GALNS (N-acetylgalactosamine-6-sulfatase, also known as galactose-6-sulfate sulfatase, GalN6S; EC 3.1.6.4) is a lysosomal sulfatase acting in the stepwise degradation of the glycosaminoglycans keratan sulfate and chondroitin-6-sulfate. It hydrolytically removes the 6-O-sulfate group from terminal N-acetyl-D-galactosamine-6-sulfate residues of chondroitin sulfate and from D-galactose-6-sulfate residues of keratan sulfate. Like all members of the sulfatase family, GALNS requires post-translational conversion of an active-site cysteine (Cys79) to CΞ±-formylglycine (3-oxoalanine) by the formylglycine-generating enzyme SUMF1; this modified residue, together with a bound Ca2+ ion, forms the catalytic nucleophile. GALNS is a homodimeric N-glycosylated glycoprotein that localises to the lysosome (lysosomal lumen), and, as a secreted lysosomal hydrolase, is also detected extracellularly. Deficiency of GALNS causes mucopolysaccharidosis type IVA (Morquio A syndrome), an autosomal recessive lysosomal storage disease with intracellular accumulation of keratan sulfate and chondroitin-6-sulfate, presenting with short stature, skeletal dysplasia, and corneal clouding.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004065 arylsulfatase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Family-level (arylsulfatase) molecular function assigned by phylogenetic inference across the sulfatase family. GALNS is a bona fide sulfatase, so this term is correct but broad relative to its specific N-acetylgalactosamine-6-sulfatase activity. Reason: The IBA sulfatase-family term is biologically correct: GALNS catalyses sulfate-ester hydrolysis and belongs to the sulfatase family. It is more general than the specific 6-sulfatase activity (GO:0043890, also annotated), and it is standard to retain the broader family MF alongside the specific one. Kept, though the specific GO:0043890 term better represents the core function. Supporting Evidence: PMID:22940367 In sulfatases, highly conserved catalytic machinery couples with diverse active site geometry, leading to cleavage of a wide variety of substrates. file:human/GALNS/GALNS-uniprot.txt Belongs to the sulfatase family. |
| GO:0005764 lysosome | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic localisation to the lysosome, consistent with UniProt SUBCELLULAR LOCATION and with direct immunolocalisation (GO:0005764 IDA from PMID:30760748). Reason: GALNS is a well-established lysosomal hydrolase; the IEA lysosome call agrees with experimental IDA evidence and UniProt curation, so it is retained as a correct core localisation. Supporting Evidence: file:human/GALNS/GALNS-uniprot.txt SUBCELLULAR LOCATION: Lysosome PMID:30760748 GALNS indeed showed a lysosomal localization in both ever smokers and COPD patients. |
| GO:0043890 N-acetylgalactosamine-6-sulfatase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Specific molecular function: removal of the 6-O-sulfate from N-acetyl-D-galactosamine-6-sulfate (chondroitin-6-sulfate) and D-galactose-6-sulfate (keratan sulfate). This is the correct core MF for GALNS (EC 3.1.6.4), inferred here electronically from InterPro/EC mapping. Reason: The GO:0043890 definition matches the experimentally established catalytic activity of GALNS exactly, and the same term is independently supported by EXP and IDA annotations. This is the core molecular function. Supporting Evidence: PMID:22940367 removes sulfate groups from a terminal N-acetylgalactosamine-6-sulfate (or galactose-6-sulfate) in mucopolysaccharides such as keratan sulfate and chondroitin-6-sulfate file:human/GALNS/GALNS-uniprot.txt Lysosomal enzyme that hydrolyzes sulfate groups from |
| GO:0043890 N-acetylgalactosamine-6-sulfatase activity | TAS Reactome:R-HSA-2263490 | ACCEPT | Summary: Reactome-asserted core molecular function (6-sulfatase acting on Gal6S/GalNAc6S in keratan sulfate and chondroitin sulfate). Reason: Reactome models GALNS hydrolysing sulfate from galactose-6-sulfate in keratan sulfate and from N-acetylgalactosamine-6-sulfate in chondroitin sulfate; this is the correct core MF and duplicates the experimentally supported GO:0043890 annotation. Supporting Evidence: Reactome:R-HSA-1630304 hydrolyses sulfate from galactose 6-sulfate units of keratan sulfate PMID:22940367 In the lysosome, GALNS removes sulfate groups from 6-sulfated galactosides and 6-sulfated N-acetylgalactosaminides in keratan sulfate and chondroitin-6-sulfate |
