GALC_CANLF
ID GALC_CANLF Reviewed; 669 AA.
AC P54804;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=Galactocerebrosidase {ECO:0000250|UniProtKB:P54803};
DE Short=GALCERase;
DE EC=3.2.1.46 {ECO:0000269|PubMed:8661004};
DE AltName: Full=Galactocerebroside beta-galactosidase;
DE AltName: Full=Galactosylceramidase {ECO:0000250|UniProtKB:P54803};
DE AltName: Full=Galactosylceramide beta-galactosidase;
DE Flags: Precursor;
GN Name=GALC {ECO:0000250|UniProtKB:P54803};
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, ROLE IN DISEASE,
RP AND VARIANTS GLD SER-158 AND SER-639.
RX PubMed=8661004; DOI=10.1006/geno.1996.0220;
RA Victoria T., Rafi M.A., Wenger D.A.;
RT "Cloning of the canine GALC cDNA and identification of the mutation causing
RT globoid cell leukodystrophy in West Highland White and Cairn terriers.";
RL Genomics 33:457-462(1996).
CC -!- FUNCTION: Hydrolyzes the galactose ester bonds of glycolipids such as
CC galactosylceramide and galactosylsphingosine (PubMed:8661004). Enzyme
CC with very low activity responsible for the lysosomal catabolism of
CC galactosylceramide, a major lipid in myelin, kidney and epithelial
CC cells of small intestine and colon (By similarity).
CC {ECO:0000250|UniProtKB:P54803, ECO:0000269|PubMed:8661004}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a beta-D-galactosyl-(1<->1')-N-acylsphing-4-enine + H2O = an
CC N-acylsphing-4-enine + D-galactose; Xref=Rhea:RHEA:14297,
CC ChEBI:CHEBI:4139, ChEBI:CHEBI:15377, ChEBI:CHEBI:18390,
CC ChEBI:CHEBI:52639; EC=3.2.1.46;
CC Evidence={ECO:0000269|PubMed:8661004};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-galactosyl-(1<->1)-sphing-4-enine + H2O = D-galactose +
CC sphing-4-enine; Xref=Rhea:RHEA:43908, ChEBI:CHEBI:4139,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:57756, ChEBI:CHEBI:57934;
CC Evidence={ECO:0000250|UniProtKB:P54803};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43909;
CC Evidence={ECO:0000250|UniProtKB:P54803};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a D-galactosylceramide + H2O = an N-acyl-sphingoid base + D-
CC galactose; Xref=Rhea:RHEA:43412, ChEBI:CHEBI:4139, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:36498, ChEBI:CHEBI:83273;
CC Evidence={ECO:0000250|UniProtKB:P54818};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43413;
CC Evidence={ECO:0000250|UniProtKB:P54818};
CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000250}.
CC -!- DISEASE: Note=Defects in GALC are the cause of globoid cell
CC leukodystrophy (GLD). This deficiency results in the insufficient
CC catabolism of several galactolipids that are important in the
CC production of normal myelin.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 59 family. {ECO:0000305}.
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DR EMBL; L76184; AAB37752.1; -; mRNA.
DR RefSeq; NP_001003238.1; NM_001003238.1.
DR AlphaFoldDB; P54804; -.
DR SMR; P54804; -.
DR STRING; 9612.ENSCAFP00000031633; -.
DR CAZy; GH59; Glycoside Hydrolase Family 59.
DR PaxDb; P54804; -.
DR PRIDE; P54804; -.
DR GeneID; 403916; -.
DR KEGG; cfa:403916; -.
DR CTD; 2581; -.
DR eggNOG; ENOG502QQ1Q; Eukaryota.
DR InParanoid; P54804; -.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0005764; C:lysosome; IBA:GO_Central.
DR GO; GO:0004336; F:galactosylceramidase activity; ISS:UniProtKB.
DR GO; GO:0006683; P:galactosylceramide catabolic process; ISS:UniProtKB.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR001286; Glyco_hydro_59.
DR InterPro; IPR035394; Glyco_hydro_59_dom.
DR InterPro; IPR017853; Glycoside_hydrolase_SF.
DR PANTHER; PTHR15172; PTHR15172; 1.
DR Pfam; PF02057; Glyco_hydro_59; 1.
DR Pfam; PF17387; Glyco_hydro_59M; 1.
DR PRINTS; PR00850; GLHYDRLASE59.
DR SUPFAM; SSF51445; SSF51445; 1.
PE 1: Evidence at protein level;
KW Disease variant; Disulfide bond; Glycoprotein; Glycosidase; Hydrolase;
KW Lipid degradation; Lipid metabolism; Lysosome; Reference proteome; Signal;
KW Sphingolipid metabolism.
FT SIGNAL 1..26
FT /evidence="ECO:0000250"
FT CHAIN 27..669
FT /note="Galactocerebrosidase"
FT /id="PRO_0000012229"
FT ACT_SITE 182
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT ACT_SITE 258
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT BINDING 93
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 135
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 181
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 380
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT CARBOHYD 363
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 387
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 543
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 586
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 271..378
FT /evidence="ECO:0000250"
FT VARIANT 158
FT /note="Y -> S (in GLD)"
FT /evidence="ECO:0000269|PubMed:8661004"
FT VARIANT 639
FT /note="P -> S (in GLD)"
FT /evidence="ECO:0000269|PubMed:8661004"
SQ SEQUENCE 669 AA; 75317 MW; 60E298B024EE154C CRC64;
MTAAAGSAGH AAVPLLLCAL LVPGGAYVLD DSDGLGREFD GVGAVSGGGA TSRLLVNYPE
PYRSQILDYL FKPNFGASLH ILKVEIGGDG QTTDGTEPSH MHYALDENFF RGYEWWLMKE
AKKRNPNIIL MGLPWSFPGW IGKGFNWPYV NLQLTAYYIM TWIVGAKHYH DLDIDYIGIW
NERSFDINYI KVLRRMLNYQ GLDRVKIIAS DNLWEPISAS MLLDSELLKV IDVIGAHYPG
THTVKDAKLT KKKLWSSEDF STLNSDVGAG CLGRILNQNY VNGYMTATIA WNLVASYYEQ
LPYGRCGLMT AQEPWSGHYV VESPIWVSAH TTQFTQPGWY YLKTVGHLEK GGSYVALTDG
LGNLTIIVET MSHKQSACIR PFLPYFNVSR QFATFVLKGS FSEIPELQVW YTKLGKPSER
YLFKQLDSLW LLDSSSTFTL ELQEDEIFTL TTLTVGSKGS YPLPPKSEPF PQIYEDDFDV
DYPFFSEAPN FADQTGVFEY FTNIEDPGEH RFTLRQVLNQ RPITWAADAY NTISIIGDYK
WSNLTVRCDV YIETPEKGGV FIAGRVNKGG ILIRSARGIF FWIFANGTYR VTGDLAGWVI
YALGRVDVTA KKWYTLTLII KGRLSSGMLN GKTVWKNIPV SFPKNGWAAI GTHSFEFAQF
DNFHVEATR
