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Protein

Lysosomal alpha-glucosidase

Gene

GAA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Essential for the degradation of glycogen in lysosomes (PubMed:1856189, PubMed:7717400, PubMed:14695532, PubMed:18429042). Has highest activity on alpha-1,4-linked glycosidic linkages, but can also hydrolyze alpha-1,6-linked glucans (PubMed:29061980).5 Publications

Catalytic activityi

Hydrolysis of terminal, non-reducing (1->4)-linked alpha-D-glucose residues with release of alpha-D-glucose.4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei404Substrate1 Publication1
Active sitei518NucleophilePROSITE-ProRule annotation1 Publication1 Publication1
Active sitei521By similarity1
Binding sitei600Substrate1 Publication1
Binding sitei616Substrate1 Publication1
Binding sitei674Substrate1 Publication1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionGlycosidase, Hydrolase

Enzyme and pathway databases

BRENDAi3.2.1.20 2681
ReactomeiR-HSA-5357609 Glycogen storage disease type II (GAA)
R-HSA-6798695 Neutrophil degranulation
R-HSA-70221 Glycogen breakdown (glycogenolysis)

Protein family/group databases

CAZyiGH31 Glycoside Hydrolase Family 31

Names & Taxonomyi

Protein namesi
Recommended name:
Lysosomal alpha-glucosidase (EC:3.2.1.204 Publications)
Alternative name(s):
Acid maltase
Aglucosidase alfa
Cleaved into the following 2 chains:
Gene namesi
Name:GAA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000171298.12
HGNCiHGNC:4065 GAA
MIMi606800 gene
neXtProtiNX_P10253

