FGB encodes the beta chain of fibrinogen, a secreted plasma complex containing two copies each of the alpha, beta and gamma chains. The beta chain contributes to interchain assembly, the coiled coils and the terminal globular domains of the complex. Thrombin releases the N-terminal fibrinopeptide B, exposing a binding sequence used during fibrin assembly. Beta chains provide structure within the resulting extracellular fibrin network; thrombin and Factor XIII perform the proteolytic and cross-linking reactions. FGB-containing fibrinogen also participates in platelet-associated and extracellular-matrix interactions, whose experimental effects often depend on the assembled complex.
Curated functional classes representing distinct biological activities. These may be splice variants, cleavage products, or other forms with different functions.
FGB_FIBRINOPEPTIDE_BPRO_0000009070 (residues 31-44) FGB_FIBRIN_BETA_CHAINPRO_0000009071 (residues 45-491) | GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005102 signaling receptor binding | IDA PMID:10903502 Fibrinogen interactions with ICAM-1 (CD54) regulate endothel... | KEEP AS NON CORE | Summary: Fibrinogen contributes to receptor-dependent endothelial adhesion and survival. Reason: PMID:10903502 tests assembled human fibrinogen with ICAM-1 recognition and blocking controls. A gamma-chain peptide reproduces important responses, so these experiments do not isolate a beta-chain receptor-binding site. Retain the imported contributes_to assertion as a non-core structural-subunit contribution to the ligand complex; it does not assign receptor activity to FGB. Supporting Evidence: |
| GO:0005102 signaling receptor binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: FGB contributes to the receptor-binding fibrinogen complex. Reason: The genuine target match places IPR012290 in the beta-chain coiled-coil region. Human fibrinogen supports receptor-dependent adhesion in PMID:10903502, but the mapped recognition peptide is from the gamma chain. Retain the complex-associated receptor-binding contribution as non-core; the domain mapping does not identify an autonomous beta-chain receptor-contact site. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: InterPro:IPR012290 SUPPORTS TRANSFER The genuine target-specific match and official entry mapping were read. The structural or receptor claim is adjudicated with target evidence, not assigned to every family-domain match. |
| GO:0005198 structural molecule activity | IDA PMID:8910396 The role of betagamma and alphagamma complexes in the assemb... | ACCEPT | Summary: The beta chain supplies structure during fibrinogen assembly. Reason: PMID:8910396 follows human fibrinogen chains expressed in BHK cells, with additional human hepatoma context. Beta-gamma intermediates and alpha-beta-gamma-containing fibrinogen are identified by immunoprecipitation and two-dimensional electrophoresis. Adding the beta chain to cells containing alpha-gamma intermediates permits assembly and secretion. This is direct structural participation, not merely a loss-of-function requirement. The broad structural term also covers soluble-complex assembly beyond matrix incorporation. Supporting Evidence: |
| GO:0005201 extracellular matrix structural constituent | HDA PMID:28344315 Proteomic characterization of human multiple myeloma bone ma... | UNDECIDED | Summary: The exact FGB proteomic target record remains unresolved in this study. Reason: The original PMID:28344315 bone-marrow proteomics Methods were recovered, but the target-level supplemental tables were not. Figure 5B is a gene-expression heatmap and its FGA label is not a FGB protein identification. Independent fibrinogen biology does not verify the particular HDA target/sample record. Preserve uncertainty without asserting that FGB was absent or misattributed. The generic gene-level claim has independent positive support. UNDECIDED is restricted to the unrecovered original HDA FGB/sample identification; it does not deny that generic biology or establish a particular cleavage product. Supporting Evidence: |
| GO:0005201 extracellular matrix structural constituent | RCA PMID:25037231 Extracellular matrix signatures of human primary metastatic ... | ACCEPT | Summary: Fibrinogen beta chain contributes structure to extracellular fibrin. Reason: PMID:25037231 identifies human FGB/P02675 in the original tissue-proteomics data. Its matrisome classification is not itself a mechanical assay. Independent human-chain assembly and structural evidence establish the beta chain as a structural component of the fibrin-forming complex. Retain the generic matrix-structural role without treating every detected peptide as polymerized fibrin or a separately measured natural cleavage product. |
| GO:0005201 extracellular matrix structural constituent | RCA PMID:28327460 Comprehensive proteomic characterization of stem cell-derive... | ACCEPT | Summary: The beta chain has a supported generic extracellular structural role. Reason: The PMID:28327460 cell-derived-matrix FGB target table was not recovered. This RCA functional classification can nevertheless be evaluated at the same generic gene-level claim using independent human-chain assembly and fibrinogen structure. Beta chain supplies structure within the fibrin-forming complex. Retain that role without claiming that the unavailable culture-specific protein record was verified; the corresponding HDA matrix-location context remains UNDECIDED. No matrix-wide cell response is assigned to FGB from this source. |
| GO:0005201 extracellular matrix structural constituent | RCA PMID:28675934 Characterization of the Extracellular Matrix of Normal and D... | ACCEPT | Summary: Fibrinogen beta chain contributes structure to extracellular fibrin. Reason: PMID:28675934 identifies human FGB/P02675 in the original tissue-proteomics data. Its matrisome classification is not itself a mechanical assay. Independent human-chain assembly and structural evidence establish the beta chain as a structural component of the fibrin-forming complex. Retain the generic matrix-structural role without treating every detected peptide as polymerized fibrin or a separately measured natural cleavage product. |
| GO:0005515 protein binding | IPI PMID:12706644 Fibrinogen Magdeburg I: a novel variant of human fibrinogen ... | UNDECIDED | Summary: The source-specific fibrinogenβthrombin interaction remains unresolved. Reason: The original PMID:12706644 abstract concerns an alpha-chain fibrinopeptide-A variant in human fibrinogen. The operative full interaction experiment was not recovered. That title and variant emphasis do not establish a beta-chain attribution error, but neither does cleavage alone establish a specific protease-binding activity of FGB. Preserve uncertainty for this imported interaction rather than replacing it from the partner name. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20162731 Hepatitis C virus core protein interacts with fibrinogen-bet... | KEEP AS NON CORE | Summary: Fibrinogen beta chain associates with a viral core-protein construct in cells. Reason: PMID:20162731 identifies FGB in a protein-fragment complementation screen and confirms association of tagged FGB and the viral core protein by co-immunoprecipitation in human Huh7 cells. Colocalization is corroborating context, not a purified binary-binding measurement. Retain the positive protein association as non-core. GO:0046790 virion binding requires binding to a virion; association with a separately expressed core-protein construct does not establish that more specific claim. No viral regulatory function is inferred from the pair. Supporting Evidence: |
