CHST6 encodes corneal N-acetylglucosamine 6-O-sulfotransferase, a type II Golgi membrane enzyme that transfers sulfate from PAPS to the 6-hydroxyl group of GlcNAc in glycan acceptors. This reaction contributes to keratan sulfate chain biosynthesis and the sulfation pattern of corneal proteoglycans. The human enzyme can also sulfate mucin glycans in a heterologous expression assay. Biallelic loss of CHST6 function or cornea-specific expression causes macular corneal dystrophy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000139 Golgi membrane | IEA GO_REF:0000120 | ACCEPT | Summary: CHST6 is a Golgi membrane-associated glycan sulfotransferase. Reason: The electronic source combines the carbohydrate-sulfotransferase domain and Golgi location. Retain the original compartment assertion, consistent with the N-terminal type II membrane topology and its established biosynthetic chemistry. Soluble recombinant constructs do not independently establish native topology. |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-2046222 | ACCEPT | Summary: CHST6 is a Golgi membrane-associated glycan sulfotransferase. Reason: The actual Reactome catalyst set resolves through CHST6 residues 1–395 to Q9GZX3 in the Golgi membrane. Retain the original compartment assertion, consistent with the N-terminal type II membrane topology and its established biosynthetic chemistry. Soluble recombinant constructs do not independently establish native topology. Supporting Evidence: Reactome:R-HSA-2046222 file:human/CHST6/CHST6-source-evidence.json |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-3656269 | ACCEPT | Summary: CHST6 is a Golgi membrane-associated glycan sulfotransferase. Reason: This disease reaction places defective CHST6 forms in the Golgi membrane; it is not a direct localization experiment for every listed mutant. Retain the original compartment assertion, consistent with the N-terminal type II membrane topology and its established biosynthetic chemistry. Soluble recombinant constructs do not independently establish native topology. Supporting Evidence: Reactome:R-HSA-3656269 file:human/CHST6/CHST6-source-evidence.json |
| GO:0001517 N-acetylglucosamine 6-O-sulfotransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: CHST6 catalyzes sulfate transfer to the 6-hydroxyl of GlcNAc in glycan acceptors. Reason: Independent human CHST6 biochemistry supports the inherited GlcNAc-6 activity. The current node PTN002473209 and all sources, including target experimental grounding and mouse Chst4/Chst5, are preserved; no conclusion about the historical node is inferred from donor number. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002473209 SUPPORTS TRANSFER Current source evidence and direct human CHST6 assays support GlcNAc-6 sulfate transfer. The listed PAINT node is curated provenance; its historical IBD placement/MSA was not reconstructed. Target self-evidence is legitimate grounding, not circularity. |
| GO:0001517 N-acetylglucosamine 6-O-sulfotransferase activity | IDA PMID:11278593 Human corneal GlcNac 6-O-sulfotransferase and mouse intestin... | ACCEPT | Summary: CHST6 catalyzes sulfate transfer to the 6-hydroxyl of GlcNAc in glycan acceptors. Reason: The original study expresses intact and secreted human corneal enzyme and measures sulfate transfer to C6 of GlcNAc in synthetic oligosaccharides. Its cultured-cell keratan readout provides a complementary biosynthetic context. Supporting Evidence: PMID:11278593 transferring sulfate to C-6 of GlcNAc |
| GO:0001517 N-acetylglucosamine 6-O-sulfotransferase activity | IDA PMID:11352640 Sulfation of endothelial mucin by corneal keratan N-acetylgl... | ACCEPT | Summary: CHST6 catalyzes sulfate transfer to the 6-hydroxyl of GlcNAc in glycan acceptors. Reason: The original abstract explicitly reports human corneal GST-4beta/CHST6 sulfation of GlyCAM-1 after coexpression in COS-7 cells. This supports catalytic activity on mucin glycans; it does not establish an endogenous lymphocyte-homing role. Independent human acceptor assays define the GlcNAc-6 chemistry. |