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Lysosome, Membrane

Pathology & Biotechi

Involvement in diseasei

Glycogen storage disease 2 (GSD2)41 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA metabolic disorder with a broad clinical spectrum. The severe infantile form, or Pompe disease, presents at birth with massive accumulation of glycogen in muscle, heart and liver. Cardiomyopathy and muscular hypotonia are the cardinal features of this form whose life expectancy is less than two years. The juvenile and adult forms present as limb-girdle muscular dystrophy beginning in the lower limbs. Final outcome depends on respiratory muscle failure. Patients with the adult form can be free of clinical symptoms for most of their life but finally develop a slowly progressive myopathy.
See also OMIM:232300
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06856446S → P in GSD2. 1 PublicationCorresponds to variant dbSNP:rs777215354Ensembl.1
Natural variantiVAR_018078103C → G in GSD2; infantile form; severe; loss of activity; shows enzyme localization primarily in the ER-Golgi compartment suggesting that mutation could affect the normal processing and stability of the enzyme. 3 PublicationsCorresponds to variant dbSNP:rs398123174EnsemblClinVar.1
Natural variantiVAR_068567103C → R in GSD2. 1 Publication1
Natural variantiVAR_068568108C → G in GSD2. 1 Publication1
Natural variantiVAR_068569127C → F in GSD2. 1 Publication1
Natural variantiVAR_068570190R → H in GSD2. 1 PublicationCorresponds to variant dbSNP:rs528367092EnsemblClinVar.1
Natural variantiVAR_046467191Y → C in GSD2; extremely low residual enzymatic activity. 1 Publication1
Natural variantiVAR_029025208L → P in GSD2. 1 Publication1
Natural variantiVAR_068571217P → L in GSD2. 1 Publication1
Natural variantiVAR_018079219G → R in GSD2; infantile form; severe; loss of activity. 3 PublicationsCorresponds to variant dbSNP:rs370950728EnsemblClinVar.1
Natural variantiVAR_068574224R → P in GSD2. 1 Publication1
Natural variantiVAR_068575224R → Q in GSD2. 1 PublicationCorresponds to variant dbSNP:rs200210219Ensembl.1
Natural variantiVAR_029026224R → W in GSD2; infantile; mild partial loss of activity. 3 PublicationsCorresponds to variant dbSNP:rs757700700EnsemblClinVar.1
Natural variantiVAR_068576234T → K in GSD2. 2 Publications1
Natural variantiVAR_068577234T → R in GSD2. 1 Publication1
Natural variantiVAR_029027237A → V in GSD2. 1 PublicationCorresponds to variant dbSNP:rs121907944EnsemblClinVar.1
Natural variantiVAR_068578251S → L in GSD2. 1 PublicationCorresponds to variant dbSNP:rs200856561EnsemblClinVar.1
Natural variantiVAR_068579254S → L in GSD2. 1 PublicationCorresponds to variant dbSNP:rs577915581EnsemblClinVar.1
Natural variantiVAR_029028262E → K in GSD2; infantile; severe. 3 PublicationsCorresponds to variant dbSNP:rs201896815EnsemblClinVar.1
Natural variantiVAR_068580266P → S in GSD2. 1 Publication1
Natural variantiVAR_018080285P → R in GSD2; juvenile form; mild; partial loss of activity. 1 PublicationCorresponds to variant dbSNP:rs764622267EnsemblClinVar.1
Natural variantiVAR_068582285P → S in GSD2. 1 PublicationCorresponds to variant dbSNP:rs886042086EnsemblClinVar.1
Natural variantiVAR_068584291L → F in GSD2. 1 PublicationCorresponds to variant dbSNP:rs773417785Ensembl.1
Natural variantiVAR_068585291L → P in GSD2. 2 Publications1
Natural variantiVAR_018081292Y → C in GSD2; juvenile form; mild; partial loss of activity. 1 PublicationCorresponds to variant dbSNP:rs1057516600Ensembl.1
Natural variantiVAR_018082293G → R in GSD2; infantile form; severe; almost complete loss of activity. 3 PublicationsCorresponds to variant dbSNP:rs121907945EnsemblClinVar.1
Natural variantiVAR_004288299L → R in GSD2; infantile form. 1 PublicationCorresponds to variant dbSNP:rs121907940EnsemblClinVar.1
