Complement factor H is a secreted complement regulator that recognizes C3b and host-associated polyanions. Its N-terminal domains support factor-I-mediated C3b cleavage and accelerate decay of the alternative-pathway C3 convertase, while C-terminal recognition domains help concentrate this protection on host surfaces. The shorter splice product FHL-1 shares the first seven complement-control domains and regulatory activity but lacks the C-terminal recognition region of full-length factor H. Factor H also associates with pentraxins, oxidation-modified proteins and selected microbial surface proteins in context-dependent interactions. Human CFH variants can impair complement control and predispose to renal or retinal disease. In mouse neurons, intracellular factor H can additionally protect against oxidative CNS injury through a C-terminal-domain-dependent mechanism.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001851 complement component C3b binding | IBA GO_REF:0000033 | ACCEPT | Summary: C3b recognition is a principal factor H activity. Reason: Retain the PAINT inference at PTN000449073. Human C3b–factor H structures and factor-I cleavage assays independently establish this activity. The ancestral node history was not reconstructed; the donor list is not a measure of phylogenetic support. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000449073 UNRESOLVED Original source entity preserved; the detailed PAINT ancestral history and source experimental chain were not reconstructed. Independent human target evidence is evaluated separately. |
| GO:0005515 protein binding | IPI PMID:16612335 Deletion of Lys224 in regulatory domain 4 of Factor H reveal... | MODIFY | Summary: The assayed interaction is factor H recognition of C3b. Reason: PMID:16612335 Results/Figure 7 and SPR Methods compare purified human plasma factor H with immobilized C3b. The source WITH identifies C3 beta chain PRO_0000005908, residues 23–667, which is retained in C3b; it is not an isolated C3b accession or evidence for a free beta-chain assay. Refine the functional interaction to C3b binding while preserving this exact source identifier. Proposed replacements: complement component C3b binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16612335 Deletion of Lys224 in regulatory domain 4 of Factor H reveal... | MODIFY | Summary: C3d binding describes the measured interaction more precisely. Reason: PMID:16612335 Figure 5b and SPR Methods measure purified human factor H binding to immobilized C3d. The exact source product PRO_0000005915 maps to C3d, residues 1002–1303. The K224-deletion comparison leaves this C-terminal recognition activity intact; the assay does not assign the same domain architecture to FHL-1. Proposed replacements: complement component C3d binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17244159 Studies on the interactions between C-reactive protein and c... | MODIFY | Summary: Modified CRP binds factor H in the tested plate assays. Reason: The selected primary Methods and Figure 5 distinguish urea-modified CRP and engineered/acylated recombinant mCRP from native pentameric CRP. The exact source-linked records retain the processed P02741-PRO_0000023526 partner and engineered-form features. Refine to pentraxin binding at that tested scope; this does not establish binding to every native CRP state or transfer CRP receptor activity to FH. Proposed replacements: pentraxin binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17293598 The factor H variant associated with age-related macular deg... | MODIFY | Summary: FH CCP6–8 and full-length FH bind immobilized CRP, with an allotype-dependent difference. Reason: Selected primary Methods and Results/Figures 1–2 show purified human FH and recombinant CCP6–8 binding in plate and SPR assays. The paper uses mature-chain His/Tyr-384 numbering; the curated precursor feature is position 402. CRP was adsorbed from carbonate buffer without specified calcium, although binding buffer contained calcium, so its native pentameric conformation is not established by these assays. Refine the known CRP partner to pentraxin binding without generalizing the fragment or allotype results. Proposed replacements: pentraxin binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17293598 The factor H variant associated with age-related macular deg... | KEEP AS NON CORE | Summary: Human FH binds bovine fibromodulin in the cited experiments. Reason: The primary Methods explicitly identify fibromodulin from bovine articular cartilage, consistent with original partner P13605 and IntAct taxon 9913. Full-length human FH and CCP6–8 variants bind this protein; the primary abstract and curated Figure 4/5 assays distinguish glycosylated from deglycosylated fibromodulin. Retain the supported association as non-core under the campaign instruction. Do not relabel it human–human, infer binding to glycans from this experiment, or assign a pentraxin term to fibromodulin. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17339482 Y402H polymorphism of complement factor H affects binding af... | MODIFY | Summary: Human FH and its SCR5–7 fragment bind plate-associated CRP. Reason: The selected full primary Methods/Results compare purified human 402Y/402H FH and recombinant SCR5–7 in CRP-coated wells, with reduced binding of the risk allotype. The positive exact human pair is supported; a purified-protein plate assay does not itself establish that adsorbed CRP retained its native pentameric conformation. Pentraxin binding is the informative partner-class refinement, with the tested allotype and fragment limits retained. Proposed replacements: pentraxin binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18627465 Complement factor H allotype 402H is associated with increas... | UNDECIDED | Summary: Positive streptococcal binding is retained as evidence, but the exact M49 source assay remains unresolved. Reason: The original abstract supports human factor-H/FH5–7 association with group-A streptococci. Official UniProt identifies the exact partner P16946 as serotype-M49 M protein. The full 2012 correction reports an erroneous FH5–7 mutagenesis position and repeat experiments with corrected constructs; most conclusions persisted, with strain-dependent Figure6 changes. The exact M49 assay and its corrected outcome have not been mapped, and figure pixels were not inspected. Preserve the original positive IPI assertion pending that specific linkage, rather than treating the correction as unknown or assuming it negates binding. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18786923 Complement factor H binds to denatured rather than to native... | MODIFY | Summary: The cited paper supports binding to structurally altered CRP. Reason: The actual full primary experiments found binding to heat- or urea-treated CRP and to CRP altered during calcium-free immobilization, while their calcium-preserved native-CRP tests were negative. Refine to pentraxin binding for the observed modified ligand. This is not a universal claim that FH binds circulating native CRP, nor a basis for discarding independent native-CRP positives obtained at different protein concentrations and buffer conditions. Proposed replacements: pentraxin binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19050261 Binding of the long pentraxin PTX3 to factor H: interacting ... | MODIFY | Summary: FH binds the long pentraxin PTX3 in the cited biochemical assays. Reason: The primary abstract and selected journal figure text, corroborated by fourteen exact source-linked human-pair records, support plate and SPR binding with FH/PTX3 domain mapping. Keep fragment, glycosylation and allotype comparisons distinct from an assay of every product. Refine to pentraxin binding; PTX3 is a long-pentraxin family member, and this does not imply that the tested molecule is a five-chain pentamer or that FH is a pentraxin receptor. Proposed replacements: pentraxin binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19084272 Human complement factor H-related protein 4 binds and recrui... | MODIFY | Summary: The FHR4-focused paper also supplies positive FH–modified-CRP evidence. Reason: The original abstract explicitly contrasts FHR4 native-CRP recognition with FH recognition of modified CRP. Exact source-linked FH ELISA records provide the target evidence; the additional serum co-immunoprecipitation has an antibody-cross-reactivity caveat and is not used to establish a purified interface. Refine the supported FH–CRP capability to pentraxin binding, retaining the form-dependent limit. The full primary body was not recovered, so unspecified assay conditions are not reconstructed from the FHR4 title. Proposed replacements: pentraxin binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19225461 Neisseria meningitidis recruits factor H using protein mimic... | KEEP AS NON CORE | Summary: Human factor H binds meningococcal factor-H-binding protein. Reason: PMID:19225461 reports SPR and the human FH6–7–fHbp crystal complex, with interface mutations reducing binding. The crystallized bacterial protein lacks its lipid anchor. This supports the source-specific pathogen association; it does not establish a separate receptor activity of factor H. Retain supported generic binding under the explicit ClinGen project instruction. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19632990 Synergy between ficolin-2 and pentraxin 3 boosts innate immu... | KEEP AS NON CORE | Summary: FH was recovered among plasma proteins captured by PTX3. Reason: The inspected primary Results report FH identification by mass spectrometry after PTX3 affinity capture from human plasma; the exact source-linked pull-down record corroborates this pair. This is positive complex-associated evidence, not an independently inspected purified FH–PTX3 binary-binding experiment in this paper. Retain this source at non-core generic binding resolution, while other directly assayed sources independently justify pentraxin-binding refinements. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19680263 Monomeric CRP contributes to complement control in fluid pha... | MODIFY | Summary: The cited study supports FH interaction with modified monomeric CRP. Reason: The original abstract directly establishes recombinant FH/mCRP binding, domain mapping and reduced binding of selected C-terminal mutants. Fourteen exact human-pair curated records distinguish binding assays from downstream factor-I-dependent C3b cleavage. Refine to pentraxin binding at the mCRP/full-length-versus-fragment scope; do not assign protease activity to FH from the assay method label. The selected normal cache is abstract-only and full publisher assay text was not recovered in this peer. Proposed replacements: pentraxin binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19850925 Complement factor H binds at two independent sites to C-reac... | MODIFY | Summary: FH binds native CRP under the particular solution and surface conditions tested. Reason: Full primary AUC, SPR and scattering experiments support FH–CRP association in 137 mM NaCl and 2 mM calcium at high, acute-phase-range and higher protein concentrations; salt and concentration materially affect the result. Refine to pentraxin binding without claiming constitutive association at normal low circulating CRP. This