FTL is the light-chain subunit of ferritin, a predominantly cytosolic protein shell that stores iron as a mineral and buffers its availability. L chains associate with one another and with FTH1 subunits; their acidic cavity-facing surfaces and effects on shell properties support iron incorporation, mineralization and release. The proportions of L and H subunits influence iron storage and the labile intracellular iron pool. The rapid ferroxidase centers characteristic of FTH1 are distinct from this L-chain contribution. Ferritin containing FTL can enter autophagic cargo compartments during iron mobilization and can also occur in extracellular and secretory contexts. Pathogenic FTL coding or regulatory variants can disturb ferritin abundance, shell behavior and iron homeostasis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005506 iron ion binding | IDA PMID:19923220 Unraveling of the E-helices and disruption of 4-fold pores a... | TOO GENERAL | Summary: Use the retained, more specific scope for iron ion binding. Reason: The original human L-chain homopolymer experiments measure incorporation/nucleation from aerobic ferrous input and iron hydrolysis. They support iron handling but do not isolate a valence-specific binding event on the L subunit. Retained ferrous- and ferric-binding assertions directly entail this broad term through official is_a edges. Keep TOO_GENERAL for redundancy without rejecting the IDA evidence or relabeling incorporation as a direct Fe(II)- or Fe(III)-binding assay. |
| GO:0005506 iron ion binding | IDA PMID:20159981 Mutant ferritin L-chains that cause neurodegeneration act in... | TOO GENERAL | Summary: Use the retained, more specific scope for iron ion binding. Reason: The original H/L heteropolymer experiments distinguish largely unchanged iron oxidation from impaired retention of oxidized iron and altered shell permeability. They support an L-chain contribution to iron handling, without independently resolving a valence-specific L-subunit binding event. The retained inferred Fe(II)/Fe(III) binding terms entail general iron binding. Keep TOO_GENERAL for granularity; preserve the original IDA source and do not manufacture a more specific experimental binding claim. |
| GO:0005506 iron ion binding | TAS PMID:7493028 Mutation in the iron responsive element of the L ferritin mR... | TOO GENERAL | Summary: Use the retained, more specific scope for iron ion binding. Reason: FTL iron binding is independently established at gene level and represented more precisely by the retained Fe(II)/Fe(III) terms. This TAS paper concerns IRE-dependent RNA regulation; do not describe its abstract as a direct protein-binding assay. |
| GO:0005515 protein binding | IPI PMID:16169070 A human protein-protein interaction network: a resource for ... | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: FTLβFTH1 association is supported by the human ORF yeast two-hybrid source and its exact IntAct record EBI-731980. This agrees with ferritin subunit association but does not determine a two-subunit heterodimer or native H:L stoichiometry. Retain the supported interaction as non-core; the specific shell-structural function is supported independently. Target-specific pull-down validation was not established. |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: The human CCSB-HI1 screen and source-qualified IntAct record EBI-759160 support FTH1βFTL association in yeast. This is consistent with mixed ferritin assembly, without determining an isolated heterodimer or a fixed native H:L ratio. Retain the positive interaction as non-core. The paper-wide orthogonal validation rate is not assigned to this individual pair. |
| GO:0005515 protein binding | IPI PMID:17143515 Cellular expression, localization and interactions of the pr... | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: The original MOST1 study recovered an FTL fragment and demonstrated reciprocal tagged co-immunoprecipitation after separately expressed hamster BHK-cell lysates were mixed. This supports contextual FTLβMOST1 association, not an endogenous human cancer-cell complex or a mitogenic activity of FTL. Retain the interaction as non-core; no more specific molecular function is established by these assays. |
| GO:0005515 protein binding | IPI PMID:18486613 Interactions between PBEF and oxidative stress proteins--a p... | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: The original PBEF/NAMPT study identifies human FTL residues 1β175 and tests reciprocal association in human pulmonary endothelial cells. This supports FTLβNAMPT binding in that context. The NAMPT perturbation and ROS endpoints do not establish FTL oxidase activity or a dedicated NAMPT-regulatory function, so the positive interaction remains non-core. |