Natural variantiVAR_046468308H → L in GSD2. 1 Publication1
Natural variantiVAR_018083308H → P in GSD2; infantile form; severe; complete loss of activity. 1 Publication1
Natural variantiVAR_018084309G → R in GSD2; severe. 2 PublicationsCorresponds to variant dbSNP:rs543300039EnsemblClinVar.1
Natural variantiVAR_018085312L → R in GSD2; infantile form; severe; loss of activity. 1 Publication1
Natural variantiVAR_068587316N → I in GSD2. 1 Publication1
Natural variantiVAR_068588318M → K in GSD2. 1 Publication1
Natural variantiVAR_004289318M → T in GSD2; severe. 1 PublicationCorresponds to variant dbSNP:rs121907936EnsemblClinVar.1
Natural variantiVAR_029029324P → L in GSD2. 1 PublicationCorresponds to variant dbSNP:rs750030887EnsemblClinVar.1
Natural variantiVAR_029030330W → G in GSD2; infantile form; severe. 1 Publication1
Natural variantiVAR_068589335G → E in GSD2. 1 PublicationCorresponds to variant dbSNP:rs730880022EnsemblClinVar.1
Natural variantiVAR_068590335G → R in GSD2. 1 PublicationCorresponds to variant dbSNP:rs202095215Ensembl.1
Natural variantiVAR_068591347P → R in GSD2. 1 Publication1
Natural variantiVAR_018086355L → P in GSD2; infantile form; severe; loss of activity. 5 PublicationsCorresponds to variant dbSNP:rs766074609EnsemblClinVar.1
Natural variantiVAR_029031361P → L in GSD2; juvenile form; severe. 3 PublicationsCorresponds to variant dbSNP:rs755253527EnsemblClinVar.1
Natural variantiVAR_018087374C → R in GSD2; infantile form; severe; loss of activity. 1 Publication1
Natural variantiVAR_046469375R → L in GSD2; extremely low residual enzymatic activity. 1 PublicationCorresponds to variant dbSNP:rs142752477EnsemblClinVar.1
Natural variantiVAR_029032377G → R in GSD2; severe. Corresponds to variant dbSNP:rs752002666EnsemblClinVar.1
Natural variantiVAR_068594397P → L in GSD2. 1 PublicationCorresponds to variant dbSNP:rs776008078EnsemblClinVar.1
Natural variantiVAR_046470401Q → R in GSD2; extremely low residual enzymatic activity. 1 Publication1
Natural variantiVAR_004290402W → R in GSD2; severe. 1
Natural variantiVAR_029033404D → N in GSD2; severe. Corresponds to variant dbSNP:rs141533320Ensembl.1
Natural variantiVAR_018088405L → P in GSD2; infantile form; severe; loss of activity. 1 Publication1
Natural variantiVAR_029034408M → V in GSD2; juvenile form; severe. 2 PublicationsCorresponds to variant dbSNP:rs560575383EnsemblClinVar.1
Natural variantiVAR_068595419D → V in GSD2. 1 Publication1
Natural variantiVAR_070017431 – 433Missing in GSD2. 1 Publication3
Natural variantiVAR_029035437R → C in GSD2; juvenile form; severe. 1 PublicationCorresponds to variant dbSNP:rs770610356EnsemblClinVar.1
Natural variantiVAR_074277437R → H in GSD2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs150868652EnsemblClinVar.1
Natural variantiVAR_029036445A → P in GSD2. 1 Publication1
Natural variantiVAR_018089455Y → F in GSD2; juvenile form; almost complete loss of activity. 1 Publication1
Natural variantiVAR_068596457P → H in GSD2. 1 Publication1
Natural variantiVAR_029040457P → L in GSD2; juvenile form. 1 Publication1
Natural variantiVAR_018090459Missing in GSD2; infantile form; severe. 1 Publication1
Natural variantiVAR_004291478G → R in GSD2; severe; loss of activity. 2 PublicationsCorresponds to variant dbSNP:rs778068209EnsemblClinVar.1
Natural variantiVAR_004292481W → R in GSD2; severe; loss of activity. 2 PublicationsCorresponds to variant dbSNP:rs772883420EnsemblClinVar.1
Natural variantiVAR_068598482P → R in GSD2. 1 Publication1
Natural variantiVAR_068599483G → V in GSD2. 1 Publication1
Natural variantiVAR_068600486A → P in GSD2. 1 Publication1
Natural variantiVAR_029037489D → N in GSD2; severe. 2 PublicationsCorresponds to variant dbSNP:rs398123169EnsemblClinVar.1
