CHST3 encodes chondroitin 6-O-sulfotransferase 1, a type II Golgi membrane enzyme that transfers sulfate from PAPS to C6 of N-acetylgalactosamine residues in chondroitin chains. This reaction shapes extracellular and cell-surface chondroitin sulfate proteoglycans. CHST3 also sulfates galactose C6 in keratan sulfate as a lower-efficiency secondary activity. Biallelic loss of CHST3 activity causes skeletal dysplasia with joint dislocations and progressive spinal involvement.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000139 Golgi membrane | IEA GO_REF:0000120 | ACCEPT | Summary: CHST3 acts in the Golgi membrane-associated glycan-sulfation pathway. Reason: The combined electronic sources and predicted N-terminal anchor support Golgi membrane association. Human soluble-enzyme assays establish glycan sulfation but remove the anchor and do not directly test native localization (PMID:9883891; PMID:15215498). |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-2018682 | ACCEPT | Summary: CHST3 acts in the Golgi membrane-associated glycan-sulfation pathway. Reason: Reactome 2018682 places the CHST3/CHST7 catalyst set in the Golgi membrane, consistent with the predicted CHST3 anchor. The soluble recombinant assays establish catalysis rather than native membrane topology. |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-2046222 | ACCEPT | Summary: CHST3 acts in the Golgi membrane-associated glycan-sulfation pathway. Reason: Reactome 2046222 assigns its CHST3-containing catalyst set to the Golgi membrane. That compartment is consistent with CHST3 independently of the unresolved GlcNAc-specific reaction reviewed separately. |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-3595175 | ACCEPT | Summary: CHST3 acts in the Golgi membrane-associated glycan-sulfation pathway. Reason: The disease event places defective CHST3 in the Golgi membrane. Retain the gene-level compartment with the predicted anchor; the event does not demonstrate correct trafficking of every mutant. |
| GO:0001517 N-acetylglucosamine 6-O-sulfotransferase activity | IBA GO_REF:0000033 | UNDECIDED | Summary: CHST3-specific GlcNAc sulfation remains unresolved despite established GalNAc and Gal acceptors. Reason: Human CHST3 assays establish GalNAc C6 transfer, and UniProt additionally curates Gal C6 transfer on keratan. Neither the inspected substrate panel nor the available pathway evidence resolves GlcNAc transfer. The PAINT assertion therefore remains uncertain at this residue-specific scope. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN002473209 UNRESOLVED The curated PTN002473209 assertion is genuine, but the target’s GlcNAc-specific chemical evidence remains unresolved. The historical IBD tree/MSA was not inspected; extant source composition does not establish the node’s breadth or a target loss. |
| GO:0001517 N-acetylglucosamine 6-O-sulfotransferase activity | TAS Reactome:R-HSA-2046222 | UNDECIDED | Summary: The Reactome source explicitly assigns CHST3 to a GlcNAc-sulfating catalyst set, but the target-specific chemistry remains unresolved. Reason: Reactome 2046222 includes CHST3 in a GlcNAc-sulfating catalyst set. Its cited papers remain abstract-limited, with no verified target-specific assay in the accessible text. The established GalNAc and Gal reactions neither verify nor exclude this separate GlcNAc reaction. |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000107 | ACCEPT | Summary: CHST3 acts in the Golgi membrane-associated glycan-sulfation pathway. Reason: The current mouse Chst3/O88199 ortholog source supports Golgi localization, consistent with the human precursor and glycan-modifying role. This is transferred compartment evidence, not a direct localization assay of the human soluble construct. |
| GO:0005975 carbohydrate metabolic process | IEA GO_REF:0000002 | MODIFY | Summary: Refine broad carbohydrate metabolism to the demonstrated chondroitin-sulfate biosynthetic step. Reason: Recombinant CHST3 product assays and deficient patient-cell chondroitin sulfation support the specific biosynthetic step (PMID:9883891; PMID:15215498). This target-level refinement converges on existing GO:0050650 coverage; it adds no NEW assertion. Proposed replacements: chondroitin sulfate proteoglycan biosynthetic process |
