ID   LYAG_BOVIN              Reviewed;         937 AA.
AC   Q9MYM4;
DT   28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   24-JAN-2024, entry version 128.
DE   RecName: Full=Lysosomal alpha-glucosidase;
DE            EC=3.2.1.20 {ECO:0000250|UniProtKB:P10253};
DE   AltName: Full=Acid maltase;
DE   Flags: Precursor;
GN   Name=GAA;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, VARIANTS ARG-103;
RP   ILE-208; TRP-451; GLY-702; PHE-779 AND PRO-825, AND INVOLVEMENT IN
RP   GENERALIZED GLYCOGENOSIS.
RC   STRAIN=Brahman, and Poll Shorthorn;
RX   PubMed=10723725; DOI=10.1007/s003350010038;
RA   Dennis J.A., Moran C., Healy P.J.;
RT   "The bovine alpha-glucosidase gene: coding region, genomic structure, and
RT   mutations that cause bovine generalized glycogenosis.";
RL   Mamm. Genome 11:206-212(2000).
CC   -!- FUNCTION: Essential for the degradation of glycogen in lysosomes
CC       (PubMed:10723725). Has highest activity on alpha-1,4-linked glycosidic
CC       linkages, but can also hydrolyze alpha-1,6-linked glucans.
CC       {ECO:0000250|UniProtKB:P10253, ECO:0000269|PubMed:10723725}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Hydrolysis of terminal, non-reducing (1->4)-linked alpha-D-
CC         glucose residues with release of alpha-D-glucose.; EC=3.2.1.20;
CC         Evidence={ECO:0000250|UniProtKB:P10253};
CC   -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000250|UniProtKB:P10253}. Lysosome
CC       membrane {ECO:0000250|UniProtKB:P10253}.
CC   -!- DISEASE: Note=Defects in GAA are the cause of generalized glycogenosis.
CC       It is characterized by a accumulation of glycogen within lysosomes.
CC       This disease has been reported in Brahman and Shorthorn breeds. Its
CC       most common clinical representation is a failure to thrive, progressive
CC       muscular weakness and an un-coordinated gait.
CC       {ECO:0000269|PubMed:10723725}.
CC   -!- SIMILARITY: Belongs to the glycosyl hydrolase 31 family. {ECO:0000305}.
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DR   EMBL; AF171665; AAF81636.1; -; mRNA.
DR   EMBL; AF171666; AAF81637.1; -; Genomic_DNA.
DR   RefSeq; NP_776338.1; NM_173913.2.
DR   RefSeq; XP_005221193.1; XM_005221136.3.
DR   AlphaFoldDB; Q9MYM4; -.
DR   SMR; Q9MYM4; -.
DR   STRING; 9913.ENSBTAP00000021325; -.
DR   BindingDB; Q9MYM4; -.
DR   ChEMBL; CHEMBL2974; -.
DR   CAZy; GH31; Glycoside Hydrolase Family 31.
DR   GlyCosmos; Q9MYM4; 9 sites, No reported glycans.
DR   PaxDb; 9913-ENSBTAP00000021325; -.
DR   PeptideAtlas; Q9MYM4; -.
DR   Ensembl; ENSBTAT00000021325.6; ENSBTAP00000021325.5; ENSBTAG00000016021.6.
DR   GeneID; 280798; -.
DR   KEGG; bta:280798; -.
DR   CTD; 2548; -.
DR   VEuPathDB; HostDB:ENSBTAG00000016021; -.
DR   VGNC; VGNC:29182; GAA.
DR   eggNOG; KOG1065; Eukaryota.
DR   GeneTree; ENSGT00940000159355; -.
DR   HOGENOM; CLU_000631_11_2_1; -.
DR   InParanoid; Q9MYM4; -.
DR   OMA; PYVINHD; -.
DR   TreeFam; TF314577; -.
DR   Reactome; R-BTA-6798695; Neutrophil degranulation.
DR   Reactome; R-BTA-70221; Glycogen breakdown (glycogenolysis).
DR   PRO; PR:Q9MYM4; -.
DR   Proteomes; UP000009136; Chromosome 19.
DR   Bgee; ENSBTAG00000016021; Expressed in biceps femoris and 104 other cell types or tissues.
DR   GO; GO:0120282; C:autolysosome lumen; IEA:Ensembl.