paper and the denatured-CRP study test different conditions; neither warrants an unconditional conclusion about all native-CRP assays. Proposed replacements: pentraxin binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20042240 Molecular basis of C-reactive protein binding and modulation... | MODIFY | Summary: The exact source contains a positive CRP-binding FH peptide-array record. Reason: IntAct EBI-22119497 links the original human pair to Figure 7C peptides 5, 6, 15 and 16, with FH binding regions 331–342/336–347 and a disruptive position-338 feature; the curator records binding only at high CRP concentration. The full primary body remains inaccessible here. Refine the identified pentraxin partner while preserving that limited peptide-assay provenance; independently inspected PMID:19850925 establishes whole-FH CRP binding under specified conditions. Do not transfer the paper’s CFHR4-specific motif or complement-activation mechanism to FH. Proposed replacements: pentraxin binding |
| GO:0005515 protein binding | IPI PMID:21317894 Structural basis for engagement by complement factor H of C3... | MODIFY | Summary: C3d recognition is directly resolved by the C-terminal factor H structure. Reason: PMID:21317894 directly resolves human FH19–20 bound to C3d and relates this interface to recognition of the C3d region within C3b on a host surface. The parent C3 accession is preserved. C3d binding is the informative molecular interaction demonstrated by this structural source; no protease activity is assigned to factor H. Proposed replacements: complement component C3d binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21979047 Complement factor H binds malondialdehyde epitopes and prote... | KEEP AS NON CORE | Summary: The source records a factor H–C3 association. Reason: The exact human pair is retained in IntAct EBI-21992363, an in-vitro ELISA record linked to PMID:21979047 Supplementary Figure 4C. This is target-level provenance, not independent replication of GOA. The precise C3 cleavage state in that panel remains unverified, so retain the supported low-resolution association rather than infer C3b or C3d specificity from other publications. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21979047 Complement factor H binds malondialdehyde epitopes and prote... | KEEP AS NON CORE | Summary: Factor H recognizes aldehyde-modified albumin in the assay. Reason: PMID:21979047 uses malondialdehyde–acetaldehyde-modified bovine serum albumin as a carrier of oxidation epitopes. Binding is supported by solid-phase and SPR experiments and exact P08603–P02769 records. Preserve this modified-protein context: the results do not establish ordinary binding to unmodified albumin or a new enzyme function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22786770 Atypical hemolytic uremic syndrome-associated variants and a... | MODIFY | Summary: Native and recombinant FH bind PTX3, with specific C-terminal variant effects. Reason: Selected full primary Methods and Results/Figures 1–2, 5–6 support human FH–PTX3 binding, including purified-protein assays, calcium/pH dependence and impaired binding of selected SCR15–20 mutants. The plasma experiments include C3-deficient material and protein-resolving blots; they are separate from the purified assays. Refine to pentraxin binding, retaining original mature-chain PTX3 partner PRO_0000023545 and distinguishing FH from separately assayed FHL-1 and FHR1. Proposed replacements: pentraxin binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23332154 Malaria parasites co-opt human factor H to prevent complemen... | KEEP AS NON CORE | Summary: Malaria gametes recruit human factor H through PfGAP50. Reason: The original primary abstract explicitly identifies PfGAP50 as the receptor for human factor H on malaria gametes and links this acquisition to C3b inactivation and complement escape. Retain the curator-mapped P08603–Q8I2X3 association at that resolution. The full target-level Methods were not recovered, so no additional construct, affinity or binary-interface claim is made. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25284781 Circulating AIM prevents hepatocellular carcinoma through co... | KEEP AS NON CORE | Summary: AIM associates with factor H in a transfection assay. Reason: PMID:25284781 Figure 5E reports co-immunoprecipitation of tagged CFH with AIM in HEK293T cells. This supports association, not a purified binary interface. The inspected main text does not independently resolve the CFH construct species; preserve the exact human curator mapping with that limitation, rather than infer species from the host cell. Mouse tumour-complement experiments are separate. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25855355 Factor H-related protein 5 interacts with pentraxin 3 and th... | MODIFY | Summary: The FHR5 paper directly includes purified FH–PTX3 comparison experiments. Reason: The full primary Results/Figures 2–3 compare purified FH and FH CCP19–20 with related proteins for PTX3 binding; Figure 5 tests displacement of FH by FHR5 and factor-I-dependent cofactor activity. These are actual FH assays despite the FHR5 title. Refine to pentraxin binding, without transferring the stronger FHR5 signal or its complement-promoting role to FH, and without inferring intrinsic FH proteolysis. Proposed replacements: pentraxin binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26468283 Complement Factor H Binds to Human Serum Apolipoprotein E an... | KEEP AS NON CORE | Summary: Factor H binds apolipoprotein E. Reason: The genuine full normal text of PMID:26468283, Figures 5–7, resolves serum affinity capture, thermophoresis and competition assays involving human FH5–7, full-length factor H and APOE. Full-length factor H binding to labelled APOE is competed by APOE and FH5–7. These support the exact association without transferring APOE lipid-transport activity to factor H. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28258151 Staphylococcus aureus SdrE captures complement factor H's C-... | KEEP AS NON CORE | Summary: Staphylococcal SdrE captures the C-terminal region of factor H. Reason: PMID:28258151 uses recombinant human FH C-terminal fragments, SdrE N2N3 and an FH1206–1226 peptide for pull-down, calorimetry and structural experiments. Retain this experimentally supported pathogen interaction. The assayed CCP20 region is absent from FHL-1; no equivalent binding by that shorter product is inferred. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28533443 FHR-1 Binds to C-Reactive Protein and Enhances Rather than I... | MODIFY | Summary: FH and its C-terminal fragments bind modified CRP in the FHR1-focused paper. Reason: The genuine author manuscript Methods and Results/Figures 3 and 5 establish mCRP binding to full-length FH and FH19–20/FH15–20 fragments; FHR1 competes with the C-terminal fragment at the tested concentrations. Native pCRP was negative in the tested lower-concentration plate conditions. Refine to pentraxin binding while retaining the actual full-length versus fragment and modified-ligand limits, not a universal native-CRP exclusion. Proposed replacements: pentraxin binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28533443 FHR-1 Binds to C-Reactive Protein and Enhances Rather than I... | MODIFY | Summary: FH CCP19–20 binds PTX3 in the cited mutant comparison. Reason: The genuine author manuscript Methods and Figure 4C compare wild-type and fourteen single-substitution FH19–20 fragments for recombinant human PTX3 binding. Refine to pentraxin binding while retaining the fragment/variant scope and original PTX3 processed-chain partner. The study is not a measurement of every full-length FH product, and the source-linked position features are preserved without inventing unresolved substitution numbering. Proposed replacements: pentraxin binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28671664 Regulator-dependent mechanisms of C3b processing by factor I... | MODIFY | Summary: C3b binding describes the factor H interaction in the processing complex. Reason: PMID:28671664 resolves C3b with miniFH and factor I, and separately assays factor-I-dependent cleavage. The WITH product PRO_0000005908 is the C3 beta chain retained in C3b, not free C3b itself. Refine to the assayed C3b-containing complex without asserting a free beta-chain binding assay. FI provides the catalytic site; FH stabilizes the processing assembly. Proposed replacements: complement component C3b binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:29374201 C-reactive protein and pentraxin-3 binding of factor H-like ... | MODIFY | Summary: The exact record supports CRP binding by the FH CCP6–8 fragment. Reason: The full primary Figure 1C–D and exact source-linked records test recombinant FH CCP6–8, including the 402 allotypes; Figure 1B independently tests full-length FH. Full FH recognized mCRP but not pCRP in these assays, whereas CCP6–8 and FHL-1 had different ligand-form profiles. Refine to pentraxin binding without treating the fragment result as proof that every full-length or splice product binds both forms. Preserve original P02741 and untagged source product fields. Proposed replacements: pentraxin binding Supporting Evidence: |
| GO:0005576 extracellular region | IBA GO_REF:0000033 | ACCEPT | Summary: Factor H acts in extracellular fluid and at exposed cell surfaces. Reason: The PAINT active-in assertion agrees with human plasma factor H binding C3b and supporting extracellular factor-I cleavage. Retain PTN000449073 and all original sources without treating a short donor list as weak evidence. Its detailed node history was not reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000449073 UNRESOLVED Original source entity preserved; the detailed PAINT ancestral history and source experimental chain were not reconstructed. Independent human target evidence is evaluated separately. |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | ACCEPT | Summary: The electronic extracellular localization matches the secreted regulatory protein. Reason: The original combined ARBA/UniProt subcellular mapping agrees with purification of human plasma factor H, secretory deficiency experiments and extracellular complement reactions. This location is central to its established complement-regulatory role. |
| GO:0005576 extracellular region | TAS PMID:9312129 Human factor H deficiency. Mutations in framework cysteine r... | ACCEPT | Summary: Human factor H is secreted into the extracellular compartment. Reason: PMID:9312129 reports secretion defects of patient factor-H variants and experiments following fibroblast protein release and intracellular retention. Its abstract supports the normal secretory destination; the complete Methods were not accessed. Independent human plasma and complement biochemistry corroborate the core extracellular location. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1006169 | ACCEPT | Summary: The curated complement event places factor H extracellularly. Reason: The selected Reactome event and current official event record place factor H in extracellular complement binding, convertase regulation or factor-I-mediated C3b processing. Retain the source-specific TAS location. These related events share a pathway-curation provenance and are not nine independent localization experiments. Supporting Evidence: Reactome:R-HSA-1006169 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-976743 | ACCEPT | Summary: The curated complement event places factor H extracellularly. Reason: The selected Reactome event and current official event record place factor H in extracellular complement binding, convertase regulation or factor-I-mediated C3b processing. Retain the source-specific TAS location. These related events share a pathway-curation provenance and are not nine independent localization experiments. Supporting Evidence: Reactome:R-HSA-976743 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-976768 | ACCEPT | Summary: The curated complement event places factor H extracellularly. Reason: The selected Reactome event and current official event record place factor H in extracellular complement binding, convertase regulation or factor-I-mediated C3b processing. Retain the source-specific TAS location. These related events share a pathway-curation provenance and are not nine independent localization experiments. Supporting Evidence: Reactome:R-HSA-976768 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-976810 | ACCEPT | Summary: The curated complement event places factor H extracellularly. Reason: The selected Reactome event and current official event record place factor H in extracellular complement binding, convertase regulation or factor-I-mediated C3b processing. Retain the source-specific TAS location. These related events share a pathway-curation provenance and are not nine independent localization experiments. Supporting Evidence: Reactome:R-HSA-976810 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-977359 | ACCEPT | Summary: The curated complement event places factor H extracellularly. Reason: The selected Reactome event and current official event record place factor H in extracellular complement binding, convertase regulation or factor-I-mediated C3b processing. Retain the source-specific TAS location. These related events share a pathway-curation provenance and are not nine independent localization experiments. Supporting Evidence: Reactome:R-HSA-977359 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-977363 | ACCEPT | Summary: The curated complement event places factor H extracellularly. Reason: The selected Reactome event and current official event record place factor H in extracellular complement binding, convertase regulation or factor-I-mediated C3b processing. Retain the source-specific TAS location. These related events share a pathway-curation provenance and are not nine independent localization experiments. Supporting Evidence: Reactome:R-HSA-977363 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-977371 | ACCEPT | Summary: The curated complement event places factor H extracellularly. Reason: The selected Reactome event and current official event record place factor H in extracellular complement binding, convertase regulation or factor-I-mediated C3b processing. Retain the source-specific TAS location. These related events share a pathway-curation provenance and are not nine independent localization experiments. Supporting Evidence: Reactome:R-HSA-977371 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-977605 | ACCEPT | Summary: The curated complement event places factor H extracellularly. Reason: The selected Reactome event and current official event record place factor H in extracellular complement binding, convertase regulation or factor-I-mediated C3b processing. Retain the source-specific TAS location. These related events share a pathway-curation provenance and are not nine independent localization experiments. Supporting Evidence: Reactome:R-HSA-977605 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-981728 | ACCEPT | Summary: The curated complement event places factor H extracellularly. Reason: The selected Reactome event and current official event record place factor H in extracellular complement binding, convertase regulation or factor-I-mediated C3b processing. Retain the source-specific TAS location. These related events share a pathway-curation provenance and are not nine independent localization experiments. Supporting Evidence: Reactome:R-HSA-981728 |
| GO:0006508 proteolysis | IDA PMID:28671664 Regulator-dependent mechanisms of C3b processing by factor I... | ACCEPT | Summary: Factor H contributes cofactor work to factor-I-mediated proteolysis. Reason: PMID:28671664 combines C3b–miniFH–FI structural analysis with cleavage assays. FH stabilizes the enzyme/substrate assembly, whereas FI supplies the protease active site. This is performed noncatalytic participation in C3b processing, not a claim that FH itself cleaves peptide bonds. Supporting Evidence: PMID:28671664 cofactor-assisted sequential cleavages of C3b by FI |
| GO:0006954 inflammatory response | IDA PMID:19299737 Complement factor H, a marker of self protects against exper... | MODIFY | Summary: The measured effect is suppression of inflammation. Reason: PMID:19299737 administers purified human factor H in acute mouse autoimmune encephalomyelitis and measures reduced inflammatory infiltration and complement deposition. Refine the broad response term to its demonstrated negative regulation, preserving the original acts_upstream_of_or_within qualifier and heterologous treatment scope. Proposed replacements: negative regulation of inflammatory response Supporting Evidence: PMID:19299737 significant decrease in clinical score, inflammation, and demyelination |