| GO:0001517 N-acetylglucosamine 6-O-sulfotransferase activity | IEA GO_REF:0000117 | ACCEPT | Summary: CHST6 catalyzes sulfate transfer to the 6-hydroxyl of GlcNAc in glycan acceptors. Reason: The electronic substrate-specific activity agrees with directly measured human sulfate transfer; it is not accepted solely from the ARBA prediction. |
| GO:0001517 N-acetylglucosamine 6-O-sulfotransferase activity | TAS PMID:11181564 Chromosomal localization and genomic organization for the ga... | ACCEPT | Summary: CHST6 catalyzes sulfate transfer to the 6-hydroxyl of GlcNAc in glycan acceptors. Reason: The original family/genomic study identifies human GST-4beta separately from GST-4alpha. Independent human biochemical work establishes CHST6 GlcNAc-6 catalysis; the family paper is not presented as a complete target-specific assay read. |
| GO:0001517 N-acetylglucosamine 6-O-sulfotransferase activity | TAS Reactome:R-HSA-2046222 | ACCEPT | Summary: CHST6 catalyzes sulfate transfer to the 6-hydroxyl of GlcNAc in glycan acceptors. Reason: The actual Reactome reaction includes the full CHST6 protein in a catalyst set. Direct target biochemistry independently supports CHST6 sulfate transfer, without adopting every specificity of other set members. Supporting Evidence: Reactome:R-HSA-2046222 file:human/CHST6/CHST6-source-evidence.json |
| GO:0001517 N-acetylglucosamine 6-O-sulfotransferase activity | TAS Reactome:R-HSA-3656269 | ACCEPT | Summary: CHST6 catalyzes sulfate transfer to the 6-hydroxyl of GlcNAc in glycan acceptors. Reason: The disease event models failure of the normal CHST6 reaction. Retention identifies the affected WT function, not an assertion that each disease variant retains catalytic activity. Supporting Evidence: Reactome:R-HSA-3656269 file:human/CHST6/CHST6-source-evidence.json |
| GO:0005794 Golgi apparatus | TAS PMID:11181564 Chromosomal localization and genomic organization for the ga... | ACCEPT | Summary: CHST6 is a Golgi membrane-associated glycan sulfotransferase. Reason: The original family study describes Golgi-resident glycan sulfotransferases. Its accessible abstract and sequence legend do not constitute target-specific Golgi imaging. Retain the original compartment assertion, consistent with the N-terminal type II membrane topology and its established biosynthetic chemistry. Soluble recombinant constructs do not independently establish native topology. |
| GO:0005802 trans-Golgi network | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the inherited trans-Golgi activity location at its stated phylogenetic scope. Reason: The actual PTN002581838 source includes human CHST4/Q8NCG5, whose current trans-Golgi annotation includes an experimental PMID:12855678 record. That extant evidence does not reconstruct the ancestral placement. CHST6 is a Golgi glycan sulfotransferase, and no target-specific loss or incompatible localization was established. Retain curator judgment without presenting recombinant secretion as native trans-Golgi imaging. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002581838 SUPPORTS TRANSFER The current CHST4/Q8NCG5 source carries experimental TGN evidence, supporting the retained curated location transfer. This does not claim independently recovered CHST6 sub-Golgi imaging or reconstruction of historical PTN002581838 placement. The broader target Golgi assignment is independently consistent. |
| GO:0005975 carbohydrate metabolic process | IEA GO_REF:0000002 | MODIFY | Summary: Refine the broad process to CHST6-mediated keratan-sulfate proteoglycan biosynthesis. Reason: The domain-based carbohydrate-metabolism annotation is sound but broad. Independent human enzyme and pathway-reconstitution experiments establish CHST6 as the catalyst of GlcNAc-6 sulfation in keratan synthesis. GO:0018146 is an evidence-based reviewer recommendation, not an automatic ontology replacement or a rewritten original donor/source assertion. Proposed replacements: keratan sulfate proteoglycan biosynthetic process |