DR   GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0004558; F:alpha-1,4-glucosidase activity; ISS:UniProtKB.
DR   GO; GO:0030246; F:carbohydrate binding; IEA:InterPro.
DR   GO; GO:0032450; F:maltose alpha-glucosidase activity; IEA:UniProtKB-EC.
DR   GO; GO:0035904; P:aorta development; IEA:Ensembl.
DR   GO; GO:0060048; P:cardiac muscle contraction; IEA:Ensembl.
DR   GO; GO:0002086; P:diaphragm contraction; IEA:Ensembl.
DR   GO; GO:0005980; P:glycogen catabolic process; ISS:UniProtKB.
DR   GO; GO:0061723; P:glycophagy; IEA:Ensembl.
DR   GO; GO:0003007; P:heart morphogenesis; IEA:Ensembl.
DR   GO; GO:0007626; P:locomotory behavior; IEA:Ensembl.
DR   GO; GO:0007040; P:lysosome organization; IBA:GO_Central.
DR   GO; GO:0046716; P:muscle cell cellular homeostasis; IEA:Ensembl.
DR   GO; GO:0050885; P:neuromuscular process controlling balance; IEA:Ensembl.
DR   GO; GO:0050884; P:neuromuscular process controlling posture; IEA:Ensembl.
DR   GO; GO:0002026; P:regulation of the force of heart contraction; IEA:Ensembl.
DR   GO; GO:0009888; P:tissue development; IEA:Ensembl.
DR   GO; GO:0043181; P:vacuolar sequestering; IEA:Ensembl.
DR   CDD; cd06602; GH31_MGAM_SI_GAA; 1.
DR   CDD; cd14752; GH31_N; 1.
DR   CDD; cd00111; Trefoil; 1.
DR   Gene3D; 3.20.20.80; Glycosidases; 1.
DR   Gene3D; 2.60.40.1760; glycosyl hydrolase (family 31); 1.
DR   Gene3D; 2.60.40.1180; Golgi alpha-mannosidase II; 2.
DR   Gene3D; 4.10.110.10; Spasmolytic Protein, domain 1; 1.
DR   InterPro; IPR011013; Gal_mutarotase_sf_dom.
DR   InterPro; IPR030458; Glyco_hydro_31_AS.
DR   InterPro; IPR048395; Glyco_hydro_31_C.
DR   InterPro; IPR030459; Glyco_hydro_31_CS.
DR   InterPro; IPR025887; Glyco_hydro_31_N_dom.
DR   InterPro; IPR000322; Glyco_hydro_31_TIM.
DR   InterPro; IPR013780; Glyco_hydro_b.
DR   InterPro; IPR017853; Glycoside_hydrolase_SF.
DR   InterPro; IPR017957; P_trefoil_CS.
DR   InterPro; IPR000519; P_trefoil_dom.
DR   InterPro; IPR044913; P_trefoil_dom_sf.
DR   PANTHER; PTHR22762; ALPHA-GLUCOSIDASE; 1.
DR   PANTHER; PTHR22762:SF92; LYSOSOMAL ALPHA-GLUCOSIDASE; 1.
DR   Pfam; PF13802; Gal_mutarotas_2; 1.
DR   Pfam; PF01055; Glyco_hydro_31_2nd; 1.
DR   Pfam; PF21365; Glyco_hydro_31_3rd; 1.
DR   Pfam; PF00088; Trefoil; 1.
DR   SMART; SM00018; PD; 1.
DR   SUPFAM; SSF51445; (Trans)glycosidases; 1.
DR   SUPFAM; SSF74650; Galactose mutarotase-like; 1.
DR   SUPFAM; SSF51011; Glycosyl hydrolase domain; 1.
DR   SUPFAM; SSF57492; Trefoil; 1.
DR   PROSITE; PS00129; GLYCOSYL_HYDROL_F31_1; 1.
DR   PROSITE; PS00707; GLYCOSYL_HYDROL_F31_2; 1.
DR   PROSITE; PS00025; P_TREFOIL_1; 1.
DR   PROSITE; PS51448; P_TREFOIL_2; 1.
