C3 is a secreted central component of the complement system whose proteolytic and chemical processing creates functionally distinct effectors. Activated C3b uses an internal thioester to attach covalently to nearby surfaces, provides a nonenzymatic platform for complement convertases, and marks targets for recognition by complement receptors. Further processing produces iC3b and C3d-containing fragments that connect opsonic recognition to phagocytes and B-cell co-receptors. Soluble C3a activates the G-protein-coupled receptor C3AR1 and elicits context-dependent inflammatory responses. These activities support microbial defense and removal or remodeling of tagged material; complement-dependent neural pruning and metabolic effects of the distinct C3a-desArg product depend on experimental and tissue context.
Curated functional classes representing distinct biological activities. These may be splice variants, cleavage products, or other forms with different functions.
C3_C3APRO_0000005910 (residues 672-748) C3_C3BPRO_0000005911 (residues 749-1663) PRO_0000005908 (residues 23-667) C3_C3DPRO_0000005915 (residues 1002-1303) C3_ASPPRO_0000419935 (residues 672-747) | GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001934 positive regulation of protein phosphorylation | IDA PMID:15833747 C5L2 is a functional receptor for acylation-stimulating prot... | KEEP AS NON CORE | Summary: ASP stimulates receptor-associated phosphorylation in the reported metabolic signaling system. Reason: The complete cached abstract reports increased C5L2 phosphorylation and beta-arrestin redistribution after acylation-stimulating protein (ASP; C3a-desArg) treatment. Retain the observed positive regulation as a context-dependent response, without assigning kinase activity to C3 or treating C5L2 as an uncontested ASP receptor. The original full assay was not inspected; independent human C3a experiments also demonstrate ligand-induced downstream phosphorylation, but involve C3AR1 rather than establishing the disputed ASP receptor identity. |
| GO:0001970 positive regulation of activation of membrane attack complex | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: C3 supports downstream membrane-attack-complex activation. Reason: Mouse orthology supplies this source assertion. The inspected MGI comparative table traces it to a mouse laser-injury experiment; its publisher-indexed abstract reports complement deposition and C3-deficient animals. Independent human complement reconstitution shows how C3b helps form C5 convertase and enables terminal complement activation. Retain the regulatory outcome without assigning C3 the membrane pore or C5-cleaving protease activity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P01027 Β· mouse C3 SUPPORTS TRANSFER Ortholog identity is established. Specific mouse provenance and original-assay access limits are stated in the review; retained human applicability does not turn mouse phenotypes into direct human experiments. |
| GO:0002430 complement receptor mediated signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: C3 fragments engage complement receptors to initiate signaling. Reason: The mouse-derived assertion agrees with direct human C3d-CR2 structural evidence and C3a-C3AR1 activation. These are ligand activities of different cleavage products, not signaling-receptor activity of C3 itself. The exact original mouse assay was not independently inspected; target-specific human evidence supports retention. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P01027 Β· mouse C3 SUPPORTS TRANSFER Ortholog identity is established. Specific mouse provenance and original-assay access limits are stated in the review; retained human applicability does not turn mouse phenotypes into direct human experiments. |
| GO:0004866 endopeptidase inhibitor activity | IEA GO_REF:0000002 | REMOVE | Summary: Reject inhibitor activity propagated through shared macroglobulin domains onto complement C3. Reason: The IPR001599/IPR002890 hits identify shared macroglobulin architecture, not the functional specificity of every member. Primary structural descriptions distinguish the complement anaphylatoxin segment from the protease-cleavable bait sequence of alpha-macroglobulin inhibitors. In the inhibitor mechanism, cleavage triggers steric trapping of the attacking protease; C3 instead exposes its thioester for attachment to complement-activating surfaces. The human C3 experiments in PMID:6903192 directly support that surface-attachment chemistry and convertase assembly, while PMID:39914456 supports its complement-platform role. The domain-based inhibitor transfer therefore crosses a documented functional divergence and should be removed. This rejects this electronic mapping rather than proving that C3 cannot affect any protease under any condition. It does not depend on a claim that the unavailable historical PAINT node explicitly excluded C3, nor on treating an inherited domain name as proof of a functional bait sequence. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE Sources checked: InterPro:IPR001599 SUPPORTS SOURCE BUT NOT TARGET The shared macroglobulin domain is a genuine structural match. Inhibitory function of bait-cleavage/protease-trapping family members does not transfer to the complement surface-attachment mechanism of C3. InterPro:IPR002890 SUPPORTS SOURCE BUT NOT TARGET The shared macroglobulin domain is a genuine structural match. Inhibitory function of bait-cleavage/protease-trapping family members does not transfer to the complement surface-attachment mechanism of C3. |
| GO:0005102 signaling receptor binding | TAS PMID:9164946 The mouse anaphylatoxin C3a receptor: molecular cloning, gen... | MODIFY | Summary: C3a is an activating receptor ligand rather than only a receptor-binding protein. Reason: The complete cached original abstract describes cloned mouse C3AR1 expressed in HEK293 or rat RBL-2H3 cells, C3a binding and calcium responses; it does not specify the C3a reagent species. Independent human C3a and human C3AR1 purification, receptor-bound structures and cellular transducer assays in PMID:37852260 and PMID:37169960 establish receptor ligand activity directly. Refine the broad binding assertion without assigning signaling-receptor activity to the soluble ligand. Proposed replacements: receptor ligand activity |
| GO:0005515 protein binding | IPI PMID:11387479 Structure of complement receptor 2 in complex with its C3d l... | MODIFY | Summary: C3d acts as a CR2/CD21 ligand in B-cell co-receptor signaling. Reason: The original crystallographic abstract supports physical C3dβCR2 association. The independently read PMID:21527715 abstract confirms human receptor binding and its immune-response context while revising the earlier proposed interface. Together with the receptor-ligand assertion already supported by that source and the human B-cell signaling model, this supports GO:0048018 receptor ligand activity rather than stopping at signaling receptor binding. Preserve the processed-C3d context and the original source: the early interface geometry is disputed, not the receptor association, and uncleaved C3 is not assumed to expose the same site. This refines an existing row and adds no NEW assertion or duplicate core. Proposed replacements: receptor ligand activity |
| GO:0005515 protein binding | IPI PMID:11705926 Mycobacterial protein HbhA binds human complement component ... | KEEP AS NON CORE | Summary: Human C3 associates with mycobacterial HbhA. Reason: The complete abstract reports binding of human C3 to recombinant full-length HbhA and to an HbhA C-terminal fusion, with loss of binding after C-terminal truncation. This supports the partner-specific interaction. Retain supported generic binding under the standing project instruction without transferring bacterial adhesin activity to C3 or claiming the bead/macrophage phenotype is solely complement dependent. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:12438350 Decreased infectivity despite unaltered C3 binding by a Delt... | KEEP AS NON CORE | Summary: Human C3 associates with mycobacterial HupB. Reason: The complete abstract identifies HupB as a second mycobacterial protein binding human C3. The role of intact-organism HupB remains unresolved in that abstract; this limits a physiological mechanism, not the demonstrated binding claim. Retain the exact partner and generic binding without assigning the bacterial proteinβs DNA-related activity to C3. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:12540846 The chemoattractant receptor-like protein C5L2 binds the C3a... | UNDECIDED | Summary: Binding of C3a/C3a-desArg to C5L2/C5aR2 is experimentally disputed. Reason: The original positive abstract identifies ASP/C3a-desArg binding to C5L2/C5AR2, but two independently read normal primary abstracts report contrary binding results. PMID:17068344 uses radioligand and fluorescent-ligand assays and reports no C3a or C3a-desArg binding; PMID:12899627 also reports no C3a interaction. Full original assay conditions were not inspected, so differences in ligand preparation and receptor expression are not resolved. Keep the exact Q9P296 partner and original positive source as UNDECIDED; established C3a-C3AR1 signaling cannot substitute for ASP-C5L2 binding. Supporting Evidence: PMID:17068344 neither C3a nor C3a-des-Arg(77) binds to C5L2 |
| GO:0005515 protein binding | IPI PMID:16530040 CRIg: a macrophage complement receptor required for phagocyt... | KEEP AS NON CORE | Summary: C3b/iC3b binds the complement receptor CRIg/VSIG4. Reason: The complete abstract directly reports C3b/iC3b binding to CRIg and receptor-dependent clearance of opsonized particles, including mouse Kupffer-cell loss-of-function evidence. Preserve the exact curated Q9Y279-1 partner: the abstract does not independently resolve that product-specific experimental construct. The structural study PMID:17051150 corroborates the interaction. Retain binding by source evidence and curator deference without converting a phagocytic receptor interaction into an untested ligand-specific signaling mechanism. |
| GO:0005515 protein binding | IPI PMID:16530040 CRIg: a macrophage complement receptor required for phagocyt... | KEEP AS NON CORE | Summary: C3b/iC3b binds the complement receptor CRIg/VSIG4. Reason: The complete abstract directly reports C3b/iC3b binding to CRIg and receptor-dependent clearance of opsonized particles, including mouse Kupffer-cell loss-of-function evidence. Preserve the exact curated Q9Y279-2 partner: the abstract does not independently resolve that product-specific experimental construct. The structural study PMID:17051150 corroborates the interaction. Retain binding by source evidence and curator deference without converting a phagocytic receptor interaction into an untested ligand-specific signaling mechanism. |
