B4GALT7 encodes a 327-residue, manganese-dependent type-II Golgi membrane glycosyltransferase of the GT7 family. Its lumen-facing catalytic domain transfers galactose from UDP-galactose to xylose attached to a serine of a proteoglycan core protein, forming a beta1,4 linkage. This first galactose is the second sugar of the shared tetrasaccharide linker used to assemble chondroitin sulfate, dermatan sulfate, heparan sulfate and heparin proteoglycans. Defective linker synthesis impairs proteoglycan glycanation and extracellular-matrix organization; biallelic pathogenic variants cause a spondylodysplastic Ehlers-Danlos syndrome.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000139 Golgi membrane | IEA GO_REF:0000117 | ACCEPT | Summary: Golgi membrane is the site of the membrane-anchored linker enzyme. Reason: The type-II membrane enzyme adds the first galactose to the proteoglycan linker at the Golgi. Independent localization and the curated reaction support this compartment; the disease reaction describes disruption of the normal enzyme activity, not relocation of every mutant. |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-1889981 | ACCEPT | Summary: Golgi membrane is the site of the membrane-anchored linker enzyme. Reason: The type-II membrane enzyme adds the first galactose to the proteoglycan linker at the Golgi. Independent localization and the curated reaction support this compartment; the disease reaction describes disruption of the normal enzyme activity, not relocation of every mutant. |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-3560804 | ACCEPT | Summary: Golgi membrane is the site of the membrane-anchored linker enzyme. Reason: The type-II membrane enzyme adds the first galactose to the proteoglycan linker at the Golgi. Independent localization and the curated reaction support this compartment; the disease reaction describes disruption of the normal enzyme activity, not relocation of every mutant. |
| GO:0003831 beta-N-acetylglucosaminylglycopeptide beta-1,4-galactosyltransferase activity | IDA PMID:24052259 Crystal structures of Ξ²-1,4-galactosyltransferase 7 enzyme r... | MODIFY | Summary: The demonstrated acceptor is xylose on the proteoglycan linker. Reason: B4GALT7 transfers galactose to xylose in proteoglycan-linker synthesis. The experiments in PMID:24052259 characterize this xylose-directed reaction; GlcNAc-directed B4GALT1 is a comparison. GO:0003831 instead specifies a GlcNAc glycopeptide acceptor. GO:0046525 captures the experimentally supported B4GALT7 activity. Proposed replacements: xylosylprotein 4-beta-galactosyltransferase activity Supporting Evidence: PMID:10438455 galactosyltransferase activity specific for p-nitrophenyl-beta-D-xylopyranoside. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: A curated binary interaction is retained outside the catalytic core. Reason: The IPI assertion records an interaction with UniProtKB:P53611 in the cited interactome study. This binary interaction does not establish a substrate, stable functional complex, or regulatory mechanism for B4GALT7. It is retained as non-core interaction evidence; the specific supplementary pair record was not independently inspected. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: A curated binary interaction is retained outside the catalytic core. Reason: The IPI assertion records an interaction with UniProtKB:P60409 in the cited interactome study. This binary interaction does not establish a substrate, stable functional complex, or regulatory mechanism for B4GALT7. It is retained as non-core interaction evidence; the specific supplementary pair record was not independently inspected. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: A curated binary interaction is retained outside the catalytic core. Reason: The IPI assertion records an interaction with UniProtKB:A8MQ03 in the cited interactome study. This binary interaction does not establish a substrate, stable functional complex, or regulatory mechanism for B4GALT7. It is retained as non-core interaction evidence; the specific supplementary pair record was not independently inspected. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: A curated binary interaction is retained outside the catalytic core. Reason: The IPI assertion records an interaction with UniProtKB:P53611 in the cited interactome study. This binary interaction does not establish a substrate, stable functional complex, or regulatory mechanism for B4GALT7. It is retained as non-core interaction evidence; the specific supplementary pair record was not independently inspected. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: A curated binary interaction is retained outside the catalytic core. Reason: The IPI assertion records an interaction with UniProtKB:Q15323 in the cited interactome study. This binary interaction does not establish a substrate, stable functional complex, or regulatory mechanism for B4GALT7. It is retained as non-core interaction evidence; the specific supplementary pair record was not independently inspected. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: A curated binary interaction is retained outside the catalytic core. Reason: The IPI assertion records an interaction with UniProtKB:Q9NUH8 in the cited interactome study. This binary interaction does not establish a substrate, stable functional complex, or regulatory mechanism for B4GALT7. It is retained as non-core interaction evidence; the specific supplementary pair record was not independently inspected. Supporting Evidence: |
| GO:0005794 Golgi apparatus | IBA GO_REF:0000033 | ACCEPT | Summary: Golgi localization is consistent with the curated phylogenetic inference. Reason: The PAINT Golgi-localization inference agrees with independent localization of the human enzyme and its role in proteoglycan-linker synthesis. |
| GO:0005794 Golgi apparatus | IDA PMID:10506123 Molecular basis for the progeroid variant of Ehlers-Danlos s... | ACCEPT | Summary: Wild-type human enzyme shows Golgi localization. Reason: The abstract reports a Golgi staining pattern for wild-type and A186D constructs, whereas L206P is diffusely cytoplasmic. Preserve the wild-type location without assigning all mutant proteins the same distribution. Full microscopy methods were not available. Supporting Evidence: |
| GO:0005794 Golgi apparatus | IDA PMID:34533190 A quantitative study of the Golgi retention of glycosyltrans... | ACCEPT | Summary: The curated Golgi localization agrees with independent human evidence. Reason: The curated Golgi-localization assertion is corroborated by the independent wild-type localization in PMID:10506123. The available abstract of PMID:34533190 describes a systematic Golgi-retention study; its target-specific constructs and localization measurements were not available for assessment. |
| GO:0005975 carbohydrate metabolic process | IEA GO_REF:0000002 | MODIFY | Summary: The broad carbohydrate description can be replaced by the demonstrated linker-building step. Reason: B4GALT7 transfers galactose to protein-linked xylose during glycosaminoglycan-protein linker synthesis. GO:0120532 identifies that biochemical role more precisely than the broad InterPro-derived carbohydrate-metabolism assignment. Proposed replacements: glycosaminoglycan-protein linkage region biosynthetic process |
| GO:0006024 glycosaminoglycan biosynthetic process | IDA PMID:10438455 Human homolog of Caenorhabditis elegans sqv-3 gene is galact... | ACCEPT | Summary: The linker reaction contributes directly to glycosaminoglycan biosynthesis. Reason: B4GALT7 catalyzes an actual glycosyl-transfer step, rather than merely being required by perturbation. Human enzyme expression rescues defective GAG synthesis and xyloside-priming experiments connect acceptor transfer to chain initiation. The shared linker serves chondroitin/dermatan/heparan sulfate and heparin proteoglycans; this does not extend the reaction to every GAG class. |
| GO:0006024 glycosaminoglycan biosynthetic process | IDA PMID:20809901 Biochemical and thermodynamic characterization of mutated Ξ²1... | ACCEPT | Summary: The linker reaction contributes directly to glycosaminoglycan biosynthesis. Reason: B4GALT7 catalyzes an actual glycosyl-transfer step, rather than merely being required by perturbation. Human enzyme expression rescues defective GAG synthesis and xyloside-priming experiments connect acceptor transfer to chain initiation. The shared linker serves chondroitin/dermatan/heparan sulfate and heparin proteoglycans; this does not extend the reaction to every GAG class. |
