Fukutin (FKTN) is a Golgi membrane ribitol-phosphate transferase that initiates the ribitol-phosphate linker on the core M3 O-mannosyl glycan of alpha-dystroglycan. It transfers ribitol phosphate from CDP-ribitol to the C3 hydroxyl of the GalNAc residue. FKRP subsequently adds a second ribitol-phosphate unit, allowing further glycan extension and assembly of the extracellular-matrix-binding matriglycan chain. Fukutin associates with POMGNT1 and with the enzymatically active FKRP–RXYLT1 complex. Loss of fukutin impairs functional dystroglycan glycosylation and causes recessive muscular dystrophy with variable brain and eye abnormalities. Nuclear and extracellular pools have also been observed in particular experimental contexts.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000139 Golgi membrane | EXP PMID:25279699 The glucuronyltransferase B4GAT1 is required for initiation ... | ACCEPT | Summary: Human tagged FKTN localizes with the Golgi marker Giantin. Reason: The actual cloning Methods identify human FKTN pTW322; C-terminal Myc constructs colocalized with Giantin in HEK293T. This supports core Golgi localization, while membrane topology is not independently established by colocalization alone. |
| GO:0000139 Golgi membrane | IBA GO_REF:0000033 | ACCEPT | Summary: The Golgi-membrane IBA follows a verified ancestral assertion on the human FKTN lineage. Reason: Original Golgi-membrane IBD PTN000395622 is on the human target path and agrees with experimental localization. Human FKTN among the experimental seeds is legitimate grounding rather than circular support. |
| GO:0000139 Golgi membrane | IDA PMID:17034757 Molecular interaction between fukutin and POMGnT1 in the gly... | ACCEPT | Summary: FKTN and POMGNT1 colocalize in the Golgi in the reported experiments. Reason: The original abstract and curated human FKTN/POMGNT1 colocalization records support Golgi localization. Preserve the membrane assignment with curated/topological support; colocalization by itself is not a membrane-insertion assay. |
| GO:0000139 Golgi membrane | IDA PMID:26923585 Identification of a Post-translational Modification with Rib... | ACCEPT | Summary: FKTN activity is associated with Golgi fractions, consistent with its independently supported Golgi-membrane location. Reason: The separately recovered original PMID:26923585 paper reports mouse-liver membrane fractionation with FKTN activity tracking a Golgi marker; the relevant supplement was not inspected. This is not direct human immunofluorescence. Retain the curated Golgi-membrane IDA because human FKTN Giantin colocalization in PMID:25279699 and membrane organization independently corroborate the core location. Colocalization alone does not demonstrate membrane topology. |
| GO:0000139 Golgi membrane | IDA PMID:29477842 Cell endogenous activities of fukutin and FKRP coexist with ... | ACCEPT | Summary: Expressed FKTN colocalizes with GM130 in the recovered author summary. Reason: The author summary describes tagged FKTN/FKRP/TMEM5 colocalization with GM130. Retain curated Golgi-membrane localization with corroborating evidence; exact insert provenance and the complete journal Methods remain unresolved here. |
| GO:0000139 Golgi membrane | IEA GO_REF:0000120 | ACCEPT | Summary: The combined electronic mapping identifies the established Golgi-membrane pool. Reason: Retain the combined orthology/SL-0134 electronic context for the established Golgi-membrane location. Mouse donor identity is verified, and independent human FKTN localization supports the core placement. |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-9940735 | ACCEPT | Summary: The FKTN first ribitol-phosphate transfer is modeled at the Golgi membrane. Reason: The FKTN first-transfer reaction is modeled at the Golgi membrane. Retain this location context in agreement with direct localization; the complex label does not prove fixed stoichiometry or obligate assembly. |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-9940756 | ACCEPT | Summary: FKTN shares the Golgi compartment with the complex containing FKRP. Reason: FKTN is represented in the complex surrounding the FKRP second-transfer step. Retain its Golgi-membrane context without assigning FKRP catalytic activity or its metal/dimer properties to FKTN. |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-9940805 | ACCEPT | Summary: FKTN shares the Golgi compartment with the complex containing RXYLT1. Reason: Retain the Golgi-membrane context for FKTN in the modeled complex containing the RXYLT1 reaction. Complex membership does not make FKTN a xylosyltransferase. |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-9948070 | ACCEPT | Summary: The modeled FKTN-containing assembly occupies the Golgi membrane. Reason: Reactome places the FKTN-containing assembly at the Golgi membrane. Tagged-complex GM130 colocalization in PMID:29477842 and the independent human FKTN Giantin colocalization in PMID:25279699 support this compartment. This location claim does not depend on treating every modeled assembly dependency as an experimentally established mechanism. Supporting Evidence: Reactome:R-HSA-9948070 file:human/FKTN/FKTN-source-evidence.md |