| GO:0006044 obsolete N-acetylglucosamine metabolic process | IBA GO_REF:0000033 | MODIFY | Summary: Refine the broad process to CHST6-mediated keratan-sulfate proteoglycan biosynthesis. Reason: GO:0006044 is obsolete as an unnecessary grouping term and has no official replacement. The original IBA object and node remain intact. Independent human enzyme and pathway-reconstitution experiments establish CHST6 as the catalyst of GlcNAc-6 sulfation in keratan synthesis. GO:0018146 is an evidence-based reviewer recommendation, not an automatic ontology replacement or a rewritten original donor/source assertion. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: PANTHER:PTN002473209 SUPPORTS TRANSFER Source enzyme evidence supports the underlying GlcNAc chemistry. The obsolete metabolic grouping has no official replacement; the keratan recommendation is grounded independently in human CHST6 catalysis. Historical PTN002473209 placement was not reconstructed. Proposed replacements: keratan sulfate proteoglycan biosynthetic process |
| GO:0006044 obsolete N-acetylglucosamine metabolic process | IC PMID:11181564 Chromosomal localization and genomic organization for the ga... | MODIFY | Summary: Refine the broad process to CHST6-mediated keratan-sulfate proteoglycan biosynthesis. Reason: The original IC object infers a GlcNAc process from GO:0001517. Its obsolete term has no official replacement, and the family paper does not itself establish the full keratan pathway. Independent human enzyme and pathway-reconstitution experiments establish CHST6 as the catalyst of GlcNAc-6 sulfation in keratan synthesis. GO:0018146 is an evidence-based reviewer recommendation, not an automatic ontology replacement or a rewritten original donor/source assertion. Proposed replacements: keratan sulfate proteoglycan biosynthetic process |
| GO:0006044 obsolete N-acetylglucosamine metabolic process | IDA PMID:11352640 Sulfation of endothelial mucin by corneal keratan N-acetylgl... | MODIFY | Summary: Represent the demonstrated GlyCAM-1 glycan sulfation with the direct sulfation process. Reason: The old GlcNAc metabolic grouping is obsolete without an official replacement. PMID:11352640 explicitly reports CHST6-catalyzed GlyCAM-1 sulfation in COS-7 coexpression. GO:0051923 describes adding sulfate to a molecule and fits that performed step. GO:0006477 instead requires sulfate esterification of a protein amino acid and is not justified by glycan sulfation. This source is not recast as a keratan assay or evidence for physiological leukocyte adhesion. Proposed replacements: sulfation Supporting Evidence: PMID:11352640 catalyzes sulfation of GlyCAM-1 file:human/CHST6/CHST6-source-evidence.json |
| GO:0006044 obsolete N-acetylglucosamine metabolic process | IEA GO_REF:0000117 | MODIFY | Summary: Refine the broad process to CHST6-mediated keratan-sulfate proteoglycan biosynthesis. Reason: The obsolete ARBA grouping term has no official replacement; its original identifier is preserved. Independent human enzyme and pathway-reconstitution experiments establish CHST6 as the catalyst of GlcNAc-6 sulfation in keratan synthesis. GO:0018146 is an evidence-based reviewer recommendation, not an automatic ontology replacement or a rewritten original donor/source assertion. Proposed replacements: keratan sulfate proteoglycan biosynthetic process |
| GO:0006790 sulfur compound metabolic process | IBA GO_REF:0000033 | MODIFY | Summary: Refine the broad process to CHST6-mediated keratan-sulfate proteoglycan biosynthesis. Reason: The inherited sulfur-metabolism assertion is chemically correct but broadly scoped. Independent human enzyme and pathway-reconstitution experiments establish CHST6 as the catalyst of GlcNAc-6 sulfation in keratan synthesis. GO:0018146 is an evidence-based reviewer recommendation, not an automatic ontology replacement or a rewritten original donor/source assertion. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: PANTHER:PTN002473209 SUPPORTS TRANSFER The source and target sulfate-transfer chemistry supports the broad sulfur-metabolism assertion. The issue is useful term specificity, not unsupported chemistry or donor count. Historical node placement was not reconstructed. Proposed replacements: keratan sulfate proteoglycan biosynthetic process |
