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   24-JAN-2024, entry version 158.
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=a globoside Gb3Cer (d18:1(4E)) + H2O = a beta-D-Gal-(1->4)-
CC         beta-D-Glc-(1<->1)-Cer(d18:1(4E)) + D-galactose;
CC         Xref=Rhea:RHEA:21112, ChEBI:CHEBI:4139, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:17950, ChEBI:CHEBI:18313;
CC         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=a globoside Gb3Cer + H2O = a 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.ENSMUSP00000159121; -.
DR   CAZy; GH27; Glycoside Hydrolase Family 27.
DR   GlyCosmos; P51569; 3 sites, No reported glycans.
DR   GlyGen; P51569; 3 sites.
DR   iPTMnet; P51569; -.
DR   PhosphoSitePlus; P51569; -.
DR   EPD; P51569; -.
DR   MaxQB; P51569; -.
DR   PaxDb; 10090-ENSMUSP00000033621; -.
DR   PeptideAtlas; P51569; -.
DR   ProteomicsDB; 296076; -.
DR   Pumba; P51569; -.
DR   Antibodypedia; 377; 485 antibodies from 34 providers.
DR   Ensembl; ENSMUST00000033621.8; ENSMUSP00000033621.8; ENSMUSG00000031266.8.
DR   AGR; MGI:1347344; -.
DR   MGI; MGI:1347344; Gla.
DR   VEuPathDB; HostDB:ENSMUSG00000031266; -.
DR   eggNOG; KOG2366; Eukaryota.
DR   GeneTree; ENSGT00390000008751; -.
DR   InParanoid; P51569; -.
DR   Reactome; R-MMU-6798695; Neutrophil degranulation.
DR   Reactome; R-MMU-9840310; Glycosphingolipid catabolism.
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 208 other cell types or 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:0016936; F:galactoside binding; ISO:MGI.
DR   GO; GO:0016787; F:hydrolase activity; IDA:MGI.
DR   GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR   GO; GO:0005102; F:signaling receptor binding; ISS:UniProtKB.
DR   GO; GO:0035904; P:aorta development; IMP:MGI.
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; 3.20.20.70; Aldolase class I; 1.
DR   Gene3D; 2.60.40.1180; Golgi alpha-mannosidase II; 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:SF14; ALPHA-GALACTOSIDASE A; 1.
DR   PANTHER; PTHR11452; ALPHA-GALACTOSIDASE/ALPHA-N-ACETYLGALACTOSAMINIDASE; 1.
DR   Pfam; PF16499; Melibiase_2; 1.
DR   Pfam; PF17450; Melibiase_2_C; 1.
DR   PRINTS; PR00740; GLHYDRLASE27.
DR   SUPFAM; SSF51445; (Trans)glycosidases; 1.
DR   SUPFAM; SSF51011; Glycosyl hydrolase domain; 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
//