PE   2: Evidence at transcript level;
KW   Disulfide bond; Glycoprotein; Glycosidase; Hydrolase; Lysosome; Membrane;
KW   Reference proteome; Signal.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000255"
FT   PROPEP          24..60
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000260438"
FT   CHAIN           61..937
FT                   /note="Lysosomal alpha-glucosidase"
FT                   /id="PRO_0000260439"
FT   DOMAIN          68..118
FT                   /note="P-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00779"
FT   ACT_SITE        505
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10066"
FT   ACT_SITE        508
FT                   /evidence="ECO:0000250"
FT   BINDING         391
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P10253"
FT   BINDING         587
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P10253"
FT   BINDING         603
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P10253"
FT   BINDING         661
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P10253"
FT   CARBOHYD        127
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        220
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        259
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        377
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        457
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        639
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        867
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        888
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        910
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        70..97
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00779"
FT   DISULFID        80..96
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00779"
FT   DISULFID        91..114
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00779"
FT   DISULFID        520..545
FT                   /evidence="ECO:0000250|UniProtKB:P10253"
FT   DISULFID        634..645
FT                   /evidence="ECO:0000250|UniProtKB:P10253"
FT   VARIANT         103
FT                   /note="W -> R"
FT                   /evidence="ECO:0000269|PubMed:10723725"
FT   VARIANT         208
FT                   /note="V -> I"
FT                   /evidence="ECO:0000269|PubMed:10723725"
FT   VARIANT         451
FT                   /note="R -> W (70% to 80% decrease in activity)"
FT                   /evidence="ECO:0000269|PubMed:10723725"
FT   VARIANT         702
FT                   /note="R -> G"
FT                   /evidence="ECO:0000269|PubMed:10723725"
FT   VARIANT         779
FT                   /note="L -> F"
FT                   /evidence="ECO:0000269|PubMed:10723725"
FT   VARIANT         825
FT                   /note="H -> P"
FT                   /evidence="ECO:0000269|PubMed:10723725"
SQ   SEQUENCE   937 AA;  104757 MW;  B7E9A2D66BAF5026 CRC64;
     MMRWPPCSRP LLGVCTLLSL ALLGHILLHD LEVVPRELRG FSQDEIHQAC QPGASSPECR
     GSPRAAPTQC DLPPNSRFDC APDKGITPQQ CEARGCCYMP AEWPPDAQMG QPWCFFPPSY
     PSYRLENLTT TETGYTATLT RAVPTFFPKD IMTLRLDMLM ETESRLHFTI KDPANRRYEV
     PLETPRVYSQ APFTLYSVEF SEEPFGVVVR RKLDGRVLLN TTVAPLFFAD QFLQLSTSLP
     SQHITGLAEH LGSLMLSTNW TKITLWNRDI APEPNVNLYG SHPFYLVLED GGLAHGVFLL
     NSNAMDVVLQ PSPALSWRST GGILDVYIFL GPEPKSVVQQ YLDVVGYPFM PPYWGLGFHL
     CRWGYSTSAI TRQVVENMTR AYFPLDVQWN DLDYMDARRD FTFNKDHFGD FPAMVQELHQ
     GGRRYIMIVD PAISSSGPAG TYRPYDEGLR RGVFITNETG QPLIGQVWPG LTAFPDFTNP
     ETLDWWQDMV TEFHAQVPFD GMWIDMNEPS NFVRGSVDGC PDNSLENPPY LPGVVGGTLR
     AATICASSHQ FLSTHYDLHN LYGLTEALAS HRALVKARGM RPFVISRSTF AGHGRYSGHW
     TGDVWSNWEQ LSYSVPEILL FNLLGVPLVG ADICGFLGNT SEELCVRWTQ LGAFYPFMRN
     HNALNSQPQE PYRFSETAQQ AMRKAFTLRY VLLPYLYTLF HRAHVRGETV ARPLFLEFPE
     DPSTWTVDRQ LLWGEALLIT PVLEAEKVEV TGYFPQGTWY DLQTVPMEAF GSLPPPAPLT
     SVIHSKGQWV TLSAPLDTIN VHLRAGHIIP MQGPALTTTE SRKQHMALAV ALTASGEAQG
     ELFWDDGESL GVLDGGDYTQ LIFLAKNNTF VNKLVHVSSE GASLQLRNVT VLGVATAPQQ
     VLCNSVPVSN FTFSPDTETL AIPVSLTMGE QFVISWS
//