FKRP is a Golgi membrane ribitol-phosphate transferase that extends the phosphorylated core M3 O-mannosyl glycan of alpha-dystroglycan. It transfers a second ribitol-phosphate unit from CDP-ribitol onto the ribitol-phosphate previously installed by fukutin, forming the tandem linker required for subsequent assembly of the matrix-binding matriglycan chain. Its luminal catalytic and stem domains cooperate across a protomer pair to recognize the glycan acceptor. FKRP associates with fukutin and RXYLT1 in an enzymatically active complex. Impaired FKRP activity disrupts functional dystroglycan glycosylation and causes a spectrum of recessive muscular dystrophies.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000139 Golgi membrane | EXP PMID:17554798 Fukutin-related protein localizes to the Golgi apparatus and... | ACCEPT | Summary: Normal FKRP localizes to the Golgi in the human and mouse systems reported in this study. Reason: PMID:17554798 explicitly reports Golgi localization of normal human and mouse FKRP in muscle fibers and altered localization of mutants. The recovered abstract supports the organelle assignment; the full Methods, tags and exact endogenous-versus-expressed preparations were not recovered. Independent endogenous human muscle evidence in PMID:21886772 and the membrane topology support this core location. Preserve the original EXP context without claiming an independently inspected membrane-insertion assay. |
| GO:0000139 Golgi membrane | EXP PMID:21886772 Fukutin-related protein resides in the Golgi cisternae of sk... | ACCEPT | Summary: Endogenous FKRP is detected in Golgi cisternae of human skeletal muscle. Reason: PMID:21886772 uses affinity-purified peptide antibodies and double immunogold microscopy of a control human rectus femoris specimen, with MG160 colocalization and separation from PDI and beta-dystroglycan. This supports Golgi residence together with the membrane-protein organization. The result is specimen-specific and does not establish that all other reported cellular pools are absent. |
| GO:0000139 Golgi membrane | EXP PMID:25279699 The glucuronyltransferase B4GAT1 is required for initiation ... | ACCEPT | Summary: The inspected ortholog experiment supports the conserved Golgi localization of FKRP. Reason: PMID:25279699 reports Giantin colocalization in HEK293T cells. The cloning Methods identify mouse Fkrp pTW323, whereas the companion FKTN construct is human; the human host does not make the FKRP insert human. Retain the supplied EXP annotation because the Golgi function is independently supported in human muscle by PMID:21886772. Preserve the original provenance and disclose the ortholog construct boundary. |
| GO:0000139 Golgi membrane | IBA GO_REF:0000033 | ACCEPT | Summary: The Golgi-membrane IBA follows a verified ancestral assertion on the human FKRP lineage. Reason: The original PAINT IBD for GO:0000139 is placed at PANTHER:PTN001007059, which lies on the human Q9H9S5 path in the complete 102-node PTHR13627 tree. Endogenous human localization in PMID:21886772 independently agrees with the inherited location. Human FKRP among the experimental seeds is legitimate grounding of the ancestral inference, not circularity. The source guide records the separate topology, IBD and GOA receipts. |
| GO:0000139 Golgi membrane | IDA PMID:26923585 Identification of a Post-translational Modification with Rib... | ACCEPT | Summary: The curated Golgi-membrane localization agrees with independent human evidence. Reason: The cached PMID:26923585 abstract establishes the ribitol-phosphate pathway but does not reconstruct its localization assay. Retain the original curated IDA for a location supported independently by human muscle microscopy in PMID:21886772 and FKRP membrane organization. This acceptance does not claim that the unavailable full Methods or membrane topology experiment in PMID:26923585 was inspected. |
| GO:0000139 Golgi membrane | IDA PMID:29477842 Cell endogenous activities of fukutin and FKRP coexist with ... | ACCEPT | Summary: FKRP is assigned to the Golgi membrane in both source contexts represented by this seeded row. Reason: PMID:29477842 reports association of FKTN, FKRP and TMEM5/RXYLT1 with retained enzyme activities; the author-deposited doctoral summary describes GM130 colocalization of tagged proteins. The full journal Methods and exact construct provenance were not recovered. Colocalization supports the Golgi compartment, while membrane placement also uses curated topology and independent human evidence in PMID:21886772. QuickGO contexts 357933270 (UniProt) and 357933271 (ComplexPortal) project to this one identical seeded annotation; both are retained in the source TSV and evidence guide. |