| GO:0005515 protein binding | IPI PMID:17051150 Structure of C3b in complex with CRIg gives insights into re... | KEEP AS NON CORE | Summary: C3b forms a structurally characterized complex with CRIg. Reason: The complete abstract reports a C3bβCRIg crystal structure and receptor mutants, directly corroborating the interaction. It separately assigns alternative-convertase inhibition to CRIg; that activity must not be transferred to C3. Retain the supported generic interaction with its processed-C3 context, without adding a catalytic or signaling activity merely from the partner identity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18796626 Mutations in complement C3 predispose to development of atyp... | KEEP AS NON CORE | Summary: C3b binding to CD46/MCP is independently supported. Reason: The original PMID:18796626 abstract describes C3 variants and complement dysregulation but does not expose its CD46 assay. The independently inspected Results and ELISA Methods of PMID:23086448 explicitly test C3bβCD46 binding as a positive control. Retain the original reference and partner by curator deference plus this direct corroboration; do not pretend that the original target-specific assay was independently read or transfer CD46 cofactor activity to C3. |
| GO:0005515 protein binding | IPI PMID:19255449 Functional basis of protection against age-related macular d... | MODIFY | Summary: C3b binds complement factor B during proconvertase assembly. Reason: The complete abstract reports plasma-derived and recombinant factor B variants, Biacore measurements of C3b binding, and functional convertase differences. Factor B is a complement-cascade component, so complement binding is a supported refinement of generic binding. This does not assign factor B/Bb protease activity to C3, and the measured C3b interaction should not be generalized to every C3-derived product. Proposed replacements: complement binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20042240 Molecular basis of C-reactive protein binding and modulation... | MODIFY | Summary: C3b binding to CFHR4 is supported by independent targeted evidence. Reason: The original complete abstract foregrounds CFHR4βCRP binding and C3-fragment deposition, rather than exposing the source-specific C3b-binding assay. PMID:22518841 independently describes the C-terminal CFHR4βC3b interaction and binding-site mutants. Retain the literal Q92496-1 partner and original reference by curator deference; refine to complement binding on this corroborated complement-regulator interaction, without claiming all CFHR4 products were assayed. Proposed replacements: complement binding |
| GO:0005515 protein binding | IPI PMID:21317894 Structural basis for engagement by complement factor H of C3... | MODIFY | Summary: C3d and the C3b thioester domain bind factor H. Reason: Inspected primary Results combine C3dβFH19β20 crystallography, NMR, SPR and interface mutations. This directly supports binding a complement regulator and the complement-binding refinement. The paper distinguishes C3d structures from their constrained extrapolation to C3b; do not assign factor H glycan recognition or factor I proteolysis to C3. Proposed replacements: complement binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21527715 A crystal structure of the complex between human complement ... | MODIFY | Summary: Human C3d supplies CR2/CD21 receptor-ligand activity through a revised structural interface. Reason: The complete abstract reports the human CR2(SCR1β2)βC3d structure, explains disagreement with the earlier interface and links receptor engagement to enhanced antibody responses. The same source already supports the accepted GO:0048018 assertion and the C3d receptor-ligand core. Refine this generic binding row to that activity, preserving the distinction between the soluble processed ligand and the receptor. The corrected interface does not refute C3dβCR2 association, and the structural experiment is not relabeled as a stand-alone measurement of every downstream B-cell response. Proposed replacements: receptor ligand activity Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21979047 Complement factor H binds malondialdehyde epitopes and prote... | MODIFY | Summary: C3b participates in factor H-dependent complement regulation. Reason: The inspected Results directly assay factor H-dependent generation of iC3b on MDA-bearing surfaces. This is reaction-context support rather than an independently isolated binary-affinity experiment in this paper; the direct FHβC3d/C3b interface is independently supported by PMID:21317894. Retain the exact original assertion and refine to complement binding, without attributing factor Hβs MDA binding or factor Iβs cleavage chemistry to C3. Proposed replacements: complement binding |
| GO:0005515 protein binding | IPI PMID:22518841 Factor H-related protein 4 activates complement by serving a... | MODIFY | Summary: C3b binds CFHR4 in a complement-assembly platform. Reason: The complete abstract explicitly reports CFHR4 C-terminal C3b binding and loss of binding in site-directed mutants. Refine to complement binding, preserving the literal Q92496-1 annotation and curator-assigned product scope. Recruitment of factor B/properdin and active convertase formation do not make C3 or CFHR4 the protease. Proposed replacements: complement binding Supporting Evidence: PMID:22518841 sustained ability of CFHR4-bound C3b to bind factor B and properdin |
| GO:0005515 protein binding | IPI PMID:23086448 The CD46-Jagged1 interaction is critical for human TH1 immun... | KEEP AS NON CORE | Summary: C3b binds CD46 in a direct positive-control assay. Reason: The inspected Results explicitly show C3b binding to CD46; the Methods identify serum-purified C3b and the ELISA setup. The titleβs focus on Jagged1 does not invalidate this target assay. Retain supported generic binding without transferring CD46/Jagged signaling or regulatory activities to the C3 product solely from physical association. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26627825 Extracellular Fibrinogen-binding Protein (Efb) from Staphylo... | KEEP AS NON CORE | Summary: C3 is recovered among Efb-associated proteins. Reason: The inspected Results explicitly identify complement C3 among known Efb interactors recovered by pulldown and mass spectrometry from platelet preparations; the associated Methods and caption describe replicated Efb-loaded versus empty-bead controls. Retain this association without claiming the paper purified a binary C3βEfb complex or transferring its separate P-selectin/platelet conclusions to C3. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:27814381 Mapping the Complement Factor H-Related Protein 1 (CFHR1):C3... | MODIFY | Summary: C3b/C3d binds complement factor H-related protein 1. Reason: Inspected primary Results show dose-dependent binding of recombinant CFHR1 to serum-derived C3b and recombinant C3d, with mutations disrupting binding and competition with CFH. Complement binding is the appropriate direction of refinement: C3 binds CFHR1, not an assertion that C3 itself binds C3b. Preserve the literal processed partner UniProtKB:Q03591-PRO_0000005896 and avoid converting it to an unqualified accession. Proposed replacements: complement binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: A curated HuRI binary interaction is retained with its exact partner. Reason: The complete abstract and inspected primary Methods/Results describe systematic human Y2H screening, quadruplicate pairwise retesting and sequence confirmation. The exact source partner is also recorded in the preserved UniProt IntAct section. Retain the source-specific curated binding assertion under the standing project policy, while explicitly deferring to curators for the individual target pair and construct in the uninspected supplementary table. No target-specific orthogonal validation, native-cell mechanism, or functional role is inferred from the global framework or NbExp count. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: A curated HuRI binary interaction is retained with its exact partner. Reason: The complete abstract and inspected primary Methods/Results describe systematic human Y2H screening, quadruplicate pairwise retesting and sequence confirmation. The exact source partner is also recorded in the preserved UniProt IntAct section. Retain the source-specific curated binding assertion under the standing project policy, while explicitly deferring to curators for the individual target pair and construct in the uninspected supplementary table. No target-specific orthogonal validation, native-cell mechanism, or functional role is inferred from the global framework or NbExp count. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: A curated HuRI binary interaction is retained with its exact partner. Reason: The complete abstract and inspected primary Methods/Results describe systematic human Y2H screening, quadruplicate pairwise retesting and sequence confirmation. The exact source partner is also recorded in the preserved UniProt IntAct section. Retain the source-specific curated binding assertion under the standing project policy, while explicitly deferring to curators for the individual target pair and construct in the uninspected supplementary table. No target-specific orthogonal validation, native-cell mechanism, or functional role is inferred from the global framework or NbExp count. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: A curated HuRI binary interaction is retained with its exact partner. Reason: The complete abstract and inspected primary Methods/Results describe systematic human Y2H screening, quadruplicate pairwise retesting and sequence confirmation. The exact source partner is also recorded in the preserved UniProt IntAct section. Retain the source-specific curated binding assertion under the standing project policy, while explicitly deferring to curators for the individual target pair and construct in the uninspected supplementary table. No target-specific orthogonal validation, native-cell mechanism, or functional role is inferred from the global framework or NbExp count. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: A curated HuRI binary interaction is retained with its exact partner. Reason: The complete abstract and inspected primary Methods/Results describe systematic human Y2H screening, quadruplicate pairwise retesting and sequence confirmation. The exact source partner is also recorded in the preserved UniProt IntAct section. Retain the source-specific curated binding assertion under the standing project policy, while explicitly deferring to curators for the individual target pair and construct in the uninspected supplementary table. No target-specific orthogonal validation, native-cell mechanism, or functional role is inferred from the global framework or NbExp count. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: A curated HuRI binary interaction is retained with its exact partner. Reason: The complete abstract and inspected primary Methods/Results describe systematic human Y2H screening, quadruplicate pairwise retesting and sequence confirmation. The exact source partner is also recorded in the preserved UniProt IntAct section. Retain the source-specific curated binding assertion under the standing project policy, while explicitly deferring to curators for the individual target pair and construct in the uninspected supplementary table. No target-specific orthogonal validation, native-cell mechanism, or functional role is inferred from the global framework or NbExp count. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: A curated C3βHCN1 association is retained from BioPlex. Reason: The complete abstract and fuller authenticated source variant describe affinity purification of tagged baits from 293T/HCT116 cells, mass spectrometry and interaction scoring. The exact HCN1 partner is independently present in the preserved UniProt IntAct record. Retain the curated association with explicit deference for its uninspected table entry and cell-line allocation. This does not establish direct binary affinity or a C3 ion-channel regulatory function. The inspected Methods are in the immutable fetched variant; the shorter canonical cache was preserved. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:37207277 Using brain cell-type-specific protein interactomes to inter... | KEEP AS NON CORE | Summary: C3 has a curated association with HCN1 in a neuronal interactome. Reason: The inspected primary Results and Methods include HCN1 among successfully immunoprecipitated baits in human induced cortical neurons, with replicate IP-MS and control-IgG comparisons. The preserved UniProt record corroborates the exact partner edge. Retain the curator-supported interaction while stating that its C3-specific supplementary row was not independently inspected. Coassociation is not purified binary binding or evidence that C3 shares the baitβs channel activity; the paperβs separate C4A findings must not be reassigned to C3. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:37207277 Using brain cell-type-specific protein interactomes to inter... | KEEP AS NON CORE | Summary: C3 has a curated association with CACNA1C in a neuronal interactome. Reason: The inspected primary Results and Methods include CACNA1C among successfully immunoprecipitated baits in human induced cortical neurons, with replicate IP-MS and control-IgG comparisons. The preserved UniProt record corroborates the exact partner edge. Retain the curator-supported interaction while stating that its C3-specific supplementary row was not independently inspected. Coassociation is not purified binary binding or evidence that C3 shares the baitβs channel activity; the paperβs separate C4A findings must not be reassigned to C3. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:7483825 gp13 (EHV-gC): a complement receptor induced by equine herpe... | UNDECIDED | Summary: The exact human C3βequine herpesvirus gp13 assertion remains unverified. Reason: The complete cached and official PubMed abstracts report gp13-mediated C3 binding, preferential recognition of the viral hostβs complement and explicit horse-complement assays. They do not resolve the human-C3 result for this exact curated viral partner. Preserve the experimental assertion rather than reject it from species or title; the source-specific human target data remain uninspected, so retain uncertainty instead of extrapolating the horse result. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:7483825 gp13 (EHV-gC): a complement receptor induced by equine herpe... | UNDECIDED | Summary: The exact human C3βequine herpesvirus gp13 assertion remains unverified. Reason: The complete cached and official PubMed abstracts report gp13-mediated C3 binding, preferential recognition of the viral hostβs complement and explicit horse-complement assays. They do not resolve the human-C3 result for this exact curated viral partner. Preserve the experimental assertion rather than reject it from species or title; the source-specific human target data remain uninspected, so retain uncertainty instead of extrapolating the horse result. Supporting Evidence: |
| GO:0005576 extracellular region | EXP PMID:1238393 Human anaphylatoxin (C3a) from the third component of comple... | ACCEPT | Summary: C3 or its processed products operate extracellularly. Reason: Human C3a was purified from activated human serum and its primary structure determined. This does not imply every fragment has the same receptor or activity. |
| GO:0005576 extracellular region | EXP PMID:3653927 Phagocytosis of target particles bearing C3b-IgG covalent co... | ACCEPT | Summary: C3 or its processed products operate extracellularly. Reason: Purified C3b-IgG complexes act on extracellular target particles in assays with human phagocytes. This does not imply every fragment has the same receptor or activity. |
| GO:0005576 extracellular region | EXP PMID:3897448 IgG bearing covalently bound C3b has enhanced bactericidal a... | ACCEPT | Summary: C3 or its processed products operate extracellularly. Reason: Extracellular C3b-IgG opsonins enhance human polymorphonuclear-cell bactericidal responses; the phenotype is not C3 pore formation. This does not imply every fragment has the same receptor or activity. |
| GO:0005576 extracellular region | EXP PMID:6903192 Relation of putative thioester bond in C3 to activation of t... | ACCEPT | Summary: C3 or its processed products operate extracellularly. Reason: Purified human C3 and target-surface attachment experiments establish an extracellular complement protein. This does not imply every fragment has the same receptor or activity. Supporting Evidence: |
| GO:0005576 extracellular region | EXP PMID:7240134 Limited proteolysis of the third component of human compleme... | ACCEPT | Summary: C3 or its processed products operate extracellularly. Reason: The heat-cleavage experiment uses purified human C3; extracellular localization is independently established, rather than inferred from heat proteolysis itself. This does not imply every fragment has the same receptor or activity. |
| GO:0005576 extracellular region | EXP PMID:833545 The role of membrane receptors for C3b and C3d in phagocytos... | ACCEPT | Summary: C3 or its processed products operate extracellularly. Reason: Purified complement fragments on extracellular targets engage receptors on human phagocytes. This does not imply every fragment has the same receptor or activity. |
| GO:0005576 extracellular region | EXP PMID:8349625 Preferential formation of C3b-IgG complexes in vitro and in ... | ACCEPT | Summary: C3 or its processed products operate extracellularly. Reason: C3 activation produces covalent C3b-IgG complexes on oxidatively stressed and senescent red-cell surfaces. This does not imply every fragment has the same receptor or activity. |
| GO:0005576 extracellular region | HDA PMID:16502470 Human colostrum: identification of minor proteins in the aqu... | ACCEPT | Summary: C3 or its processed products operate extracellularly. Reason: The human-colostrum aqueous-phase proteomic framework was read, but its individual C3 entry was not re-examined. Retain the curator location with direct independent serum-C3 evidence. This does not imply every fragment has the same receptor or activity. |
| GO:0005576 extracellular region | HDA PMID:23580065 Shotgun proteomics reveals specific modulated protein patter... | ACCEPT | Summary: C3 or its processed products operate extracellularly. Reason: The human-tear shotgun-proteomics abstract was read, not the individual C3 target table. The extracellular location is independently established by purified serum-C3 studies. This does not imply every fragment has the same receptor or activity. |
| GO:0005576 extracellular region | IBA GO_REF:0000033 | ACCEPT | Summary: Extracellular localization is conserved and directly supported in human C3. Reason: The source retains PTN000151285 and its mouse, rat and human descendants. This exact PTN is absent from the available PTHR11412 PAINT export, so its node placement was not independently reconstructed. Human C3 itself is a legitimate experimental descendant, not circular evidence; human serum and purified-protein studies independently establish the location. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000151285 UNRESOLVED Exact GOA node absent from the available PTHR11412 PAINT export; cached PTN002605320 is not substituted. Independent human experimental support sustains the biological annotation. UniProtKB:P01024 SUPPORTS TRANSFER Target experimental descendant is legitimate source evidence, not circularity. |
| GO:0005576 extracellular region | IDA PMID:25645918 Human neutrophils secrete bioactive paucimannosidic proteins... | ACCEPT | Summary: C3 or its processed products operate extracellularly. Reason: The abstract reports secretion of neutrophil azurophilic-granule proteins. The C3-specific proteomic entry was not read; direct independent serum-C3 evidence supports this broad location. This does not imply every fragment has the same receptor or activity. |
