LOCUS       NP_078828                394 aa            linear   PRI 28-APR-2025
DEFINITION  ceramide synthase 4 [Homo sapiens].
ACCESSION   NP_078828
VERSION     NP_078828.2
DBSOURCE    REFSEQ: accession NM_024552.3
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 394)
  AUTHORS   Shao,C., Ye,J., Dong,Z., Liao,B., Feng,S., Hu,S. and Zhong,B.
  TITLE     Phospholipid metabolism-related genotypes of PLA2R1 and CERS4
            contribute to nonobese MASLD
  JOURNAL   Hepatol Commun 8 (6), e0388 (2024)
   PUBMED   38836837
  REMARK    GeneRIF: Phospholipid metabolism-related genotypes of PLA2R1 and
            CERS4 contribute to nonobese MASLD.
            Publication Status: Online-Only
REFERENCE   2  (residues 1 to 394)
  AUTHORS   Kim,S.J., Seo,I., Kim,M.H., Park,J.W., Kim,S. and Park,W.J.
  TITLE     Ceramide synthase 4 overexpression exerts oncogenic properties in
            breast cancer
  JOURNAL   Lipids Health Dis 22 (1), 183 (2023)
   PUBMED   37885013
  REMARK    GeneRIF: Ceramide synthase 4 overexpression exerts oncogenic
            properties in breast cancer.
            Publication Status: Online-Only
REFERENCE   3  (residues 1 to 394)
  AUTHORS   Hayama,T., Hama,K., Ozawa,T., Fujiwara,Y., Nozawa,K., Matsuda,K.,
            Yokoyama,K., Hashiguchi,Y., Ochiai,H., Misawa,T. and Fukagawa,T.
  TITLE     Ceramide synthase CERS4 gene downregulation is associated with KRAS
            mutation in colorectal cancer
  JOURNAL   Sci Rep 13 (1), 16249 (2023)
   PUBMED   37758931
  REMARK    GeneRIF: Ceramide synthase CERS4 gene downregulation is associated
            with KRAS mutation in colorectal cancer.
            Publication Status: Online-Only
REFERENCE   4  (residues 1 to 394)
  AUTHORS   Matsuzaka,T., Kuba,M., Koyasu,S., Yamamoto,Y., Motomura,K.,
            Arulmozhiraja,S., Ohno,H., Sharma,R., Shimura,T., Okajima,Y.,
            Han,S.I., Aita,Y., Mizunoe,Y., Osaki,Y., Iwasaki,H., Yatoh,S.,
            Suzuki,H., Sone,H., Takeuchi,Y., Yahagi,N., Miyamoto,T., Sekiya,M.,
            Nakagawa,Y., Ema,M., Takahashi,S., Tokiwa,H. and Shimano,H.
  TITLE     Hepatocyte ELOVL Fatty Acid Elongase 6 Determines Ceramide
            Acyl-Chain Length and Hepatic Insulin Sensitivity in Mice
  JOURNAL   Hepatology 71 (5), 1609-1625 (2020)
   PUBMED   31529722
REFERENCE   5  (residues 1 to 394)
  AUTHORS   Luck,K., Kim,D.K., Lambourne,L., Spirohn,K., Begg,B.E., Bian,W.,
            Brignall,R., Cafarelli,T., Campos-Laborie,F.J., Charloteaux,B.,
            Choi,D., Cote,A.G., Daley,M., Deimling,S., Desbuleux,A., Dricot,A.,
            Gebbia,M., Hardy,M.F., Kishore,N., Knapp,J.J., Kovacs,I.A.,
            Lemmens,I., Mee,M.W., Mellor,J.C., Pollis,C., Pons,C.,
            Richardson,A.D., Schlabach,S., Teeking,B., Yadav,A., Babor,M.,
            Balcha,D., Basha,O., Bowman-Colin,C., Chin,S.F., Choi,S.G.,
            Colabella,C., Coppin,G., D'Amata,C., De Ridder,D., De Rouck,S.,
            Duran-Frigola,M., Ennajdaoui,H., Goebels,F., Goehring,L., Gopal,A.,
            Haddad,G., Hatchi,E., Helmy,M., Jacob,Y., Kassa,Y., Landini,S.,
            Li,R., van Lieshout,N., MacWilliams,A., Markey,D., Paulson,J.N.,
            Rangarajan,S., Rasla,J., Rayhan,A., Rolland,T., San-Miguel,A.,
            Shen,Y., Sheykhkarimli,D., Sheynkman,G.M., Simonovsky,E., Tasan,M.,
            Tejeda,A., Tropepe,V., Twizere,J.C., Wang,Y., Weatheritt,R.J.,
            Weile,J., Xia,Y., Yang,X., Yeger-Lotem,E., Zhong,Q., Aloy,P.,
            Bader,G.D., De Las Rivas,J., Gaudet,S., Hao,T., Rak,J.,
            Tavernier,J., Hill,D.E., Vidal,M., Roth,F.P. and Calderwood,M.A.