| GO:0005576 extracellular region | EXP PMID:10074346 Conformational changes in fragments D and double-D from huma... | ACCEPT | Summary: Fibrinogen beta chain occurs in the extracellular plasma protein complex. Reason: PMID:10074346 provides a human fibrinogen/fibrin fragment structural abstract. Its operative full structural experiment was not recovered. The same broad extracellular claim is independently supported by purification of human plasma fibrinogen in PMID:19296670 and secretion of assembled human chains in PMID:8910396. Retain the general location without claiming that the unavailable source-specific details were rechecked. |
| GO:0005576 extracellular region | EXP PMID:19296670 Crystal structure of human fibrinogen. | ACCEPT | Summary: Human plasma fibrinogen contains extracellular beta chains. Reason: PMID:19296670 purifies fibrinogen from human blood plasma and resolves its alpha, beta and gamma chains structurally. This directly supports the broad extracellular location. The crystal preparation underwent some alpha-chain proteolysis and minor fibrinopeptide cleavage; it is not an isolated beta-chain or released fibrinopeptide-B localization assay. Supporting Evidence: |
| GO:0005576 extracellular region | EXP PMID:9628725 Crystal structure of fragment double-D from human fibrin wit... | ACCEPT | Summary: Fibrinogen beta chain occurs in the extracellular plasma protein complex. Reason: PMID:9628725 provides a human fibrinogen/fibrin fragment structural abstract. Its operative full structural experiment was not recovered. The same broad extracellular claim is independently supported by purification of human plasma fibrinogen in PMID:19296670 and secretion of assembled human chains in PMID:8910396. Retain the general location without claiming that the unavailable source-specific details were rechecked. |
| GO:0005576 extracellular region | HDA PMID:16502470 Human colostrum: identification of minor proteins in the aqu... | UNDECIDED | Summary: The specific colostrum proteomic FGB identification remains unverified. Reason: PMID:16502470 describes aqueous-phase human colostrum proteomics, but neither the operative original nor the exact FGB target table was recovered. Publisher access failed and repository metadata provide only identity/abstract context. Independent plasma localization does not verify this particular HDA sample record. Retain uncertainty without claiming absence, wrong-gene attribution, or detection of free fibrinopeptide B. The generic gene-level claim has independent positive support. UNDECIDED is restricted to the unrecovered original HDA FGB/sample identification; it does not deny that generic biology or establish a particular cleavage product. Supporting Evidence: |
| GO:0005576 extracellular region | IDA PMID:19996109 Identification of human plasma proteins as major clients for... | ACCEPT | Summary: Fibrinogen beta chain is present in extracellular plasma protein complexes. Reason: PMID:19996109 uses human plasma and identifies the beta chain among clusterin-associated clients by mass spectrometry. Table 1 and the fibrinogen-chain immunoblots directly support the extracellular plasma context. The stress-dependent client complexes include fragments and heterogeneous assemblies, rather than a separately localized mature beta chain or fibrinopeptide B. Supporting Evidence: |
| GO:0005576 extracellular region | IDA PMID:6777381 Ca2+-mediated association of glycoprotein G (thrombinsensiti... | ACCEPT | Summary: Platelet-derived fibrinogen becomes extracellular fibrin after release. Reason: PMID:6777381 directly detects fibrinogen-derived material released by activated human platelets and identifies surface-associated fibrin chains. Retain the extracellular location at the parent-gene level, while distinguishing the measured fibrin product from intact circulating fibrinogen and from free fibrinopeptide B. Supporting Evidence: |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | ACCEPT | Summary: Fibrinogen beta-chain material is secreted into the extracellular compartment. Reason: Reviewed UniProt SL-0243 denotes Secreted, consistent with human plasma fibrinogen and its beta-chain structure in PMID:19296670. The target's two recorded FunFam identifiers exactly satisfy positive condition branch 154 of ARBA00027128, which outputs GO:0005576. This establishes the actual combined source mapping; the rule is a prediction source rather than an independent secretion experiment. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00027128 SUPPORTS TRANSFER Captured condition branch 154 requires positive FunFam identifiers 3.90.215.10:FF:000006 and 4.10.530.10:FF:000004, both explicitly recorded for target P02675 in the accepted UniProt file. It outputs extracellular region with no additional taxonomic condition. This is a verified rule match, not a new target assay. UniProtKB-SubCell:SL-0243 SUPPORTS TRANSFER SL-0243 is the reviewed UniProt Secreted mapping, consistent with human plasma fibrinogen. It is not an HPA localization assay. |
| GO:0005576 extracellular region | NAS PMID:14718574 The human plasma proteome: a nonredundant list developed by ... | ACCEPT | Summary: Fibrinogen beta chain occurs in the extracellular plasma protein complex. Reason: PMID:14718574 provides a human plasma-proteome compilation abstract. Its operative target list was not recovered. The same broad extracellular claim is independently supported by purification of human plasma fibrinogen in PMID:19296670 and secretion of assembled human chains in PMID:8910396. Retain the general location without claiming that the unavailable source-specific details were rechecked. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-114560 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-114560 reaches entity 140584 (45β491, extracellular region); entity 140917 (45β491, plasma membrane). The beta chain is in fibrin bound to platelet integrin Ξ±IIbΞ²3; the association is on the extracellular face. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-140840 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-140840 reaches entity 140876 (31β44, extracellular region); entity 140846 (31β491, extracellular region); entity 140584 (45β491, extracellular region). The event distinguishes fibrinogen beta residues 31β491, released fibrinopeptide B at 31β44, and the remaining fibrin chain at 45β491. Thrombin performs the cleavage. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-140842 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-140842 reaches entity 140584 (45β491, extracellular region). Beta residues 45β491 contribute to the assembling fibrin polymer; the modeled three-monomer size is not a fixed physiological stoichiometry. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-140851 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-140851 reaches entity 140584 (45β491, extracellular region). Beta is part of the fibrin input. Factor XIIIa performs cross-linking, principally represented at alpha/gamma sites; the OtherEntity output has no explicit beta-subunit route. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-166072 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-166072 reaches entity 140876 (31β44, extracellular region). The ligand-containing route for MyD88 recruitment includes the modeled fibrinopeptide-B entity 140876 (31β44). Its extracellular position is explicit; the event does not independently establish isolated-peptide agonism or transfer the intracellular reaction to FGB. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-166082 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-166082 reaches entity 140876 (31β44, extracellular region). The ligand-containing route for IRAK4 recruitment includes the modeled fibrinopeptide-B entity 140876 (31β44). Its extracellular position is explicit; the event does not independently establish isolated-peptide agonism or transfer the intracellular reaction to FGB. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-166091 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-166091 reaches entity 140876 (31β44, extracellular region). The ligand-containing route for IRAK1/IRAK2 recruitment includes the modeled fibrinopeptide-B entity 140876 (31β44). Its extracellular position is explicit; the event does not independently establish isolated-peptide agonism or transfer the intracellular reaction to FGB. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-166119 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-166119 reaches entity 140876 (31β44, extracellular region). The ligand-containing route for initial IRAK1 phosphorylation includes the modeled fibrinopeptide-B entity 140876 (31β44). Its extracellular position is explicit; the event does not independently establish isolated-peptide agonism or transfer the intracellular reaction to FGB. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-166284 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-166284 reaches entity 140876 (31β44, extracellular region). The ligand-containing route for further IRAK1 phosphorylation includes the modeled fibrinopeptide-B entity 140876 (31β44). Its extracellular position is explicit; the event does not independently establish isolated-peptide agonism or transfer the intracellular reaction to FGB. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-166286 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-166286 reaches entity 140876 (31β44, extracellular region). The ligand-containing route for IRAK1 autophosphorylation includes the modeled fibrinopeptide-B entity 140876 (31β44). Its extracellular position is explicit; the event does not independently establish isolated-peptide agonism or transfer the intracellular reaction to FGB. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-166362 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-166362 reaches entity 140876 (31β44, extracellular region). The ligand-containing route for IRAK1 dissociation includes the modeled fibrinopeptide-B entity 140876 (31β44). Its extracellular position is explicit; the event does not independently establish isolated-peptide agonism or transfer the intracellular reaction to FGB. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-166363 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-166363 reaches entity 140876 (31β44, extracellular region). The ligand-containing route for TRAF6 binding to IRAK1 includes the modeled fibrinopeptide-B entity 140876 (31β44). Its extracellular position is explicit; the event does not independently establish isolated-peptide agonism or transfer the intracellular reaction to FGB. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-216069 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-216069 reaches entity 140584 (45β491, extracellular region). The target is in the extracellular fibrin ligand bound to integrin Ξ±DΞ²2. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-216082 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-216082 reaches entity 140584 (45β491, extracellular region). The target is in the extracellular fibrin ligand bound to integrin Ξ±XΞ²2. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2201316 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-2201316 reaches entity 140876 (31β44, extracellular region). The ligand-containing route for TIRAP recruitment includes the modeled fibrinopeptide-B entity 140876 (31β44). Its extracellular position is explicit; the event does not independently establish isolated-peptide agonism or transfer the intracellular reaction to FGB. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2201322 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-2201322 reaches entity 140876 (31β44, extracellular region). The ligand-containing route for BTK-dependent TIRAP phosphorylation includes the modeled fibrinopeptide-B entity 140876 (31β44). Its extracellular position is explicit; the event does not independently establish isolated-peptide agonism or transfer the intracellular reaction to FGB. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2262775 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-2262775 reaches entity 140876 (31β44, extracellular region). The ligand-containing route for IRAK2/TRAF6 dissociation includes the modeled fibrinopeptide-B entity 140876 (31β44). Its extracellular position is explicit; the event does not independently establish isolated-peptide agonism or transfer the intracellular reaction to FGB. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2262777 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-2262777 reaches entity 140876 (31β44, extracellular region). The ligand-containing route for TRAF6 binding to IRAK2 includes the modeled fibrinopeptide-B entity 140876 (31β44). Its extracellular position is explicit; the event does not independently establish isolated-peptide agonism or transfer the intracellular reaction to FGB. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2559414 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-2559414 reaches entity 140876 (31β44, extracellular region). The ligand-containing route for BTK recruitment includes the modeled fibrinopeptide-B entity 140876 (31β44). Its extracellular position is explicit; the event does not independently establish isolated-peptide agonism or transfer the intracellular reaction to FGB. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-354066 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-354066 reaches entity 140584 (45β491, extracellular region). Beta residues 45β491 persist in the extracellular fibrin ligand during PTK2 recruitment; the named signaling reaction belongs to the receptor-associated machinery. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-354073 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-354073 reaches entity 140584 (45β491, extracellular region). Beta residues 45β491 persist in the extracellular fibrin ligand during PTK2 autophosphorylation; the named signaling reaction belongs to the receptor-associated machinery. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-354087 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-354087 reaches entity 140584 (45β491, extracellular region). Beta residues 45β491 persist in the extracellular fibrin ligand during GRB2 recruitment; the named signaling reaction belongs to the receptor-associated machinery. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-354124 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-354124 reaches entity 140584 (45β491, extracellular region). Beta residues 45β491 persist in the extracellular fibrin ligand during SRC-dependent PTK2 phosphorylation; the named signaling reaction belongs to the receptor-associated machinery. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-354149 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-354149 reaches entity 140584 (45β491, extracellular region). Beta residues 45β491 persist in the extracellular fibrin ligand during integrin ligand binding; the named signaling reaction belongs to the receptor-associated machinery. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-354165 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-354165 reaches entity 140584 (45β491, extracellular region). Beta residues 45β491 persist in the extracellular fibrin ligand during SOS recruitment; the named signaling reaction belongs to the receptor-associated machinery. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-372693 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-372693 reaches entity 140584 (45β491, extracellular region). Beta residues 45β491 persist in the extracellular fibrin ligand during BCAR1 phosphorylation; the named signaling reaction belongs to the receptor-associated machinery. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-372697 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-372697 reaches entity 140584 (45β491, extracellular region). Beta residues 45β491 persist in the extracellular fibrin ligand during CRK recruitment; the named signaling reaction belongs to the receptor-associated machinery. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-372705 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-372705 reaches entity 140584 (45β491, extracellular region). Beta residues 45β491 persist in the extracellular fibrin ligand during BCAR1 recruitment; the named signaling reaction belongs to the receptor-associated machinery. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-377640 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-377640 reaches entity 140584 (45β491, extracellular region). Beta residues 45β491 persist in the extracellular fibrin ligand during SRC autophosphorylation; the named signaling reaction belongs to the receptor-associated machinery. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-377641 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-377641 reaches entity 140584 (45β491, extracellular region). Beta residues 45β491 persist in the extracellular fibrin ligand during integrin clustering; the named signaling reaction belongs to the receptor-associated machinery. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-377643 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-377643 reaches entity 140584 (45β491, extracellular region). Beta residues 45β491 persist in the extracellular fibrin ligand during SRC dephosphorylation; the named signaling reaction belongs to the receptor-associated machinery. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-377644 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-377644 reaches entity 140584 (45β491, extracellular region). Beta residues 45β491 persist in the extracellular fibrin ligand during CSK release; the named signaling reaction belongs to the receptor-associated machinery. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-429415 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-429415 reaches entity 140584 (45β491, extracellular region). Beta residues 45β491 persist in the extracellular fibrin ligand during SYK recruitment; the named signaling reaction belongs to the receptor-associated machinery. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-429441 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-429441 reaches entity 140584 (45β491, extracellular region). Beta residues 45β491 persist in the extracellular fibrin ligand during SYK phosphorylation; the named signaling reaction belongs to the receptor-associated machinery. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-481007 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-481007 reaches entity 140921 (31β491, platelet alpha granule lumen); entity 140846 (31β491, extracellular region). Fibrinogen beta residues 31β491 move from the alpha-granule lumenal cargo set to the extracellular released set. This identifies cargo location, not an exocytosis-machine activity. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5602353 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-5602353 reaches entity 140876 (31β44, extracellular region). The ligand-containing route for defective IRAK4 signaling includes the modeled fibrinopeptide-B entity 140876 (31β44). Its extracellular position is explicit; the event does not independently establish isolated-peptide agonism or transfer the intracellular reaction to FGB. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5602383 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-5602383 reaches entity 140876 (31β44, extracellular region). The ligand-containing route for defective MyD88 oligomerization includes the modeled fibrinopeptide-B entity 140876 (31β44). Its extracellular position is explicit; the event does not independently establish isolated-peptide agonism or transfer the intracellular reaction to FGB. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5602606 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-5602606 reaches entity 140876 (31β44, extracellular region). The ligand-containing route for defective MyD88 binding includes the modeled fibrinopeptide-B entity 140876 (31β44). Its extracellular position is explicit; the event does not independently establish isolated-peptide agonism or transfer the intracellular reaction to FGB. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8870678 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-8870678 reaches entity 140876 (31β44, extracellular region). The ligand-containing route for extracellular TLR4 ligand binding includes the modeled fibrinopeptide-B entity 140876 (31β44). Its extracellular position is explicit; the event does not independently establish isolated-peptide agonism or transfer the intracellular reaction to FGB. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-937022 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-937022 reaches entity 140876 (31β44, extracellular region). The ligand-containing route for IRAK4 autophosphorylation includes the modeled fibrinopeptide-B entity 140876 (31β44). Its extracellular position is explicit; the event does not independently establish isolated-peptide agonism or transfer the intracellular reaction to FGB. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-937059 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-937059 reaches entity 140876 (31β44, extracellular region). The ligand-containing route for IRAK2 phosphorylation includes the modeled fibrinopeptide-B entity 140876 (31β44). Its extracellular position is explicit; the event does not independently establish isolated-peptide agonism or transfer the intracellular reaction to FGB. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-937079 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-937079 reaches entity 140876 (31β44, extracellular region). The ligand-containing route for MyD88 oligomerization includes the modeled fibrinopeptide-B entity 140876 (31β44). Its extracellular position is explicit; the event does not independently establish isolated-peptide agonism or transfer the intracellular reaction to FGB. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9936699 | ACCEPT | Summary: The source explicitly places FGB-derived material extracellularly. Reason: R-HSA-9936699 reaches entity 140846 (31β491, extracellular region). The extracellular entity is fibrinogen associated with amyloid-beta fibrils and zinc. It does not identify FGB as the amyloid precursor. |
| GO:0005577 fibrinogen complex | IDA PMID:16846481 The fibrinogen Aalpha R16C mutation results in fibrinolytic ... | ACCEPT | Summary: The beta chain is a constituent of the fibrinogen complex. Reason: The complete original abstract of PMID:16846481 was checked, but its operative full experiment was not recovered. The reported variant concerns another chain, which does not by itself invalidate the complex annotation. Independent human-chain assembly experiments in PMID:8910396 and the human plasma complex structure in PMID:19296670 directly establish beta-chain membership. Retain this identical generic complex claim without certifying the unavailable source-specific mechanism or processing boundary. |
| GO:0005577 fibrinogen complex | IDA PMID:18676163 Congenital hypofibrinogenemia: characterization of two misse... | ACCEPT | Summary: The beta chain is a constituent of the fibrinogen complex. Reason: The complete original abstract of PMID:18676163 was checked, but its operative full experiment was not recovered. The reported variant concerns another chain, which does not by itself invalidate the complex annotation. Independent human-chain assembly experiments in PMID:8910396 and the human plasma complex structure in PMID:19296670 directly establish beta-chain membership. Retain this identical generic complex claim without certifying the unavailable source-specific mechanism or processing boundary. |
| GO:0005577 fibrinogen complex | IDA PMID:6688356 Characterization of complementary deoxyribonucleic acid and ... | ACCEPT | Summary: The beta chain is a constituent of the fibrinogen complex. Reason: The complete original abstract of PMID:6688356 was checked, but its operative full experiment was not recovered. The old cDNA study identifies a human beta-chain sequence; a bovine probe does not make the target protein bovine. Independent human-chain assembly experiments in PMID:8910396 and the human plasma complex structure in PMID:19296670 directly establish beta-chain membership. Retain this identical generic complex claim without certifying the unavailable source-specific mechanism or processing boundary. |
| GO:0005577 fibrinogen complex | IDA PMID:8910396 The role of betagamma and alphagamma complexes in the assemb... | ACCEPT | Summary: Human beta chains assemble into the fibrinogen complex. Reason: PMID:8910396 detects beta-gamma intermediates and assembled alpha-beta-gamma fibrinogen after fusion of BHK cells expressing complementary human chains. Two-dimensional gels distinguish the chain composition, and secretion is measured. Human hepatoma-cell observations provide additional context. The recipient-cell species and expressed human chains are kept distinct. Supporting Evidence: |
| GO:0005577 fibrinogen complex | IEA GO_REF:0000002 | ACCEPT | Summary: The beta chain is a structural component of fibrinogen. Reason: IPR012290 matches the target coiled coil. Human-chain assembly experiments identify beta-containing intermediates and assembled secreted fibrinogen in PMID:8910396; the human complex structure in PMID:19296670 independently contains beta chains. This establishes complex membership beyond the generic domain prediction. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR012290 SUPPORTS TRANSFER The genuine target-specific match and official entry mapping were read. The structural or receptor claim is adjudicated with target evidence, not assigned to every family-domain match. |
| GO:0005783 endoplasmic reticulum | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: FGB has a supported biosynthetic endoplasmic-reticulum location. Reason: The actual HPA record assigns enhanced ER localization in HepG2 cells using HPA001900 and HPA001901. Both selected images were inspected and show compatible reticular/perinuclear staining, with heterogeneous intensity. Retain this secretory-pathway compartment as non-core. The images do not resolve ER-lumen topology, released fibrinopeptide B or a distinct processed product. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-114560 | TOO GENERAL | Summary: The specific external-side annotation covers this surface-associated fibrin. Reason: R-HSA-114560 reaches beta entity 140917 in the membrane-associated fibrin complex. The beta chain is in fibrin bound to platelet integrin Ξ±IIbΞ²3; the association is on the extracellular face. GO:0009897 is a verified part_of child of plasma membrane and is retained with positive human evidence at row 72. No additional membrane topology is established here. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9921091 | TOO GENERAL | Summary: The specific external-side annotation covers this surface-associated fibrin. Reason: R-HSA-9921091 reaches beta entity 140917 in the membrane-associated fibrin complex. Beta residues 45β491 remain in surface-associated fibrin during factor-XIII cross-linking; beta is not the transglutaminase. GO:0009897 is a verified part_of child of plasma membrane and is retained with positive human evidence at row 72. No additional membrane topology is established here. |