Natural variantiVAR_004293519M → T in GSD2; severe; loss of activity. 1 PublicationCorresponds to variant dbSNP:rs786204720EnsemblClinVar.1
Natural variantiVAR_004294519M → V in GSD2. 1 Publication1
Natural variantiVAR_004295521E → K in GSD2; severe. 1 PublicationCorresponds to variant dbSNP:rs121907937EnsemblClinVar.1
Natural variantiVAR_068601521E → Q in GSD2. 1 Publication1
Natural variantiVAR_046471522P → A in GSD2; no residual enzymatic activity. 2 PublicationsCorresponds to variant dbSNP:rs1057517146Ensembl.1
Natural variantiVAR_068602522P → S in GSD2. 1 PublicationCorresponds to variant dbSNP:rs892129065Ensembl.1
Natural variantiVAR_068603523S → Y in GSD2. 1 Publication1
Natural variantiVAR_068604525F → Y in GSD2. 1 Publication1
Natural variantiVAR_004296529S → V in GSD2; mild; requires 2 nucleotide substitutions. 1 PublicationCorresponds to variant dbSNP:rs121907941EnsemblClinVar.1
Natural variantiVAR_004297545P → L in GSD2; mild; partial loss of activity. 4 PublicationsCorresponds to variant dbSNP:rs121907942EnsemblClinVar.1
Natural variantiVAR_018091549G → R in GSD2; juvenile form; mild; partial loss of activity. 2 Publications1
Natural variantiVAR_018092552L → P in GSD2; infantile/juvenile form; severe; loss of activity. 3 PublicationsCorresponds to variant dbSNP:rs779556619EnsemblClinVar.1
Natural variantiVAR_068605557I → F in GSD2. 1 Publication1
Natural variantiVAR_068606558C → S in GSD2. 2 Publications1
Natural variantiVAR_004298566S → P in GSD2; infantile form. 1 Publication1
Natural variantiVAR_070018568H → L in GSD2. 1 Publication1
Natural variantiVAR_068607570N → K in GSD2. 1 Publication1
Natural variantiVAR_068608572H → Q in GSD2. 1 PublicationCorresponds to variant dbSNP:rs772962666Ensembl.1
Natural variantiVAR_068609575Y → C in GSD2. 1 Publication1
Natural variantiVAR_018093575Y → S in GSD2; juvenile form. 1 Publication1
Natural variantiVAR_068610576G → R in GSD2. 1 Publication1
Natural variantiVAR_018094579E → K in GSD2; infantile form; severe; loss of activity. 1 PublicationCorresponds to variant dbSNP:rs991082382EnsemblClinVar.1
Natural variantiVAR_046472585R → M in GSD2. 1 Publication1
Natural variantiVAR_068612594R → H in GSD2. 1 PublicationCorresponds to variant dbSNP:rs775450536EnsemblClinVar.1
Natural variantiVAR_068613594R → P in GSD2. 2 PublicationsCorresponds to variant dbSNP:rs775450536EnsemblClinVar.1
Natural variantiVAR_046473599S → Y in GSD2; no residual enzymatic activity. 1 PublicationCorresponds to variant dbSNP:rs753505203EnsemblClinVar.1
Natural variantiVAR_018095600R → C in GSD2; juvenile form; loss of activity. 2 PublicationsCorresponds to variant dbSNP:rs764670084Ensembl.1
Natural variantiVAR_008689600R → H in GSD2; infantile form. Corresponds to variant dbSNP:rs377544304EnsemblClinVar.1
Natural variantiVAR_068614601S → L in GSD2. 2 PublicationsCorresponds to variant dbSNP:rs374470794EnsemblClinVar.1
Natural variantiVAR_068615602T → A in GSD2. 1 PublicationCorresponds to variant dbSNP:rs781484283Ensembl.1
Natural variantiVAR_046474607 – 612Missing in GSD2. 1 Publication6
Natural variantiVAR_018096607G → D in GSD2; infantile form; severe; loss of activity. 1 Publication1
Natural variantiVAR_068616610A → V in GSD2. 1 Publication1
Natural variantiVAR_029038612H → Q in GSD2. 1 Publication1
Natural variantiVAR_068618612H → Y in GSD2. 1 Publication1
Natural variantiVAR_068619614T → K in GSD2. 1 PublicationCorresponds to variant dbSNP:rs369531647EnsemblClinVar.1
Natural variantiVAR_008690615G → R in GSD2; infantile/adult form. 1 PublicationCorresponds to variant dbSNP:rs549029029EnsemblClinVar.1
Natural variantiVAR_046475619S → R in GSD2; loss of function of the mutant enzyme. 1 Publication1
Natural variantiVAR_068620627S → P in GSD2. 1 Publication1
Natural variantiVAR_068622635N → K in GSD2. 1 PublicationCorresponds to variant dbSNP:rs1414146587Ensembl.1