| GO:0000139 Golgi membrane | IEA GO_REF:0000044 | ACCEPT | Summary: The UniProt subcellular-location mapping identifies the core Golgi-membrane pool. Reason: GO_REF:0000044 maps UniProt SL-0134 to Golgi membrane. The assignment agrees with endogenous human muscle localization in PMID:21886772 and the annotated single-pass type II membrane organization. Retain this electronic context as its own provenance; it does not imply exclusive Golgi localization in every specimen. |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-9940735 | ACCEPT | Summary: FKRP is a Golgi-localized member of the complex containing the first-step enzyme FKTN. Reason: Reactome:R-HSA-9940735 describes FKTN transfer of the first ribitol-phosphate to the phosphorylated core M3 acceptor in a complex containing FKRP. Its compartment is consistent with the independently established Golgi-membrane localization of FKRP. Retain the location annotation without assigning FKTN first-transfer chemistry to FKRP. Supporting Evidence: Reactome:R-HSA-9940735 file:human/FKRP/FKRP-source-evidence.md |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-9940756 | ACCEPT | Summary: The FKRP ribitol-phosphate transfer reaction is modeled at the Golgi membrane. Reason: Reactome:R-HSA-9940756 describes the FKRP second-transfer step in the glycan biosynthetic complex. The associated Golgi-membrane annotation is consistent with human localization and biochemical evidence. The modeled Mg2+ cofactor does not independently determine which catalytic metal is used in cells; PMID:31949166 tests metal support in vitro and leaves the cellular metal unresolved. Supporting Evidence: Reactome:R-HSA-9940756 file:human/FKRP/FKRP-source-evidence.md |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-9940805 | ACCEPT | Summary: FKRP shares the Golgi compartment with the complex containing RXYLT1. Reason: Reactome:R-HSA-9940805 describes the RXYLT1 xylosyl-transfer step in a complex containing FKRP. Retain its compatible Golgi-membrane context. Complex membership does not transfer the partner xylosyltransferase activity to FKRP, whose demonstrated reaction is ribitol-phosphate transfer. Supporting Evidence: Reactome:R-HSA-9940805 file:human/FKRP/FKRP-source-evidence.md |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-9948070 | ACCEPT | Summary: The modeled assembly containing FKRP occupies the Golgi membrane. Reason: Reactome:R-HSA-9948070 models formation of the FKRP:FKTN:RXYLT1 complex in the Golgi compartment. Its FKRP location agrees with independent human evidence and is retained. This location row neither asserts that FKRP catalyzes assembly nor proves the modeled POMGNT1-dependent assembly mechanism. Supporting Evidence: Reactome:R-HSA-9948070 file:human/FKRP/FKRP-source-evidence.md |
| GO:0005515 protein binding | IPI PMID:27601598 Direct Mapping of Additional Modifications on Phosphorylated... | KEEP AS NON CORE | Summary: Tagged human FKRP associates with FKTN in cellular co-immunoprecipitation experiments. Reason: PMID:27601598 uses tagged human proteins in HEK293T and recovers FKRP with FKTN in the interaction experiments. These assays support association, with the controls described in the primary paper, but do not establish a purified binary contact or an informative alternative molecular function. Keep the supported generic interaction as non-core under the project instruction; do not transfer a partner enzyme activity to FKRP. |
| GO:0005515 protein binding | IPI PMID:29477842 Cell endogenous activities of fukutin and FKRP coexist with ... | KEEP AS NON CORE | Summary: FKRP associates with FKTN and TMEM5/RXYLT1 in an enzymatically active preparation. Reason: The PMID:29477842 abstract and author-deposited summary support complex recovery and retained enzyme activities, including recovery of endogenous FKRP activity with expressed TMEM5. Endogenous FKRP protein was not independently visualized in the summary immunoblot, and the full journal Methods remain unavailable. The evidence supports a non-core association annotation, without asserting direct pairwise contact, fixed stoichiometry or substrate channeling. |
| GO:0005576 extracellular region | IDA PMID:19900540 Mutations alter secretion of fukutin-related protein. | KEEP AS NON CORE | Summary: FKRP secretion into culture medium is a reported experimental context. Reason: PMID:19900540 explicitly reports normal FKRP in CHO culture medium, reduced secretion of L276I and little secretion of P448L/C318Y; the E310X truncation also appeared in medium. Retain the extracellular observation as non-core. Exact construct species, tags and endogenous tissue secretion were not independently established from the recovered abstract. Artificially secreted constructs in later enzyme assays are not independent evidence for a native extracellular catalytic role. |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The UniProt mapping retains a reported extracellular FKRP pool. Reason: GO_REF:0000044 maps SL-0243 to extracellular region, consistent with the culture-medium secretion reported in PMID:19900540. Retain this contextual location as non-core to the Golgi glycan-transfer role. The mapping does not show that extracellular catalysis is physiologically important or that soluble experimental constructs are natural alternative products. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | TOO GENERAL | Summary: Cytoplasm is true but already entailed by the accepted Golgi localization. Reason: The official GO path is GO:0000139 Golgi membrane part_of GO:0005794 Golgi apparatus part_of GO:0005737 cytoplasm. The accepted, experimentally supported Golgi annotations therefore already entail this broad SL-0086 mapping. TOO_GENERAL judges the term's precision, not the truth or provenance of this electronic assertion. It does not exclude additional intracellular pools, imply soluble cytosolic catalysis, or place the glycan acceptor on the cytosolic face of a membrane. |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | TOO GENERAL | Summary: Cytoplasm is true but already entailed by the accepted Golgi localization. Reason: The WITH/FROM donor UniProtKB:Q8CG64 is verified mouse Fkrp; its original donor experiment was not independently replayed. The official GO path is GO:0000139 Golgi membrane part_of GO:0005794 Golgi apparatus part_of GO:0005737 cytoplasm. The accepted target Golgi annotations already entail this broad term, so TOO_GENERAL judges its precision rather than rejecting the ortholog transfer or claiming a distinct cytosolic pool. No source misattribution, false localization, or negative localization evidence is inferred from the unreplayed donor experiment. |
| GO:0005791 rough endoplasmic reticulum | IDA PMID:15213246 Subcellular localization of fukutin and fukutin-related prot... | KEEP AS NON CORE | Summary: Endogenous FKRP has been detected in rough ER in muscle-cell preparations. Reason: The original PMID:15213246 article reports endogenous FKRP in differentiated human myotubes, mouse C2C12 cells and a normal human muscle biopsy, with calnexin/BiP overlap and separation from much of the GM130 pattern. This is not solely mutant retention or ectopic expression. Retain the experimental rough-ER context as non-core while the broader evidence supports Golgi glycan catalysis. Partial overlap and differing specimens prevent an exclusive localization conclusion. |
| GO:0005791 rough endoplasmic reticulum | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The UniProt rough-ER mapping has original experimental support. Reason: GO_REF:0000044 maps SL-0235 to rough endoplasmic reticulum. PMID:15213246 provides endogenous human myotube/biopsy and mouse C2C12 observations supporting this context. Preserve the mapping as non-core rather than dismissing it as a mutant or overexpression artifact; it does not establish rough ER as the principal site of FKRP ribitol transfer. Supporting Evidence: GO_REF:0000044 file:human/FKRP/FKRP-source-evidence.md |
| GO:0005794 Golgi apparatus | IDA GO_REF:0000052 | ACCEPT | Summary: The HPA Golgi annotation corroborates an independently established location. Reason: Retain the GO_REF:0000052 HPA IDA as trusted curated localization, consistent with endogenous human muscle microscopy in PMID:21886772. The HPA image, cell line, antibody specificity and scoring were not independently inspected for this review. The independent evidence supports acceptance of the core Golgi location without inventing source-specific assay details. |
| GO:0005794 Golgi apparatus | IDA PMID:19900540 Mutations alter secretion of fukutin-related protein. | ACCEPT | Summary: The Golgi localization is consistent with the broader FKRP evidence. Reason: The recovered PMID:19900540 abstract focuses on secretion and does not reconstruct its Golgi-localization experiment. Retain the original curated IDA because Golgi localization is independently demonstrated in human muscle by PMID:21886772 and supported by the wider biochemical picture. The unavailable Methods are an access boundary, not evidence that the curated localization is false. |
| GO:0005794 Golgi apparatus | IDA PMID:25279699 The glucuronyltransferase B4GAT1 is required for initiation ... | ACCEPT | Summary: Mouse Fkrp colocalization in a human host supports conserved Golgi residence. Reason: The inspected PMID:25279699 Giantin-colocalization experiment used mouse Fkrp pTW323 in HEK293T. Preserve the supplied human annotation and its original IDA provenance while explicitly distinguishing insert species from host species. Endogenous human muscle evidence in PMID:21886772 supports the same core compartment. |
| GO:0005794 Golgi apparatus | IDA PMID:29477842 Cell endogenous activities of fukutin and FKRP coexist with ... | ACCEPT | Summary: The expressed FKRP-containing complex is reported to colocalize with the Golgi marker GM130. Reason: The author-deposited summary associated with PMID:29477842 describes Golgi colocalization of the expressed proteins. This supports the organelle-level context and agrees with endogenous human evidence. The journal full Methods and exact species of each construct were not verified; neither the summary nor colocalization alone proves membrane insertion or an obligatory complex. |