| GO:0005938 cell cortex | IEA GO_REF:0000107 | MODIFY | Summary: The accessible donor experiment measures external fibrinogen binding rather than intracellular cortex residence. Reason: The exact mouse ortholog transfer traces to PMID:15914557. Its Methods and Figure 1 measure externally added fluorescent fibrinogen at the periphery of mouse megakaryocytes; the reagent species is not stated. GO:0005938 denotes the region beneath the plasma membrane, which this experiment does not localize. Independently, PMID:6777381 detects human platelet-surface fibrin alpha, beta and gamma chains. Replace the compartment with GO:0009897, which includes peripheral extracellular association. This lateral correction does not identify the donor reagent as endogenous mouse Fgb or infer beta-chain membrane insertion. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: UniProtKB:Q8K0E8 SUPPORTS SOURCE BUT NOT TARGET The mouse Q8K0E8 donor row traces to PMID:15914557. Its external fibrinogen-binding assay does not establish the imported intracellular-cortex compartment; reagent species is unspecified. ensembl:ENSMUSP00000039472 SUPPORTS TRANSFER The actual Ensembl protein lookup and human-to-donor one-to-one orthology record were verified. Orthology does not itself verify the source experiment or a human tissue-specific response. Proposed replacements: external side of plasma membrane |
| GO:0007160 cell-matrix adhesion | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Beta-chain-containing fibrinogen contributes to cell-matrix adhesion. Reason: The exact target leaf PTN002498958 is descended from IBD node PTN002709771 in the recovered version-19 tree, and its ungapped sequence matches the 491-residue human protein. PMID:10903502 supports adhesion to assembled human fibrinogen, with gamma-peptide receptor recognition. FGB supplies structural membership in that adhesive complex; this does not assign the gamma recognition site to beta. Retain this contextual complex effect as non-core. No target loss or clade-placement contradiction was found. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002709771 SUPPORTS TRANSFER The preserved positive IBD term/node/donors match the literal TSV. Actual version-19 topology places the exact human 491-residue MSA sequence beneath this node; current family normal identifiers remain unchanged. The reason states the biological and product scope. |
| GO:0007160 cell-matrix adhesion | IDA PMID:10903502 Fibrinogen interactions with ICAM-1 (CD54) regulate endothel... | KEEP AS NON CORE | Summary: Assembled fibrinogen supports endothelial cellβmatrix adhesion. Reason: PMID:10903502 measures adhesion to human fibrinogen-coated substrates and tests ICAM-1 recognition. FGB contributes as a structural chain of the ligand complex; the gamma-chain peptide results do not identify an autonomous beta-chain adhesion site. Retain the supported cellular context as non-core rather than equating it with every FGB product. Supporting Evidence: |
| GO:0007596 blood coagulation | IEA GO_REF:0000002 | TOO GENERAL | Summary: The broad coagulation mapping is covered by retained fibrin-clot formation. Reason: The target IPR037579 match supports a fibrinogen-family structural role. GO:0072378 is a verified part_of descendant of GO:0007596 and is retained at row 103. That specific clot-formation assertion covers the structural contribution supported here, without extending FGB to every enzymatic stage of coagulation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR037579 SUPPORTS TRANSFER The genuine target-specific match and official entry mapping were read. The structural or receptor claim is adjudicated with target evidence, not assigned to every family-domain match. |
| GO:0009897 external side of plasma membrane | IDA PMID:6777381 Ca2+-mediated association of glycoprotein G (thrombinsensiti... | KEEP AS NON CORE | Summary: Fibrin beta chains can associate with the external platelet surface. Reason: PMID:6777381 identifies surface-iodinated fibrin alpha, beta and gamma chains after human platelet activation. Divalent-cation conditions alter retention. Retain this conditional extracellular surface association as non-core; it does not establish membrane insertion or make the free fibrinopeptide a surface protein. Supporting Evidence: |
| GO:0009986 cell surface | IDA PMID:6777381 Ca2+-mediated association of glycoprotein G (thrombinsensiti... | TOO GENERAL | Summary: Cell surface is broader than the retained external plasma-membrane location. Reason: The same PMID:6777381 surface-labeling experiment supports the external side of the platelet plasma membrane. Official typed ancestry places GO:0009897 below GO:0009986. The broader term adds no distinct compartment in this source context; the positive surface association is preserved in the more precise annotation. Supporting Evidence: |
| GO:0030168 platelet activation | IEA GO_REF:0000002 | TOO GENERAL | Summary: Platelet aggregation covers the supported specific part of this activation mapping. Reason: IPR012290 maps broadly to platelet activation. The retained IBA row 100 covers platelet aggregation, a verified part_of child of GO:0030168. Intact fibrinogen participates in platelet bridging, whereas the evidence does not make the beta chain an executor of all activation or release reactions. The narrower existing term retains this positive contribution. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR012290 SUPPORTS TRANSFER The genuine target-specific match and official entry mapping were read. The structural or receptor claim is adjudicated with target evidence, not assigned to every family-domain match. |
| GO:0031012 extracellular matrix | HDA PMID:25037231 Extracellular matrix signatures of human primary metastatic ... | KEEP AS NON CORE | Summary: FGB is identified in human tissue ECM-enriched fractions. Reason: PMID:25037231 Additional File 2 identifies FGB/P02675 in row 14 of the complete-MS sheet and its matrisome subset. The underlying accession group and human colon/liver sample columns are retained. Keep the measured ECM-associated location as non-core; enrichment does not prove a pure fibrin matrix, an autonomous beta-chain scaffold, or a particular natural cleavage product. The two sheets repeat one underlying identification. Supporting Evidence: |
| GO:0031012 extracellular matrix | HDA PMID:28327460 Comprehensive proteomic characterization of stem cell-derive... | UNDECIDED | Summary: The exact FGB record in the cell-derived matrix remains unresolved. Reason: PMID:28327460 examines ECM from human mesenchymal stromal cells and neonatal fibroblasts. The original Methods specify serum-containing culture and a human database search, but the exact FGB supplemental record and peptides were not recovered. Thus the study-specific deposition or medium-associated origin cannot be resolved. Retain uncertainty without declaring a species error or absence; independent structural function does not settle this HDA source context. The generic gene-level claim has independent positive support. UNDECIDED is restricted to the unrecovered original HDA FGB/sample identification; it does not deny that generic biology or establish a particular cleavage product. Supporting Evidence: |
| GO:0031012 extracellular matrix | HDA PMID:28344315 Proteomic characterization of human multiple myeloma bone ma... | UNDECIDED | Summary: The exact FGB proteomic target record remains unresolved in this study. Reason: The original PMID:28344315 bone-marrow proteomics Methods were recovered, but the target-level supplemental tables were not. Figure 5B is a gene-expression heatmap and its FGA label is not a FGB protein identification. Independent fibrinogen biology does not verify the particular HDA target/sample record. Preserve uncertainty without asserting that FGB was absent or misattributed. The generic gene-level claim has independent positive support. UNDECIDED is restricted to the unrecovered original HDA FGB/sample identification; it does not deny that generic biology or establish a particular cleavage product. Supporting Evidence: |