| GO:0005576 extracellular region | IDA PMID:37852260 Molecular basis of anaphylatoxin binding, activation, and si... | ACCEPT | Summary: Processed C3a acts extracellularly on cell-surface C3AR1. Reason: The original GOA product is C3a (P01024-PRO_0000005910), and that scope is retained. The inspected primary Methods and Results show externally applied human C3a activating human receptor-expressing cells and human macrophages, and purified ligand engaging the extracellular face of C3AR1. This supports the extracellular active location; the structural protein expressed in bacteria and receptor expressed in insect cells are human constructs, not evidence for a bacterial or insect physiological location. Supporting Evidence: |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | ACCEPT | Summary: The combined electronic sources correctly place C3 extracellularly. Reason: The secretion and domain mappings agree with the signal-peptide-bearing UniProt product and direct human serum-C3 studies. Mixed source provenance is retained without treating each InterPro or ARBA entry as an independently read experiment. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1006143 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: The cached reaction places the shared C3b ligand in extracellular interactions with complement factor H-related proteins. Supporting Evidence: Reactome:R-HSA-1006143 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-166817 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: C3 is cleaved extracellularly; the released C3b thioester attaches to target surfaces and enables amplification. C3 is not the protease that cleaves its precursor. Supporting Evidence: Reactome:R-HSA-166817 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-173636 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: C3b recruits a further C3b molecule to support extracellular C5-convertase assembly. Supporting Evidence: Reactome:R-HSA-173636 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-173680 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: The C3b-containing classical-pathway convertase cleaves C5 extracellularly; C2a supplies the protease activity. Supporting Evidence: Reactome:R-HSA-173680 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-173739 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: Spontaneous thioester hydrolysis yields extracellular C3(H2O), distinct from proteolytic C3a release. Supporting Evidence: Reactome:R-HSA-173739 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-173740 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: Factor B binds extracellular C3(H2O), which supplies a nonenzymatic assembly platform. Supporting Evidence: Reactome:R-HSA-173740 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-173745 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: Factor D cleaves C3(H2O)-bound factor B extracellularly; the cleavage is not catalyzed by C3. Supporting Evidence: Reactome:R-HSA-173745 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-173754 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: Properdin stabilizes extracellular surface-associated C3b:Bb. Supporting Evidence: Reactome:R-HSA-173754 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-174551 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: C3b-containing alternative-pathway C5 convertase functions extracellularly; Bb supplies the protease activity. Supporting Evidence: Reactome:R-HSA-174551 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-183122 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: Factor D cleaves factor B already bound to extracellular C3b. Supporting Evidence: Reactome:R-HSA-183122 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-183126 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: Factor B binds covalently surface-bound C3b during extracellular convertase assembly. Supporting Evidence: Reactome:R-HSA-183126 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-183130 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: The C3b:Bb complex cleaves extracellular C3; Bb is the enzyme and C3b provides the assembly platform. Supporting Evidence: Reactome:R-HSA-183130 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-199518 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: C3-fragment-bearing antigen engages the extracellular portion of the CR2 co-receptor complex. Supporting Evidence: Reactome:R-HSA-199518 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-3266557 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: Factor I processes surface-associated iC3b, leaving C3dg attached and releasing C3c extracellularly. Supporting Evidence: Reactome:R-HSA-3266557 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-380073 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: C3-derived agonist binds the extracellular face of its GPCR while the heterotrimeric G protein acts inside the cell. Supporting Evidence: Reactome:R-HSA-380073 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-444647 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: C3a binds the extracellular face of C3AR1; this is a soluble ligand, not a membrane receptor. Supporting Evidence: Reactome:R-HSA-444647 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6798748 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: C3 is included among extracellular proteins released during neutrophil degranulation; no granule-enzyme activity is transferred. Supporting Evidence: Reactome:R-HSA-6798748 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6798751 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: C3 is included among cargo released by azurophilic-granule exocytosis. Supporting Evidence: Reactome:R-HSA-6798751 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-749454 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: The ligand:GPCR complex initiates Gi signaling across the membrane, with the C3-derived ligand remaining extracellular. Supporting Evidence: Reactome:R-HSA-749454 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-749456 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: Activated receptor/G-protein events place the C3-derived ligand extracellularly rather than in the cytosolic signaling machinery. Supporting Evidence: Reactome:R-HSA-749456 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8851436 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: Factor H-related dimers interact with extracellular C3b and can alter competition with factor H. Supporting Evidence: Reactome:R-HSA-8851436 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8852809 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: Extracellular carboxypeptidases remove terminal arginine from C3a/C5a. C3a is their substrate, not the carboxypeptidase. Supporting Evidence: Reactome:R-HSA-8852809 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-976743 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: Factor H binds extracellular C3b; its regulatory action is not an intrinsic C3 protease-inhibitor assay. Supporting Evidence: Reactome:R-HSA-976743 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-976768 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: Factor I cleaves C3b in an extracellular factor-H-associated reaction. Supporting Evidence: Reactome:R-HSA-976768 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-976810 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: Factor-H-assisted processing produces extracellular iC3b, with factor I performing proteolysis. Supporting Evidence: Reactome:R-HSA-976810 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-977359 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: Membrane cofactor protein/CD46 interacts with C3b on the external cell surface. Supporting Evidence: Reactome:R-HSA-977359 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-977363 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: Factor I processes CD46-associated C3b outside the cell. Supporting Evidence: Reactome:R-HSA-977363 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-977371 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: The CD46-mediated processing reaction is on the external membrane surface, not within the lipid bilayer. Supporting Evidence: Reactome:R-HSA-977371 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-977375 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: Processed C3 fragments dissociate from the external CD46-associated reaction. Supporting Evidence: Reactome:R-HSA-977375 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-977602 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: CR1 binds extracellularly deposited C3b. Supporting Evidence: Reactome:R-HSA-977602 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-977605 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: Factor I processes CR1-bound C3b outside the cell. Supporting Evidence: Reactome:R-HSA-977605 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-977615 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: The CR1-associated C3b-processing reaction takes place on the external membrane surface. Supporting Evidence: Reactome:R-HSA-977615 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-977619 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: Further processing of receptor-associated C3 fragments occurs extracellularly. Supporting Evidence: Reactome:R-HSA-977619 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-977629 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: Receptor-associated C3-processing products are released into the extracellular compartment. Supporting Evidence: Reactome:R-HSA-977629 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-981535 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: The decay-accelerating factor reaction disassembles extracellular surface convertases. Supporting Evidence: Reactome:R-HSA-981535 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-981539 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: The C3b reactive thioester covalently attaches C3b to a nearby target surface. Supporting Evidence: Reactome:R-HSA-981539 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-981621 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: Convertase decay separates extracellular C3b and its protease partner. Supporting Evidence: Reactome:R-HSA-981621 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-981728 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: Factor H and decay-accelerating factor influence extracellular convertase dissociation. Supporting Evidence: Reactome:R-HSA-981728 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9957021 | ACCEPT | Summary: The curated reaction locates C3-derived material extracellularly. Reason: Compstatin-family drugs bind extracellular C3. Being inhibited by a therapeutic molecule does not make C3 an inhibitor enzyme. Supporting Evidence: Reactome:R-HSA-9957021 |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-8952289 | KEEP AS NON CORE | Summary: Secretory-pathway C3 can be present in the ER lumen. Reason: The cached FAM20C reaction concerns phosphorylation of secreted proteins during biosynthetic transit. Retain the luminal cargo location as non-core, not an ER-resident function or C3 kinase activity. Supporting Evidence: Reactome:R-HSA-8952289 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-3266557 | MODIFY | Summary: C3 fragments associate with the external face of the plasma membrane. Reason: The specific cached pathway reaction concerns extracellular receptor-associated or covalently deposited C3 fragments. GO:0009897 explicitly includes externally attached peripheral proteins and is more precise than undifferentiated plasma membrane; no transmembrane segment or cytosolic orientation is implied. Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-3266557 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8852874 | MODIFY | Summary: C3 fragments associate with the external face of the plasma membrane. Reason: The specific cached pathway reaction concerns extracellular receptor-associated or covalently deposited C3 fragments. GO:0009897 explicitly includes externally attached peripheral proteins and is more precise than undifferentiated plasma membrane; no transmembrane segment or cytosolic orientation is implied. Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-8852874 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8853252 | MODIFY | Summary: C3 fragments associate with the external face of the plasma membrane. Reason: The specific cached pathway reaction concerns extracellular receptor-associated or covalently deposited C3 fragments. GO:0009897 explicitly includes externally attached peripheral proteins and is more precise than undifferentiated plasma membrane; no transmembrane segment or cytosolic orientation is implied. Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-8853252 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-977371 | MODIFY | Summary: C3 fragments associate with the external face of the plasma membrane. Reason: The specific cached pathway reaction concerns extracellular receptor-associated or covalently deposited C3 fragments. GO:0009897 explicitly includes externally attached peripheral proteins and is more precise than undifferentiated plasma membrane; no transmembrane segment or cytosolic orientation is implied. Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-977371 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-977615 | MODIFY | Summary: C3 fragments associate with the external face of the plasma membrane. Reason: The specific cached pathway reaction concerns extracellular receptor-associated or covalently deposited C3 fragments. GO:0009897 explicitly includes externally attached peripheral proteins and is more precise than undifferentiated plasma membrane; no transmembrane segment or cytosolic orientation is implied. Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-977615 |
| GO:0006954 inflammatory response | IEA GO_REF:0000002 | ACCEPT | Summary: C3a receptor agonism contributes directly to inflammatory responses. Reason: The anaphylatoxin-domain inference agrees with direct human C3a-C3AR1 activation and macrophage responses. C3 is a precursor of the ligand; receptor coupling and downstream kinase reactions belong to other proteins. Inflammatory effects depend on cell context and need not always increase every cytokine. Supporting Evidence: |
| GO:0006955 immune response | TAS PMID:4097977 Studies in vivo and in vitro on an abnormality in the metabo... | KEEP AS NON CORE | Summary: C3 is a central innate immune effector. Reason: The broad immune-response term is valid but adds less mechanistic information than complement activation. The original patient study identifies abnormal C3 turnover and impaired complement function; it does not establish that the patient had a C3 coding-gene lesion. Direct complement and opsonin studies independently support the biological role. |
| GO:0006956 complement activation | IBA GO_REF:0000033 | ACCEPT | Summary: C3 directly participates in complement activation across pathways. Reason: The conserved precursor supplies surface-reactive C3b and nonenzymatic convertase assembly, so it performs complement work rather than merely being consumed by cleavage. The exact source PTN000151285 is absent from the available PAINT export; another cached complement IBD is not silently substituted. Human experimental support independently sustains the annotation. Human C3 in WITH/FROM is legitimate descendant evidence, not circularity. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000151285 UNRESOLVED Exact GOA node absent from the available PTHR11412 PAINT export; cached PTN002605320 is not substituted. Independent human experimental support sustains the biological annotation. UniProtKB:P01024 SUPPORTS TRANSFER Target experimental descendant is legitimate source evidence, not circularity. |
| GO:0006956 complement activation | IDA PMID:37852260 Molecular basis of anaphylatoxin binding, activation, and si... | MODIFY | Summary: For this processed-C3a source assertion, the direct activity is C3AR1 signaling. Reason: This GOA row is explicitly on C3a, not the C3b product that supplies complement-convertase/cofactor and surface-deposition functions. The inspected human ligand/receptor experiments assay C3AR1 binding and G-protein/ arrestin signaling, not activation of a complement-cascade step. GO:0006956 concerns activation of complement-cascade steps. The three inspected GO-CAM models intentionally nest the C3a activity under leukocyte chemotaxis and complement activation; this proposal questions that process placement against the actual assay, rather than claiming the curator omitted the product. Refine this source-specific row to complement receptor mediated signaling pathway. Its official definition includes signaling initiated when a complement protein or its fragment binds a complement receptor; it therefore captures the measured C3aβC3AR1 ligand step more specifically than generic GPCR signaling, without equating receptor activation with a complement-cascade cleavage step. Other C3/C3b complement-activation assertions are not adjudicated by this change. Proposed replacements: complement receptor mediated signaling pathway Supporting Evidence: |
| GO:0006956 complement activation | IEA GO_REF:0000120 | ACCEPT | Summary: The electronic complement assignment agrees with C3 chemistry and assembly. Reason: C3b supplies its own thioester-mediated surface attachment and convertase platform; C3a supplies a released inflammatory ligand. The broad process is appropriate because C3 serves classical, lectin, alternative and granzyme-K-initiated complement, not just one narrower branch. |
| GO:0006956 complement activation | IMP PMID:19302245 Complement classical pathway components are all important in... | ACCEPT | Summary: Human C3 participates in complement-mediated opsonization. Reason: The human-serum study measures C3 deposition and phagocytosis of apoptotic Jurkat cells with complement-deficient sera. Its perturbation evidence agrees with the independently established physical contribution of C3 fragments to target opsonization. C3 need not catalyze precursor cleavage to participate in complement activation. |
| GO:0007165 signal transduction | TAS PMID:10085065 Chimeric receptors of the human C3a receptor and C5a recepto... | MODIFY | Summary: C3a participates as the activating ligand in complement receptor signaling. Reason: The complete cached abstract reports human C3aR/C5aR chimeras expressed in HEK293 cells, ligand binding and calcium mobilization with and without coexpressed G-alpha16. The intact C3aR N-terminal deletion retains C3a binding and activation. GO:0002430 explicitly includes signals initiated by complement fragments binding complement receptors, so it gives the appropriate process specificity. The inspected modern human C3a/C3AR1 experiments independently support this ligand-mediated signaling step; no intrinsic GTPase or receptor activity is assigned to C3. Proposed replacements: complement receptor mediated signaling pathway |
| GO:0007186 G protein-coupled receptor signaling pathway | TAS PMID:9164946 The mouse anaphylatoxin C3a receptor: molecular cloning, gen... | ACCEPT | Summary: C3a directly initiates C3AR1-mediated G protein signaling. Reason: The original complete abstract establishes a functional cloned mouse C3a receptor in heterologous cells, while the C3a reagent species is not stated there. Inspected human C3a/C3AR1 structural and cAMP experiments independently establish the same ligand-driven pathway on human products. C3a performs the extracellular ligand step; its being generated by proteolysis does not make it merely a substrate of this signaling process. |
| GO:0008009 chemokine activity | IDA PMID:342601 Chemotactic response to human C3a and C5a anaphylatoxins. I.... | REMOVE | Summary: The cited C3a chemokine assertion is contradicted by the source and uses the wrong activity class. Reason: The canonical cache contains no abstract, but the complete original publisher abstract was independently inspected. It explicitly reports purified human C3a inactive in human polymorphonuclear-leukocyte migration assays and in a rabbit-neutrophil skin-window assay. The published correction additionally changes the trypsin-treated human C3 result from active to inactive; it does not retract the paper. This is positive counterevidence to this source-linked assertion, not an inference from a title or missing full text. Separately, GO:0008009 requires chemokine-family activity and chemokine-receptor binding, whereas C3a is a complement anaphylatoxin acting through C3AR1. The full original paper was not inspected and no universal absence of C3a chemotaxis in other cell contexts is asserted. This row and the three companion UniProt IDA GO:0008009 rows on C3 (PMID:5778786, PMID:37169960, PMID:37852260) seeded the PTN008967461 PAINT IBD in PTHR11412. Supporting Evidence: |
| GO:0008009 chemokine activity | IDA PMID:37169960 Revealing the signaling of complement receptors C3aR and C5a... | REMOVE | Summary: Mis-annotation of the complement C3a anaphylatoxin as a chemokine; C3a receptor ligand activity on C3AR1 is captured separately under GO:0048018. Reason: The complete cached abstract describes C3a-bound C3aR cryo-EM structures and functional mutagenesis, and explicitly distinguishes complement-anaphylatoxin recognition from chemokine-receptor recognition. The full paper was not inspected. Independent inspected human C3a/C3AR1 Methods and Results in PMID:37852260 corroborate ligand-mediated receptor activation. GO:0008009 is a chemokine-family activity under GO:0042379 (chemokine receptor binding) defined for CC/CXC/C/CX3C chemokines, whereas C3a is a four-helix-bundle complement anaphylatoxin (PTHR11412:SF86) acting on C3AR1. Because GO:0008009 is false for C3 and receptor ligand activity (GO:0048018) is already captured on C3 (including the MODIFY on GO:0005102 citing PMID:37169960 and PMID:37852260), this row is removed to maintain term-level action consistency across all four GO:0008009 IDA rows that seeded PAINT node PTN008967461 in PTHR11412. |
| GO:0008009 chemokine activity | IDA PMID:37852260 Molecular basis of anaphylatoxin binding, activation, and si... | REMOVE | Summary: Mis-annotation of the complement C3a anaphylatoxin as a chemokine; C3a receptor ligand activity on C3AR1 is captured separately under GO:0048018. Reason: Selected complete primary Results and Methods show recombinant human C3a, purified human C3AR1, a ligand-bound G-protein complex, and cellular cAMP, arrestin and macrophage responses. C3a-desArg is distinguished from C3a; no C3a-desArg-bound C3AR1 structure was demonstrated. The experiments establish GO:0048018 (receptor ligand activity) on C3AR1 (already captured on C3 via GO:0048018 and the MODIFY on GO:0005102 citing PMID:37852260), not chemokine-receptor binding or membership in the cysteine-motif chemokine family that GO:0008009 entails. Removing this wrong-branch annotation aligns all four UniProt IDA GO:0008009 rows on C3 that seeded PAINT node PTN008967461 in PTHR11412. Supporting Evidence: |