| GO:0016780 phosphotransferase activity, for other substituted phosphate groups | IBA GO_REF:0000033 | ACCEPT | Summary: FKRP inherits a phosphotransferase function placed on its verified ancestral lineage. Reason: The original GO:0016780 IBD at PANTHER:PTN001007059 lies on the human Q9H9S5 path in PTHR13627. Transfer of ribitol-phosphate from CDP-ribitol falls within the official substituted-phosphate definition and is directly supported by human FKRP assays in PMID:31949166. The broad term accurately covers the chemistry; human experimental seed membership is legitimate and no guessed polymer-transferase replacement is needed. |
| GO:0016780 phosphotransferase activity, for other substituted phosphate groups | IDA PMID:26923585 Identification of a Post-translational Modification with Rib... | ACCEPT | Summary: FKRP performs the second ribitol-phosphate transfer in the tandem linker. Reason: PMID:26923585 identifies FKTN and FKRP as sequentially acting ribitol-phosphate transferases using CDP-ribitol. The cached primary abstract supports this core activity, which is independently resolved by the human structural and biochemical work in PMID:31949166. Retain the curated IDA without claiming that the unavailable original full Methods were examined. GO:0016780 accurately covers substituted-phosphate transfer. |
| GO:0016780 phosphotransferase activity, for other substituted phosphate groups | IDA PMID:27194101 ISPD produces CDP-ribitol used by FKTN and FKRP to transfer ... | ACCEPT | Summary: Direct donor-transfer assays support the FKRP phosphotransferase activity. Reason: PMID:27194101 measures transfer of radiolabeled ribitol and phosphate to dystroglycan, with heat-inactivation and acceptor-omission controls and a reported check against FKTN contamination. The inspected constructs are mouse enzymes and rabbit dystroglycan fragments expressed in human host cells. Preserve the supplied annotation code while disclosing that scope; independent human FKRP evidence in PMID:31949166 supports the activity. Retained total ribitol in FKRP-knockout cells does not refute the second-transfer reaction because prior FKTN modification contributes ribitol. |
| GO:0016780 phosphotransferase activity, for other substituted phosphate groups | IDA PMID:29477842 Cell endogenous activities of fukutin and FKRP coexist with ... | ACCEPT | Summary: Recovered FKRP activity supports its ribitol-phosphate transfer function in the enzyme complex. Reason: PMID:29477842 reports recovery of FKRP activity with endogenous FKTN and expressed TMEM5/RXYLT1. The abstract and author summary support substituted-phosphate transfer, although the full journal Methods were not recovered and endogenous FKRP protein was not independently detected in the summary immunoblot. Retain the activity, independently corroborated by human FKRP biochemistry, without equating activity recovery with complete purification of a native complex. |
| GO:0016780 phosphotransferase activity, for other substituted phosphate groups | IDA PMID:31949166 Crystal structures of fukutin-related protein (FKRP), a ribi... | ACCEPT | Summary: Human FKRP catalyzes ribitol-phosphate transfer to a phosphorylated core M3 glycopeptide. Reason: PMID:31949166 combines structures and HPLC/MS activity measurements for soluble human FKRP. The acceptor carries the prior FKTN-derived ribitol-phosphate and the O-mannose 6-phosphate; removing the latter prevents product formation under the tested conditions. This directly supports GO:0016780. Magnesium and manganese support activity in vitro, whereas the physiological catalytic metal remains unresolved; structural zinc is a separate stabilizing feature. Independent soluble-enzyme assays in PMID:29884773 demonstrate lower-efficiency glycerol-phosphate transfer and CDP-glycerol inhibition of ribitol transfer in vitro. These observations inform donor specificity without establishing physiological donor regulation. |
| GO:0035269 protein O-linked glycosylation via mannose | IBA GO_REF:0000033 | ACCEPT | Summary: FKRP directly extends an O-mannose-derived glycan as an inherited function. Reason: The original GO:0035269 IBD at PANTHER:PTN001007059 is on the verified human FKRP lineage. The official process definition includes extension of the O-mannose glycan, not just the initiating mannose transfer. FKRP itself performs a later ribitol-phosphate addition, as shown in PMID:31949166, so this is direct process participation rather than necessity inferred only from perturbation. |
| GO:0035269 protein O-linked glycosylation via mannose | IDA PMID:29477842 Cell endogenous activities of fukutin and FKRP coexist with ... | ACCEPT | Summary: The FKRP-containing catalytic preparation participates in extension of the O-mannose glycan. Reason: PMID:29477842 reports a complex retaining FKRP ribitol-phosphate transfer activity. This is a step in biosynthesis of the O-mannose-derived glycan and supports the curated ComplexPortal process annotation. Retain it without claiming that FKRP initiates O-mannosylation, carries the partner xylosyltransferase activity, or has proven substrate-channeling activity. |