| GO:0006044 obsolete N-acetylglucosamine metabolic process | IBA GO_REF:0000033 | REMOVE | Summary: Withdraw the obsolete GlcNAc-process grouping; the underlying target chemistry remains unresolved. Reason: GO:0006044 was obsoleted because it was made in error as an unnecessary grouping term; no replacement is supplied. Withdraw this obsolete grouping as an annotation target while preserving its original source assertion. This disposition does not refute GlcNAc chemistry or establish an incorrect historical PAINT placement. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: PANTHER:PTN002473209 UNRESOLVED The term is an obsolete unnecessary grouping. Historical PTN002473209 placement and the target-specific GlcNAc chemistry remain unresolved; removing the grouping does not adjudicate either question. |
| GO:0006790 sulfur compound metabolic process | IBA GO_REF:0000033 | MODIFY | Summary: Refine sulfur-compound metabolism to CHST3-mediated chondroitin-sulfate biosynthesis. Reason: Sulfate transfer from PAPS makes the broad sulfur-metabolism assertion sound. Human target biochemistry supports the more informative chondroitin sulfate biosynthetic step, already represented by GO:0050650. This is a target-level specificity recommendation, not a revised IBD placement at PTN002473209. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: PANTHER:PTN002473209 SUPPORTS TRANSFER The curated transfer and human target chemistry support the original sulfur-metabolism premise. The replacement specifies the demonstrated target step, not the ancestral node; historical IBD placement and MSA remain uninspected. Proposed replacements: chondroitin sulfate proteoglycan biosynthetic process |
| GO:0006790 sulfur compound metabolic process | IDA PMID:9883891 Functional expression and genomic structure of human chondro... | MODIFY | Summary: Refine sulfur-compound metabolism to CHST3-mediated chondroitin-sulfate biosynthesis. Reason: PMID:9883891 directly assays chondroitin sulfation, supporting the more specific biosynthetic process. The refinement converges on the same paper’s existing GO:0050650 annotation rather than adding a new claim; the original broad IDA assertion remains preserved. Proposed replacements: chondroitin sulfate proteoglycan biosynthetic process |
| GO:0006790 sulfur compound metabolic process | IEA GO_REF:0000117 | MODIFY | Summary: Refine sulfur-compound metabolism to CHST3-mediated chondroitin-sulfate biosynthesis. Reason: The broad ARBA sulfur-metabolism assertion is chemically correct. Human sulfate-transfer assays support the specific chondroitin sulfate biosynthetic step, converging on existing GO:0050650 coverage without changing the rule output or adding an assertion. Proposed replacements: chondroitin sulfate proteoglycan biosynthetic process |
| GO:0008146 sulfotransferase activity | IEA GO_REF:0000002 | MODIFY | Summary: Use the substrate-specific chondroitin 6-sulfotransferase activity. Reason: The InterPro-derived sulfotransferase class is correct. Human product assays support the specific chondroitin GalNAc-6 activity, already present as GO:0008459; the separate keratan capability is retained. Proposed replacements: chondroitin 6-sulfotransferase activity |
| GO:0008459 chondroitin 6-sulfotransferase activity | EXP PMID:9714738 Molecular cloning and expression of human chondroitin 6-sulf... | ACCEPT | Summary: CHST3 directly catalyzes chondroitin GalNAc-6 sulfation. Reason: The original cloning annotation is retained, with independent direct human recombinant product assays in PMID:9883891 and PMID:15215498 corroborating the activity. The selected PMID:9714738 cache itself is abstract-only. |
