TABLE 1.
List of human SL metabolism genes and the fly orthologs.
| Human genes | Fly genes | DIOPT score† (out of 16) | Activity | References†† |
| Sphingolipid de novo synthesis pathway | ||||
| SPTLC1 | Spt-I | 15 | Serine palmitoyltransferase, serine + acyl-CoA → 3-ketosphinganine | Oswald et al., 2015 |
| SPTLC2/3 | lace | 15 (SPTLC2) | Adachi-Yamada et al., 1999 | |
| SPTSSA/B | CG34293*/ CG34194*/ghi | 8 (SPTSSA-CG34293) | Guan et al., 2013 | |
| ORMDL1/2/3 | Ormdl | 14 (ORMDL3) | SPT activity suppression | Hjelmqvist et al., 2002 |
| KDSR | CG10425* | 15 | 3-keto-dhSph reductase, 3-ketosphinganine → dhSph | |
| CERS 1/2/3/4/5/6 | schlank | 13 (CERS5/6) | Ceramide synthase, dhSph + acyl-CoA → dhCer Sph + acyl-CoA → Cer | Bauer et al., 2009 |
| DEGS1/2 | ifc | 15 (DEGS2) | SL delta(4)-desaturase, dhCer → Cer | Ternes et al., 2002 |
| SM and CPE synthesis | ||||
| CERT1 | Cert | 14 | ER–Golgi Cer trafficking | Rao et al., 2007 |
| SGMS1/2 | No fly ortholog | N/A | SM synthase, Cer + phosphatidylcholine → SM + DG | |
| SAMD8 | SMSr | 13 | CPE synthase, Cer + phosphatidylethanolamine → CPE + DG | Vacaru et al., 2013 |
| No human ortholog | Cpes | N/A | CPE synthase, Cer + CDP-ethanolamine → CPE + CMP | |
| GSL synthesis (mono- and di- glycosyl ceramide) | ||||
| UGCG | GlcT | 15 | Cer glucosyltransferase, Cer + UDP-glucose → GlcCer + UDP | Kohyama-Koganeya et al., 2004 |
| UGT8 | Ugt50B3* | 10 | Cer galactosyltransferase, Cer + UDP-galactose → GalCer + UDP | |
| B4GALT5/6 | No fly ortholog | N/A | GlcCer beta-1,4-galactosyltransferase, GlcCer + UDP-galactose → LacCer + UDP | |
| No human ortholog | egh | N/A | GlcCer glycosyltransferase, GlcCer + GDP-mannose → MacCer + GDP | Wandall et al., 2003 |
| SM and salvage pathways | ||||
| PSAP | Sap-r | 12 | Facilitate GSL hydrolysis | Hindle et al., 2017; Sellin et al., 2017 |
| SMPD1 | CG3376*/ CG15533*/ CG15534* | 15 (CG3376) | Acidic sphingomyelinase, SM → Cer + PC (human) | |
| SMPD2 | nSMase | 15 | Neutral sphingomyelinase, SM → Cer + PC (human) CPE → Cer + PE (fly) | Chen et al., 2022 |
| SMPD3 | No fly ortholog | N/A | Neutral sphingomyelinase, SM → Cer + PC (human) | |
| SMPD4 | CG6962* | 15 | ||
| SMPD5 | No fly ortholog | N/A | ||
| ENPP7 | No fly ortholog | N/A | Alkaline sphingomyelinase, SM → Cer + PC (human) | |
| GBA | Gba1a/b | 14 (Gba1a/b) | Acidic glucosylceramidase, GlcCer → Cer + Glucose | Davis et al., 2016 |
| GBA2 | CG33090* | 15 | Neutral glucosylceramidase, GlcCer → Cer + Glucose | |
| GALC | No fly ortholog | N/A | Acidic galactosylceramidase, GalCer → Cer + Galactose | |
| ASAH1 | No fly ortholog | N/A | Acidic ceramidase, Cer → Sph + fatty acid | |
| ASAH2 | Cdase | 9 | Neutral ceramidase, Cer → Sph + fatty acid# | Yuan et al., 2011 |
| ACER1/2/3 | bwa | 14 (ACER2) | ||
| SGPP1/2 | No fly ortholog | N/A | S1P phosphatase, S1P → Sph | |
| S1P synthesis and catabolism | ||||
| SPHK1/2 | Sk1/2 | 13 (SPHK1-Sk2) | Sph kinase, Sph → S1P | Herr et al., 2004 |
| SGPL1 | Sply | 15 | S1P lyase, S1P → PE + fatty aldehyde | Herr et al., 2003 |
| C1P synthesis | ||||
| CERK | Cerk | 14 | Ceramide kinase, Cer → C1P | Dasgupta et al., 2009 |
†DRSC integrative ortholog prediction tool (DIOPT) score indicates the level of homology between human and fly orthologs (Hu et al., 2011). The score is evaluated for each pair of human-fly orthologs. A high score indicates a high level of homology between orthologs, and the maximum score is 16. Only the highest score is listed in the table, and the gene symbol indicates the ortholog or the human-fly ortholog pairs that receive the score.
††The references indicate the studies on the fly orthologs.
*Predicted orthologs in flies.
#Fly Bwa does not have ceramidase activity.
SPT, serine palmitoyltransferase; Sph, sphingosine; dhSph, dihydrosphingosine; Cer, ceramide; dhCer, dihydroceramide; SM, sphingomyelin; PC, phosphocholine; CPE, ceramide phosphoethanolamine; PE, phosphoethanolamine; GlcCer, glucosylceramide; GalCer, galactosylceramide; LacCer, lactosylceramide; MacCer, mannosyl glucosylceramide; GSL, glycosphingolipid; S1P, sphingosine-1-phosphate; C1P, ceramide-1-phosphate.