| GO:0005515 protein binding | IPI PMID:17034757 Molecular interaction between fukutin and POMGnT1 in the gly... | KEEP AS NON CORE | Summary: FKTN associates with POMGNT1 in both source contexts represented by this seeded row. Reason: The primary abstract and curated IntAct experiments support FKTN association with POMGNT1. Keep the interaction context as non-core; co-IP/two-hybrid association and localization effects do not demonstrate purified allosteric activation or an adaptor mechanism. The IntAct source also carries alternative ER/Golgi location extensions in the original QuickGO response. Curated experiments use tagged human proteins, principally in COS-7; do not generalize the mutant-associated ER redistribution to every native FKTN molecule. Those alternatives are retained in the source evidence guide; the deterministic seed and TSV schema do not represent extension objects. QuickGO contexts 447030759 (UniProt) and 447030760 (IntAct) project to this single seed row. Both source records and the latter record's original extension alternatives remain documented, without adding a synthetic annotation. |
| GO:0005515 protein binding | IPI PMID:27601598 Direct Mapping of Additional Modifications on Phosphorylated... | KEEP AS NON CORE | Summary: Tagged human FKTN associates with FKRP and RXYLT1 in cellular co-immunoprecipitation experiments. Reason: Human tagged FKTN co-IP recovers FKRP and TMEM5/RXYLT1 in HEK293T. Negative controls support association; the experiment does not establish purified binary contacts, obligate trimer stoichiometry, or transfer of a partner enzyme activity to FKTN. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: The curated BioPlex2.0 record supports an FKTN–RXYLT1 association. Reason: Retain the curated FKTN–RXYLT1 association as non-core. The BioPlex 2.0 primary Methods describe tagged human baits and AP-MS, which detects co-complex associations. The independent source assessment did not replay the exact supplementary edge, bait direction or spectra; independent targeted complex evidence corroborates the association. Supporting Evidence: file:human/FKTN/FKTN-source-evidence.md |
| GO:0005515 protein binding | IPI PMID:29477842 Cell endogenous activities of fukutin and FKRP coexist with ... | KEEP AS NON CORE | Summary: FKTN associates with FKRP and RXYLT1 in an enzymatically active preparation. Reason: Retain association with FKRP and RXYLT1 as a separate non-core UniProt context. The author summary supports complex recovery and activity, without proving each pairwise contact or a compulsory catalytic assembly. |
| GO:0005515 protein binding | IPI PMID:29477842 Cell endogenous activities of fukutin and FKRP coexist with ... | KEEP AS NON CORE | Summary: The separate IntAct context records association of FKTN with RXYLT1. Reason: Preserve the separate IntAct FKTN–RXYLT1 provenance. Co-complex recovery supports this interaction context; neither the abstract nor author summary establishes purified binary affinity or an enzyme-activator MF. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: The curated BioPlex association supports FKTN–RXYLT1 co-complex recovery. Reason: Retain the curated FKTN–RXYLT1 BioPlex association as non-core, corroborated by targeted complex studies. The cache contains abstract/introduction/discussion despite its full-text flag; exact edge, cell-line allocation, Methods and supplementary data were not independently replayed. Do not claim both cell lines tested this pair. Supporting Evidence: file:human/FKTN/FKTN-source-evidence.md |
| GO:0005576 extracellular region | TAS PMID:9690476 An ancient retrotransposal insertion causes Fukuyama-type co... | KEEP AS NON CORE | Summary: The original discovery reported transfection evidence suggesting secretion of fukutin. Reason: The original abstract explicitly combines an amino-terminal signal-sequence prediction with transfection results suggesting secretion. Retain this historical TAS as contextual non-core evidence; the full construct design, processing and endogenous tissue secretion were not verified. Core Golgi localization does not erase the reported pool. |
| GO:0005634 nucleus | IDA PMID:18808525 A role of fukutin, a gene responsible for Fukuyama type cong... | KEEP AS NON CORE | Summary: Nuclear fractionation and immunogold support a contextual nuclear fukutin pool. Reason: Nuclear extracts and immunogold support a nuclear pool in the studied human cancer cells, with absorption/RNAi controls. Preserve this observation as non-core and retain the authors’ residual antibody/artifact/isoform uncertainty; it is not disproved by the principal Golgi role. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The UniProt mapping records a contextual nuclear pool. Reason: Preserve the SL-0191 electronic nuclear mapping as a non-core location, consistent with controlled human-cell observations. Neither this mapping nor engineered expression assigns the nuclear pool to natural isoform 2. Supporting Evidence: GO_REF:0000044 file:human/FKTN/FKTN-source-evidence.md |