| GO:0008459 chondroitin 6-sulfotransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: CHST3 directly catalyzes chondroitin GalNAc-6 sulfation. Reason: Human recombinant product assays directly establish chondroitin GalNAc-6 sulfation (PMID:9883891; PMID:15215498), corroborating the curated PTN002581850 transfer. The current source includes legitimate target experimental evidence; historical node placement was not reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002581850 SUPPORTS TRANSFER The curated PTN002581850 transfer is corroborated by direct human chondroitin 6-sulfotransferase assays and current experimental source records. Historical IBD placement/MSA was not independently reconstructed. |
| GO:0008459 chondroitin 6-sulfotransferase activity | IDA PMID:15215498 Loss of chondroitin 6-O-sulfotransferase-1 function results ... | ACCEPT | Summary: CHST3 directly catalyzes chondroitin GalNAc-6 sulfation. Reason: Human soluble CHST3, with residues 1–48 replaced by an insulin-signal/protein-A fusion, was expressed in COS-1 cells and captured on IgG-Sepharose. PAPS-dependent chondroitin sulfation and product analysis showed WT activity and loss with R304Q (PMID:15215498). Supporting Evidence: PMID:15215498 R304Q-mutated C6ST-1 did not show any detectable activity |
| GO:0008459 chondroitin 6-sulfotransferase activity | IDA PMID:9883891 Functional expression and genomic structure of human chondro... | ACCEPT | Summary: CHST3 directly catalyzes chondroitin GalNAc-6 sulfation. Reason: Human soluble recombinant enzyme in COS-1 cells transferred sulfate to GalNAc position 6 in the GlcA-linked chondroitin context. The product specificity distinguishes it from dermatan IdoA-linked sequences and pre-4-sulfated GalNAc substrates. |
| GO:0008459 chondroitin 6-sulfotransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: CHST3 directly catalyzes chondroitin GalNAc-6 sulfation. Reason: EC:2.8.2.17, RHEA:11108 and mouse Chst3/O88199 agree with the independently measured human chondroitin GalNAc-6 reaction. |
| GO:0008459 chondroitin 6-sulfotransferase activity | TAS Reactome:R-HSA-2018682 | ACCEPT | Summary: CHST3 directly catalyzes chondroitin GalNAc-6 sulfation. Reason: The actual Reactome reaction represents PAPS-dependent GalNAc-6 sulfation by the CHST3/CHST7 catalyst set. Independent human assays establish the CHST3 member rather than relying only on set membership. |
| GO:0008459 chondroitin 6-sulfotransferase activity | TAS Reactome:R-HSA-3595175 | ACCEPT | Summary: CHST3 directly catalyzes chondroitin GalNAc-6 sulfation. Reason: The original Reactome event models loss of transfer by defective CHST3. It describes the affected normal chemistry, not a claim that the assayed R304Q mutant remains active. WT recombinant CHST3 activity is independently demonstrated. |
| GO:0018146 keratan sulfate proteoglycan biosynthetic process | TAS Reactome:R-HSA-2022854 | KEEP AS NON CORE | Summary: Keratan-sulfate biosynthesis is retained as a secondary substrate context. Reason: Recombinant human CHST3 utilization of corneal keratan sulfate supports a secondary sulfation role (PMID:9883891, Results 3.2, data not shown). It does not establish dominance over dedicated keratan enzymes or verify the separate GlcNAc-specific Reactome assignment. Supporting Evidence: Reactome:R-HSA-2022854 file:human/CHST3/CHST3-uniprot.txt Gal residues of keratan sulfate, another glycosaminoglycan |
| GO:0045130 keratan sulfotransferase activity | EXP PMID:9714738 Molecular cloning and expression of human chondroitin 6-sulf... | KEEP AS NON CORE | Summary: Keratan sulfotransferase activity is a supported secondary capability. Reason: The original experimental keratan capability is independently corroborated by recombinant human utilization in PMID:9883891, Results 3.2 (data not shown). UniProt curates Gal C6 as the keratan acceptor residue; that residue assignment is distinguished from the displayed GalNAc product analysis in the later paper. Keratan activity remains secondary. Supporting Evidence: file:human/CHST3/CHST3-uniprot.txt Gal residues of keratan sulfate, another glycosaminoglycan |