| GO:0006954 inflammatory response | IEA GO_REF:0000117 | MODIFY | Summary: Negative regulation specifies factor H’s inflammatory effect. Reason: Independent human-FH treatment and oxidation-epitope experiments support suppression of inflammatory responses. Refine the electronic broad term to this demonstrated direction, without claiming that its exact historical ARBA training path was reconstructed. Proposed replacements: negative regulation of inflammatory response |
| GO:0006956 complement activation | IBA GO_REF:0000033 | MODIFY | Summary: Factor H limits alternative-pathway amplification. Reason: Retain the considered PAINT provenance, including legitimate target self-evidence, but specify the target’s inhibitory role. Human FH-dependent factor-I cleavage and convertase-decay experiments support negative regulation of alternative-pathway activation. This is functional specificity, not an assertion of a misplaced ancestral node. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: PANTHER:PTN000449073 UNRESOLVED Original source entity preserved; the detailed PAINT ancestral history and source experimental chain were not reconstructed. Independent human target evidence is evaluated separately. Proposed replacements: negative regulation of complement activation, alternative pathway |
| GO:0006956 complement activation | IDA PMID:24835392 Identification of a Haemophilus influenzae factor H-Binding ... | MODIFY | Summary: Pathogen-bound factor H retains complement-inhibitory cofactor activity. Reason: PMID:24835392 Figure 6 directly tests human factor H recruited by H. influenzae or recombinant PH. Bound FH supports factor-I-mediated C3b degradation, while the PH deletion reduces recruitment and serum resistance. The performed human-FH role is inhibition of alternative-pathway amplification, not activation. Proposed replacements: negative regulation of complement activation, alternative pathway Supporting Evidence: |
| GO:0006956 complement activation | TAS PMID:9312129 Human factor H deficiency. Mutations in framework cysteine r... | MODIFY | Summary: The secretion-deficiency phenotype reflects loss of inhibitory complement control. Reason: PMID:9312129 links deficient extracellular factor H to abnormal complement control. Independent cleavage and convertase-decay assays resolve the normal role as inhibition of alternative-pathway activation. Preserve the original TAS reference and use the informative directional process. Proposed replacements: negative regulation of complement activation, alternative pathway |
| GO:0006957 complement activation, alternative pathway | IDA PMID:19299737 Complement factor H, a marker of self protects against exper... | MODIFY | Summary: Human factor H suppresses alternative-pathway complement activity. Reason: PMID:19299737 tests purified human factor H in a mouse-serum zymosan assay that isolates the alternative pathway, followed by a mouse inflammatory-disease model. The measured direction is decreased complement deposition. Preserve the original upstream-or-within qualifier while making this inhibitory direction explicit. Proposed replacements: negative regulation of complement activation, alternative pathway Supporting Evidence: |
| GO:0006957 complement activation, alternative pathway | IEA GO_REF:0000117 | MODIFY | Summary: The electronic pathway assertion can be made directionally precise. Reason: Human factor H supports C3b inactivation by factor I and accelerates C3bBb decay. Negative regulation of alternative-pathway activation expresses this established role more accurately than the broad activation term. The original ARBA identifier and evidence type remain unchanged. Proposed replacements: negative regulation of complement activation, alternative pathway |
| GO:0008201 heparin binding | IDA PMID:22471560 Bivalent and co-operative binding of complement factor H to ... | ACCEPT | Summary: Factor H directly binds sulfated glycosaminoglycans including heparin. Reason: PMID:22471560 reports human FH–heparin binding by SPR, sedimentation and scattering, including full-length FH and domain fragments. Its abstract explicitly supplies the positive binding results; full Methods were not recovered. This is part of its polyanion-recognition capability, while heparin is an experimental analogue of host-surface heparan sulfate. Supporting Evidence: PMID:22471560 Surface plasmon resonance of immobilized heparin |
| GO:0008201 heparin binding | IEA GO_REF:0000117 | ACCEPT | Summary: The electronic heparin-binding assertion is supported by direct biochemistry. Reason: The mapped activity agrees with the full-length FH and heparin-fragment assays reported in PMID:22471560 and with the independently inspected heparin-affinity experiments in PMID:16612335. Retain the original electronic provenance rather than relabel it experimental. |
| GO:0022008 neurogenesis | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Factor-H loss alters developmental production of retinal cells in mice. Reason: The independently recovered full PMID:30705315 measures delayed mitotic and pyknotic profiles in the developing mouse retina, including altered timing of cell production from birth through day 7 in Cfh-null animals. This provides positive ortholog evidence relevant to the broad generation-of-nervous-system-cells definition, separately from adult neuronal survival in PMID:42686909. Retain the original human electronic assertion as non-core with explicit mouse and developmental-stage scope; the study does not establish a human cell-autonomous neurogenic mechanism or reconstruct the historical ARBA assignment. Secreted complement-regulatory activity is not a reason to exclude developmental effects. |