| GO:0006024 glycosaminoglycan biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: The linker reaction contributes directly to glycosaminoglycan biosynthesis. Reason: B4GALT7 catalyzes an actual glycosyl-transfer step, rather than merely being required by perturbation. Human enzyme expression rescues defective GAG synthesis and xyloside-priming experiments connect acceptor transfer to chain initiation. The shared linker serves chondroitin/dermatan/heparan sulfate and heparin proteoglycans; this does not extend the reaction to every GAG class. |
| GO:0006029 proteoglycan metabolic process | IMP PMID:16583246 Defective glycosylation of decorin and biglycan, altered col... | MODIFY | Summary: Specify proteoglycan biosynthesis within the broader metabolic annotation. Reason: The observed defect is in synthesis of the carbohydrate linker on proteoglycans. Human-enzyme activity and the reduced glycanation of decorin/biglycan support a biosynthetic role; the evidence does not establish a proteoglycan degradation function. Proposed replacements: proteoglycan biosynthetic process |
| GO:0006029 proteoglycan metabolic process | TAS PMID:10473568 Cloning and expression of a proteoglycan UDP-galactose:beta-... | MODIFY | Summary: Specify proteoglycan biosynthesis within the broader metabolic annotation. Reason: The observed defect is in synthesis of the carbohydrate linker on proteoglycans. Human-enzyme activity and the reduced glycanation of decorin/biglycan support a biosynthetic role; the evidence does not establish a proteoglycan degradation function. Proposed replacements: proteoglycan biosynthetic process |
| GO:0006487 protein N-linked glycosylation | IDA PMID:24052259 Crystal structures of Ξ²-1,4-galactosyltransferase 7 enzyme r... | MODIFY | Summary: The demonstrated process builds the O-serine-linked proteoglycan linker. Reason: B4GALT7 catalyzes xylose-directed proteoglycan-linker synthesis, as characterized in PMID:24052259. GO:0006487 instead specifies Asn-linked protein glycosylation. N-glycosylation of B4GALT7 itself would not establish that it catalyzes this process; GO:0120532 describes the supported biosynthetic step. Proposed replacements: glycosaminoglycan-protein linkage region biosynthetic process Supporting Evidence: PMID:10473568 first galactose in the proteoglycan linkage region GlcAbeta1-3Galbeta1-3Galbeta1-4Xylbeta1-O-Ser. |
| GO:0008378 galactosyltransferase activity | IDA PMID:10506123 Molecular basis for the progeroid variant of Ehlers-Danlos s... | MODIFY | Summary: Specify xylosylprotein-directed beta1,4-galactose transfer. Reason: The broad galactosyltransferase label omits the acceptor specificity established by human enzyme expression, product analysis and mutant activity measurements. The more specific term describes UDP-galactose transfer to O-linked xylose. Variant effects remain allele-specific. Proposed replacements: xylosylprotein 4-beta-galactosyltransferase activity |
| GO:0008378 galactosyltransferase activity | IMP PMID:16583246 Defective glycosylation of decorin and biglycan, altered col... | MODIFY | Summary: Specify xylosylprotein-directed beta1,4-galactose transfer. Reason: The broad galactosyltransferase label omits the acceptor specificity established by human enzyme expression, product analysis and mutant activity measurements. The more specific term describes UDP-galactose transfer to O-linked xylose. Variant effects remain allele-specific. Proposed replacements: xylosylprotein 4-beta-galactosyltransferase activity |
| GO:0008378 galactosyltransferase activity | TAS PMID:10473568 Cloning and expression of a proteoglycan UDP-galactose:beta-... | MODIFY | Summary: Specify xylosylprotein-directed beta1,4-galactose transfer. Reason: The broad galactosyltransferase label omits the acceptor specificity established by human enzyme expression, product analysis and mutant activity measurements. The more specific term describes UDP-galactose transfer to O-linked xylose. Variant effects remain allele-specific. Proposed replacements: xylosylprotein 4-beta-galactosyltransferase activity |