Natural variantiVAR_068623638G → V in GSD2. 1 Publication1
Natural variantiVAR_046476638G → W in GSD2. 2 PublicationsCorresponds to variant dbSNP:rs757617999EnsemblClinVar.1
Natural variantiVAR_074278641L → V in GSD2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1420043899Ensembl.1
Natural variantiVAR_004301643G → R in GSD2; infantile form. 5 PublicationsCorresponds to variant dbSNP:rs28937909EnsemblClinVar.1
Natural variantiVAR_004302645D → E in GSD2; infantile form; most common mutation; deficient in phosphorylation and in proteolytic processing. 3 PublicationsCorresponds to variant dbSNP:rs28940868EnsemblClinVar.1
Natural variantiVAR_004303645D → H in GSD2; almost complete loss of activity. 1 PublicationCorresponds to variant dbSNP:rs368438393EnsemblClinVar.1
Natural variantiVAR_004304645D → N in GSD2. 3 PublicationsCorresponds to variant dbSNP:rs368438393EnsemblClinVar.1
Natural variantiVAR_004305647C → W in GSD2. 3 PublicationsCorresponds to variant dbSNP:rs776948121EnsemblClinVar.1
Natural variantiVAR_068624648G → D in GSD2. 1 PublicationCorresponds to variant dbSNP:rs1448515860Ensembl.1
Natural variantiVAR_004306648G → S in GSD2. 1 PublicationCorresponds to variant dbSNP:rs536906561EnsemblClinVar.1
Natural variantiVAR_046477660R → H in GSD2; loss of function of the mutant enzyme. 1 PublicationCorresponds to variant dbSNP:rs374143224EnsemblClinVar.1
Natural variantiVAR_004307672R → Q in GSD2. 1 PublicationCorresponds to variant dbSNP:rs778418246EnsemblClinVar.1
Natural variantiVAR_046478672R → T in GSD2. 1 Publication1
Natural variantiVAR_004308672R → W in GSD2. 2 PublicationsCorresponds to variant dbSNP:rs757111744EnsemblClinVar.1
Natural variantiVAR_008692675Missing in GSD2; infantile form. 1
Natural variantiVAR_046479702R → C in GSD2; no enzymatic activity; shows enzyme localization primarily in the ER-Golgi compartment suggesting that mutation could affect the normal processing and stability of the enzyme. 1 PublicationCorresponds to variant dbSNP:rs786204645EnsemblClinVar.1
Natural variantiVAR_068626702R → L in GSD2. 1 PublicationCorresponds to variant dbSNP:rs398123172EnsemblClinVar.1
Natural variantiVAR_074279705L → P in GSD2; unknown pathological significance. 1 Publication1
Natural variantiVAR_004310725R → W in GSD2; adult form. 1 PublicationCorresponds to variant dbSNP:rs121907938EnsemblClinVar.1
Natural variantiVAR_068629737T → N in GSD2. 1 PublicationCorresponds to variant dbSNP:rs1381005435Ensembl.1
Natural variantiVAR_068630743Q → K in GSD2. 1 Publication1
Natural variantiVAR_068631746W → G in GSD2. 1 PublicationCorresponds to variant dbSNP:rs1479740763Ensembl.1
Natural variantiVAR_068632746W → S in GSD2. 1 PublicationCorresponds to variant dbSNP:rs752921215EnsemblClinVar.1
Natural variantiVAR_070019766Y → C in GSD2. 1 PublicationCorresponds to variant dbSNP:rs144016984EnsemblClinVar.1
Natural variantiVAR_004312768P → R in GSD2; infantile form. 1 Publication1
Natural variantiVAR_068633819R → P in GSD2. 1 Publication1
Natural variantiVAR_018097880A → D in GSD2; infantile form; severe; loss of activity. 1 Publication1
Natural variantiVAR_029039901L → Q in GSD2; infantile form; severe. 1 Publication1
Natural variantiVAR_004315903Missing in GSD2; infantile form; severe; loss of activity. 1 Publication1
Natural variantiVAR_070020913P → R in GSD2. 1 PublicationCorresponds to variant dbSNP:rs1480070037Ensembl.1
Natural variantiVAR_068634916V → F in GSD2. 1 Publication1
Natural variantiVAR_004316925N → NGVPVSN in GSD2. 1 Publication1
Natural variantiVAR_068635935L → P in GSD2. 1 Publication1
Natural variantiVAR_004318949V → D in GSD2. Corresponds to variant dbSNP:rs1245412108Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi516W → R: Loss of activity. 1 Publication1
Mutagenesisi518D → G, N or E: Loss of activity. 1 Publication1

