UniProt functional annotation for P06280



	UniProt functional annotation for P06280

UniProt code: P06280.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Catalyzes the hydrolysis of glycosphingolipids and participates to their degradation in the lysosome. {ECO:0000269|PubMed:10838196, ECO:0000269|PubMed:8804427}.

Catalytic activity: Reaction=Hydrolysis of terminal, non-reducing alpha-D-galactose residues in alpha-D-galactosides, including galactose oligosaccharides, galactomannans and galactolipids.; EC=3.2.1.22; Evidence={ECO:0000269|PubMed:26415523, ECO:0000269|PubMed:27211852};

Catalytic activity: Reaction=globoside Gb3Cer (d18:1(4E)) + H2O = a beta-D-Gal-(1->4)-beta- D-Glc-(1<->1)-Cer(d18:1(4E)) + D-galactose; Xref=Rhea:RHEA:21112, ChEBI:CHEBI:4139, ChEBI:CHEBI:15377, ChEBI:CHEBI:17950, ChEBI:CHEBI:18313; EC=3.2.1.47; Evidence={ECO:0000269|PubMed:10838196, ECO:0000269|PubMed:8804427}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21113; Evidence={ECO:0000305|PubMed:10838196, ECO:0000305|PubMed:8804427};

Catalytic activity: Reaction=globoside Gb3Cer + H2O = beta-D-galactosyl-(1->4)-beta-D- glucosyl-(1<->1)-ceramide + D-galactose; Xref=Rhea:RHEA:48020, ChEBI:CHEBI:4139, ChEBI:CHEBI:15377, ChEBI:CHEBI:79208, ChEBI:CHEBI:88154; Evidence={ECO:0000269|PubMed:10838196, ECO:0000269|PubMed:8804427}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48021; Evidence={ECO:0000305|PubMed:10838196, ECO:0000305|PubMed:8804427};

Activity regulation: Galactosylgalactosylglucosylceramidase activity is stimulated by saposin B and ammonium chloride. {ECO:0000269|PubMed:10838196, ECO:0000269|PubMed:8804427}.

Subunit: Homodimer. {ECO:0000269|PubMed:15003450}.

Subcellular location: Lysosome.

Rna editing: Modified_positions=396 {ECO:0000269|PubMed:7503918}; Note=Partially edited.;

Disease: Fabry disease (FD) [MIM:301500]: Rare X-linked sphingolipidosis disease where glycolipid accumulates in many tissues. The disease consists of an inborn error of glycosphingolipid catabolism. FD patients show systemic accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids in the plasma and cellular lysosomes throughout the body. Clinical recognition in males results from characteristic skin lesions (angiokeratomas) over the lower trunk. Patients may show ocular deposits, febrile episodes, and burning pain in the extremities. Death results from renal failure, cardiac or cerebral complications of hypertension or other vascular disease. Heterozygous females may exhibit the disorder in an attenuated form, they are more likely to show corneal opacities. {ECO:0000269|PubMed:10090526, ECO:0000269|PubMed:10208848, ECO:0000269|PubMed:10666480, ECO:0000269|PubMed:10838196, ECO:0000269|PubMed:10916280, ECO:0000269|PubMed:11076046, ECO:0000269|PubMed:11295840, ECO:0000269|PubMed:11668641, ECO:0000269|PubMed:11889412, ECO:0000269|PubMed:12694230, ECO:0000269|PubMed:12786754, ECO:0000269|PubMed:1315715, ECO:0000269|PubMed:15162124, ECO:0000269|PubMed:15712228, ECO:0000269|PubMed:16533976, ECO:0000269|PubMed:1846223, ECO:0000269|PubMed:19621417, ECO:0000269|PubMed:2152885, ECO:0000269|PubMed:2171331, ECO:0000269|PubMed:2539398, ECO:0000269|PubMed:26415523, ECO:0000269|PubMed:27142856, ECO:0000269|PubMed:27211852, ECO:0000269|PubMed:7504405, ECO:0000269|PubMed:7531540, ECO:0000269|PubMed:7575533, ECO:0000269|PubMed:7596372, ECO:0000269|PubMed:7599642, ECO:0000269|PubMed:7759078, ECO:0000269|PubMed:8069316, ECO:0000269|PubMed:8395937, ECO:0000269|PubMed:8738659, ECO:0000269|PubMed:8807334, ECO:0000269|PubMed:8834244, ECO:0000269|PubMed:8863162, ECO:0000269|PubMed:8875188, ECO:0000269|PubMed:8931708, ECO:0000269|PubMed:9100224, ECO:0000269|PubMed:9105656, ECO:0000269|PubMed:9452068, ECO:0000269|PubMed:9452090, ECO:0000269|PubMed:9452111, ECO:0000269|PubMed:9554750}. Note=The disease is caused by variants affecting the gene represented in this entry.

Pharmaceutical: Available under the names Replagal (from Shire) and Fabrazyme (from Genzyme). Used as a long-term enzyme replacement therapy in patients with a confirmed diagnosis of Fabry disease. The differences between Replagal (also known as agalsidase alpha) and Fabrazyme (also known as agalsidase beta) lies in the glycosylation patterns. Agalsidase beta is produced in the hamster CHO cell line while agalsidase alpha is produced in human cell lines.