| GO:0008009 chemokine activity | IDA PMID:5778786 Isolation of a fragment (C3a) of the third component of huma... | REMOVE | Summary: Mis-annotation of the complement C3a anaphylatoxin as a chemokine on a contested early chemotaxis report. Reason: The complete cached 1969 abstract reports chemotactic activity in isolated human C3a preparations and persistence of that activity after a treatment that abolishes anaphylatoxin activity. The independently inspected 1978 original abstract (PMID:342601) fails to reproduce C3a/short-trypsin-C3 chemotaxis under human-PMN conditions and raises possible C5 contamination of earlier C3 preparations. Regardless of how that historical chemotaxis discrepancy is resolved, GO:0008009 (chemokine activity, under GO:0042379 chemokine receptor binding) is the wrong ontology branch for the complement anaphylatoxin C3a (PTHR11412:SF86), which is not a chemokine and does not bind chemokine receptors. Removing GO:0008009 across all four UniProt IDA rows on C3 resolves the term-level action inconsistency and documents the upstream source defect that seeded PAINT node PTN008967461 in PTHR11412. |
| GO:0009986 cell surface | EXP PMID:3653927 Phagocytosis of target particles bearing C3b-IgG covalent co... | ACCEPT | Summary: Activated C3 fragments associate with extracellular target-cell surfaces. Reason: The original source concerns complement-decorated targets, purified C3 fragments or C3b-IgG complexes. The cell surface assignment is compatible with covalent deposition and receptor association; it does not imply C3 is an integral membrane protein or that soluble C3a remains surface attached. |
| GO:0009986 cell surface | EXP PMID:3897448 IgG bearing covalently bound C3b has enhanced bactericidal a... | ACCEPT | Summary: Activated C3 fragments associate with extracellular target-cell surfaces. Reason: The original source concerns complement-decorated targets, purified C3 fragments or C3b-IgG complexes. The cell surface assignment is compatible with covalent deposition and receptor association; it does not imply C3 is an integral membrane protein or that soluble C3a remains surface attached. |
| GO:0009986 cell surface | EXP PMID:6903192 Relation of putative thioester bond in C3 to activation of t... | ACCEPT | Summary: Activated C3 fragments associate with extracellular target-cell surfaces. Reason: The original source concerns complement-decorated targets, purified C3 fragments or C3b-IgG complexes. The cell surface assignment is compatible with covalent deposition and receptor association; it does not imply C3 is an integral membrane protein or that soluble C3a remains surface attached. Supporting Evidence: |
| GO:0009986 cell surface | EXP PMID:833545 The role of membrane receptors for C3b and C3d in phagocytos... | ACCEPT | Summary: Activated C3 fragments associate with extracellular target-cell surfaces. Reason: The original source concerns complement-decorated targets, purified C3 fragments or C3b-IgG complexes. The cell surface assignment is compatible with covalent deposition and receptor association; it does not imply C3 is an integral membrane protein or that soluble C3a remains surface attached. |
| GO:0009986 cell surface | EXP PMID:8349625 Preferential formation of C3b-IgG complexes in vitro and in ... | ACCEPT | Summary: Activated C3 fragments associate with extracellular target-cell surfaces. Reason: The original source concerns complement-decorated targets, purified C3 fragments or C3b-IgG complexes. The cell surface assignment is compatible with covalent deposition and receptor association; it does not imply C3 is an integral membrane protein or that soluble C3a remains surface attached. |
| GO:0009986 cell surface | IEA GO_REF:0000120 | ACCEPT | Summary: Surface deposition is conserved and directly established for human C3b. Reason: The mouse/subcellular electronic assertion agrees with human thioester and opsonin studies. Retain the exact sources; no new human assay is inferred from the orthology record itself. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P01027 Β· mouse C3 SUPPORTS TRANSFER Ortholog identity is established. Specific mouse provenance and original-assay access limits are stated in the review; retained human applicability does not turn mouse phenotypes into direct human experiments. |
| GO:0010575 positive regulation of vascular endothelial growth factor production | IDA PMID:16452172 Drusen complement components C3a and C5a promote choroidal n... | KEEP AS NON CORE | Summary: C3a increases VEGF production in a retinal epithelial context. Reason: Inspected primary Results and Methods show C3a treatment of primary human retinal pigment epithelial cultures, including cells from donors with normal fundi, followed by increased secreted VEGF measured by ELISA. The study also includes D407 cells and separate mouse intravitreal/knockout/choroidal-neovascularization experiments. Retain the directly observed human production response as a contextual non-core effect of receptor signaling; do not transfer mouse angiogenesis outcomes wholesale to human C3 or describe C3a as synthesizing VEGF. Supporting Evidence: PMID:16452172 C3a and C5a induce VEGF expression in vitro and in vivo |
| GO:0010828 positive regulation of D-glucose transmembrane transport | IDA PMID:15833747 C5L2 is a functional receptor for acylation-stimulating prot... | KEEP AS NON CORE | Summary: ASP promotes glucose uptake in the reported metabolic assay. Reason: The complete original abstract reports increased glucose transport after ASP treatment of human-C5L2-transfected HEK293 cells. Its metabolic response can be retained without treating the proposed C5L2 receptor mechanism as settled. The original full transport assay was not inspected, and ASP/C3a-desArg must not be conflated with arginine-retaining C3a. C3 supplies a signaling ligand, not the glucose transporter. Supporting Evidence: |
| GO:0010828 positive regulation of D-glucose transmembrane transport | IDA PMID:9059512 Acylation-stimulating protein (ASP) regulates glucose transp... | KEEP AS NON CORE | Summary: Human plasma ASP stimulates glucose transport in differentiated rat myotubes. Reason: The complete cached abstract explicitly identifies human plasma ASP tested on rat L6 myotubes. It reports increased 2-deoxyglucose transport, increased transport capacity and translocation of GLUT1, GLUT3 and GLUT4, with an additive insulin response. Retain the direct functional response of the human-derived ligand as a non-core metabolic context while preserving the rat recipient-cell boundary. This source does not identify C5L2 or demonstrate an intrinsic transport activity of C3. Supporting Evidence: |
| GO:0010866 regulation of triglyceride biosynthetic process | IDA PMID:10432298 Acylation-stimulating protein (ASP): structure-function dete... | KEEP AS NON CORE | Summary: ASP regulates triglyceride synthesis through a structure-dependent signaling effect. Reason: The complete cached abstract distinguishes C3a-desArg/ASP from arginine-retaining C3a and reports chemical modification, enzymatic cleavage and synthetic-fragment experiments on ASP binding and stimulation of triglyceride synthesis. The disulfide-linked core is required for the functional response but not all binding, supporting a ligand-mediated regulatory effect. Retain this contextual regulation without assigning triglyceride-synthetic enzyme activity or equating the two processed peptides. The full assay Methods were not inspected. Supporting Evidence: |
| GO:0010884 positive regulation of lipid storage | IDA PMID:9555951 Coordinated release of acylation stimulating protein (ASP) a... | KEEP AS NON CORE | Summary: ASP is associated with postprandial adipose storage and has independent metabolic activity. Reason: The complete original abstract describes arterial/venous measurements in twelve human subjects: postprandial adipose ASP production correlates with fatty-acid incorporation into adipose tissue. That study supplies physiological association rather than an isolated causal perturbation of lipid storage. Independent ASP structure/function and triglyceride-synthesis experiments support retention of the curated storage context as non-core, without claiming the correlation itself proves receptor identity or a direct triglyceride-synthesis reaction by C3. |
| GO:0016322 neuron remodeling | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: C3-dependent tagging supports neuronal circuit remodeling in mice. Reason: The inspected official MGI experimental table maps the mouse donor neuron-remodeling assertion to the cached developmental synapse study. Its complete abstract reports C3-deficient retinogeniculate refinement defects; the independent Alzheimer-model main text shows C3 deposition and C3-dependent synapse loss. This is a contextual application of complement tagging, not neuronal-intrinsic C3 enzymatic remodeling or a direct human developmental experiment. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P01027 Β· mouse C3 SUPPORTS TRANSFER Ortholog identity is established. Specific mouse provenance and original-assay access limits are stated in the review; retained human applicability does not turn mouse phenotypes into direct human experiments. |
| GO:0016322 neuron remodeling | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: C3-dependent tagging supports neuronal circuit remodeling in mice. Reason: The inspected official MGI experimental table maps the mouse donor neuron-remodeling assertion to the cached developmental synapse study. Its complete abstract reports C3-deficient retinogeniculate refinement defects; the independent Alzheimer-model main text shows C3 deposition and C3-dependent synapse loss. This is a contextual application of complement tagging, not neuronal-intrinsic C3 enzymatic remodeling or a direct human developmental experiment. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P01027 Β· mouse C3 SUPPORTS TRANSFER Ortholog identity is established. Specific mouse provenance and original-assay access limits are stated in the review; retained human applicability does not turn mouse phenotypes into direct human experiments. |
| GO:0030595 leukocyte chemotaxis | IDA PMID:342601 Chemotactic response to human C3a and C5a anaphylatoxins. I.... | REMOVE | Summary: The cited paper reports negative C3a leukotaxis in its tested systems. Reason: Although the canonical cache lacks an abstract, the complete original publisher abstract was inspected and explicitly reports purified human C3a inactive for human PMN chemotaxis and rabbit-neutrophil skin-window accumulation. The complete published correction also changes the trypsin-treated human C3 result to inactive. The positive IDA assertion attached to this reference is therefore contradicted by the stated assays; this is not a title-only attribution objection or inference from an inaccessible assay. The full paper remains unread, and this decision does not assert that C3a cannot influence migration of another leukocyte type or in another context. The positive GO-CAM nesting of this exact reference is explicitly flagged for reconciliation. Supporting Evidence: |