  TITLE     A reference map of the human binary protein interactome
  JOURNAL   Nature 580 (7803), 402-408 (2020)
   PUBMED   32296183
REFERENCE   6  (residues 1 to 394)
  AUTHORS   Ebel,P., Imgrund,S., Vom Dorp,K., Hofmann,K., Maier,H., Drake,H.,
            Degen,J., Dormann,P., Eckhardt,M., Franz,T. and Willecke,K.
  TITLE     Ceramide synthase 4 deficiency in mice causes lipid alterations in
            sebum and results in alopecia
  JOURNAL   Biochem J 461 (1), 147-158 (2014)
   PUBMED   24738593
REFERENCE   7  (residues 1 to 394)
  AUTHORS   Hartmann,D., Wegner,M.S., Wanger,R.A., Ferreiros,N., Schreiber,Y.,
            Lucks,J., Schiffmann,S., Geisslinger,G. and Grosch,S.
  TITLE     The equilibrium between long and very long chain ceramides is
            important for the fate of the cell and can be influenced by
            co-expression of CerS
  JOURNAL   Int J Biochem Cell Biol 45 (7), 1195-1203 (2013)
   PUBMED   23538298
  REMARK    GeneRIF: Co-expression of CerS2 with CerS4/CerS6 reversed the
            inhibitory effect of long chain ceramides on cell proliferation and
            the induction of apoptosis. we detected no effect on cell
            proliferation.
REFERENCE   8  (residues 1 to 394)
  AUTHORS   Rosenthal,E.A., Ronald,J., Rothstein,J., Rajagopalan,R.,
            Ranchalis,J., Wolfbauer,G., Albers,J.J., Brunzell,J.D.,
            Motulsky,A.G., Rieder,M.J., Nickerson,D.A., Wijsman,E.M. and
            Jarvik,G.P.
  TITLE     Linkage and association of phospholipid transfer protein activity
            to LASS4
  JOURNAL   J Lipid Res 52 (10), 1837-1846 (2011)
   PUBMED   21757428
  REMARK    GeneRIF: The linkage and association of phospholipid transfer
            protein activity to LASS4 were studied.
REFERENCE   9  (residues 1 to 394)
  AUTHORS   Xu,J., Zheng,S.L., Isaacs,S.D., Wiley,K.E., Wiklund,F., Sun,J.,
            Kader,A.K., Li,G., Purcell,L.D., Kim,S.T., Hsu,F.C., Stattin,P.,
            Hugosson,J., Adolfsson,J., Walsh,P.C., Trent,J.M., Duggan,D.,
            Carpten,J., Gronberg,H. and Isaacs,W.B.
  TITLE     Inherited genetic variant predisposes to aggressive but not
            indolent prostate cancer
  JOURNAL   Proc Natl Acad Sci U S A 107 (5), 2136-2140 (2010)
   PUBMED   20080650
  REMARK    GeneRIF: Observational study of gene-disease association. (HuGE
            Navigator)
REFERENCE   10 (residues 1 to 394)
  AUTHORS   Lahiri,S., Lee,H., Mesicek,J., Fuks,Z., Haimovitz-Friedman,A.,
            Kolesnick,R.N. and Futerman,A.H.
