Gene Ontology annotation through association of InterPro records with GO terms

Annotation inferences using phylogenetic trees

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

GO_REF:0000116

Automatic Gene Ontology annotation based on Rhea mapping

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:11937514

Identification and characterization of a sphingolipid delta 4-desaturase family.

Identified and biochemically characterized the human sphingolipid Delta4-desaturase (dihydroceramide desaturase), the enzyme underlying the core DEGS1 catalytic activity; basis for UniProt EC 1.14.19.17.

PMID:1317856

Subcellular localization and membrane topology of serine palmitoyltransferase, 3-dehydrosphinganine reductase, and sphinganine N-acyltransferase in mouse liver.

Established that the de novo sphingolipid-synthesis enzymes reside in the ER and face its cytosolic side, providing the pathway and topology context used for DEGS1 ceramide biosynthesis and cytosolic-ER-face annotations.

PMID:16120614

Serinc, an activity-regulated protein family, incorporates serine into membrane lipid synthesis.

Places DEGS1 among the ER sphingolipid-biosynthetic enzymes acting on the cytosolic face; basis for experimental ceramide-biosynthesis and cytosolic-ER-face annotations.

PMID:19647031

N-Myristoylation targets dihydroceramide Delta4-desaturase 1 to mitochondria: partial involvement in the apoptotic effect of myristic acid.

N-myristoylation of DES1 (Gly-2) targets a fraction of the enzyme to mitochondria and increases ceramide production and apoptosis; native desaturase activity occurs in both ER and mitochondria. Explains the secondary mitochondrial localization.

PMID:23143414

Identification of DES1 as a vitamin A isomerase in Müller glial cells of the retina.

DES1 is a retinol (vitamin A) isomerase (isomerase-2) in retinal Muller cells, a distinct moonlighting activity; purified DES1 has robust activity and coimmunoprecipitates with CRALBP. Basis for the retinol isomerase activity annotation.

PMID:24209621

A four-step cycle driven by PI(4)P hydrolysis directs sterol/PI(4)P exchange by the ER-Golgi tether OSBP.

ER-Golgi lipid-exchange context (OSBP cycle) relevant to downstream sphingolipid and sphingomyelin trafficking; cited for the DEGS1 sphingomyelin-biosynthesis annotation.

PMID:30620337

Loss of the sphingolipid desaturase DEGS1 causes hypomyelinating leukodystrophy.

Biallelic DEGS1 loss-of-function causes hypomyelinating leukodystrophy (HLD18); DEGS1 inserts the Δ4,5-trans double bond into dihydroceramide as the final step of de novo ceramide synthesis; critical for myelin development and maintenance.

PMID:30620338

DEGS1-associated aberrant sphingolipid metabolism impairs nervous system function in humans.

Homozygous DEGS1 p.Ala280Val causes a multisystem neurological disorder; the variant reduces enzyme activity by about 80% with accumulation of dihydro-sphingolipids; DEGS1 catalyzes the last step of ceramide synthesis. IMP basis for the core MF and myelin annotations.

PMID:32296183

A reference map of the human binary protein interactome.

High-throughput binary interactome (HuRI) reporting DEGS1 interactions (ARLN, SEMA4G); source of the uninformative bare protein-binding IPIs.

PMID:34080016

Glucosylceramide and galactosylceramide, small glycosphingolipids with significant impact on health and disease.

Review of glucosyl- and galactosyl-ceramide biology; glucosylceramide is the founder of hundreds of glycosphingolipids, all built from ceramide (the DEGS1 product). Context for the downstream glycosphingolipid-biosynthesis annotation.

PMID:9188692

The product of the MLD gene is a member of the membrane fatty acid desaturase family: overexpression of MLD inhibits EGF receptor biosynthesis.

Original cloning of the human MLD gene (DEGS1) as a membrane fatty acid desaturase family member localized to the ER and predicted to be multi-pass. Basis for early ER, membrane, and fatty-acid annotations.

Reactome:R-HSA-1660661

Sphingolipid de novo biosynthesis

Reactome:R-HSA-428259

DEGS1 dehydrogenates dihydroceramide

Reactome curated reaction in which DEGS1, at the cytosolic face of the ER, desaturates dihydroceramide to ceramide as part of an enzyme complex with cytochrome b5 (Fe2+) refreshed by NADH.

Reactome:R-HSA-6799350

Exocytosis of specific granule membrane proteins

Neutrophil specific-granule exocytosis pathway; source of the plasma-membrane and specific-granule-membrane over-annotations for DEGS1 (bulk granule proteomics).

file:human/DEGS1/DEGS1-uniprot.txt

UniProtKB entry O15121 (DEGS1_HUMAN)

UniProt records the core catalytic activity (EC 1.14.19.17; N-acylsphinganine plus O2 plus Fe(II)-cytochrome b5 giving N-acylsphing-4-enine), ER and mitochondrion membrane localization, DEGS-subfamily membership, and causation of HLD18.