| GO:0016020 membrane | IDA PMID:10438455 Human homolog of Caenorhabditis elegans sqv-3 gene is galact... | MODIFY | Summary: The supported membrane location can be specified as the Golgi membrane. Reason: The cloning study identifies a type-II membrane enzyme, and independent localization places wild-type B4GALT7 at the Golgi. Together these data support Golgi membrane localization. They do not independently resolve a particular Golgi cisterna. Proposed replacements: Golgi membrane |
| GO:0016757 glycosyltransferase activity | IEA GO_REF:0000002 | MODIFY | Summary: Replace the broad glycosyltransferase category with the demonstrated reaction. Reason: The transfer uses UDP-galactose as donor and protein-linked xylose as acceptor, with a beta1,4 linkage. This experimentally established specificity refines the broad InterPro assignment. Proposed replacements: xylosylprotein 4-beta-galactosyltransferase activity |
| GO:0030145 manganese ion binding | IDA PMID:24052259 Crystal structures of Ξ²-1,4-galactosyltransferase 7 enzyme r... | ACCEPT | Summary: Manganese is part of the catalytic cofactor environment. Reason: Human catalytic-domain crystal structures contain Mn and UDP in the active-site pocket. This supports enzyme-associated manganese binding; it is integrated into the glycosyltransferase core and does not imply an independent metal-homeostasis role. Supporting Evidence: file:human/B4GALT7/B4GALT7-uniprot.txt Name=Mn(2+); Xref=ChEBI:CHEBI:29035; |
| GO:0030166 proteoglycan biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: The curated phylogenetic annotation matches the direct biosynthetic reaction. Reason: The PAINT proteoglycan-biosynthesis inference is corroborated by human enzyme expression and product analysis showing galactose addition to the proteoglycan linker. |
| GO:0032580 Golgi cisterna membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Golgi cisterna membrane is a supported enzyme location. Reason: The UniProt subcellular-location mapping is consistent with type-II topology and independent Golgi localization. The luminal orientation follows the annotated topology; experimental staining alone does not establish every membrane boundary. |
| GO:0036211 protein modification process | TAS PMID:10473568 Cloning and expression of a proteoglycan UDP-galactose:beta-... | MODIFY | Summary: Specify synthesis of the protein-linked glycosaminoglycan linker. Reason: The cited expression study identifies galactose addition to xylose attached to a proteoglycan core protein. Glycosaminoglycan-protein linkage-region biosynthesis describes this demonstrated role more precisely than general protein modification. Proposed replacements: glycosaminoglycan-protein linkage region biosynthetic process Supporting Evidence: |
| GO:0046525 xylosylprotein 4-beta-galactosyltransferase activity | EXP PMID:24052259 Crystal structures of Ξ²-1,4-galactosyltransferase 7 enzyme r... | ACCEPT | Summary: B4GALT7 catalyzes the xylose-directed first galactose addition. Reason: The specific term matches the human enzyme reaction: UDP-galactose donates galactose to O-linked xylose, forming the first galactose of the proteoglycan linker. Human expression, product analysis and acceptor-binding assays support the assignment. The structural study distinguishes human catalytic-domain structures from the Drosophila D211N donor/acceptor complex; the latter is not presented as human wild-type ternary crystallography. |
| GO:0046525 xylosylprotein 4-beta-galactosyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: B4GALT7 catalyzes the xylose-directed first galactose addition. Reason: The PAINT activity inference agrees with the human enzyme reaction: UDP-galactose donates galactose to O-linked xylose, forming the first galactose of the proteoglycan linker. Human expression, product analysis and acceptor-binding assays independently support the assignment. |
| GO:0046525 xylosylprotein 4-beta-galactosyltransferase activity | IDA PMID:10438455 Human homolog of Caenorhabditis elegans sqv-3 gene is galact... | ACCEPT | Summary: B4GALT7 catalyzes the xylose-directed first galactose addition. Reason: The specific term matches the human enzyme reaction: UDP-galactose donates galactose to O-linked xylose, forming the first galactose of the proteoglycan linker. Human expression, product analysis and acceptor-binding assays support the assignment. |