| GO:0005515 protein binding | IPI PMID:21516116 Next-generation sequencing to generate interactome datasets. | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: Original HI-NGS Supplementary Table 2, PDF page 13, explicitly lists FTH1βFTL (Entrez 2495β2512) from human ORFeome yeast two-hybrid screening and pairwise retesting. This supports the original pair despite its absence from the current bounded IntAct response. Neither target-specific PCA/wNAPPA validation nor two-subunit/native shell stoichiometry is established, so retain the interaction as non-core. |
| GO:0005515 protein binding | IPI PMID:23275563 Development and application of a DNA microarray-based yeast ... | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: FTL associates with an HTT N-terminal 1β506 fragment in source-qualified yeast two-hybrid and HEK293 LUMIER records (EBI-6451053 and EBI-6451991), consistent with the original construct Methods. The positive fragment interaction does not establish full-length endogenous HTT contact or an FTL disease-modifier function. Retain it as non-core; the original target supplementary row was not independently reread. |
| GO:0005515 protein binding | IPI PMID:23685131 Ferritin light chain interacts with PEN-2 and affects Ξ³-secr... | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: The original study distinguishes the initial PEN2 34β65 loop screen from reciprocal co-immunoprecipitation of full tagged human FTL and PEN2 in HEK293 cells. This establishes contextual association. Changes in PEN2, PS1, AΞ² and NICD abundance after FTL perturbation do not demonstrate FTL secretase activity or directly measure PEN2 degradation kinetics. Retain the interaction as non-core. |
| GO:0005515 protein binding | IPI PMID:25327288 Selective VPS34 inhibitor blocks autophagy and uncovers a ro... | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: Selected original supplementary evidence recovers FTL-containing ferritin with SBP-NCOA4 in human DLD1 cells; the knockout/rescue experiment separately attributes productive subunit contact to FTH1. This supports FTL-containing co-complex association, not direct FTLβNCOA4 contact or receptor activity. Retain the association as non-core, with the detailed source-access limits recorded in the guide. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: Three source-qualified IntAct records, including validated two-hybrid EBI-10511054, support human FTLβO00505 association in yeast. The original screening Methods describe pairwise retesting and sequence confirmation. Retain this positive interaction as non-core; neither a dedicated molecular activity nor target-specific mammalian orthogonal validation is established. The original supplementary row was not independently reread. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: Human FTLβO00560 association is supported by three source-qualified two-hybrid records, including EBI-10499328, and the original retesting Methods. These establish a screened interaction but not a specific FTL activity with this partner or a physiological complex in every tissue. Retain as non-core; original target-table and orthogonal-assay access limits remain in the guide. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: Five exact source-qualified two-hybrid records, including EBI-10511038 and reciprocal array/pooling orientations, support FTLβFTH1 association. This is compatible with independently established mixed ferritin assembly but does not itself resolve a two-subunit heterodimer or native H:L stoichiometry. Retain the interaction as non-core; target-specific mammalian validation was not independently established. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: Three exact source-qualified two-hybrid records, including EBI-10514876, support FTLβMYOG/P15173 association in yeast. This positive interaction does not establish FTL transcriptional regulation or participation in muscle differentiation. Retain as non-core, with the original target-table and mammalian-validation limits stated in the source guide. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: Five source-qualified two-hybrid records, including EBI-10571066 and additional array/pooling orientations, support human FTLβQ6NZ44 association. The original screening and retesting Methods support a positive pair, not a defined FTL molecular mechanism with that partner. Retain the interaction as non-core; no target-specific orthogonal assay is inferred. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: Three exact source-qualified two-hybrid records, including EBI-10588566, identify FTLβQ8N6Y0 association. Their retested yeast reporter result supports the interaction but does not assign a more specific FTL activity or endogenous tissue role. Retain as non-core; the source guide distinguishes these curated target records from the original supplementary row that was not reread. |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: Original Table S3A rows 960 and 962 positively score wild-type human FTH1βFTL in both bait orientations; A96T/H133P FTL variants separately lose the tested interaction, whereas FTH1 K54R retains it. This supports WT subunit association in yeast, not a two-subunit native heterodimer. Retain as non-core. The complete S3B GPCA sheet has no FTL/FTH1 entry, so human-cell GPCA validation is not assigned. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: The exact BioPlex2 record EBI-21573202 recovers FTL with C-terminally tagged FTH1 by anti-tag purification in HEK293T cells. The spoke-expanded AP-MS association is consistent with ferritin co-complex recovery but does not resolve direct heterodimer formation. Retain the positive association as non-core; the independently established shell function is a separate conclusion. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: BioPlex2 record EBI-21817633 identifies FTL in a tagged NCOA4 purification from HEK293T cells. This is positive ferritin-associated co-complex recovery under the original AP-MS filtering protocol. Spoke expansion does not establish direct FTLβNCOA4 binding or make FTL an autophagy receptor, so retain the association as non-core. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: The original variant-screen tables and EBI-22136341 support a positive FTLβFTH1 WT baseline, with FTH1 K54R retaining the tested interaction. Other FTL variant outcomes remain specific to the 2019 study and do not overwrite the different 2014 calls. Retain the association as non-core: the yeast assay does not resolve native heterodimer stoichiometry, and no FTL-specific PCA result is claimed. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: The original 2019 target tables and EBI-22127297 support the FTLβMYOG WT interaction and classify MYOG R147C/P49H as non-disruptive in that assay. Retain the positive association as non-core; neither MYOG's transcriptional activity nor a muscle-differentiation role transfers to FTL from this pair. No FTL-specific PCA validation is inferred. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: Three exact HuRI records, including validated two-hybrid EBI-24363136, support the FTLβO00560 pair using human ORFs in yeast. The original assay design includes quadruplicate verification and sequence confirmation. Retain the interaction as non-core; target-specific mammalian or structural validation and a more specific FTL activity are not established by this screen result. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: The FTLβQ6FHY5 HuRI pair has three source-qualified records, including EBI-24504422, consistent with the original human-ORF two-hybrid verification workflow. This supports positive association, without establishing a dedicated molecular activity for FTL with this partner. Retain as non-core; no target-specific orthogonal validation is inferred from the study-wide validation program. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: Three source-qualified HuRI records, including EBI-24319742, support human FTLβQ96HA8 association in yeast. Retain this positive interaction as non-core. The reporter assay does not establish an endogenous compartment, a specific regulatory function or a target-specific structural validation; the original target Table 9 row was not independently reread. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: Three source-qualified records identify FTLβO76024 association in the original disease-protein two-hybrid screen, including validated pair EBI-26206091. This supports a positive interaction in yeast. It does not establish a disease-modifying FTL mechanism or confirm that this pair underwent DULIP/LuTHy validation, so retain the interaction as non-core. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: FTLβSNCA/P37840 association is supported by three source-qualified two-hybrid records, including EBI-26249001. The positive screen does not establish that FTL drives SNCA aggregation or acts in a specific neurodegenerative pathway. Retain the association as non-core, without assigning target-specific mammalian validation from the study's broader assay program. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: The exact FTLβHTT records preserve six HTT fragment ranges: 1β88, 1β504, 1β511, 1β546, 1221β1939 and 1932β2642. Eighteen records cover pooling, array and validated two-hybrid assays. These positive fragment interactions support non-core association, not full-length endogenous binding or a disease-modifier mechanism. They do not imply target-specific DULIP/LuTHy confirmation. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: Three source-qualified two-hybrid records, including EBI-26197872, support FTL association with the exact PSEN1 partner P49768-2. Preserve that tested partner isoform; the screen does not establish an isoform-selective FTL mechanism or Ξ³-secretase activity of FTL. Retain as non-core, without inferring target-specific mammalian validation. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: FTL association with PSEN2/P49810 is supported by three source-qualified two-hybrid records, including EBI-26198180. This positive pair does not establish a Ξ³-secretase function for FTL or demonstrate an endogenous protease complex. Retain the association as non-core; no target-specific DULIP/LuTHy result is assigned. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: Three source-qualified two-hybrid records, including EBI-26155143, support FTL association with the exact DNM2 partner P50570-2. Retain the tested isoform and the positive interaction as non-core. Neither dynamin GTPase activity nor a defined membrane-remodeling role is established for FTL by this screen, and no target-specific mammalian validation is inferred. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: Six source-qualified two-hybrid records support FTLβATXN1/P54253 association, with some records explicitly describing an N-terminal fragment whose endpoint is unspecified. Retain this positive interaction as non-core and preserve the unresolved construct boundary. It is not evidence for universal full-length endogenous contact or a disease-modifying FTL mechanism. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: BioPlex3 record EBI-54492829 recovers O00560 with tagged FTL in HEK293T anti-HA AP-MS. The source records a spoke-expanded association, which can reflect co-complex membership. Retain it as non-core; direct binary affinity, a specific molecular activity and an endogenous compartment are not established by this experiment. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: Three BioPlex3 records (EBI-54548558, EBI-54927063 and EBI-55014077) recover FTL with tagged FTH1 in HEK293T/HCT116 AP-MS. These support ferritin co-complex association but do not resolve a two-subunit heterodimer or fixed native H:L ratio. Retain the association as non-core, keeping the independently supported structural-shell function distinct. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: Exact BioPlex3 records EBI-54737455 and EBI-54977003 identify FTL associated with tagged NCOA4 in HEK293T/HCT116 cells. Retain the positive co-complex association as non-core. It does not establish direct L-chain receptor contact or FTL autophagy machinery; the different curated expansion labels are preserved in the source records. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: The author-linked 2025 NDEx network contains the exact FTLβFTH1 edge 561950 from human U2OS HA-FLAG ORF AP-MS. This independently supports co-complex association despite the absent source pair in the current IntAct response. Retain it as non-core: AP-MS does not resolve a two-subunit heterodimer, direct affinity or native H:L stoichiometry. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: The author-linked 2025 NDEx network contains the exact FTLβNCOA4 edge 562046 from human U2OS HA-FLAG ORF AP-MS. This is positive contextual co-complex evidence despite its absence from the current IntAct response. Retain the association as non-core; it does not establish direct FTL receptor contact or an autophagy activity of the cargo subunit. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6798751 | KEEP AS NON CORE | Summary: Retain supported extracellular region as contextual evidence. Reason: The actual Reactome release event includes exact human P02792 residues 2β175 in its extracellular output set. This supports a release/extracellular context, not the principal intracellular iron-storage location or a newly measured secretion assay. Supporting Evidence: Reactome:R-HSA-6798751 |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | TOO GENERAL | Summary: Use the retained, more specific scope for cytoplasm. Reason: The cytoplasm IBA has a literal positive IBD at AN0/PTN000153092 on the exact human target lineage, including legitimate experimentally grounded target self-donor evidence. Cytosol is independently established and is part_of cytoplasm, so the broad term is redundant in granularity with retained cytosol annotations. This does not challenge the ancestral placement or change any original qualifier, donor or source. The is_active_in versus located_in wording does not drive a different disposition under the applicable qualifier convention. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000153092 Β· PTN000153092 SUPPORTS TRANSFER Literal positive GO:0005737 IBD at AN0 is on the human AN31/PTN002478947 lineage in the retained PTHR11431 topology; original descendant-evidence donor set matches. Biological term granularity is evaluated separately from this grounding. UniProtKB:P02792 Β· FTL SUPPORTS TRANSFER The target is valid descendant evidence for the ancestral cytoplasm assertion, not a circular transfer. Supporting Evidence: Reactome:R-HSA-1562626 |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | TOO GENERAL | Summary: Use the retained, more specific scope for cytoplasm. Reason: The UniProt cytoplasm mapping is biologically reasonable but entailed by the retained cytosol localization via official part_of. This is a granularity decision, not a false-localization claim. Supporting Evidence: Reactome:R-HSA-1562626 |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | TOO GENERAL | Summary: Use the retained, more specific scope for cytoplasm. Reason: Cytoplasmic localization is compatible with the mouse donor and independently established human ferritin biology. The retained located_in cytosol terms are more specific through the official cytosol part_of cytoplasm edge; preserve the original donor literal. Supporting Evidence: Reactome:R-HSA-1562626 |