Similarity: Belongs to the glycosyl hydrolase 27 family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Catalyzes the hydrolysis of glycosphingolipids and participates to their degradation in the lysosome. {ECO:0000269\|PubMed:10838196, ECO:0000269\|PubMed:8804427}.


Catalytic activity:		Reaction=Hydrolysis of terminal, non-reducing alpha-D-galactose residues in alpha-D-galactosides, including galactose oligosaccharides, galactomannans and galactolipids.; EC=3.2.1.22; Evidence={ECO:0000269\|PubMed:26415523, ECO:0000269\|PubMed:27211852};
Catalytic activity:		Reaction=globoside Gb3Cer (d18:1(4E)) + H2O = a beta-D-Gal-(1->4)-beta- D-Glc-(1<->1)-Cer(d18:1(4E)) + D-galactose; Xref=Rhea:RHEA:21112, ChEBI:CHEBI:4139, ChEBI:CHEBI:15377, ChEBI:CHEBI:17950, ChEBI:CHEBI:18313; EC=3.2.1.47; Evidence={ECO:0000269\|PubMed:10838196, ECO:0000269\|PubMed:8804427}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21113; Evidence={ECO:0000305\|PubMed:10838196, ECO:0000305\|PubMed:8804427};
Catalytic activity:		Reaction=globoside Gb3Cer + H2O = beta-D-galactosyl-(1->4)-beta-D- glucosyl-(1<->1)-ceramide + D-galactose; Xref=Rhea:RHEA:48020, ChEBI:CHEBI:4139, ChEBI:CHEBI:15377, ChEBI:CHEBI:79208, ChEBI:CHEBI:88154; Evidence={ECO:0000269\|PubMed:10838196, ECO:0000269\|PubMed:8804427}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48021; Evidence={ECO:0000305\|PubMed:10838196, ECO:0000305\|PubMed:8804427};
Activity regulation:		Galactosylgalactosylglucosylceramidase activity is stimulated by saposin B and ammonium chloride. {ECO:0000269\|PubMed:10838196, ECO:0000269\|PubMed:8804427}.
Subunit:		Homodimer. {ECO:0000269\|PubMed:15003450}.
Subcellular location:		Lysosome.
Rna editing:		Modified_positions=396 {ECO:0000269\|PubMed:7503918}; Note=Partially edited.;
Disease:		Fabry disease (FD) [MIM:301500]: Rare X-linked sphingolipidosis disease where glycolipid accumulates in many tissues. The disease consists of an inborn error of glycosphingolipid catabolism. FD patients show systemic accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids in the plasma and cellular lysosomes throughout the body. Clinical recognition in males results from characteristic skin lesions (angiokeratomas) over the lower trunk. Patients may show ocular deposits, febrile episodes, and burning pain in the extremities. Death results from renal failure, cardiac or cerebral complications of hypertension or other vascular disease. Heterozygous females may exhibit the disorder in an attenuated form, they are more likely to show corneal opacities. {ECO:0000269\|PubMed:10090526, ECO:0000269\|PubMed:10208848, ECO:0000269\|PubMed:10666480, ECO:0000269\|PubMed:10838196, ECO:0000269\|PubMed:10916280, ECO:0000269\|PubMed:11076046, ECO:0000269\|PubMed:11295840, ECO:0000269\|PubMed:11668641, ECO:0000269\|PubMed:11889412, ECO:0000269\|PubMed:12694230, ECO:0000269\|PubMed:12786754, ECO:0000269\|PubMed:1315715, ECO:0000269\|PubMed:15162124, ECO:0000269\|PubMed:15712228, ECO:0000269\|PubMed:16533976, ECO:0000269\|PubMed:1846223, ECO:0000269\|PubMed:19621417, ECO:0000269\|PubMed:2152885, ECO:0000269\|PubMed:2171331, ECO:0000269\|PubMed:2539398, ECO:0000269\|PubMed:26415523, ECO:0000269\|PubMed:27142856, ECO:0000269\|PubMed:27211852, ECO:0000269\|PubMed:7504405, ECO:0000269\|PubMed:7531540, ECO:0000269\|PubMed:7575533, ECO:0000269\|PubMed:7596372, ECO:0000269\|PubMed:7599642, ECO:0000269\|PubMed:7759078, ECO:0000269\|PubMed:8069316, ECO:0000269\|PubMed:8395937, ECO:0000269\|PubMed:8738659, ECO:0000269\|PubMed:8807334, ECO:0000269\|PubMed:8834244, ECO:0000269\|PubMed:8863162, ECO:0000269\|PubMed:8875188, ECO:0000269\|PubMed:8931708, ECO:0000269\|PubMed:9100224, ECO:0000269\|PubMed:9105656, ECO:0000269\|PubMed:9452068, ECO:0000269\|PubMed:9452090, ECO:0000269\|PubMed:9452111, ECO:0000269\|PubMed:9554750}. Note=The disease is caused by variants affecting the gene represented in this entry.
Pharmaceutical:		Available under the names Replagal (from Shire) and Fabrazyme (from Genzyme). Used as a long-term enzyme replacement therapy in patients with a confirmed diagnosis of Fabry disease. The differences between Replagal (also known as agalsidase alpha) and Fabrazyme (also known as agalsidase beta) lies in the glycosylation patterns. Agalsidase beta is produced in the hamster CHO cell line while agalsidase alpha is produced in human cell lines.
Similarity:		Belongs to the glycosyl hydrolase 27 family. {ECO:0000305}.