| GO:0005634 nucleus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The orthology-based nuclear assignment agrees with independent human-cell observations. Reason: The official UniProt donor record identifies Q8R507 as mouse Fktn. Independent human HeLa/ZR-75-1 and 1321N1 fractionation and imaging observations support a contextual nuclear pool. Retain the original ISS donor provenance with this independent human corroboration, without claiming to have verified the donor study experiments, a universal nuclear function or a natural isoform assignment. Supporting Evidence: GO_REF:0000024 file:human/FKTN/FKTN-source-evidence.md |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | TOO GENERAL | Summary: Cytoplasm is a correct but less informative ancestor of the accepted Golgi compartment. Reason: Official GO relations establish GO:0000139 Golgi membrane part_of GO:0005794 Golgi apparatus part_of GO:0005737 cytoplasm. The accepted specific compartment therefore entails the broad source assignment. This is a precision judgment, not rejection of the original UniProt SL-0086 mapping. It does not imply soluble cytosolic ribitol-transfer catalysis. The source guide records the official path. |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | TOO GENERAL | Summary: The broad orthology-based cytoplasm assignment is entailed by the accepted Golgi compartment. Reason: The official GO path places accepted Golgi membrane GO:0000139 part_of Golgi apparatus GO:0005794 part_of cytoplasm GO:0005737. Cytoplasm is therefore true but adds no location precision. The official donor record verifies mouse Fktn Q8R507 identity; the original ISS source context is preserved without claiming an independent replay of its donor localization experiment. |
| GO:0005783 endoplasmic reticulum | IDA PMID:18808525 A role of fukutin, a gene responsible for Fukuyama type cong... | UNDECIDED | Summary: The original immunogold experiment does not resolve the ER-specific location. Reason: The recovered primary text assigns cytoplasmic immunogold particles only tentatively to ER and/or Golgi. It does not independently separate those organelles in this assay. Preserve the original ER IDA but leave the ER-specific interpretation unresolved; Golgi corroboration and mutant ER redistribution do not settle native ER occupancy. |
| GO:0005794 Golgi apparatus | IDA PMID:18808525 A role of fukutin, a gene responsible for Fukuyama type cong... | ACCEPT | Summary: Golgi localization is supported holistically despite tentative organelle assignment in this experiment. Reason: The paper tentatively identifies immunogold-positive organelles as Golgi and/or ER. Retain trusted Golgi IDA because independent human FKTN localization corroborates the core organelle; do not describe this paper alone as resolving the ER-versus-Golgi ambiguity. |
| GO:0005794 Golgi apparatus | IDA PMID:25279699 The glucuronyltransferase B4GAT1 is required for initiation ... | ACCEPT | Summary: Human Myc-tagged FKTN colocalizes with Giantin in HEK293T cells. Reason: Human FKTN pTW322, expressed as a C-terminal Myc construct in HEK293T, colocalizes with Giantin. Retain this core Golgi context and the exact species/construct scope. |
| GO:0005794 Golgi apparatus | IDA PMID:29477842 Cell endogenous activities of fukutin and FKRP coexist with ... | ACCEPT | Summary: The author summary supports Golgi localization of expressed FKTN. Reason: The author-deposited summary reports GM130 colocalization of the expressed proteins. Retain the Golgi context with independent support, without asserting full journal Methods access or verified species for every insert. |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000107 | ACCEPT | Summary: The orthology mapping agrees with the established human Golgi location. Reason: The mouse-orthology Golgi mapping agrees with direct human FKTN localization and its biosynthetic role. Preserve the distinct electronic context and verified donor identity. |
| GO:0005801 cis-Golgi network | IDA PMID:15213246 Subcellular localization of fukutin and fukutin-related prot... | ACCEPT | Summary: Transfected myc-fukutin serves as the cis-Golgi comparator in the localization study. Reason: The original scanned article uses transfected myc-fukutin as the cis-Golgi comparator to endogenous FKRP. Retain the curated cis-Golgi observation, while disclosing that exact insert species was not stated in the recovered Methods; endogenous FKRP rough-ER evidence is not FKTN evidence. |