| GO:0006790 sulfur compound metabolic process | IDA PMID:11352640 Sulfation of endothelial mucin by corneal keratan N-acetylgl... | MODIFY | Summary: Represent the demonstrated GlyCAM-1 glycan sulfation with the direct sulfation process. Reason: The sulfur-compound metabolism term captures the chemistry but is broad. PMID:11352640 explicitly reports CHST6-catalyzed GlyCAM-1 sulfation in COS-7 coexpression. GO:0051923 describes adding sulfate to a molecule and fits that performed step. GO:0006477 instead requires sulfate esterification of a protein amino acid and is not justified by glycan sulfation. This source is not recast as a keratan assay or evidence for physiological leukocyte adhesion. Proposed replacements: sulfation Supporting Evidence: PMID:11352640 catalyzes sulfation of GlyCAM-1 file:human/CHST6/CHST6-source-evidence.json |
| GO:0006790 sulfur compound metabolic process | IEA GO_REF:0000117 | MODIFY | Summary: Refine the broad process to CHST6-mediated keratan-sulfate proteoglycan biosynthesis. Reason: The electronic sulfur-metabolism assertion is chemically correct but broadly scoped. Independent human enzyme and pathway-reconstitution experiments establish CHST6 as the catalyst of GlcNAc-6 sulfation in keratan synthesis. GO:0018146 is an evidence-based reviewer recommendation, not an automatic ontology replacement or a rewritten original donor/source assertion. Proposed replacements: keratan sulfate proteoglycan biosynthetic process |
| GO:0008146 sulfotransferase activity | IEA GO_REF:0000002 | MODIFY | Summary: Refine generic sulfotransferase activity to the demonstrated GlcNAc-6 reaction. Reason: The sulfotransferase-domain assignment is correct. Human CHST6 acceptor assays establish sulfate transfer at GlcNAc C6, supporting the informative substrate-specific activity rather than only family membership. Proposed replacements: N-acetylglucosamine 6-O-sulfotransferase activity |
| GO:0009101 glycoprotein biosynthetic process | IEA GO_REF:0000117 | MODIFY | Summary: Refine the broad process to CHST6-mediated keratan-sulfate proteoglycan biosynthesis. Reason: Glycoprotein biosynthesis is a correct broad context, but the enzyme performs a specific sulfation step. Independent human enzyme and pathway-reconstitution experiments establish CHST6 as the catalyst of GlcNAc-6 sulfation in keratan synthesis. GO:0018146 is an evidence-based reviewer recommendation, not an automatic ontology replacement or a rewritten original donor/source assertion. Proposed replacements: keratan sulfate proteoglycan biosynthetic process |
| GO:0018146 keratan sulfate proteoglycan biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: CHST6 performs GlcNAc-6 sulfation during keratan-sulfate biosynthesis. Reason: Human target biochemistry and the authenticated mouse Chst5 ortholog context support inherited participation. The exact PTN000075901 node is retained without a claim to reconstruct its historical placement. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000075901 SUPPORTS TRANSFER Human target experiments and the mouse Chst5 source support performed keratan biosynthesis. This supports transfer at the stated curated scope without claiming reconstruction of the historical PTN000075901 placement. |
| GO:0018146 keratan sulfate proteoglycan biosynthetic process | IDA PMID:11278593 Human corneal GlcNac 6-O-sulfotransferase and mouse intestin... | ACCEPT | Summary: CHST6 performs GlcNAc-6 sulfation during keratan-sulfate biosynthesis. Reason: The enzyme directly supplies GlcNAc-6 sulfate during keratan production. Sulfate-transfer assays and coexpression with the Gal-6 enzyme distinguish its own chemistry from mere necessity for a corneal phenotype. |
| GO:0018146 keratan sulfate proteoglycan biosynthetic process | IDA PMID:17690104 Enzymes responsible for synthesis of corneal keratan sulfate... | ACCEPT | Summary: CHST6 performs GlcNAc-6 sulfation during keratan-sulfate biosynthesis. Reason: The study combines CGn6ST with beta3GnT7/beta4GalT4 to generate extended GlcNAc-sulfated chains and then adds the Gal-6 enzyme. The sulfotransferase performs the chemical modification; the corneal-cell knockdowns in the abstract target the two glycosyltransferases, not CHST6. |
