GAA

This gene encodes lysosomal alpha-glucosidase, which is essential for the degradation of glycogen to glucose in lysosomes. The encoded preproprotein is proteolytically processed to generate multiple intermediate forms and the mature form of the enzyme. Defects in this gene are the cause of glycogen storage disease II, also known as Pompe's disease, which is an autosomal recessive disorder with a broad clinical spectrum. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

Full Name

glucosidase alpha,acid

Function

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).

Biological Process

Cardiac muscle contraction Source: BHF-UCL
Diaphragm contraction Source: BHF-UCL
Glucose metabolic process Source: BHF-UCL
Glycogen catabolic process Source: UniProtKB
Heart morphogenesis Source: Ensembl
Locomotory behavior Source: Ensembl
Lysosome organization Source: BHF-UCL
Maltose metabolic process Source: BHF-UCL
Muscle cell cellular homeostasis Source: Ensembl
Neuromuscular process controlling balance Source: Ensembl
Neuromuscular process controlling posture Source: Ensembl
Regulation of the force of heart contraction Source: Ensembl
Sucrose metabolic process Source: BHF-UCL
Tissue development Source: Ensembl
Vacuolar sequestering Source: BHF-UCL

Cellular Location

Lysosome; Lysosome membrane

Involvement in disease

Glycogen storage disease 2 (GSD2):
A 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.

PTM

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