| GO:0031012 extracellular matrix | HDA PMID:28675934 Characterization of the Extracellular Matrix of Normal and D... | KEEP AS NON CORE | Summary: Human FGB is measured in ECM-oriented breast and omental proteomics. Reason: The genuine PMID:28675934 SI002 workbook contains 22 FGB/P02675 records across breast and omentum measurements, including crude, urea-soluble and selected pellet preparations. Retain the supported ECM-associated context as non-core. The comparison omentum is clinical material, not a statement of healthy-donor sampling, and neither fraction detection nor the hydroxylation list establishes a unique natural product or direct mechanical function. Supporting Evidence: |
| GO:0031012 extracellular matrix | IBA GO_REF:0000033 | ACCEPT | Summary: FGB contributes structural material to extracellular fibrin matrices. Reason: The genuine target path passes through the broad ECM IBD node PTN000441162 and the target MSA sequence matches human FGB exactly. Human fibrinogen structure and the actual fibrin-polymer entity routes support the extracellular matrix role of assembled beta-chain-containing fibrin. Soluble fibrinogen and released fibrinopeptide B are distinct product states; the matrix assertion is not applied indiscriminately to them. The broad ancestral placement is not challenged merely because its experimental descendants include other family members. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000441162 SUPPORTS TRANSFER The preserved positive IBD term/node/donors match the literal TSV. Actual version-19 topology places the exact human 491-residue MSA sequence beneath this node; current family normal identifiers remain unchanged. The reason states the biological and product scope. |
| GO:0031091 platelet alpha granule | IDA PMID:6777381 Ca2+-mediated association of glycoprotein G (thrombinsensiti... | KEEP AS NON CORE | Summary: Platelet alpha granules are a contextual storage compartment for fibrinogen. Reason: PMID:6777381 analyzes proteins released from activated human platelets and discusses fibrinogen among established alpha-granule constituents. Its chain-resolved surface experiments directly measure extracellular fibrin after release, rather than a new beta-chain-specific granule image. Retain the curator-supported storage location as non-core with that boundary explicit; thrombospondin-specific observations are not reassigned to FGB. Supporting Evidence: |
| GO:0031093 platelet alpha granule lumen | TAS Reactome:R-HSA-481007 | KEEP AS NON CORE | Summary: Fibrinogen beta is modeled as platelet alpha-granule lumen cargo. Reason: The actual input route 481007 β 481003 β 114617 β 140921 reaches beta residues 31β491 in the alpha-granule lumen. Fibrinogen beta residues 31β491 move from the alpha-granule lumenal cargo set to the extracellular released set. This identifies cargo location, not an exocytosis-machine activity. Retain this storage location as non-core without assigning an entry or release mechanism to FGB. |
| GO:0031639 plasminogen activation | IDA PMID:16846481 The fibrinogen Aalpha R16C mutation results in fibrinolytic ... | UNDECIDED | Summary: The beta-chain contribution to plasminogen activation is not resolved by the accessible source. Reason: PMID:16846481 reports normal plasminogen activation but delayed lysis of an alpha-chain-variant fibrin clot. The operative full assay was not recovered. This supports neither a claim that beta chain is uninvolved nor a separately established beta-chain cofactor mechanism. The independently read alpha-C oligomer experiments used for FGA do not isolate FGB. Preserve source-specific uncertainty for plasminogen activation, while evaluating beta-chain structural participation in clot formation separately. Supporting Evidence: |
| GO:0034116 positive regulation of heterotypic cell-cell adhesion | IDA PMID:8100742 Fibrinogen mediates leukocyte adhesion to vascular endotheli... | UNDECIDED | Summary: The specific heterotypic cell-adhesion experiment remains incompletely accessible. Reason: PMID:8100742 reports fibrinogen-dependent leukocyteβendothelial adhesion and ICAM-1 recognition in its original abstract. The operative full Methods and Results were not recovered. Other receptor-binding or endothelial-survival assays do not substitute for this particular cell-pair experiment or isolate a beta-chain contribution. Retain uncertainty without asserting misattribution. Supporting Evidence: |
| GO:0042730 fibrinolysis | IDA PMID:16846481 The fibrinogen Aalpha R16C mutation results in fibrinolytic ... | UNDECIDED | Summary: The beta-chain contribution to fibrinolysis is not resolved by the accessible source. Reason: PMID:16846481 reports normal plasminogen activation but delayed lysis of an alpha-chain-variant fibrin clot. The operative full assay was not recovered. This supports neither a claim that beta chain is uninvolved nor a separately established beta-chain cofactor mechanism. The independently read alpha-C oligomer experiments used for FGA do not isolate FGB. Preserve source-specific uncertainty for fibrinolysis, while evaluating beta-chain structural participation in clot formation separately. Supporting Evidence: |
| GO:0043152 induction of bacterial agglutination | IDA PMID:24367264 The Staphylococcus aureus ArlRS two-component system is a no... | KEEP AS NON CORE | Summary: Fibrinogen supplies extracellular material to bacterial aggregates. Reason: PMID:24367264 directly compares purified human fibrinogen with other protein conditions and images labeled fibrinogen within bacterial clumps. This establishes a structural ligand contribution of the intact fibrinogen complex. Retain the beta-subunit contribution as contextual and non-core; the experiment neither isolates a beta-chain binding site nor establishes an antimicrobial enzyme activity. Supporting Evidence: |
| GO:0044320 cellular response to leptin stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: A leptin-responsive Fgb transcript is supported in a rat cellular context. Reason: The rat ortholog donor traces to PMID:17521427, where arrays and Northern blots detect increased Fgb transcript in RINm5F cells following leptin stimulation. Receptor-pathway controls contextualize that response. This supports a non-core expression response, not an FGB signaling-effector activity. The study uses rat recipients and engineered receptor conditions; equivalent human transcriptional regulation was not directly tested. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P14480 SUPPORTS TRANSFER Rat P14480 carries the PMID:17521427 expression-response annotation; the original rat-cell evidence was read, without claiming a human regulatory assay. ensembl:ENSRNOP00000050663 SUPPORTS TRANSFER The actual Ensembl protein lookup and human-to-donor one-to-one orthology record were verified. Orthology does not itself verify the source experiment or a human tissue-specific response. |