| GO:0022010 central nervous system myelination | IDA PMID:19299737 Complement factor H, a marker of self protects against exper... | MARK AS OVER ANNOTATED | Summary: The cited experiment measures protection from demyelination, not myelin formation. Reason: The actual PMID:19299737 Methods and Figure 4 assess myelin loss after acute inflammatory injury in adult mice treated with human FH. Reduced demyelination is a real protective result, but does not establish the oligodendrocyte-wrapping process specified by CNS myelination. Preserve the original upstream-or-within qualifier and positive protection finding; the overannotation judgment is source-specific. Supporting Evidence: |
| GO:0030449 regulation of complement activation | IDA PMID:25284781 Circulating AIM prevents hepatocellular carcinoma through co... | ACCEPT | Summary: Factor H participates in complement control at the cellular surface. Reason: PMID:25284781 places CFH among complement regulators associated with AIM, alongside separate mouse tumour-complement experiments. The neutral upstream-or-within assertion is consistent with FH’s independently established complement-regulatory work. Retain it without treating the combined RCA perturbation model as a selective human-CFH assay. This neutral, upstream-or-within source assertion is retained as a core complement-regulatory role using independent direct FH evidence; the separate ARBA row is refined to the directional alternative-pathway term. The source difference does not imply opposite biological conclusions or require downgrading an otherwise defining function solely for indirect experimental scope. |
| GO:0030449 regulation of complement activation | IEA GO_REF:0000117 | MODIFY | Summary: The regulatory effect is inhibition of alternative-pathway amplification. Reason: Refine this broad electronic regulation term using direct human factor-I cofactor and convertase-decay evidence. Preserve the original ARBA source object; this is a target-function refinement, not a claim that the historical rule path was independently reconstructed. Proposed replacements: negative regulation of complement activation, alternative pathway |
| GO:0030451 regulation of complement activation, alternative pathway | IDA PMID:20378178 Both domain 19 and domain 20 of factor H are involved in bin... | MODIFY | Summary: C-terminal C3b/C3d recognition supports inhibitory alternative-pathway control. Reason: PMID:20378178 reports FH19–20 mutant binding and crystal controls that distinguish interface effects from global structural changes. The abstract supports the recognition mechanism; full Methods remain unavailable. Independent full FH cleavage and decay experiments establish the inhibitory direction, allowing a more precise regulatory term without inventing a new mutant convertase assay. Proposed replacements: negative regulation of complement activation, alternative pathway |
| GO:0030451 regulation of complement activation, alternative pathway | IDA PMID:28671664 Regulator-dependent mechanisms of C3b processing by factor I... | MODIFY | Summary: Factor-H-dependent C3b processing negatively regulates pathway amplification. Reason: PMID:28671664 demonstrates FH-supported factor-I processing of C3b. The inhibitory direction is established by the substrate inactivation mechanism, so refine the neutral regulation term while retaining the original IDA source. This does not assign intrinsic protease activity to FH. Proposed replacements: negative regulation of complement activation, alternative pathway Supporting Evidence: |
| GO:0042802 identical protein binding | IPI PMID:19505476 Electrostatic interactions contribute to the folded-back con... | KEEP AS NON CORE | Summary: Factor H self-associates under concentration- and buffer-dependent conditions. Reason: PMID:19505476 reports native human FH oligomers whose abundance decreases with increasing salt. Two exact human FH–FH IntAct cosedimentation records match the source. Retain the existing self-binding assertion at that assay resolution, without turning it into an obligate physiological homodimer or a separate core activity. Supporting Evidence: |
| GO:0042802 identical protein binding | IPI PMID:19850925 Complement factor H binds at two independent sites to C-reac... | KEEP AS NON CORE | Summary: FH exhibits condition-dependent self-association in solution. Reason: The inspected full primary Results/Figure 2A–B identify FH dimer and higher-oligomer peaks whose proportions depend on concentration and ionic strength. Two exact FH–FH IntAct records support the original identical-protein-binding assertion. Retain as non-core: this does not establish an obligate physiological dimer, and the ambiguous stoichiometry of mixed FH–CRP boundaries is not used as independent self-binding evidence. Supporting Evidence: |
| GO:0042802 identical protein binding | IPI PMID:26468283 Complement Factor H Binds to Human Serum Apolipoprotein E an... | MARK AS OVER ANNOTATED | Summary: Competition for APOE is not itself a self-binding experiment. Reason: The single exact FH–FH expansion for PMID:26468283 is EBI-22230723, Figure 7C, with FH5–7 explicitly annotated as a competitor. The full Results and radioligand Methods test full FH and FH5–7 competing for APOE binding. This does not demonstrate association of those FH molecules with each other. The source-specific overannotation judgment preserves independent self-association evidence from other papers. Supporting Evidence: |