| GO:0031715 C5L2 anaphylatoxin chemotactic receptor binding | IDA PMID:15833747 C5L2 is a functional receptor for acylation-stimulating prot... | UNDECIDED | Summary: ASP binding to C5L2/C5AR2 remains disputed. Reason: The original complete cached abstract links ASP responses to C5L2 transfection/antisense and describes receptor phosphorylation and arrestin redistribution. The earlier positive binding paper reports an ASP-binding site, whereas normal cached PMID:17068344 reports negative radioligand/fluorescent C3a and C3a-desArg binding and PMID:12899627 reports no C3a interaction. The competing full assays were not inspected and the source conditions have not been reconciled. Retain uncertainty for this receptor-specific assertion rather than erase the observed metabolic responses or substitute established C3a-C3AR1 binding for ASP-C5L2 binding. |
| GO:0032991 protein-containing complex | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: C3 products participate in several protein assemblies. Reason: The mouse-derived broad complex assertion is compatible with independently demonstrated human C3d-CR2 and C3b-factor-B/regulator assemblies. The donor experiment maps to factor-H-related complexes; there is no single justified specific complex that replaces every C3 form. Retain the broad source claim as non-core and do not invent a complex identifier. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P01027 Β· mouse C3 SUPPORTS TRANSFER Ortholog identity is established. Specific mouse provenance and original-assay access limits are stated in the review; retained human applicability does not turn mouse phenotypes into direct human experiments. |
| GO:0034774 secretory granule lumen | TAS Reactome:R-HSA-6798748 | KEEP AS NON CORE | Summary: A C3 pool is packaged in secretory granules. Reason: The specific cached neutrophil degranulation pathway lists C3 among luminal cargo released extracellularly. This is a storage/trafficking context, not its general site of molecular action. Supporting Evidence: Reactome:R-HSA-6798748 |
| GO:0035578 azurophil granule lumen | TAS Reactome:R-HSA-6798751 | KEEP AS NON CORE | Summary: A neutrophil C3 pool is associated with azurophilic-granule lumen. Reason: The cached exocytosis event and the original human-neutrophil secretion study support the source context. The original C3-specific proteomic entry was not inspected; no lysosomal-enzyme activity is assigned to this cargo protein. |
| GO:0042113 B cell activation | IDA PMID:30107486 CD21 and FCRL5 form a receptor complex with robust B-cell ac... | ACCEPT | Summary: C3-fragment ligands contribute to B-cell co-receptor activation. Reason: The source abstract reports CD21-FCRL5 association and enhanced calcium responses during CD21/BCR/FCRL5 co-engagement in human lines and tonsil B cells. It does not make C3 a B-cell kinase. Direct C3d-CR2 structural recognition and the curated GO-CAM receptor-ligand model support the ligand contribution, while the exact physiological immune-complex arrangement remains a model. |
| GO:0045745 positive regulation of G protein-coupled receptor signaling pathway | IDA PMID:15833747 C5L2 is a functional receptor for acylation-stimulating prot... | UNDECIDED | Summary: The original ASP experiment does not settle a C5L2 G-protein signaling mechanism. Reason: The original ASP abstract reports C5L2 phosphorylation, beta-arrestin redistribution and metabolic responses; these do not by themselves establish heterotrimeric G-protein coupling. Independent normal primary PMID:12899627 reports C5L2 uncoupling from heterotrimeric G proteins, and PMID:17068344 contradicts ASP binding. Both complete abstracts were read, but not their full assay conditions. The original claim is therefore unresolved at the stated GPCR-mechanism level. The modern C3AR1/C5AR1 study discusses C5AR2 arrestin signaling but does not directly assay ASP-C5AR2; C3a-C3AR1 activation is not substituted for the distinct C3a-desArg product. Supporting Evidence: PMID:12899627 obligately uncoupled from heterotrimeric G proteins |
| GO:0045766 positive regulation of angiogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: C3-dependent complement signaling can promote pathological angiogenesis. Reason: The official mouse annotation maps in part to the inspected laser-injury/RPE study. That work directly shows C3a-induced VEGF secretion by primary human RPE, whereas choroidal neovascularization and receptor knockout experiments are mouse experiments. Retain the contextual regulatory process without claiming C3 constructs blood vessels or that all C3 signaling is angiogenic. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P01027 Β· mouse C3 SUPPORTS TRANSFER Ortholog identity is established. Specific mouse provenance and original-assay access limits are stated in the review; retained human applicability does not turn mouse phenotypes into direct human experiments. |
| GO:0048018 receptor ligand activity | IDA PMID:21527715 A crystal structure of the complex between human complement ... | ACCEPT | Summary: The C3d fragment is a ligand for CR2/CD21. Reason: The human C3d-CR2 crystal structure establishes specific receptor recognition; the curated B-cell model and source experiments place that recognition upstream of co-receptor signaling. This is receptor ligand activity of a processed fragment, not receptor activity of the uncleaved precursor. The revised interface does not invalidate the binding interaction. |
| GO:0048260 positive regulation of receptor-mediated endocytosis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: C3 opsonization promotes receptor-dependent uptake. Reason: The official mouse donor maps to primary microglial uptake studies. The normal full text of PMID:22438044 reports C3/Mac-1 knockout and siRNA effects in mouse primary/N9 microglia and recombinant human C3a rescue of uptake by C3-null mouse microglia. The authors leave the serum-free molecular mechanism partly unresolved; the recipient-cell evidence is not human. Independent human phagocyte experiments establish the general C3-opsonin uptake mechanism. Retain contextual regulation without assigning an endocytic enzyme or treating all C3a responses as C3b surface tagging. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P01027 Β· mouse C3 SUPPORTS TRANSFER Ortholog identity is established. Specific mouse provenance and original-assay access limits are stated in the review; retained human applicability does not turn mouse phenotypes into direct human experiments. |
| GO:0048260 positive regulation of receptor-mediated endocytosis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: C3 opsonization promotes receptor-dependent uptake. Reason: The official mouse donor maps to primary microglial uptake studies. The normal full text of PMID:22438044 reports C3/Mac-1 knockout and siRNA effects in mouse primary/N9 microglia and recombinant human C3a rescue of uptake by C3-null mouse microglia. The authors leave the serum-free molecular mechanism partly unresolved; the recipient-cell evidence is not human. Independent human phagocyte experiments establish the general C3-opsonin uptake mechanism. Retain contextual regulation without assigning an endocytic enzyme or treating all C3a responses as C3b surface tagging. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P01027 Β· mouse C3 SUPPORTS TRANSFER Ortholog identity is established. Specific mouse provenance and original-assay access limits are stated in the review; retained human applicability does not turn mouse phenotypes into direct human experiments. |
| GO:0051707 response to other organism | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: C3 contributes to host responses to microbes. Reason: The broad ARBA-derived process is biologically consistent with complement-mediated recognition, opsonization and inflammatory signaling. More mechanistic activities are represented separately, and host-defense activity is not inferred for every microbial binding partner or screen interaction. |
| GO:0060100 positive regulation of phagocytosis, engulfment | IEA GO_REF:0000107 | ACCEPT | Summary: C3-fragment opsonins promote phagocytic engulfment. Reason: Mouse-derived annotation is independently supported by human monocyte and polymorphonuclear-cell experiments with C3b-IgG targets and by complement-dependent apoptotic-cell uptake. Deposited C3 fragments supply recognition ligands, while phagocytes perform engulfment. This is an actual extracellular effector contribution rather than transfer of a phagocyte-intrinsic enzyme activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P01027 Β· mouse C3 SUPPORTS TRANSFER Ortholog identity is established. Specific mouse provenance and original-assay access limits are stated in the review; retained human applicability does not turn mouse phenotypes into direct human experiments. |
| GO:0060100 positive regulation of phagocytosis, engulfment | ISS GO_REF:0000024 | ACCEPT | Summary: C3-fragment opsonins promote phagocytic engulfment. Reason: Mouse-derived annotation is independently supported by human monocyte and polymorphonuclear-cell experiments with C3b-IgG targets and by complement-dependent apoptotic-cell uptake. Deposited C3 fragments supply recognition ligands, while phagocytes perform engulfment. This is an actual extracellular effector contribution rather than transfer of a phagocyte-intrinsic enzyme activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P01027 Β· mouse C3 SUPPORTS TRANSFER Ortholog identity is established. Specific mouse provenance and original-assay access limits are stated in the review; retained human applicability does not turn mouse phenotypes into direct human experiments. |