| GO:0046525 xylosylprotein 4-beta-galactosyltransferase activity | IDA PMID:20809901 Biochemical and thermodynamic characterization of mutated Ξ²1... | ACCEPT | Summary: B4GALT7 catalyzes the xylose-directed first galactose addition. Reason: The specific term matches the human enzyme reaction: UDP-galactose donates galactose to O-linked xylose, forming the first galactose of the proteoglycan linker. Human expression, product analysis and acceptor-binding assays support the assignment. |
| GO:0046525 xylosylprotein 4-beta-galactosyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: B4GALT7 catalyzes the xylose-directed first galactose addition. Reason: The specific term matches the human enzyme reaction: UDP-galactose donates galactose to O-linked xylose, forming the first galactose of the proteoglycan linker. Human expression, product analysis and acceptor-binding assays support the assignment. |
| GO:0046525 xylosylprotein 4-beta-galactosyltransferase activity | TAS Reactome:R-HSA-1889981 | ACCEPT | Summary: B4GALT7 catalyzes the xylose-directed first galactose addition. Reason: The specific term matches the human enzyme reaction: UDP-galactose donates galactose to O-linked xylose, forming the first galactose of the proteoglycan linker. Human expression, product analysis and acceptor-binding assays support the assignment. |
| GO:0046525 xylosylprotein 4-beta-galactosyltransferase activity | TAS Reactome:R-HSA-3560804 | ACCEPT | Summary: B4GALT7 catalyzes the xylose-directed first galactose addition. Reason: The specific term matches the human enzyme reaction: UDP-galactose donates galactose to O-linked xylose, forming the first galactose of the proteoglycan linker. Human expression, product analysis and acceptor-binding assays support the assignment. The disease reaction reports disruption of this normal activity; A186D and R270C can retain activity and should not be summarized as universally null. |
| GO:0048147 negative regulation of fibroblast proliferation | IMP PMID:16583246 Defective glycosylation of decorin and biglycan, altered col... | UNDECIDED | Summary: The direction of the fibroblast-proliferation assertion remains unresolved. Reason: The abstract of PMID:16583246 reports reduced proliferation in R270C patient fibroblasts with reduced enzyme activity. The associated cellular abnormalities make it unclear whether this reflects a specific regulatory role or secondary cell dysfunction. The unavailable full paper is needed to resolve the direction of the experimental proliferation annotation. Supporting Evidence: PMID:16583246 decreased proliferation rates. |
| GO:0097435 supramolecular fiber organization | IMP PMID:16583246 Defective glycosylation of decorin and biglycan, altered col... | KEEP AS NON CORE | Summary: Altered collagen fibrils are a downstream phenotype of deficient proteoglycan glycanation. Reason: Patient fibroblasts display abnormal collagen suprastructures along with defective decorin/biglycan glycanation. Retain the IMP phenotype outside the enzyme core; it does not demonstrate that B4GALT7 itself is a collagen-assembly scaffold or extracellular fibril component. Supporting Evidence: PMID:16583246 the collagen suprastructures were altered |
| GO:0120532 glycosaminoglycan-protein linkage region biosynthetic process | TAS Reactome:R-HSA-1971475 | ACCEPT | Summary: The enzyme catalyzes the second sugar-addition step of the common proteoglycan linker. Reason: B4GALT7 adds the first galactose to xylose on a core-protein serine, contributing directly to the linker used for chondroitin/dermatan/heparan sulfate or heparin chains. The subsequent galactose and glucuronate additions are performed by other enzymes. |
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Download this section (compressed HTML)Q: Which full-text experiment underlies the negative-regulation-of-fibroblast-proliferation annotation from PMID:16583246, given the abstract reports reduced proliferation in the deficient cells?
Q: Should the GlcNAc-specific activity and N-linked glycosylation assertions citing PMID:24052259, and the GlcNAc ligand label in the raw UniProt binding-site feature, be reconciled with the demonstrated xylose-specific proteoglycan-linker reaction?
Q: How do partial-activity B4GALT7 alleles alter linker occupancy and the different downstream proteoglycan classes in human connective tissues?
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