  TITLE     Kinetic characterization of mammalian ceramide synthases:
            determination of K(m) values towards sphinganine
  JOURNAL   FEBS Lett 581 (27), 5289-5294 (2007)
   PUBMED   17977534
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            DA381485.1, BC009828.2, AK222621.1 and AC022146.8.
            
            On Sep 20, 2008 this sequence version replaced NP_078828.1.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AK222621.1, SRR1660803.175441.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000251363.10/ ENSP00000251363.5
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..394
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="19"
                     /map="19p13.2"
     Protein         1..394
                     /product="ceramide synthase 4"
                     /EC_number="2.3.1.24"
                     /note="LAG1 homolog, ceramide synthase 4; LAG1 longevity
                     assurance homolog 4; sphingosine N-acyltransferase CERS4"
                     /calculated_mol_wt=46268
     Site            19
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (Q9HA82.2)"
     Site            32..52
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9HA82.2)"
     Region          67..128
                     /region_name="Homeobox-like. /evidence=ECO:0000305"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9HA82.2)"
     Region          71..128
                     /region_name="homeodomain"
                     /note="Homeodomain; DNA binding domains involved in the
                     transcriptional regulation of key eukaryotic developmental
                     processes; may bind to DNA as monomers or as homo- and/or
                     heterodimers, in a sequence-specific manner; cd00086"
                     /db_xref="CDD:238039"
     Site            order(71..74,76,94,100,113,115..116,119..120,122..124,
                     126..127)
                     /site_type="DNA binding"
                     /note="DNA binding site [nucleotide binding]"
                     /db_xref="CDD:238039"
     Site            order(72,75,116,119..120,123)
                     /site_type="other"
                     /note="specific DNA base contacts [nucleotide binding]"
                     /db_xref="CDD:238039"
     Region          131..332
                     /region_name="TLC"
                     /note="TRAM, LAG1 and CLN8 homology domains; smart00724"
                     /db_xref="CDD:214789"
     Site            140..160
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9HA82.2)"
     Site            179..199
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9HA82.2)"
     Site            209..229
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9HA82.2)"
     Site            260..280
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9HA82.2)"
     Region          291..301
                     /region_name="Last loop motif.
                     /evidence=ECO:0000269|PubMed:29632068"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9HA82.2)"
     Site            304..324
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9HA82.2)"
     Region          341..394
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9HA82.2)"
     Site            342
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000250|UniProtKB:Q9D6J1; propagated from
                     UniProtKB/Swiss-Prot (Q9HA82.2)"
     Site            349
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000250|UniProtKB:Q9D6J1; propagated from
                     UniProtKB/Swiss-Prot (Q9HA82.2)"
     Site            350
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000250|UniProtKB:Q9D6J1; propagated from
                     UniProtKB/Swiss-Prot (Q9HA82.2)"
     CDS             1..394
                     /gene="CERS4"
                     /gene_synonym="LASS4; Trh1"
                     /coded_by="NM_024552.3:284..1468"
                     /db_xref="CCDS:CCDS12197.1"
                     /db_xref="GeneID:79603"
                     /db_xref="HGNC:HGNC:23747"
                     /db_xref="MIM:615334"
ORIGIN      
        1 mlssfnewfw qdrfwlppnv twteledrdg rvyphpqdll aalplalvll amrlaferfi
       61 glplsrwlgv rdqtrrqvkp natlekhflt eghrpkepql sllaaqcglt lqqtqrwfrr
      121 rrnqdrpqlt kkfceaswrf lfylssfvgg lsvlyheswl wapvmcwdry pnqtlkpsly
      181 wwyllelgfy lsllirlpfd vkrkdfkeqv ihhfvavilm tfsysanllr igslvlllhd
      241 ssdylleack mvnymqyqqv cdalflifsf vffytrlvlf ptqilyttyy esisnrgpff
      301 gyyffngllm llqllhvfws clilrmlysf mkkgqmekdi rsdveesdss eeaaaaqepl
      361 qlkngaaggp rpaptdgprs rvagrltnrh ttat
//