| GO:0070062 extracellular exosome | HDA PMID:21362503 Protein profile of exosomes from trabecular meshwork cells. | KEEP AS NON CORE | Summary: Detected in an extracellular-vesicle proteome. The protein is plausible EV content, but this is not where it functions. Reason: Secreted complement C3; C3b binds covalently to cell surfaces through its exposed thioester, and its review accepts five cell-surface rows by EXP. Secreted or lumenal protein (UniProt) with an experimentally documented cell-surface or plasma-membrane pool that its own review keeps. MISEV2018 (PMID:30637094) category 5 allows such proteins onto EVs through specific or promiscuous receptors on the EV surface, and small EVs budding from the plasma membrane can carry a surface-bound pool, so the detection is plausible. True, but not its core location. (Manual re-review for OMICS_EVIDENCE, 2026-10-10; previous action: UNDECIDED.) Supporting Evidence: |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: Detected in an extracellular-vesicle proteome. The protein is plausible EV content, but this is not where it functions. Reason: Secreted complement C3; C3b binds covalently to cell surfaces through its exposed thioester, and its review accepts five cell-surface rows by EXP. Secreted or lumenal protein (UniProt) with an experimentally documented cell-surface or plasma-membrane pool that its own review keeps. MISEV2018 (PMID:30637094) category 5 allows such proteins onto EVs through specific or promiscuous receptors on the EV surface, and small EVs budding from the plasma membrane can carry a surface-bound pool, so the detection is plausible. True, but not its core location. (Manual re-review for OMICS_EVIDENCE, 2026-10-10; previous action: UNDECIDED.) Supporting Evidence: |
| GO:0072562 blood microparticle | HDA PMID:22516433 Proteomic analysis of microvesicles from plasma of healthy d... | KEEP AS NON CORE | Summary: Detected in an extracellular-vesicle proteome. The protein is plausible EV content, but this is not where it functions. Reason: Secreted complement C3; C3b binds covalently to cell surfaces through its exposed thioester, and its review accepts five cell-surface rows by EXP. Secreted or lumenal protein (UniProt) with an experimentally documented cell-surface or plasma-membrane pool that its own review keeps. MISEV2018 (PMID:30637094) category 5 allows such proteins onto EVs through specific or promiscuous receptors on the EV surface, and small EVs budding from the plasma membrane can carry a surface-bound pool, so the detection is plausible. True, but not its core location. (Manual re-review for OMICS_EVIDENCE, 2026-10-10; previous action: UNDECIDED.) Supporting Evidence: |
| GO:0097242 amyloid-beta clearance | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: C3-derived effectors support microglial amyloid uptake and clearance in bounded experimental contexts. Reason: The official MGI donor table traces this assertion to microglial amyloid uptake studies. Normal PMID:22438044 Methods/Results directly test C3/Mac-1 loss or knockdown in mouse microglia and reduced cortical clearance in knockout mice; its Discussion identifies recombinant human C3a rescue of uptake in C3-null mouse microglia. Thus the work includes a human processed-product reagent, while the recipient cells and in vivo model are mouse. The mechanism of the serum-free C3a effect is not resolved and C3 is not an amyloid-degrading enzyme. PMID:20199584 supplies related CR3/LRP uptake context, not a separately inspected C3 manipulation. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P01027 Β· mouse C3 SUPPORTS TRANSFER Ortholog identity is established. Specific mouse provenance and original-assay access limits are stated in the review; retained human applicability does not turn mouse phenotypes into direct human experiments. Supporting Evidence: PMID:22438044 recombinant human complement component C3a significantly and concentration-dependently enhanced the uptake of fAΞ² by C3β/β microglia |
| GO:0097242 amyloid-beta clearance | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: C3-derived effectors support microglial amyloid uptake and clearance in bounded experimental contexts. Reason: The official MGI donor table traces this assertion to microglial amyloid uptake studies. Normal PMID:22438044 Methods/Results directly test C3/Mac-1 loss or knockdown in mouse microglia and reduced cortical clearance in knockout mice; its Discussion identifies recombinant human C3a rescue of uptake in C3-null mouse microglia. Thus the work includes a human processed-product reagent, while the recipient cells and in vivo model are mouse. The mechanism of the serum-free C3a effect is not resolved and C3 is not an amyloid-degrading enzyme. PMID:20199584 supplies related CR3/LRP uptake context, not a separately inspected C3 manipulation. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P01027 Β· mouse C3 SUPPORTS TRANSFER Ortholog identity is established. Specific mouse provenance and original-assay access limits are stated in the review; retained human applicability does not turn mouse phenotypes into direct human experiments. |
| GO:0150062 complement-mediated synapse pruning | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: C3-dependent opsonization contributes to synapse pruning in mouse models. Reason: The exact mouse donor annotation maps to the cached developmental study, whose abstract reports C3-null refinement defects. The separately read Alzheimer-model main text shows synaptic C3 deposition, protection in C3-deficient animals and CR3-dependent microglial engulfment. C3 supplies an extracellular tag; the microglia execute engulfment. Neither study is a direct human synapse-pruning experiment. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P01027 Β· mouse C3 SUPPORTS TRANSFER Ortholog identity is established. Specific mouse provenance and original-assay access limits are stated in the review; retained human applicability does not turn mouse phenotypes into direct human experiments. Supporting Evidence: PMID:27033548 genetic deletion of C3 ameliorates synapse loss in APP/PS1 mice |
| GO:0150062 complement-mediated synapse pruning | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: C3-dependent opsonization contributes to synapse pruning in mouse models. Reason: The exact mouse donor annotation maps to the cached developmental study, whose abstract reports C3-null refinement defects. The separately read Alzheimer-model main text shows synaptic C3 deposition, protection in C3-deficient animals and CR3-dependent microglial engulfment. C3 supplies an extracellular tag; the microglia execute engulfment. Neither study is a direct human synapse-pruning experiment. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P01027 Β· mouse C3 SUPPORTS TRANSFER Ortholog identity is established. Specific mouse provenance and original-assay access limits are stated in the review; retained human applicability does not turn mouse phenotypes into direct human experiments. |
| GO:0150064 vertebrate eye-specific patterning | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: C3 contributes to refinement of eye-specific central projections in mice. Reason: The developmental source abstract describes failed retinogeniculate refinement and excess retinal innervation in C3-deficient mice. This refers to neural projection patterning, not formation of the eye globe or autonomous axon-guidance catalysis by C3. Retain the bounded orthology annotation as non-core; the original full Methods were not available in the canonical abstract-only cache. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P01027 Β· mouse C3 SUPPORTS TRANSFER Ortholog identity is established. Specific mouse provenance and original-assay access limits are stated in the review; retained human applicability does not turn mouse phenotypes into direct human experiments. Supporting Evidence: PMID:18083105 failure of anatomical refinement of retinogeniculate connections and the retention of excess retinal innervation |
| GO:0150064 vertebrate eye-specific patterning | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: C3 contributes to refinement of eye-specific central projections in mice. Reason: The developmental source abstract describes failed retinogeniculate refinement and excess retinal innervation in C3-deficient mice. This refers to neural projection patterning, not formation of the eye globe or autonomous axon-guidance catalysis by C3. Retain the bounded orthology annotation as non-core; the original full Methods were not available in the canonical abstract-only cache. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P01027 Β· mouse C3 SUPPORTS TRANSFER Ortholog identity is established. Specific mouse provenance and original-assay access limits are stated in the review; retained human applicability does not turn mouse phenotypes into direct human experiments. Supporting Evidence: |
| GO:0160257 complement activation, GZMK pathway | IDA PMID:39914456 Granzyme K activates the entire complement cascade. | ACCEPT | Summary: C3 participates in granzyme-K-initiated complement activation. Reason: The primary study reconstitutes human complement using purified components and assays C3a signaling, surface deposition and downstream activation. GZMK cleaves upstream complement components, whereas C3b supplies its own surface-reactive thioester and convertase platform. C3 is not assigned GZMK protease activity or direct GZMK cleavage of C3. Supporting Evidence: PMID:39914456 C3 convertase that cleaves C3, enabling the assembly of a C5 convertase |
| GO:2000427 positive regulation of apoptotic cell clearance | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: C3-fragment deposition promotes apoptotic-cell clearance. Reason: The human complement-deficient-serum/Jurkat/monocyte-derived-macrophage study directly measures C3 deposition and uptake. This fits the established opsonic role, but the apoptotic-cell context is narrower than the general complement effector mechanism. The ARBA and IMP source objects remain separate. Supporting Evidence: |
| GO:2000427 positive regulation of apoptotic cell clearance | IMP PMID:19302245 Complement classical pathway components are all important in... | KEEP AS NON CORE | Summary: C3-fragment deposition promotes apoptotic-cell clearance. Reason: The human complement-deficient-serum/Jurkat/monocyte-derived-macrophage study directly measures C3 deposition and uptake. This fits the established opsonic role, but the apoptotic-cell context is narrower than the general complement effector mechanism. The ARBA and IMP source objects remain separate. Supporting Evidence: PMID:19302245 Sera from individuals deficient in C1q, C4, C2 or C3 all showed decreased phagocytosis |
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Download this section (compressed HTML)Q: How should the explicit C3a GO-CAM chemokine/leukocyte-chemotaxis placements be reconciled with the original negative PMID:342601 abstract and its correction, and with modern C3AR1 ligand assays?
Q: Which defined ASP/C3a-desArg preparations and receptor-expression conditions explain the conflicting C5L2/C5AR2 binding reports, and do any directly establish G-protein signaling?
Q: Can the exact PTN000151285 PAINT release and individual C3 exosome/microparticle or viral-gp13 target assays be retrieved to resolve the remaining source-specific uncertainty?
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