Keywords - Diseasei

Disease mutation, Glycogen storage disease

Organism-specific databases

DisGeNETi2548
GeneReviewsiGAA
MalaCardsiGAA
MIMi232300 phenotype
OpenTargetsiENSG00000171298
Orphaneti308552 Glycogen storage disease due to acid maltase deficiency, infantile onset
420429 Glycogen storage disease due to acid maltase deficiency, late-onset
PharmGKBiPA28476

Protein family/group databases

Allergomei9614 Hom s Glucosidase

Chemistry databases

ChEMBLiCHEMBL2608
DrugBankiDB00284 Acarbose
DB05200 AT2220
DB00491 Miglitol
GuidetoPHARMACOLOGYi2611

Polymorphism and mutation databases

BioMutaiGAA
DMDMi317373572

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 27Sequence analysisAdd BLAST27
PropeptideiPRO_000001856528 – 691 PublicationAdd BLAST42
ChainiPRO_000001856670 – 952Lysosomal alpha-glucosidaseAdd BLAST883
ChainiPRO_0000018567123 – 95276 kDa lysosomal alpha-glucosidaseAdd BLAST830
ChainiPRO_0000018568204 – 95270 kDa lysosomal alpha-glucosidaseAdd BLAST749

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi82 ↔ 109PROSITE-ProRule annotationCombined sources2 Publications
Disulfide bondi92 ↔ 108PROSITE-ProRule annotationCombined sources2 Publications
Disulfide bondi103 ↔ 127PROSITE-ProRule annotationCombined sources2 Publications
Glycosylationi140N-linked (GlcNAc...) asparagineCombined sources4 Publications1
Glycosylationi233N-linked (GlcNAc...) asparagineCombined sources3 Publications1
Glycosylationi390N-linked (GlcNAc...) asparagineCombined sources4 Publications1
Glycosylationi470N-linked (GlcNAc...) asparagineCombined sources5 Publications1
Disulfide bondi533 ↔ 558Combined sources2 Publications
Disulfide bondi647 ↔ 658Combined sources2 Publications
Glycosylationi652N-linked (GlcNAc...) asparagineCombined sources3 Publications1
Glycosylationi882N-linked (GlcNAc...) asparagineCombined sources4 Publications1
Glycosylationi925N-linked (GlcNAc...) asparagine2 Publications1

Post-translational modificationi

The different forms of acid glucosidase are obtained by proteolytic processing.1 Publication
Phosphorylation of mannose residues ensures efficient transport of the enzyme to the lysosomes via the mannose 6-phosphate receptor.

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP10253
MaxQBiP10253
PaxDbiP10253
PeptideAtlasiP10253
PRIDEiP10253
ProteomicsDBi52587

PTM databases

GlyConnecti723
iPTMnetiP10253
PhosphoSitePlusiP10253
UniCarbKBiP10253

Expressioni

Gene expression databases

BgeeiENSG00000171298 Expressed in 207 organ(s), highest expression level in right testis
CleanExiHS_GAA
ExpressionAtlasiP10253 baseline and differential
GenevisibleiP10253 HS

Organism-specific databases

HPAiHPA026970
HPA029126

Interactioni

Protein-protein interaction databases

BioGridi108823, 47 interactors
IntActiP10253, 8 interactors
MINTiP10253
STRINGi9606.ENSP00000305692

Chemistry databases

BindingDBiP10253

Structurei

Secondary structure

1952
Legend: HelixTurnBeta strandPDB Structure known for this area
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