AGAL_MOUSE
ID AGAL_MOUSE Reviewed; 419 AA.
AC P51569;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Alpha-galactosidase A {ECO:0000305};
DE EC=3.2.1.22 {ECO:0000250|UniProtKB:P06280};
DE AltName: Full=Alpha-D-galactosidase A;
DE AltName: Full=Alpha-D-galactoside galactohydrolase;
DE AltName: Full=Galactosylgalactosylglucosylceramidase GLA {ECO:0000250|UniProtKB:P06280};
DE AltName: Full=Melibiase;
DE Flags: Precursor;
GN Name=Gla {ECO:0000312|MGI:MGI:1347344}; Synonyms=Ags;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney;
RX PubMed=8543175; DOI=10.1016/0378-1119(95)00592-7;
RA Ohshima T., Murray G.J., Nagle J.W., Quirk J.M., Kraus M.H., Barton N.W.,
RA Brady R.O., Kulkarni A.B.;
RT "Structural organization and expression of the mouse gene encoding alpha-
RT galactosidase A.";
RL Gene 166:277-280(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=C129;
RX PubMed=7626884; DOI=10.1007/bf00364796;
RA Oeltjen J.C., Liu X., Lu J., Allen R.C., Muzny D.M., Belmont J.W.,
RA Gibbs R.A.;
RT "Sixty-nine kilobases of contiguous human genomic sequence containing the
RT alpha-galactosidase A and Bruton's tyrosine kinase loci.";
RL Mamm. Genome 6:334-338(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=8733892; DOI=10.1006/bmme.1996.0020;
RA Gotlib R.W., Bishop D.F., Wang A.M., Zeidner K.M., Ioannou Y.I.,
RA Adler D.A., Disteche C.M., Desnick R.J.;
RT "The entire genomic sequence and cDNA expression of mouse alpha-
RT galactosidase A.";
RL Biochem. Mol. Med. 57:139-148(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-186, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Catalyzes the hydrolysis of glycosphingolipids and
CC participates in their degradation in the lysosome.
CC {ECO:0000250|UniProtKB:P06280}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of terminal, non-reducing alpha-D-galactose
CC residues in alpha-D-galactosides, including galactose
CC oligosaccharides, galactomannans and galactolipids.; EC=3.2.1.22;
CC Evidence={ECO:0000250|UniProtKB:P06280};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=globoside Gb3Cer (d18:1(4E)) + H2O = a beta-D-Gal-(1->4)-beta-
CC D-Glc-(1<->1)-Cer(d18:1(4E)) + D-galactose; Xref=Rhea:RHEA:21112,
CC ChEBI:CHEBI:4139, ChEBI:CHEBI:15377, ChEBI:CHEBI:17950,
CC ChEBI:CHEBI:18313; Evidence={ECO:0000250|UniProtKB:P06280};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21113;
CC Evidence={ECO:0000250|UniProtKB:P06280};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=globoside Gb3Cer + H2O = beta-D-galactosyl-(1->4)-beta-D-
CC glucosyl-(1<->1)-ceramide + D-galactose; Xref=Rhea:RHEA:48020,
CC ChEBI:CHEBI:4139, ChEBI:CHEBI:15377, ChEBI:CHEBI:79208,
CC ChEBI:CHEBI:88154; Evidence={ECO:0000250|UniProtKB:P06280};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48021;
CC Evidence={ECO:0000250|UniProtKB:P06280};
CC -!- ACTIVITY REGULATION: Galactosylgalactosylglucosylceramidase activity is
CC stimulated by saposin B and ammonium chloride.
CC {ECO:0000250|UniProtKB:P06280}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P06280}.
CC -!- SUBCELLULAR LOCATION: Lysosome.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 27 family. {ECO:0000305}.
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DR EMBL; U34071; AAA96749.1; -; mRNA.
DR EMBL; L46651; AAA74453.1; -; Genomic_DNA.
DR EMBL; U58105; AAB47244.1; -; Genomic_DNA.
DR EMBL; U50716; AAC52584.1; -; mRNA.
DR EMBL; U50715; AAC52583.1; -; Genomic_DNA.
DR EMBL; BC009021; AAH09021.1; -; mRNA.
DR PIR; JC4522; JC4522.
DR AlphaFoldDB; P51569; -.
DR SMR; P51569; -.
DR STRING; 10090.ENSMUSP00000033621; -.
DR CAZy; GH27; Glycoside Hydrolase Family 27.
DR GlyGen; P51569; 3 sites.
DR iPTMnet; P51569; -.
DR PhosphoSitePlus; P51569; -.
DR EPD; P51569; -.
DR MaxQB; P51569; -.
DR PaxDb; P51569; -.
DR PeptideAtlas; P51569; -.
DR PRIDE; P51569; -.
DR ProteomicsDB; 296076; -.