| GO:0005776 autophagosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retain supported autophagosome as contextual evidence. Reason: Ferritin can enter autophagosomal cargo compartments during turnover. Keep this transient degradative location separate from performing autophagy and from the principal cytosolic storage site; preserve this IEA provenance rather than upgrading it to a newly observed FTL assay. Supporting Evidence: |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1562626 | ACCEPT | Summary: Retain cytosol as a core ferritin function or location. Reason: The actual iron-handling Reactome complex is cytosolic and includes exact human FTL in its 24-subunit FTH1/FTL model. Cytosol is a characteristic site of ferritin storage; the complex catalytic activity is not assigned to the individual L chain. Supporting Evidence: Reactome:R-HSA-1562626 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-434362 | ACCEPT | Summary: Retain cytosol as a core ferritin function or location. Reason: The actual Reactome transition contains the exact cytosolic FTL-containing ferritin entity. Retain the core starting location; Golgi-associated handling does not establish integral membrane topology. Supporting Evidence: Reactome:R-HSA-434362 |
| GO:0006826 iron ion transport | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Retain pore-dependent iron movement as a contextual ferritin function. Reason: The official term includes directed iron movement within a cell through a pore; it does not require crossing a biological membrane. Human L-chain and mixed H/L ferritin experiments connect shell pores, permeability and iron incorporation/retention. This supports a contextual L-chain contribution to movement into and out of the storage cavity, distinct from H-chain catalytic oxidation and lysosomal degradation of ferritin. Retain KEEP_AS_NON_CORE with this explicit shell scope; a different paralog review does not override the term definition or these primary experiments. Supporting Evidence: PMID:20159981 alter the permeability of 1-2 of the 6 hydrophobic channels file:human/FTL/FTL-source-evidence.yaml |
| GO:0006879 intracellular iron ion homeostasis | IEA GO_REF:0000002 | ACCEPT | Summary: Retain intracellular iron ion homeostasis as a core ferritin function or location. Reason: L-chain composition regulates intracellular iron storage and availability. The family inference agrees with human functional L-chain deficiency/transduction evidence; not all L-chain loss decreases iron storage, because H homopolymers can sequester iron excessively. Supporting Evidence: |
| GO:0006879 intracellular iron ion homeostasis | NAS PMID:30325535 Ferritin heavy/light chain (FTH1/FTL) expression, serum ferr... | ACCEPT | Summary: Retain intracellular iron ion homeostasis as a core ferritin function or location. Reason: Intracellular iron homeostasis is a core gene-level capacity supported independently by human L-chain functional evidence. The authentic 30325535 abstract includes FTL/FTH1 expression/prognostic data; its specific NAS mechanism is not certified from an unread full text. |
| GO:0006879 intracellular iron ion homeostasis | NAS PMID:38714719 Structural basis for the intracellular regulation of ferriti... | ACCEPT | Summary: Retain intracellular iron ion homeostasis as a core ferritin function or location. Reason: Retain core intracellular iron homeostasis. The source actually assays WT human FTL and engineered L2H in ferritin-cargo regulation, but the broader capacity is supported independently; do not transfer engineered receptor contact or H-chain catalysis to WT FTL. |
| GO:0006879 intracellular iron ion homeostasis | TAS PMID:7492760 Molecular basis for the recently described hereditary hyperf... | ACCEPT | Summary: Retain intracellular iron ion homeostasis as a core ferritin function or location. Reason: FTL regulation is directly relevant to cellular iron balance and ferritin abundance. The authentic 7492760 abstract concerns an IRE-related hyperferritinemia/cataract syndrome; independent functional studies establish the gene-level homeostasis claim beyond this clinical/regulatory source. |
| GO:0006914 autophagy | NAS PMID:38714719 Structural basis for the intracellular regulation of ferriti... | MARK AS OVER ANNOTATED | Summary: Ferritin cargo turnover does not establish that FTL executes autophagy. Reason: The inspected 2024 source supports FTL-containing ferritin as cargo and distinguishes WT FTL from the productive FTH1 receptor-contact interface. It does not demonstrate WT FTL performs an autophagic step. Mark the broad participation claim over-annotated while preserving cargo localization and turnover; functional cargo-composition necessity/rescue alone does not settle participation. |
