LOCUS       NP_001365718             383 aa            linear   PRI 30-APR-2025
DEFINITION  ceramide synthase 3 isoform 2 [Homo sapiens].
ACCESSION   NP_001365718
VERSION     NP_001365718.1
DBSOURCE    REFSEQ: accession NM_001378789.1
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 383)
  AUTHORS   Jan,H., Wasif,N., Naqvi,S.K., Ullah,I. and Ahmad,W.
  TITLE     A novel homozygous splice site variant in CERS3 causes autosomal
            recessive congenital ichthyosis
  JOURNAL   Congenit Anom (Kyoto) 63 (4), 127-128 (2023)
   PUBMED   37128664
  REMARK    GeneRIF: A novel homozygous splice site variant in CERS3 causes
            autosomal recessive congenital ichthyosis.
REFERENCE   2  (residues 1 to 383)
  AUTHORS   Cai,J., Liu,Y., Li,Q., Wen,Z., Li,Y. and Chen,X.
  TITLE     Ceramide synthase 3 affects invasion and metastasis of
            hepatocellular carcinoma via the SMAD6 gene
  JOURNAL   Zhong Nan Da Xue Xue Bao Yi Xue Ban 47 (5), 588-599 (2022)
   PUBMED   35753729
  REMARK    GeneRIF: Ceramide synthase 3 affects invasion and metastasis of
            hepatocellular carcinoma via the SMAD6 gene.', trans '3SMAD6.
REFERENCE   3  (residues 1 to 383)
  AUTHORS   Takeda,S., Terazawa,S., Shimoda,H. and Imokawa,G.
  TITLE     beta-Sitosterol 3-O-D-glucoside increases ceramide levels in the
            stratum corneum via the up-regulated expression of ceramide
            synthase-3 and glucosylceramide synthase in a reconstructed human
            epidermal keratinization model
  JOURNAL   PLoS One 16 (3), e0248150 (2021)
   PUBMED   33684145
  REMARK    GeneRIF: beta-Sitosterol 3-O-D-glucoside increases ceramide levels
            in the stratum corneum via the up-regulated expression of ceramide
            synthase-3 and glucosylceramide synthase in a reconstructed human
            epidermal keratinization model.
            Publication Status: Online-Only
REFERENCE   4  (residues 1 to 383)
  AUTHORS   Muthusamy,K., Macke,E.L., Klee,E.W., Tebben,P.J., Hand,J.L.,
            Hasadsri,L., Marcou,C.A. and Schimmenti,L.A.
  TITLE     Congenital ichthyosis in Prader-Willi syndrome associated with
            maternal chromosome 15 uniparental disomy: Case report and review
            of autosomal recessive conditions unmasked by UPD
  JOURNAL   Am J Med Genet A 182 (10), 2442-2449 (2020)
   PUBMED   32815268
  REMARK    GeneRIF: Congenital ichthyosis in Prader-Willi syndrome associated
            with maternal chromosome 15 uniparental disomy: Case report and
            review of autosomal recessive conditions unmasked by UPD.
REFERENCE   5  (residues 1 to 383)
  AUTHORS   Rabionet,M., Bayerle,A., Jennemann,R., Heid,H., Fuchser,J.,
            Marsching,C., Porubsky,S., Bolenz,C., Guillou,F., Grone,H.J.,
            Gorgas,K. and Sandhoff,R.
  TITLE     Male meiotic cytokinesis requires ceramide synthase 3-dependent
            sphingolipids with unique membrane anchors
  JOURNAL   Hum Mol Genet 24 (17), 4792-4808 (2015)
   PUBMED   26045466
  REMARK    GeneRIF: testis-specific SLs, which we also link to CerS3 in human
            testis, are quintessential for male fertility.
REFERENCE   6  (residues 1 to 383)
  AUTHORS   Radner,F.P., Marrakchi,S., Kirchmeier,P., Kim,G.J., Ribierre,F.,
            Kamoun,B., Abid,L., Leipoldt,M., Turki,H., Schempp,W., Heilig,R.,
            Lathrop,M. and Fischer,J.
  TITLE     Mutations in CERS3 cause autosomal recessive congenital ichthyosis
            in humans
  JOURNAL   PLoS Genet 9 (6), e1003536 (2013)
   PUBMED   23754960
  REMARK    GeneRIF: these data present a novel pathway involved in ARCI
            development and, moreover, provide the first evidence that CERS3
            plays an essential role in human sphingolipid metabolism for the
            maintenance of epidermal lipid homeostasis.
            Erratum:[PLoS Genet. 2013 Jun;9(6):
            doi/10.1371/annotation/df5af830-8e1d-495a-a206-f881ed85e7fe]
REFERENCE   7  (residues 1 to 383)
  AUTHORS   Vaquerizas,J.M., Kummerfeld,S.K., Teichmann,S.A. and Luscombe,N.M.