DR Antibodypedia; 377; 439 antibodies from 34 providers.
DR Ensembl; ENSMUST00000033621; ENSMUSP00000033621; ENSMUSG00000031266.
DR MGI; MGI:1347344; Gla.
DR VEuPathDB; HostDB:ENSMUSG00000031266; -.
DR eggNOG; KOG2366; Eukaryota.
DR GeneTree; ENSGT00390000008751; -.
DR InParanoid; P51569; -.
DR Reactome; R-MMU-1660662; Glycosphingolipid metabolism.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR SABIO-RK; P51569; -.
DR ChiTaRS; Gla; mouse.
DR PRO; PR:P51569; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; P51569; protein.
DR Bgee; ENSMUSG00000031266; Expressed in placenta labyrinth and 205 other tissues.
DR ExpressionAtlas; P51569; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:MGI.
DR GO; GO:0004557; F:alpha-galactosidase activity; IDA:MGI.
DR GO; GO:0003824; F:catalytic activity; ISS:UniProtKB.
DR GO; GO:0017041; F:galactosylgalactosylglucosylceramidase activity; ISS:UniProtKB.
DR GO; GO:0016787; F:hydrolase activity; IDA:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0052692; F:raffinose alpha-galactosidase activity; IEA:UniProtKB-EC.
DR GO; GO:0005102; F:signaling receptor binding; ISS:UniProtKB.
DR GO; GO:0016139; P:glycoside catabolic process; IBA:GO_Central.
DR GO; GO:0046479; P:glycosphingolipid catabolic process; ISO:MGI.
DR GO; GO:0046477; P:glycosylceramide catabolic process; IDA:MGI.
DR GO; GO:0045019; P:negative regulation of nitric oxide biosynthetic process; IMP:UniProtKB.
DR GO; GO:0051001; P:negative regulation of nitric-oxide synthase activity; IMP:UniProtKB.
DR GO; GO:0009311; P:oligosaccharide metabolic process; ISS:UniProtKB.
DR CDD; cd14792; GH27; 1.
DR Gene3D; 2.60.40.1180; -; 1.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR002241; Glyco_hydro_27.
DR InterPro; IPR000111; Glyco_hydro_27/36_CS.
DR InterPro; IPR013780; Glyco_hydro_b.
DR InterPro; IPR017853; Glycoside_hydrolase_SF.
DR InterPro; IPR035373; Melibiase/NAGA_C.
DR PANTHER; PTHR11452; PTHR11452; 1.
DR Pfam; PF16499; Melibiase_2; 1.
DR Pfam; PF17450; Melibiase_2_C; 1.
DR PRINTS; PR00740; GLHYDRLASE27.
DR SUPFAM; SSF51445; SSF51445; 1.
DR PROSITE; PS00512; ALPHA_GALACTOSIDASE; 1.
PE 1: Evidence at protein level;
KW Disulfide bond; Glycoprotein; Glycosidase; Hydrolase; Lipid metabolism;
KW Lysosome; Phosphoprotein; Reference proteome; Signal.
FT SIGNAL 1..31
FT /evidence="ECO:0000250"
FT CHAIN 32..419
FT /note="Alpha-galactosidase A"
FT /id="PRO_0000001005"
FT ACT_SITE 170
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 231
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT BINDING 203..207
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 186
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18034455"
FT CARBOHYD 139
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 192
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 215
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT DISULFID 52..94
FT /evidence="ECO:0000250"
FT DISULFID 56..63
FT /evidence="ECO:0000250"
FT DISULFID 142..172
FT /evidence="ECO:0000250"
FT DISULFID 202..223
FT /evidence="ECO:0000250"
FT DISULFID 378..382
FT /evidence="ECO:0000250"
SQ SEQUENCE 419 AA; 47643 MW; BD5E6A99AC113613 CRC64;
MKLLSRDTRL VCELALCPLA LVFWSILGVR ALDNGLARTP TMGWLHWERF MCNLDCQEEP
DACISEQLFM QMAELMVSDG WRDAGYDYLC IDDCWMAPER DSKGRLQADP QRFPSGIKHL
ANYVHSKGLK LGIYADVGNK TCAGFPGSFG SYDIDAQTFA DWGVDLLKFD GCHCDSVVSL
ENGYKYMALA LNRTGRSIVY SCEWPLYLRP FHKPNYTDIQ YYCNHWRNFD DVYDSWESIK
NILSWTVVYQ KEIVEVAGPG SWNDPDMLVI GNFGLSWDQQ VTQMALWAIM AAPLLMSNDL
RQISSQAKAL LQNKDVIAIN QDPLGKQGYC FRKENHIEVW ERPLSNLAWA VAVRNLQEIG
GPCPYTIQIS SLGRGLACNP GCIITQLLPE KVHLGFYEWT LTLKTRVNPS GTVLFRLER