| GO:0018146 keratan sulfate proteoglycan biosynthetic process | TAS Reactome:R-HSA-2022854 | ACCEPT | Summary: CHST6 performs GlcNAc-6 sulfation during keratan-sulfate biosynthesis. Reason: The actual pathway contains the CHST6 GlcNAc sulfation reaction. Independent enzymatic experiments demonstrate catalytic participation rather than assigning a process from pathway membership alone. Supporting Evidence: Reactome:R-HSA-2022854 file:human/CHST6/CHST6-source-evidence.json |
| GO:0045130 keratan sulfotransferase activity | EXP PMID:11278593 Human corneal GlcNac 6-O-sulfotransferase and mouse intestin... | ACCEPT | Summary: CHST6 has keratan sulfotransferase activity at the GlcNAc residue. Reason: The original human experiments demonstrate GlcNAc sulfate transfer and keratan production; keratan sulfotransferase activity is a valid broader substrate-context description. The official EC2.8.2.21 explicitly includes C6 sulfation of both Gal and GlcNAc, despite the GO term's Gal-specific exact synonym; acceptance does not attribute Gal-6 specificity to CHST6. |
| GO:0045130 keratan sulfotransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: CHST6 has keratan sulfotransferase activity at the GlcNAc residue. Reason: The exact PTN000075901, target and mouse Chst5 source fields remain intact. Direct human activity independently supports this capability, without interpreting target self-evidence as circular. The official EC2.8.2.21 explicitly includes C6 sulfation of both Gal and GlcNAc, despite the GO term's Gal-specific exact synonym; acceptance does not attribute Gal-6 specificity to CHST6. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000075901 SUPPORTS TRANSFER Human target and mouse Chst5 enzyme evidence support the keratan capability; official EC2.8.2.21 includes GlcNAc sulfation. Historical node placement was not reconstructed, and target self-evidence is not circular. |
| GO:0045130 keratan sulfotransferase activity | IDA PMID:17690104 Enzymes responsible for synthesis of corneal keratan sulfate... | ACCEPT | Summary: CHST6 has keratan sulfotransferase activity at the GlcNAc residue. Reason: The enzyme is included as the GlcNAc sulfotransferase in an in-vitro keratan-chain synthesis system. It is not the Gal-6 enzyme or either chain-elongating glycosyltransferase. The official EC2.8.2.21 explicitly includes C6 sulfation of both Gal and GlcNAc, despite the GO term's Gal-specific exact synonym; acceptance does not attribute Gal-6 specificity to CHST6. |
| GO:0045130 keratan sulfotransferase activity | IEA GO_REF:0000003 | ACCEPT | Summary: CHST6 has keratan sulfotransferase activity at the GlcNAc residue. Reason: The EC-derived keratan sulfotransferase class agrees with measured human CHST6 activity. The more residue-specific GlcNAc-6 activity describes the same catalytic function in the core, rather than a second autonomous activity. The official EC2.8.2.21 explicitly includes C6 sulfation of both Gal and GlcNAc, despite the GO term's Gal-specific exact synonym; acceptance does not attribute Gal-6 specificity to CHST6. |
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Download this section (compressed HTML)Q: Which native non-keratan glycans are physiological CHST6 substrates outside the cornea, given the positive GlyCAM-1 coexpression result?
Q: What direct localization and phylogenetic evidence resolve CHST6 trans-Golgi activity at PTN002581838 relative to the broader Golgi membrane localization?
Q: How does CHST6 coordinate with glycosyltransferases and Gal-6 sulfotransferase to control keratan-chain length and sulfation without conflating their catalytic steps?
Q: Should the Gal-6-specific exact synonym of GO:0045130 be revised to match its broader official EC2.8.2.21 scope, which includes both Gal and GlcNAc sulfation?
Experiment: Use sequence-verified human CHST6 with chemically defined short and extended glycan acceptors, positional sulfate-product analysis and matched inactive controls, then compare with endogenous glycan products after cell-specific complementation. Distinguish GlcNAc-6 transfer from Gal-6 sulfation and chain elongation.
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