| GO:0043395 heparan sulfate proteoglycan binding | IDA PMID:22471560 Bivalent and co-operative binding of complement factor H to ... | MODIFY | Summary: The assayed ligand supports specific heparan-sulfate binding. Reason: PMID:22471560 directly reports factor H binding to isolated heparan-sulfate glycan fragments, with much weaker recognition of minimally sulfated regions than highly sulfated heparin analogues. GO:1904399 identifies the chemical ligand actually assayed more precisely than the proteoglycan-level assertion. This is not a claim that GO:0043395 requires direct contact with a proteoglycan core protein: recognizing its glycan moiety can also support proteoglycan binding. Preserve the original IDA object and the abstract-only primary access limit while recommending the chemically precise term. Proposed replacements: heparan sulfate binding |
| GO:0048468 cell development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Mouse factor H contributes to normal retinal developmental progression. Reason: Full PMID:30705315 documents delayed retinal lamination, altered immature neuroblast morphology and an altered trajectory toward differentiated retinal architecture in Cfh-null mice. This is positive developmental context for the broad original inference, not only survival of mature neurons. The precise interaction between RPE factor H and retinal precursors is explicitly unresolved, and tissue-layer maturation is not a lineage-resolved human differentiation assay. Retain the original electronic source as non-core with these limits rather than rejecting it because an ARBA training chain was not reconstructed. Supporting Evidence: PMID:30705315 delayed and disrupted maturation |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | UNDECIDED | Summary: Exact factor-H detection in the source exosome table remains to be verified. Reason: The full PMID:23533145 text describes proteomics of extracellular-vesicle preparations from expressed prostatic secretions in urine, but the exact CFH accession/peptide entry in the supplementary dataset is not yet resolved. Preserve the HDA assertion and distinguish this target-level gap from evidence against vesicle association. Supporting Evidence: |
| GO:0072562 blood microparticle | HDA PMID:22516433 Proteomic analysis of microvesicles from plasma of healthy d... | UNDECIDED | Summary: The source microparticle proteomics needs target-level verification. Reason: PMID:22516433 describes healthy-donor plasma microvesicle proteomics. Its exact CFH entry and identification criteria were not recovered from the target dataset. Retain the original HDA source unchanged; an abundant secreted protein could associate with vesicles, so neither contamination nor a wrong annotation is inferred from the abstract alone. Supporting Evidence: |
| GO:0106139 symbiont cell surface | IDA PMID:23332154 Malaria parasites co-opt human factor H to prevent complemen... | KEEP AS NON CORE | Summary: Human factor H is recruited to a parasite surface. Reason: PMID:23332154 explicitly reports acquisition of human factor H by malaria gametes through PfGAP50. GO:0106139 is a location on the surface of the symbiont relative to the annotated host protein, so the taxonomic framing is appropriate. Retain this infection-context location without making it a constitutive location or an assay of every CFH product. Supporting Evidence: |
| GO:1903659 regulation of complement-dependent cytotoxicity | IDA PMID:25284781 Circulating AIM prevents hepatocellular carcinoma through co... | KEEP AS NON CORE | Summary: Factor H is implicated in regulation of complement-dependent cell injury. Reason: PMID:25284781 connects AIM association with cell-surface complement regulators, including CFH, to mouse tumour-cell complement susceptibility. Retain the original broad upstream-or-within assertion as contextual regulation, with the model’s combined-regulator and construct-species limits explicit. It does not demonstrate a separate cytotoxic effector activity of human FH. Supporting Evidence: |
| GO:1905370 serine-type endopeptidase complex | IPI PMID:28671664 Regulator-dependent mechanisms of C3b processing by factor I... | ACCEPT | Summary: Factor H is a noncatalytic member of the C3b-processing assembly. Reason: PMID:28671664 resolves a complex containing C3b, miniFH and catalytically inactive FI-S525A and separately assays cleavage. The complex term denotes an assembly with protease capability, not catalytic activity of each component. Retain part_of for FH while assigning the active site to FI and preserving the engineered structural construct limit. Supporting Evidence: |
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Download this section (compressed HTML)Q: Which native CRP forms, concentrations and tissue conditions support factor-H association in vivo, and how do full-length FH and FHL-1 differ?
Q: Which RPE-to-retinal-precursor mechanism explains the altered timing of cell production and maturation in Cfh-deficient mice, and how does it transfer to human developmental contexts?
Q: Can the original exosome/microparticle accession and peptide records, and the exact M49 assay linkage after the streptococcal-binding correction, be recovered?
Q: How closely do human neuronal CFH mechanisms match the intracellular SCR20-dependent protection demonstrated with mouse constructs?
Q: Can the GO:0001864 definition distinguish pentraxin family membership from oligomeric state explicitly, so monomeric CRP and long-pentraxin PTX3 binding retain accurate chemical-form scope?
Experiment: Compare native full-length human FH and FHL-1 with defined CRP conformers at controlled calcium, ionic strength and concentration, using solution binding and matched surface assays.
Experiment: Test endogenous human neuronal CFH loss and rescue with secretion-competent and intracellularly retained constructs, separating lipid-peroxidation protection from neuronal generation or myelin formation.
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