| GO:0008198 ferrous iron binding | IBA GO_REF:0000033 | ACCEPT | Summary: Retain ferrous iron binding as a core ferritin function or location. Reason: Literal ferrous-binding IBD at AN0/PTN000153092 lies on the exact human target lineage with matching donors. No inspected target-specific loss of binding is established. Lack of an H-like ferroxidase center is not loss of Fe(II) binding; do not invent purified affinity evidence. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000153092 Β· PTN000153092 SUPPORTS TRANSFER Literal positive GO:0008198 IBD at AN0 is on the human AN31/PTN002478947 lineage in the retained PTHR11431 topology; original descendant-evidence donor set matches. Biological term granularity is evaluated separately from this grounding. |
| GO:0008199 ferric iron binding | IBA GO_REF:0000033 | ACCEPT | Summary: Retain ferric iron binding as a core ferritin function or location. Reason: The literal ferric-binding IBD at AN0/PTN000153092 is on the exact target path, with original donor set preserved. Independent L-chain mineralization/storage biology agrees; donor count and deep ancestral placement are not themselves deficiencies. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000153092 Β· PTN000153092 SUPPORTS TRANSFER Literal positive GO:0008199 IBD at AN0 is on the human AN31/PTN002478947 lineage in the retained PTHR11431 topology; original descendant-evidence donor set matches. Biological term granularity is evaluated separately from this grounding. |
| GO:0008199 ferric iron binding | IEA GO_REF:0000002 | ACCEPT | Summary: Retain ferric iron binding as a core ferritin function or location. Reason: Ferric-ion handling/mineralization is characteristic of the L-chain-containing ferritin shell and consistent with the family assignment. This remains an IEA mapping, independently supported by the iron-incorporation/mineralization literature; it does not imply L-chain ferroxidase catalysis. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | UNDECIDED | Summary: The source-specific membrane claim remains unresolved. Reason: The authentic membrane-proteomics abstract describes human YTS NK-like cells, but the exact FTL row and full Methods were not recovered. GO membrane includes attached proteins, so absence of a transmembrane helix does not refute this HDA result; keep the source-specific claim unresolved. Supporting Evidence: |
| GO:0030218 erythrocyte differentiation | NAS PMID:26776506 NCOA4 Deficiency Impairs Systemic Iron Homeostasis. | UNDECIDED | Summary: The source-specific erythrocyte differentiation claim remains unresolved. Reason: The selected full original tests mouse NCOA4 loss and iron-restriction responses, with ferritin readouts detected through FTH1. It establishes iron supply dependence of erythropoiesis but does not isolate an FTL-specific contribution to differentiation. Retain the NAS assertion unresolved rather than alleging a wrong-gene citation from its title. Supporting Evidence: |
| GO:0035578 azurophil granule lumen | TAS Reactome:R-HSA-6798751 | KEEP AS NON CORE | Summary: Retain supported azurophil granule lumen as contextual evidence. Reason: The actual Reactome input set explicitly includes P02792 residues 2β175 in azurophil granule lumen. Retain this neutrophil secretory context with curated-model provenance, without generalizing it to the core ferritin location. Supporting Evidence: Reactome:R-HSA-6798751 |
| GO:0042802 identical protein binding | IPI PMID:16169070 A human protein-protein interaction network: a resource for ... | ACCEPT | Summary: Retain identical protein binding as a core ferritin function or location. Reason: The authentic source describes a human ORF yeast two-hybrid matrix, and the exact source-qualified IntAct records identify FTLβFTH1 and FTL self-association. These agree with independently established ferritin subunit assembly. No target-specific pull-down validation or physiological stoichiometry is inferred from the screen-wide abstract; the exact primary supplementary rows were not independently reread. Identical-subunit binding supports ferritin-shell assembly and is retained as core. Supporting Evidence: |
| GO:0042802 identical protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | ACCEPT | Summary: Retain identical protein binding as a core ferritin function or location. Reason: The authentic source describes the human CCSB-HI1 pairwise yeast two-hybrid screen, and exact source-qualified IntAct records identify FTLβFTH1 and FTL self-association. These agree with independent ferritin assembly evidence. The reported network-wide orthogonal validation rate does not certify target-specific validation; no native complex stoichiometry is inferred. Identical-subunit binding supports ferritin-shell assembly and is retained as core. Supporting Evidence: |
