSeq; XP_016882792.1; XM_017027303.1.
DR RefSeq; XP_016882793.1; XM_017027304.1.
DR RefSeq; XP_016882794.1; XM_017027305.1.
DR AlphaFoldDB; Q9HA82; -.
DR SMR; Q9HA82; -.
DR BioGRID; 122740; 70.
DR IntAct; Q9HA82; 45.
DR STRING; 9606.ENSP00000251363; -.
DR SwissLipids; SLP:000000699; -.
DR GlyConnect; 1106; 3 N-Linked glycans (1 site).
DR GlyGen; Q9HA82; 1 site, 3 N-linked glycans (1 site).
DR iPTMnet; Q9HA82; -.
DR PhosphoSitePlus; Q9HA82; -.
DR BioMuta; CERS4; -.
DR DMDM; 296434561; -.
DR EPD; Q9HA82; -.
DR jPOST; Q9HA82; -.
DR MassIVE; Q9HA82; -.
DR MaxQB; Q9HA82; -.
DR PaxDb; Q9HA82; -.
DR PeptideAtlas; Q9HA82; -.
DR PRIDE; Q9HA82; -.
DR ProteomicsDB; 81384; -.
DR Antibodypedia; 24821; 295 antibodies from 30 providers.
DR DNASU; 79603; -.
DR Ensembl; ENST00000251363.10; ENSP00000251363.5; ENSG00000090661.12.
DR Ensembl; ENST00000559450.5; ENSP00000453509.1; ENSG00000090661.12.
DR GeneID; 79603; -.
DR KEGG; hsa:79603; -.
DR MANE-Select; ENST00000251363.10; ENSP00000251363.5; NM_024552.3; NP_078828.2.
DR UCSC; uc002mjg.4; human.
DR CTD; 79603; -.
DR DisGeNET; 79603; -.
DR GeneCards; CERS4; -.
DR HGNC; HGNC:23747; CERS4.
DR HPA; ENSG00000090661; Low tissue specificity.
DR MIM; 615334; gene.
DR neXtProt; NX_Q9HA82; -.
DR OpenTargets; ENSG00000090661; -.
DR PharmGKB; PA134915173; -.
DR VEuPathDB; HostDB:ENSG00000090661; -.
DR eggNOG; KOG1607; Eukaryota.
DR GeneTree; ENSGT01030000234515; -.
DR InParanoid; Q9HA82; -.
DR OMA; DQGGDCY; -.
DR OrthoDB; 987268at2759; -.
DR PhylomeDB; Q9HA82; -.
DR TreeFam; TF314319; -.
DR BioCyc; MetaCyc:ENSG00000090661-MON; -.
DR BRENDA; 2.3.1.24; 2681.
DR BRENDA; 2.3.1.291; 2681.
DR BRENDA; 2.3.1.297; 2681.
DR PathwayCommons; Q9HA82; -.
DR Reactome; R-HSA-1660661; Sphingolipid de novo biosynthesis.
DR SignaLink; Q9HA82; -.
DR UniPathway; UPA00222; -.
DR BioGRID-ORCS; 79603; 25 hits in 1093 CRISPR screens.
DR ChiTaRS; CERS4; human.
DR GenomeRNAi; 79603; -.
DR Pharos; Q9HA82; Tbio.
DR PRO; PR:Q9HA82; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9HA82; protein.
DR Bgee; ENSG00000090661; Expressed in lower esophagus mucosa and 115 other tissues.
DR ExpressionAtlas; Q9HA82; baseline and differential.
DR Genevisible; Q9HA82; 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: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: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 Endoplasmic reticulum; Glycoprotein; Lipid biosynthesis; Lipid metabolism;
KW Membrane; Phosphoprotein; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..394
FT /note="Ceramide synthase 4"
FT /id="PRO_0000185512"
FT TOPO_DOM 1..31
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:29632068"
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 209..229
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 260..280
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 304..324
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 325..394
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 341..394
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 291..301
FT /note="Last loop motif"
FT /evidence="ECO:0000269|PubMed:29632068"
FT MOD_RES 342
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9D6J1"
FT MOD_RES 349
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9D6J1"
FT MOD_RES 350
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9D6J1"
FT CARBOHYD 19
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 119
FT /note="R -> Q (in dbSNP:rs17159388)"
FT /id="VAR_034065"
FT VARIANT 301
FT /note="G -> S (in dbSNP:rs2288413)"
FT /id="VAR_019556"
FT VARIANT 353
FT /note="A -> V (in dbSNP:rs17160348)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_060263"
FT VARIANT 366
FT /note="A -> T (in dbSNP:rs36259)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_019557"
FT VARIANT 379
FT /note="R -> Q (in dbSNP:rs17160349)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_060264"
FT MUTAGEN 291..298
FT /note="ESISNRGP->YPLELYPA: Altered specificity toward acyl
FT donor; generates C24 ceramides instead of C18-C22-
FT ceramides."
FT /evidence="ECO:0000269|PubMed:29632068"
FT MUTAGEN 342..350
FT /note="SDVEESDSS->ADVEEADAA: Decreased phosphorylation."
FT /evidence="ECO:0000269|PubMed:26887952"
SQ SEQUENCE 394 AA; 46399 MW; DAA12AA386ED2802 CRC64;
MLSSFNEWFW QDRFWLPPNV TWTELEDRDG RVYPHPQDLL AALPLALVLL AMRLAFERFI
GLPLSRWLGV RDQTRRQVKP NATLEKHFLT EGHRPKEPQL SLLAAQCGLT LQQTQRWFRR
RRNQDRPQLT KKFCEASWRF LFYLSSFVGG LSVLYHESWL WAPVMCWDRY PNQTLKPSLY
WWYLLELGFY LSLLIRLPFD VKRKDFKEQV IHHFVAVILM TFSYSANLLR IGSLVLLLHD
SSDYLLEACK MVNYMQYQQV CDALFLIFSF VFFYTRLVLF PTQILYTTYY ESISNRGPFF
GYYFFNGLLM LLQLLHVFWS CLILRMLYSF MKKGQMEKDI RSDVEESDSS EEAAAAQEPL
QLKNGAAGGP RPAPTDGPRS RVAGRLTNRH TTAT