| GO:0006493 protein O-linked glycosylation | IMP PMID:17034757 Molecular interaction between fukutin and POMGnT1 in the gly... | ACCEPT | Summary: FKTN participates in O-linked glycan maturation through a demonstrated transfer step. Reason: The reported POMGNT1 association, localization effect and mutant-model activity phenotype support a role in O-linked glycosylation. Later direct FKTN ribitol-phosphate chemistry independently establishes actual participation. Do not equate this paper alone with direct catalytic activation of POMGNT1. This pathway-level term remains informative alongside the more specific O-mannose-glycan extension step because FKTN directly performs part of glycoprotein synthesis. |
| GO:0006493 protein O-linked glycosylation | TAS Reactome:R-HSA-8931838 | ACCEPT | Summary: FKTN contributes directly to the dystroglycan O-glycosylation pathway. Reason: The DAG1 glycosylation pathway includes extension of O-mannose-derived glycans, in which FKTN performs the first RboP transfer. Retain the broad pathway context without interpreting the displayed linear sequence as biological serialization of all three core pathways. This pathway-level term remains informative alongside the more specific O-mannose-glycan extension step because FKTN directly performs part of glycoprotein synthesis. |
| GO:0007399 nervous system development | TAS PMID:9690476 An ancient retrotransposal insertion causes Fukuyama-type co... | KEEP AS NON CORE | Summary: FKTN loss is associated with congenital neurological development abnormalities. Reason: The original abstract links FKTN loss to congenital brain malformation and impaired neuronal migration. Preserve this historical TAS developmental association as non-core; the abstract does not establish a direct neural signaling activity, and full publisher Methods remained inaccessible. |
| GO:0007517 muscle organ development | TAS PMID:9690476 An ancient retrotransposal insertion causes Fukuyama-type co... | KEEP AS NON CORE | Summary: FKTN loss is associated with congenital muscular dystrophy and developmental muscle dysfunction. Reason: The original discovery establishes FKTN involvement in congenital muscular dystrophy. Retain the curated muscle-development context as a non-core organismal consequence, without making developmental regulation its catalytic core or claiming detailed developmental assays from the abstract. |
| GO:0008285 negative regulation of cell population proliferation | IMP PMID:18808525 A role of fukutin, a gene responsible for Fukuyama type cong... | KEEP AS NON CORE | Summary: Fukutin knockdown increased the proliferating fraction in the studied HeLa and ZR-75-1 cultures. Reason: At the five-day endpoint after 20 nM F697 treatment, HeLa and ZR-75-1 cultures had increased Ki-67-positive fractions, supporting a contextual inhibitory proliferation phenotype. Retain that existing claim as non-core. PMID:34830034 found the opposite proliferation response in 1321N1 cells using 40 nM F697 and a four-day endpoint. The different cell, dose and time contexts limit a general sign assignment; these experiments do not isolate which variable explains the difference. The structured reference findings retain both measured outcomes as CURRENT and record the opposing directions and context limits, without treating either result as overturned. No proliferation rescue or direct catalytic mechanism was established. |
| GO:0009101 glycoprotein biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: The glycoprotein-biosynthesis IBA agrees with the demonstrated glycan-extension reaction. Reason: The original glycoprotein-biosynthesis IBD at PTN001034988 lies on the human FKTN ancestry. The broad process fits its demonstrated glycan-extension reaction; fungal seeds and the human target among experimental seeds do not invalidate the phylogenetic assertion. This pathway-level term remains informative alongside the more specific O-mannose-glycan extension step because FKTN directly performs part of glycoprotein synthesis. |
| GO:0016780 phosphotransferase activity, for other substituted phosphate groups | IDA PMID:26923585 Identification of a Post-translational Modification with Rib... | ACCEPT | Summary: FKTN transfers the first ribitol-phosphate unit to the GalNAc residue of the glycan acceptor. Reason: The original PMID:26923585 Results and NMR identify transfer of the first ribitol-phosphate unit from CDP-ribitol to GalNAc C3, with HAP1 loss/rescue and glycopeptide MS supporting the sequential pathway. Soluble His/Myc-tagged enzymes were expressed in HEK293T, but the inspected main text does not establish every insert's species. Separate NMR acceptors lack mannose phosphate, so the natural phosphorylated core-M3 substrate does not justify a universal phosphate requirement for every artificial acceptor. PMID:29884773 additionally demonstrates glycerol-phosphate transfer and CDP-glycerol competition in vitro; those assays do not establish physiological glycerol regulation. GO:0016780 accurately covers the substituted-phosphate chemistry. Supporting Evidence: file:human/FKTN/FKTN-source-evidence.md |
| 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: Purified Fktn transfers ribitol phosphate in the reported donor/acceptor assays. Reason: Purified mouse Fktn transfer assays and human FKTN-knockout/mouse-Fktn rescue support substituted-phosphate transfer. The dystroglycan construct was rabbit in human host cells. This paper alone did not resolve the exact attachment site; do not relabel its constructs as human. |