| GO:0042802 identical protein binding | IPI PMID:16790936 Structure of human ferritin L chain. | ACCEPT | Summary: Retain identical protein binding as a core ferritin function or location. Reason: The authentic primary abstract and author-deposited PDB structures identify recombinant human L-chain ferritin assemblies. Identical-subunit association is intrinsic to the L-chain ferritin shell and agrees with independent human homopolymer experiments. The crystallographic cadmium channel observation is not an Fe oxidation assay or evidence of H-chain-like ferroxidase activity; full article Methods were not recovered. Identical-subunit binding supports ferritin-shell assembly and is retained as core. Supporting Evidence: |
| GO:0042802 identical protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | ACCEPT | Summary: Retain identical protein binding as a core ferritin function or location. Reason: Original Results and Methods describe human ORF yeast two-hybrid screening with pairwise quadruplicate retesting and sequence confirmation. Exact source-qualified IntAct records identify this original FTL pair in Table S2G. This is positive screened association, not a claim that this pair was among the separate MAPPIT/PCA/wNAPPA subset or functions together in every tissue. The original target supplementary row was not independently reread. Identical-subunit binding supports ferritin-shell assembly and is retained as core. Supporting Evidence: |
| GO:0042802 identical protein binding | IPI PMID:25502805 A massively parallel pipeline to clone DNA variants and exam... | ACCEPT | Summary: Retain identical protein binding as a core ferritin function or location. Reason: Original Table S2 rows 62β65 and its explicit legend identify WT-based FTL homomer assay contexts with Q26L/A27V/T30I/A96T GFP1 and Y2H1, meaning stable/no disruption in this study. The later 2019 original reports different perturbation calls; keep study-specific results and the WT baseline association. Do not read the generic IntAct mutation feature tags as proof of loss in this 2014 table. Identical-subunit binding supports ferritin-shell assembly and is retained as core. Supporting Evidence: |
| GO:0042802 identical protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | ACCEPT | Summary: Retain identical protein binding as a core ferritin function or location. Reason: Original Table S3A row 963 positively scores wild-type human FTLβFTL in yeast two-hybrid; rows 965 and 967 separately show loss of the tested interaction with A96T and H133P. No target GPCA result occurs in Table S3B. Wild-type self-association agrees with independently characterized human L-chain ferritin shells and is a core assembly property. This does not resolve purified affinity, an exact natural isoform or native oligomer stoichiometry from the screen alone. Supporting Evidence: |
| GO:0042802 identical protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | ACCEPT | Summary: Retain identical protein binding as a core ferritin function or location. Reason: Original Methods and exact Supplementary Data 2/4 rows establish detectable WT baselines for the FTL pair. Data 2 records non-disruptive MYOG R147C/P49H, FTH1 K54R and FTL E57K contexts; Data 4 records FTL Q26L/A27V/T30I/A96T as disruptive. This differs from the 2014 original Table S2 calls; preserve the study-specific outcomes without declaring a curation error or universal mutant loss. No FTL-specific PCA result is claimed. Identical-subunit binding supports ferritin-shell assembly and is retained as core. Supporting Evidence: |
| GO:0044754 autolysosome | IDA PMID:25327288 Selective VPS34 inhibitor blocks autophagy and uncovers a ro... | KEEP AS NON CORE | Summary: Retain supported autolysosome as contextual evidence. Reason: The authentic 25327288 abstract and selected original captions identify ferritin cargo targeting/turnover in human-cell experiments. Retain autolysosomal cargo localization at gene level, while explicitly noting that full main Methods and the detailed localization panel were not recovered; do not certify an unseen subunit-specific imaging assay. Supporting Evidence: |
| GO:0044754 autolysosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retain supported autolysosome as contextual evidence. Reason: The UniProt autolysosome mapping agrees with the ferritin-cargo destination. This is a degradation compartment rather than a core activity site, and does not imply the L chain carries out autophagic transport. Supporting Evidence: |
| GO:0044754 autolysosome | IPI PMID:25327288 Selective VPS34 inhibitor blocks autophagy and uncovers a ro... | KEEP AS NON CORE | Summary: Retain supported autolysosome as contextual evidence. Reason: This original annotation is autolysosome cellular component. Selected original ferritin-cargo targeting evidence supports the contextual destination. Preserve the IPI provenance and do not reinterpret it as an autophagy process or binary-pair claim; detailed subunit-specific localization panels remain outside the recovered selected-original scope. This is a transient cargo destination rather than the principal cytosolic storage location. Supporting Evidence: |
