LYAG_BOVIN
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 03-AUG-2022, entry version 122.
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 PaxDb; Q9MYM4; -.
DR PeptideAtlas; Q9MYM4; -.
DR PRIDE; Q9MYM4; -.
DR Ensembl; ENSBTAT00000021325; ENSBTAP00000021325; ENSBTAG00000016021.
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; YDTYTRG; -.
DR OrthoDB; 151244at2759; -.
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 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:0004553; F:hydrolase activity, hydrolyzing O-glycosyl compounds; IBA:GO_Central.
DR GO; GO:0032450; F:maltose alpha-glucosidase activity; IEA:UniProtKB-EC.
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; cd00111; Trefoil; 1.
DR Gene3D; 2.60.40.1180; -; 2.
DR Gene3D; 4.10.110.10; -; 1.
DR InterPro; IPR031727; Gal_mutarotase_N.
DR InterPro; IPR011013; Gal_mutarotase_sf_dom.
DR InterPro; IPR000322; Glyco_hydro_31.
DR InterPro; IPR030458; Glyco_hydro_31_AS.
DR InterPro; IPR030459; Glyco_hydro_31_CS.
DR InterPro; IPR025887; Glyco_hydro_31_N_dom.
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 Pfam; PF13802; Gal_mutarotas_2; 1.
DR Pfam; PF01055; Glyco_hydro_31; 1.
DR Pfam; PF16863; NtCtMGAM_N; 1.
DR Pfam; PF00088; Trefoil; 1.
DR SMART; SM00018; PD; 1.
DR SUPFAM; SSF51445; SSF51445; 1.
DR SUPFAM; SSF57492; SSF57492; 1.
DR SUPFAM; SSF74650; SSF74650; 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