| GO:0016780 phosphotransferase activity, for other substituted phosphate groups | IDA PMID:29477842 Cell endogenous activities of fukutin and FKRP coexist with ... | ACCEPT | Summary: FKTN transfer activity is retained in the recovered complex preparation. Reason: The recovered complex retains FKTN transfer activity and its product was checked by MS in the author summary. Retain the broad substituted-phosphate MF while distinguishing endogenous FKTN immunoblot recovery from unresolved full journal Methods and construct details. |
| GO:0016780 phosphotransferase activity, for other substituted phosphate groups | IEA GO_REF:0000107 | ACCEPT | Summary: The orthology mapping agrees with demonstrated substituted-phosphate transfer. Reason: The Ensembl mouse-orthology mapping agrees with independently demonstrated FKTN substituted-phosphate transfer. Q8R507 is verified mouse Fktn; no pairwise donor count substitutes for the biochemical evidence. Supporting Evidence: GO_REF:0000107 file:human/FKTN/FKTN-source-evidence.md |
| GO:0016780 phosphotransferase activity, for other substituted phosphate groups | TAS Reactome:R-HSA-9940735 | ACCEPT | Summary: The modeled FKTN reaction describes transfer of the first ribitol-phosphate unit. Reason: The exact-main reaction record assigns FKTN the first RboP transfer to the phospho-core-M3 GalNAc acceptor. This matches the demonstrated broad GO:0016780 chemistry; no polymer-specific replacement term is inferred from its name. |
| GO:0035269 protein O-linked glycosylation via mannose | IDA PMID:29477842 Cell endogenous activities of fukutin and FKRP coexist with ... | ACCEPT | Summary: FKTN directly extends the O-mannose-derived core M3 glycan. Reason: FKTN activity contributes directly to extension of the O-mannose-derived core-M3 glycan. Preserve the ComplexPortal process context; neither sequential catalysis nor co-recovery proves substrate channeling. |
| GO:0035269 protein O-linked glycosylation via mannose | IMP PMID:25279699 The glucuronyltransferase B4GAT1 is required for initiation ... | ACCEPT | Summary: Human FKTN deficiency disrupts maturation of the O-mannose-derived glycan downstream of core phosphorylation. Reason: Human FKTN-defective patient fibroblasts retain core phosphorylation but fail appropriate LARGE-dependent functional glycan acquisition. Together with direct FKTN chemistry this supports extension of an O-mannose-derived glycan, not initiation of the first mannose linkage. |
| GO:0046329 negative regulation of JNK cascade | IMP PMID:18808525 A role of fukutin, a gene responsible for Fukuyama type cong... | MARK AS OVER ANNOTATED | Summary: The phospho-c-Jun phenotype does not establish negative regulation of the JNK cascade. Reason: FKTN knockdown increased phospho-c-Jun staining in HeLa and, less strongly, ZR-75-1 cells. This supports the reported staining phenotype, but the qualitative readout was not normalized to total c-Jun, and the study did not assay JNK activation or establish JNK dependence of the FKTN effect. The JNK-cascade term therefore exceeds the demonstrated pathway specificity. The later 1321N1 study found unchanged p-JNK/p-c-Jun under different conditions; that result limits generalization but does not refute the earlier staining observation. |
| GO:1902494 catalytic complex | IDA PMID:29477842 Cell endogenous activities of fukutin and FKRP coexist with ... | ACCEPT | Summary: FKTN belongs to a recovered complex with retained glycan-transfer activities. Reason: Association together with retained FKTN/FKRP/RXYLT1 activities supports catalytic-complex membership. Preserve this curated context without asserting purified binary contacts, fixed stoichiometry, obligatory assembly, rate enhancement or proven channeling. |
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Download this section (compressed HTML)Q: Which ontology term most precisely distinguishes the mammalian first ribitol-phosphate transfer to a glycopeptide-linked GalNAc acceptor from ribitol-phosphate-polymer extension? GO:0016780 is accurate; GO:0047356 should not be substituted without resolving its chemical scope.
Q: How do endogenous FKTN localization and function vary between Golgi, nuclear and extracellular pools, and do either natural product O75072-1 or O75072-2 account for those differences? The ER-specific immunogold assignment remains unresolved.
Q: Under what cellular conditions, if any, does CDP-glycerol competition regulate FKTN-dependent glycan maturation? The current donor/acceptor results establish in-vitro activity rather than physiological regulation.
Q: What explains the opposite proliferation responses and different phospho-c-Jun readouts in HeLa/ZR-75-1 and 1321N1, and which effects require the glycan-transfer activity?
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