| GO:0044754 autolysosome | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain supported autolysosome as contextual evidence. Reason: Human ferritin-complex targeting provides positive gene-level autolysosomal cargo context. Preserve P29391 as the original ISS donor, but current mouse autolysosome ISO entries point back to human P02792 and are not an independent mouse IDA experiment. Supporting Evidence: |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: Retain supported extracellular exosome as contextual evidence. Reason: The actual 19056867 main Table 1 identifies FTL in a purified human urinary exosome fraction. Retain the exact part_of UBERON:0001088 urine extension and HDA scope. Detection supports this contextual location, not vesicle biogenesis or uniform occupancy of every exosome. Supporting Evidence: |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: Retain supported extracellular exosome as contextual evidence. Reason: Extracellular-exosome localization has independent positive human evidence from PMID:19056867. The PMID:23533145 main Methods/Results were read, but its exact FTL supplement row remains unverified after access failure. Retain the unrestricted gene-level location with this explicit source limit, without adding a prostate-specific mechanism. |
| GO:0070288 ferritin complex | IDA PMID:19923220 Unraveling of the E-helices and disruption of 4-fold pores a... | ACCEPT | Summary: Retain ferritin complex as a core ferritin function or location. Reason: Human recombinant L-chain homopolymer experiments directly support ferritin-shell membership and iron handling. Preserve part_of ferritin complex; a disease frameshift construct is not a natural alternative product. Supporting Evidence: |
| GO:0070288 ferritin complex | IDA PMID:20159981 Mutant ferritin L-chains that cause neurodegeneration act in... | ACCEPT | Summary: Retain ferritin complex as a core ferritin function or location. Reason: Recombinant human H/L heteropolymers explicitly establish L-chain membership in the ferritin complex. Distinguish its structural/mineralization contribution from H-subunit active-site catalysis. Supporting Evidence: |
| GO:0070288 ferritin complex | NAS PMID:30325535 Ferritin heavy/light chain (FTH1/FTL) expression, serum ferr... | ACCEPT | Summary: Retain ferritin complex as a core ferritin function or location. Reason: Ferritin-complex membership is an established core structural role, independently supported by recombinant human L/H studies. The 30325535 NAS source is authentic and relevant but its exact assembly evidence was not verified from the abstract. |
| GO:0070288 ferritin complex | TAS PMID:7492760 Molecular basis for the recently described hereditary hyperf... | ACCEPT | Summary: Retain ferritin complex as a core ferritin function or location. Reason: Retain the established L-chain ferritin-complex role. The 7492760 source provides regulatory/clinical context rather than a newly verified complex-assembly assay; independent direct ferritin studies establish the unrestricted membership claim. |
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Download this section (compressed HTML)Q: How do endogenous H:L subunit ratios couple mineral nucleation, shell permeability and release to the labile iron pool in different human cell types? L-chain deficiency can increase sequestration in H homopolymers; storage amount and availability need not change in the same direction.
Q: Does FTL contribute a specific mechanistic step to ferritinophagy beyond determining the composition and properties of the cargo shell? Cargo knockout/rescue and receptor-associated turnover do not by themselves distinguish cargo configuration from execution of autophagy; productive NCOA4 contact has been resolved for FTH1.
Q: Which endogenous FTL-associated membrane and erythroid differentiation contexts are supported by target-specific experiments? The membrane proteomics target row remains unverified, and the inspected erythropoiesis study perturbs mouse NCOA4 rather than isolating FTL function.
Experiment: Compare sequence-verified H/L assemblies at controlled subunit ratios using separate measurements of Fe(II) oxidation, mineral nucleation, release and labile cellular iron, with H-chain active-site controls.
Experiment: Test ferritinophagy after equalizing cargo abundance and shell composition, separately measuring NCOA4 contact, sequestration and lysosomal delivery; distinguish a cargo requirement from a step performed by FTL.
Experiment: Validate endogenous FTL in the specific membrane preparation and in erythroid differentiation using target-specific detection, perturbation and rescue with iron-supply controls.
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