| GO:0005764 lysosome | IDA PMID:30760748 Expression, activity and localization of lysosomal sulfatase... | ACCEPT | Summary: Direct immunolocalisation of GALNS to the lysosome in cultured human lung fibroblasts. Reason: Experimental (IDA) evidence: co-staining with lysosomal markers showed GALNS in a lysosomal localisation. This confirms the core subcellular location. Supporting Evidence: PMID:30760748 GALNS indeed showed a lysosomal localization in both ever smokers and COPD patients. |
| GO:0043890 N-acetylgalactosamine-6-sulfatase activity | EXP PMID:22940367 The structure of human GALNS reveals the molecular basis for... | ACCEPT | Summary: Experimental characterisation (structure and enzyme kinetics) of human GALNS as an N-acetylgalactosamine-6-sulfatase acting on keratan sulfate and chondroitin-6-sulfate. Reason: Direct experimental support for the core molecular function: the crystallographic and kinetic study defines GALNS as removing 6-sulfate groups from the terminal sugars of keratan sulfate and chondroitin-6-sulfate, with a Ca2+/formylglycine active site. Supporting Evidence: PMID:22940367 In the lysosome, GALNS removes sulfate groups from 6-sulfated galactosides and 6-sulfated N-acetylgalactosaminides in keratan sulfate and chondroitin-6-sulfate |
| GO:0030207 chondroitin sulfate proteoglycan catabolic process | IDA PMID:18285341 Distinct effects of N-acetylgalactosamine-4-sulfatase and ga... | ACCEPT | Summary: GALNS contributes to catabolism of chondroitin sulfate: modulating GALNS expression inversely changes cellular chondroitin sulfate content. Reason: Experimental (IDA) evidence in MCF-7 cells shows that overexpression of GALNS lowers, and silencing raises, chondroitin sulfate content, supporting a direct role in chondroitin-6-sulfate catabolism. This is a genuine core biological process (the chondroitin side of GALNS's GAG-degradation role). Supporting Evidence: PMID:18285341 galactose-6-sulfatase (GALNS) hydrolyze sulfate groups of CS PMID:18285341 modification of expression of the lysosomal sulfatases ASB and GALNS regulates |
| GO:0043890 N-acetylgalactosamine-6-sulfatase activity | IDA PMID:18285341 Distinct effects of N-acetylgalactosamine-4-sulfatase and ga... | ACCEPT | Summary: Direct-assay support for the core 6-sulfatase molecular function of GALNS. Reason: IDA annotation to the correct specific molecular function; GALNS is characterised here as galactose-6-sulfatase that hydrolyses sulfate groups of chondroitin sulfate. Duplicates the core MF supported by other lines of evidence. Supporting Evidence: PMID:18285341 galactose-6-sulfatase (GALNS) hydrolyze sulfate groups of CS |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6798751 | KEEP AS NON CORE | Summary: Extracellular localisation asserted via Reactome neutrophil-degranulation / azurophil-granule exocytosis pathway. A secreted-fraction localisation, not the primary site of GALNS action. Reason: As a lysosomal hydrolase, GALNS can be exocytosed and detected extracellularly (e.g. via neutrophil degranulation). The localisation is real but peripheral; the core site of action is the lysosome. Supporting Evidence: Reactome:R-HSA-6798751 Azurophil granules undergo limited exocytosis in response to stimulation |
| GO:0035578 azurophil granule lumen | TAS Reactome:R-HSA-6798751 | KEEP AS NON CORE | Summary: Localisation to the azurophil (primary) granule lumen of neutrophils, asserted via the Reactome neutrophil-degranulation pathway. Reason: Azurophil granules are lysosome-related organelles of neutrophils; GALNS presence there reflects its lysosomal-hydrolase nature and the degranulation pathway, but this is not the core localisation. Supporting Evidence: Reactome:R-HSA-6798751 Azurophil granules undergo limited exocytosis in response to stimulation |
