UniProt: P54803 (GALC_HUMAN); HGNC:4115; EC 3.2.1.46; gene on chr14.
Glycosyl hydrolase family GH59 (CAZy GH59; Pfam PF02057).
GALC is a lysosomal glycosidase of glycosphingolipid catabolism. It hydrolyses the
terminal galactose from galactosylceramide (galactocerebroside) to yield ceramide +
D-galactose (EC 3.2.1.46, RHEA:14297), and also hydrolyses galactosylsphingosine
(psychosine) and other galactolipids.
Requires saposin A (SapA, from PSAP) for lipid presentation. GALC-SapA crystal
structure (murine) = 2:2 heterotetramer; open channel from GALC active site to SapA
hydrophobic cavity presents the polar glycosyl headgroup to the active site while shielding
the acyl chains. "This enzyme requires the saposin SapA for lipid processing and defects in
either of these proteins causes a severe neurodegenerative disorder, Krabbe disease"
PMID:29323104. Active-site residues (UniProt): proton donor/acceptor His... actually
ACT_SITE 198 (proton donor/acceptor), 274 (nucleophile). GH59 retaining glycosidase.
Lysosome / lysosomal lumen. GO IC annotations place it in endolysosome lumen (GO:0036021),
inferred from the general finding that endolysosomes are the principal sites of acid
hydrolase activity PMID:27498570 combined with GALC's acid-hydrolase MF (GO:0004336).
PMID:27498570 is a general endolysosome study and does NOT mention GALC by name; the
endolysosome-lumen call is a curator inference (IC). Lysosome localization is well
established (subcellular location "Lysosome"; typical acid hydrolase, mannose-6-phosphate
pathway implied).
Deficiency causes Krabbe disease / globoid cell leukodystrophy (KRB; MIM:245200),
autosomal recessive. Psychosine (galactosylsphingosine) accumulation is neurotoxic and
drives demyelination. Many pathogenic missense variants across the gene (UniProt lists
dozens of KRB variants). Four clinical forms; infantile form ~90% of cases.
GOA MF term present and current: GO:0004336 galactosylceramidase activity (verified via
OLS, not obsolete). This is the core MF used in core_functions.
Core BP: GO:0006683 galactosylceramide catabolic process (verified current).
Locations: GO:0005764 lysosome, GO:0043202 lysosomal lumen (both verified current).
Notes on individual annotations:
- PMID:15657896 is a review on GALC in cancer, annotated IDA to GO:0006683. IDA on a
review is unusual, but it does correctly describe GALC degrading galactosylcerebroside to
ceramide. Not a core-defining primary experiment; keep as non-core / accept the biology
but flag the evidence type. Per policy do NOT REMOVE (can't see full curator context) —
accept the biology, note the review nature.
- GO:0030149 sphingolipid catabolic process (IDA, PMID:8281145): broader parent-type BP;
GALC does act in sphingolipid catabolism (galactosylceramide is a glycosphingolipid).
Keep as non-core (galactosylceramide catabolic process is the precise term).
- GO:0046479 glycosphingolipid catabolic process (TAS, Reactome): correct, broader than the
precise galactosylceramide catabolic process; keep as non-core.
- Reactome/GO_REF/IEA/ISS/IBA MF and BP annotations all consistent; accept.
Falcon deep research is OUT OF CREDITS (HTTP 402) — no -deep-research-falcon.md generated.
Review grounded in GALC-uniprot.txt, GALC-goa.tsv, and cached publications/PMID_*.md.