| GO:0045130 keratan sulfotransferase activity | IEA GO_REF:0000003 | KEEP AS NON CORE | Summary: Keratan sulfotransferase activity is a supported secondary capability. Reason: EC:2.8.2.21 is a broad keratan sulfotransferase category. Human keratan utilization in PMID:9883891 supports this secondary capability; UniProt curates Gal C6 transfer. The broad EC mapping does not establish GlcNAc-specific activity. Supporting Evidence: file:human/CHST3/CHST3-uniprot.txt Gal residues of keratan sulfate, another glycosaminoglycan |
| GO:0050650 chondroitin sulfate proteoglycan biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: CHST3 performs the GalNAc-6 sulfation step in chondroitin-sulfate biosynthesis. Reason: Human CHST3 directly performs the sulfate-transfer step, corroborating the curated PTN002581850 process transfer. The current mouse, rat and human source records support biosynthesis; historical node placement was not reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002581850 SUPPORTS TRANSFER The curated PTN002581850 transfer and human recombinant/patient-cell evidence support the biosynthetic role. Current source evidence supports transfer without a claim to have reconstructed the historical tree/MSA. |
| GO:0050650 chondroitin sulfate proteoglycan biosynthetic process | IDA PMID:9883891 Functional expression and genomic structure of human chondro... | ACCEPT | Summary: CHST3 performs the GalNAc-6 sulfation step in chondroitin-sulfate biosynthesis. Reason: The human recombinant enzyme directly performs sulfate transfer onto chondroitin, a modifying step in formation of chondroitin sulfate chains. |
| GO:0050650 chondroitin sulfate proteoglycan biosynthetic process | IEA GO_REF:0000117 | ACCEPT | Summary: CHST3 performs the GalNAc-6 sulfation step in chondroitin-sulfate biosynthesis. Reason: The ARBA process prediction is independently supported by direct target catalysis and human-cell glycan product analysis, rather than accepted solely as a model prediction. |
| GO:0050650 chondroitin sulfate proteoglycan biosynthetic process | IMP PMID:15215498 Loss of chondroitin 6-O-sulfotransferase-1 function results ... | ACCEPT | Summary: CHST3 performs the GalNAc-6 sulfation step in chondroitin-sulfate biosynthesis. Reason: Patient fibroblasts carrying R304Q have deficient C6 sulfotransferase activity and altered chondroitin-sulfate products; the matching recombinant WT/mutant assays identify CHST3 as the enzyme that performs the missing step. |
| GO:0050650 chondroitin sulfate proteoglycan biosynthetic process | TAS Reactome:R-HSA-2022870 | ACCEPT | Summary: CHST3 performs the GalNAc-6 sulfation step in chondroitin-sulfate biosynthesis. Reason: Reactome 2022870 contains the specific CHST3 reaction. Human recombinant sulfate-transfer assays independently establish the modifying step in chondroitin sulfate biosynthesis (PMID:9883891; PMID:15215498). |
| GO:0050698 proteoglycan sulfotransferase activity | IEA GO_REF:0000120 | MODIFY | Summary: Use the substrate-specific chondroitin 6-sulfotransferase activity. Reason: The broad proteoglycan sulfotransferase class is sound. Human CHST3 biochemistry supports the specific chondroitin GalNAc-6 reaction, converging on existing GO:0008459 coverage. Proposed replacements: chondroitin 6-sulfotransferase activity |
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Download this section (compressed HTML)Q: Does human CHST3 sulfate GlcNAc in any defined physiological glycan, and what experimental and phylogenetic evidence places that specificity at PTN002473209?
Suggested experts: Glycosaminoglycan enzymology, PAINT curation
Q: How much of keratan Gal-6 sulfation is performed by CHST3 in native tissues relative to CHST1, and which acceptor structures distinguish their roles?
Experiment: Compare sequence-verified human CHST3 with established GlcNAc-6 and Gal-6 sulfotransferases on chemically defined glycan acceptors, using positional product analysis and matched inactive controls. Resolve GalNAc, Gal and GlcNAc reactions separately rather than inferring residue specificity from bulk keratan sulfate incorporation.
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