| GO:0043202 lysosomal lumen | TAS Reactome:R-HSA-2263490 | ACCEPT | Summary: Localisation to the lysosomal lumen, the precise compartment where GALNS acts on keratan sulfate and chondroitin-6-sulfate. Reason: Lysosomal lumen is the specific site of GALNS activity as a soluble lysosomal hydrolase; consistent with the lysosome IDA/IEA annotations and UniProt curation. Supporting Evidence: Reactome:R-HSA-1630304 hydrolyses sulfate from galactose 6-sulfate units of keratan sulfate file:human/GALNS/GALNS-uniprot.txt SUBCELLULAR LOCATION: Lysosome |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: High-throughput proteomic detection of GALNS in exosomes from expressed prostatic secretions in urine. A localisation byproduct of secreted/exosomal trafficking, not a core function. Reason: GALNS was among ~900 proteins detected by shotgun proteomics of prostatic-secretion exosomes. This supports extracellular-exosome localisation but is peripheral to the enzyme's lysosomal core role. Supporting Evidence: PMID:23533145 exosome preparations were characterized by a shotgun proteomics procedure |
| GO:0043202 lysosomal lumen | TAS Reactome:R-HSA-1630304 | ACCEPT | Summary: Lysosomal-lumen localisation asserted by Reactome for the GALNS keratan-sulfate desulfation reaction; the precise site of GALNS catalysis. Reason: Duplicate of the lysosomal-lumen localisation supported by Reactome and UniProt; correct core compartment for this soluble lysosomal sulfatase. Supporting Evidence: Reactome:R-HSA-1630304 hydrolyses sulfate from galactose 6-sulfate units of keratan sulfate file:human/GALNS/GALNS-uniprot.txt SUBCELLULAR LOCATION: Lysosome |
| GO:0008484 sulfuric ester hydrolase activity | IDA PMID:15962010 Sulphatase activities are regulated by the interaction of su... | MARK AS OVER ANNOTATED | Summary: Parent-level molecular function (sulfuric ester hydrolase). GALNS activity was measured in the SUMF1/SUMF2 study, but the specific GO:0043890 (6-sulfatase) term is the informative descendant. Reason: GO:0008484 is a broad ancestor of the specific N-acetylgalactosamine-6-sulfatase activity already annotated. GALNS activity was assayed among several sulfatases whose maturation depends on SUMF1; the general term adds little beyond the specific GO:0043890 term and is an over-annotation of specificity. Not wrong, but subsumed by the core MF. Supporting Evidence: PMID:15962010 This modification is necessary for the catalytic activities of the sulphatases PMID:15962010 we transfected Cos7 cells with several sulphatase cDNAs |
| GO:0003943 N-acetylgalactosamine-4-sulfatase activity | TAS PMID:8325655 Mucopolysaccharidosis IV A: assignment of the human N-acetyl... | MODIFY | Summary: Annotation to N-acetylgalactosamine-4-sulfatase activity, which is the wrong specificity for GALNS. GALNS is a 6-sulfatase (EC 3.1.6.4, GO:0043890); the 4-sulfatase (EC 3.1.6.12, GO:0003943) is ARSB. The cited reference is a chromosome-mapping abstract that does not assay a 4-sulfatase activity. Reason: GO:0003943 catalyses hydrolysis of the 4-sulfate groups of N-acetyl-D-galactosamine-4-sulfate (a distinct activity carried out by ARSB), whereas GALNS removes 6-sulfate groups. The original reference (PMID:8325655) only assigns the GALNS gene to chromosome 16q24 and does not support a 4-sulfatase activity. This is a wrong-specificity term (TAS, not experimental IDA); replace with the correct 6-sulfatase term GO:0043890. Proposed replacements: N-acetylgalactosamine-6-sulfatase activity Supporting Evidence: PMID:8325655 N-acetylgalactosamine-6-sulfate sulfatase (GALNS; EC 3.1.6.4) PMID:22940367 In the lysosome, GALNS removes sulfate groups from 6-sulfated galactosides and 6-sulfated N-acetylgalactosaminides in keratan sulfate and chondroitin-6-sulfate |
| GO:0042340 keratan sulfate proteoglycan catabolic process | EXP PMID:22940367 The structure of human GALNS reveals the molecular basis for... | NEW | Summary: GALNS removes the 6-O-sulfate from galactose-6-sulfate residues of keratan sulfate, a required step in keratan sulfate degradation; deficiency causes lysosomal keratan sulfate accumulation (MPS IVA). This keratan-sulfate catabolic role is not currently represented in GOA and is proposed here. Reason: The keratan-sulfate side of GALNS's core biological process is well established (UniProt FUNCTION; structural/enzymology study; Reactome "Keratan sulfate degradation") but absent from the GOA biological-process set, which only carries the chondroitin-sulfate term GO:0030207. GO:0042340 (keratan sulfate proteoglycan catabolic process) captures this core role. Supporting Evidence: PMID:22940367 removes sulfate groups from a terminal N-acetylgalactosamine-6-sulfate (or galactose-6-sulfate) in mucopolysaccharides such as keratan sulfate and chondroitin-6-sulfate file:human/GALNS/GALNS-uniprot.txt Lysosomal enzyme that hydrolyzes sulfate groups from |
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)