| GO:0035269 protein O-linked glycosylation via mannose | IMP PMID:25279699 The glucuronyltransferase B4GAT1 is required for initiation ... | ACCEPT | Summary: Human patient-cell evidence places FKRP in functional O-mannose glycan maturation. Reason: In PMID:25279699, FKRP-deficient human patient fibroblasts retain DGFc340 phosphorylation yet fail to acquire the functional glycan upon LARGE overexpression. This places FKRP downstream of core phosphorylation and before LARGE-dependent maturation. Its independently demonstrated ribitol-phosphate transfer supplies the actual biochemical step supporting process participation; the IMP phenotype alone is not the sole rationale. |
| GO:0042383 sarcolemma | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: An endogenous mouse sarcolemmal pool supports the contextual human localization mapping. Reason: PMID:17452335 reports endogenous mouse FKRP at the sarcolemma using two epitope antibodies, peptide competition and a no-primary control, with recombinant mouse and native biochemical corroboration. No Fkrp-null specificity control was described. Retain the orthology-derived SL-0238 mapping as non-core while preserving its IEA provenance: these are not direct human localization data, and sarcolemmal catalysis remained hypothetical. Human Golgi observations in PMID:21886772 do not independently disprove a different species or specimen pool. Supporting Evidence: GO_REF:0000044 file:human/FKRP/FKRP-source-evidence.md |
| GO:0042802 identical protein binding | IPI PMID:31949166 Crystal structures of fukutin-related protein (FKRP), a ribi... | ACCEPT | Summary: FKRP self-association contributes to recognition of its glycan acceptor. Reason: PMID:31949166 shows human soluble FKRP protomer pairs whose stem and catalytic domains contact different phosphate groups on the acceptor glycopeptide. Structural, mutational and activity evidence supports a functionally relevant identical-protein interaction. Retain this specific binding function as core-related, without treating the soluble tetramer as proof that tetramerization is physiologically required. |
| GO:0051262 protein tetramerization | IDA PMID:31949166 Crystal structures of fukutin-related protein (FKRP), a ribi... | KEEP AS NON CORE | Summary: Soluble human FKRP forms tetramers in crystal and solution. Reason: PMID:31949166 observes tetrameric soluble human FKRP by crystallography and SEC-SAXS. The paper distinguishes the functional importance of the protomeric dimer from the unresolved significance of the tetramer. Retain the demonstrated assembly process as non-core rather than turning tetramer formation into the defining catalytic role or a universal native stoichiometry. |
| GO:1902494 catalytic complex | IDA PMID:29477842 Cell endogenous activities of fukutin and FKRP coexist with ... | ACCEPT | Summary: FKRP participates in an enzyme complex that retains component catalytic activities. Reason: PMID:29477842 reports association of FKTN, FKRP and TMEM5/RXYLT1 with each enzyme activity retained, including recovery of endogenous FKTN/FKRP activities with expressed TMEM5. Together with independent FKRP catalysis, this supports catalytic-complex membership. The available abstract and author summary do not establish fixed stoichiometry, obligatory assembly, direct pairwise contacts or substrate channeling; none is inferred. |
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Download this section (compressed HTML)Q: Which GO term most precisely distinguishes the mammalian FKRP second ribitol-phosphate transfer onto a glycopeptide-linked tandem repeat from ribitol-phosphate polymer extension? The existing GO:0016780 is accurate; GO:0047356 needs chemical and ontology assessment before substitution.
Q: Under which native cellular conditions does FKRP form tetramers rather than catalytically competent protomer pairs, and which metal supports its Golgi activity in cells? No GO:0000287 magnesium ion binding annotation is proposed: magnesium and manganese both support the tested activity, the physiological catalytic metal is unresolved, and the structural zinc is a separate feature (PMID:31949166).
Q: How do endogenous human rough-ER, Golgi and any extracellular or sarcolemmal pools vary by tissue and developmental state, and does catalysis occur outside the Golgi?
Q: How do cellular CDP-ribitol and CDP-glycerol availability affect FKRP donor use and inhibition? PMID:29884773 demonstrates lower-efficiency glycerol-phosphate transfer and CDP-glycerol inhibition in soluble-enzyme assays, but does not establish a physiological regulatory process.
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