GALC_MACMU
ID GALC_MACMU Reviewed; 685 AA.
AC O02791;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 2.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Galactocerebrosidase {ECO:0000250|UniProtKB:P54803};
DE Short=GALCERase;
DE EC=3.2.1.46 {ECO:0000269|PubMed:9192853};
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 Macaca mulatta (Rhesus macaque).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9544;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP ROLE IN DISEASE.
RX PubMed=9192853; DOI=10.1006/geno.1997.4744;
RA Luzi P., Rafi M.A., Victoria T., Baskin G.B., Wenger D.A.;
RT "Characterization of the rhesus monkey galactocerebrosidase (GALC) cDNA and
RT gene and identification of the mutation causing globoid cell leukodystrophy
RT (Krabbe disease) in this primate.";
RL Genomics 42:319-324(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-223.
RA Wang H.-Y., Chien H.-C., Osada N., Hashimoto K., Sugano S., Gojobori T.,
RA Chou C.-K., Tsai S.-F., Wu C.-I., Shen C.-K.J.;
RL Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Hydrolyzes the galactose ester bonds of glycolipids such as
CC galactosylceramide and galactosylsphingosine (PubMed:9192853). 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:9192853}.
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:9192853};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14298;
CC Evidence={ECO:0000305|PubMed:9192853};
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); also known as Krabbe disease. This deficiency
CC results in the insufficient catabolism of several galactolipids that
CC are important in the production of normal myelin.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 59 family. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-17 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB58575.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; U87477; AAB58575.1; ALT_INIT; Genomic_DNA.
DR EMBL; U87462; AAB58575.1; JOINED; Genomic_DNA.
DR EMBL; U87463; AAB58575.1; JOINED; Genomic_DNA.
DR EMBL; U87464; AAB58575.1; JOINED; Genomic_DNA.
DR EMBL; U87465; AAB58575.1; JOINED; Genomic_DNA.
DR EMBL; U87466; AAB58575.1; JOINED; Genomic_DNA.
DR EMBL; U87467; AAB58575.1; JOINED; Genomic_DNA.
DR EMBL; U87468; AAB58575.1; JOINED; Genomic_DNA.
DR EMBL; U87469; AAB58575.1; JOINED; Genomic_DNA.
DR EMBL; U87470; AAB58575.1; JOINED; Genomic_DNA.
DR EMBL; U87471; AAB58575.1; JOINED; Genomic_DNA.
DR EMBL; U87472; AAB58575.1; JOINED; Genomic_DNA.
DR EMBL; U87473; AAB58575.1; JOINED; Genomic_DNA.
DR EMBL; U87474; AAB58575.1; JOINED; Genomic_DNA.
DR EMBL; U87475; AAB58575.1; JOINED; Genomic_DNA.
DR EMBL; U87476; AAB58575.1; JOINED; Genomic_DNA.
DR EMBL; U87628; AAB58576.1; -; mRNA.
DR EMBL; AB172678; -; NOT_ANNOTATED_CDS; mRNA.
DR RefSeq; NP_001037727.1; NM_001044262.2.
DR AlphaFoldDB; O02791; -.
DR SMR; O02791; -.
DR STRING; 9544.ENSMMUP00000022713; -.
DR CAZy; GH59; Glycoside Hydrolase Family 59.
DR Ensembl; ENSMMUT00000060256; ENSMMUP00000051400; ENSMMUG00000017261.
DR GeneID; 693322; -.
DR KEGG; mcc:693322; -.
DR CTD; 2581; -.
DR VEuPathDB; HostDB:ENSMMUG00000017261; -.
DR VGNC; VGNC:72867; GALC.
DR eggNOG; ENOG502QQ1Q; Eukaryota.
DR GeneTree; ENSGT00390000003303; -.
DR HOGENOM; CLU_015456_2_0_1; -.
DR InParanoid; O02791; -.
DR OMA; VASDNLW; -.
DR OrthoDB; 364933at2759; -.
DR TreeFam; TF312985; -.
DR BRENDA; 3.2.1.46; 3126.
DR Proteomes; UP000006718; Chromosome 7.
DR Bgee; ENSMMUG00000017261; Expressed in spermatid and 22 other tissues.
DR ExpressionAtlas; O02791; baseline.
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 GO; GO:0042552; P:myelination; IEA:Ensembl.
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 Disulfide bond; Glycoprotein; Glycosidase; Hydrolase; Lipid degradation;
KW Lipid metabolism; Lysosome; Reference proteome; Signal;
KW Sphingolipid metabolism.
FT SIGNAL 1..42
FT /evidence="ECO:0000250"
FT CHAIN 43..685
FT /note="Galactocerebrosidase"
FT /id="PRO_0000012231"
FT ACT_SITE 198
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT ACT_SITE 274
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT BINDING 109
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 151
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 197
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 396
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT CARBOHYD 143
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 379
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 403
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 451
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 556
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 559
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 602
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 287..394
FT /evidence="ECO:0000250"
SQ SEQUENCE 685 AA; 77090 MW; 6087E861AC784F13 CRC64;
MAEWLLSASR QRRVKAMTAA AGSAGRAAVP FLLCALLAPG GAYVLDDSDG LGREFDGIGA
VSGGGATSRL LVNYPEPYRS QILDYLFKPN FGASLHILKV EIGGDGQTTD GTEPSHMHYA
LDENYFRGYE WWLMKEAKKR NPNITLIGLP WSFPGWLGKG FDWPYVNLQL TAYYVVTWIV
GAKRYHDLDI DYIGIWNERS YNANYIKILR KMLNSQGLQR VKIIASDNLW ESISAAMLLD
AELFKVVDVI GAHYPGTHSV KDARLTGKKL WSSEDFSTLN SDTGAGCWGR ILNQNYVNGY
MTSTIAWNLV ASYYEQLPYG RCGLMTAQEP WSGHYVVESP VWVSAHTTQF TQPGWYYLKT
VGHLEKGGSY VALTDGLGNL TIIIETMSHK HSKCIRPFLP YFNVSQQFAT FVLKGSFSEI
PELQVWYTKL GKTSERFLFK QLDSLWLLDS NGSFTLKLQE DELFTLTTLT TGRKGSYLPP
PKSQRFPSTY KDDFNVDYPF FSEAPNFADQ TGVFEYFTNM EDPGEHHFTL RQVLNQRPIT
WAADASNTIS IIGDYNWTNL TIKCDVYIET PDTGGVFIAG RVNKGGILIR SARGIFFWIF
ANGSYRVTGD LAGWIIYALG HVEVTAKTWY TLTLTIKGRF ASGMLNDKSL WTDIPVNFPK
NGWAAIGTHS FEFAQFDNFH VEATR