  TITLE     A census of human transcription factors: function, expression and
            evolution
  JOURNAL   Nat Rev Genet 10 (4), 252-263 (2009)
   PUBMED   19274049
  REMARK    Review article
REFERENCE   8  (residues 1 to 383)
  AUTHORS   Rabionet,M., van der Spoel,A.C., Chuang,C.C., von
            Tumpling-Radosta,B., Litjens,M., Bouwmeester,D., Hellbusch,C.C.,
            Korner,C., Wiegandt,H., Gorgas,K., Platt,F.M., Grone,H.J. and
            Sandhoff,R.
  TITLE     Male germ cells require polyenoic sphingolipids with complex
            glycosylation for completion of meiosis: a link to ceramide
            synthase-3
  JOURNAL   J Biol Chem 283 (19), 13357-13369 (2008)
   PUBMED   18308723
REFERENCE   9  (residues 1 to 383)
  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
REFERENCE   10 (residues 1 to 383)
  AUTHORS   Richard,G.
  TITLE     Autosomal Recessive Congenital Ichthyosis
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301593
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC027020.12 and AC015723.8.
            This sequence is a reference standard in the RefSeqGene project.
            
            Summary: This gene is a member of the ceramide synthase family of
            genes. The ceramide synthase enzymes regulate sphingolipid
            synthesis by catalyzing the formation of ceramides from sphingoid
            base and acyl-coA substrates. This family member is involved in the
            synthesis of ceramides with ultra-long-chain acyl moieties
            (ULC-Cers), important to the epidermis in its role in creating a
            protective barrier from the environment. The protein encoded by
            this gene has also been implicated in modification of the lipid
            structures required for spermatogenesis. Mutations in this gene
            have been associated with male fertility defects, and epidermal
            defects, including ichthyosis. Alternative splicing results in
            multiple transcript variants encoding different isoforms. [provided
            by RefSeq, Aug 2015].
            
            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 :: BC034970.1, ERR279869.415.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1968968 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000679737.1/ ENSP00000506641.1
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..383
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="15"
                     /map="15q26.3"
     Protein         1..383
                     /product="ceramide synthase 3 isoform 2"
                     /EC_number="2.3.1.24"
                     /EC_number="2.3.1.297"
                     /EC_number="2.3.1.298"
                     /note="LAG1 homolog, ceramide synthase 3; LAG1 longevity
                     assurance homolog 3; dihydroceramide synthase 3;
                     sphingosine N-acyltransferase CERS3; very-long-chain
                     ceramide synthase CERS3; ultra-long-chain ceramide
                     synthase CERS3"
                     /calculated_mol_wt=46185
     Site            32..52
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8IU89.2)"
     Region          66..127
                     /region_name="Homeobox-like. /evidence=ECO:0000305"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8IU89.2)"
     Region          <82..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"
     Region          131..324
                     /region_name="TRAM_LAG1_CLN8"
                     /note="TLC domain; pfam03798"
                     /db_xref="CDD:461055"
     Site            139..159
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8IU89.2)"
     Site            174..194
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8IU89.2)"
     Site            205..225
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8IU89.2)"
     Site            264..284
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8IU89.2)"
     Site            298..318
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8IU89.2)"
     Site            340
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000305|PubMed:26887952; propagated from
                     UniProtKB/Swiss-Prot (Q8IU89.2)"
     Region          342..363
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8IU89.2)"
     CDS             1..383
                     /gene="CERS3"
                     /gene_synonym="ARCI9; LASS3"
                     /coded_by="NM_001378789.1:230..1381"
                     /note="isoform 2 is encoded by transcript variant 5"
                     /db_xref="CCDS:CCDS10384.1"
                     /db_xref="GeneID:204219"
                     /db_xref="HGNC:HGNC:23752"
                     /db_xref="MIM:615276"
ORIGIN      
        1 mfwtfkewfw lerfwlppti kwsdledhdg lvfvkpshly vtipyaflll iirrvfekfv
       61 asplaksfgi ketvrkvtpn tvlenffkhs trqplqtdiy glakkcnlte rqverwfrsr
      121 rnqerpsrlk kfqeacwrfa fylmitvagi aflydkpwly dlwevwngyp kqpllpsqyw
      181 yyilemsfyw sllfrlgfdv krkdflahii hhlaaislms fswcanyirs gtlvmivhdv
      241 adiwlesakm fsyagwtqtc ntlffifsti ffisrlivfp fwilyctlil pmyhlepffs
      301 yiflnlqlmi lqvlhlywgy yilkmlnrci fmksiqdvrs ddedyeeeee eeeeeatkgk
      361 emdclknglr aerhlipngq hgh
//