| GO:0045202 synapse | IEA GO_REF:0000107 | UNDECIDED | Summary: The exact Fgb identification underlying the synaptic-location transfer remains unresolved. Reason: The mouse donor annotations trace to PMID:16452087. Accessible original Methods describe mouse-brain postsynaptic-density preparations and large-scale protein/phosphosite identification, but the target-specific Fgb supplementary entry was not recovered. These preparations contain several neuronal compartments; that fact neither proves contamination nor verifies the precise target location. Preserve source-specific uncertainty rather than inferring a synaptic function or rejecting the annotation from fibrinogen's usual plasma location. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q8K0E8 UNRESOLVED Mouse Q8K0E8 carries the PMID:16452087 synaptic-location annotations, but the exact target supplementary identification remains uninspected. ensembl:ENSMUSP00000039472 SUPPORTS TRANSFER The actual Ensembl protein lookup and human-to-donor one-to-one orthology record were verified. Orthology does not itself verify the source experiment or a human tissue-specific response. |
| GO:0045907 positive regulation of vasoconstriction | IDA PMID:15739255 Fibrinogen and fragment D-induced vascular constriction. | KEEP AS NON CORE | Summary: Human fibrinogen can promote vasoconstriction in a rat vascular assay. Reason: PMID:15739255 tests human plasma fibrinogen and a plasmin-derived fragment D on rat vascular preparations, with endothelial, ICAM-1 and endothelin-receptor conditions. Retain the contextual response as non-core. Fragment D contains portions of several chains; the assay does not isolate beta-chain contractile activity, establish an exclusive mechanism, or measure a clinical response in humans. Supporting Evidence: |
| GO:0045921 positive regulation of exocytosis | IDA PMID:19193866 Fibrinogen-induced endothelin-1 production from endothelial ... | KEEP AS NON CORE | Summary: Fibrinogen promotes endothelial granule release. Reason: PMID:19193866 exposes rat heart microvascular endothelial cells to human fibrinogen and measures von Willebrand factor release and loss of labeled WeibelβPalade granules. These are positive ligand-dependent responses of the assembled protein. Retain the beta-subunit contribution as non-core, without claiming that FGB operates the secretion machinery, phosphorylates ERK, or itself becomes the secreted peptide hormone. The target ligand and recipient-cell species are distinct. Supporting Evidence: |
| GO:0050714 positive regulation of protein secretion | IDA PMID:19193866 Fibrinogen-induced endothelin-1 production from endothelial ... | KEEP AS NON CORE | Summary: Fibrinogen stimulates protein release from endothelial cells. Reason: PMID:19193866 exposes rat heart microvascular endothelial cells to human fibrinogen and measures von Willebrand factor and endothelin-1 in conditioned medium. These are positive ligand-dependent responses of the assembled protein. Retain the beta-subunit contribution as non-core, without claiming that FGB operates the secretion machinery, phosphorylates ERK, or itself becomes the secreted peptide hormone. The target ligand and recipient-cell species are distinct. Supporting Evidence: |
| GO:0050839 cell adhesion molecule binding | IDA PMID:9182580 A mitogenic action for fibrinogen mediated through intercell... | KEEP AS NON CORE | Summary: Fibrinogen contributes to binding the adhesion molecule ICAM-1. Reason: PMID:9182580 measures specific, saturable human fibrinogen binding to human Raji cells with ligand competition and ICAM-1 antibody blockade. Gamma-chain recognition is emphasized. The imported contributes_to assertion is therefore retained for the structural beta subunit of the assembled ligand, without claiming an autonomous beta-chain ICAM-1-binding site. Supporting Evidence: |
| GO:0051087 protein-folding chaperone binding | IPI PMID:19996109 Identification of human plasma proteins as major clients for... | KEEP AS NON CORE | Summary: Fibrinogen beta chain is recovered as a client in clusterin-associated complexes. Reason: PMID:19996109 identifies fibrinogen beta chain in clusterin immunoaffinity eluates from stressed human plasma (Table 1), with chain immunoblots and size-exclusion/ELISA corroboration. GO:0051087 describes binding to a protein-folding chaperone; it does not require the client to be a chaperone. Retain this positive non-core client association, bounded to heterogeneous complexes and fragments rather than a purified binary beta-chain affinity or a demonstrated protective function of FGB. Supporting Evidence: |
| GO:0051258 protein polymerization | IDA PMID:12706644 Fibrinogen Magdeburg I: a novel variant of human fibrinogen ... | ACCEPT | Summary: Beta chains provide structure within polymerizing fibrin. Reason: The original PMID:12706644 abstract reports fibrin formation and monomer aggregation in a human alpha-chain variant, but its full operative assay was not recovered. Independent human-chain assembly and human fibrinogen structural evidence establish the beta chain as part of the self-assembling substrate. Retain the generic polymerization claim as structural participation, without asserting that beta chain performs thrombin cleavage or that the unavailable variant experiment was rechecked. |
| GO:0051258 protein polymerization | IEA GO_REF:0000002 | ACCEPT | Summary: Beta-chain-containing fibrin participates structurally in protein polymerization. Reason: IPR012290 matches the actual beta-chain coiled coil. Human-chain assembly and human fibrinogen structure support a structural subunit, and Reactome R-HSA-140842 explicitly models polymerization of fibrin containing beta residues 45β491. This is participation through supplied polymer structure, not an assertion that FGB catalyzes thrombin cleavage or factor-XIII cross-linking. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR012290 SUPPORTS TRANSFER The genuine target-specific match and official entry mapping were read. The structural or receptor claim is adjudicated with target evidence, not assigned to every family-domain match. |
| GO:0051592 response to calcium ion | IDA PMID:6777381 Ca2+-mediated association of glycoprotein G (thrombinsensiti... | KEEP AS NON CORE | Summary: Extracellular fibrin retention responds to calcium conditions. Reason: PMID:6777381 varies divalent-cation conditions and measures retention of fibrin chains on activated human platelets. Retain the contextual response of fibrinogen-derived extracellular material as non-core. It does not establish beta chain as a calcium sensor or show that FGB executes platelet secretion. Supporting Evidence: |
| GO:0065003 protein-containing complex assembly | IDA PMID:8910396 The role of betagamma and alphagamma complexes in the assemb... | ACCEPT | Summary: Human beta chains participate directly in fibrinogen-complex assembly. Reason: PMID:8910396 combines complementary human chains in BHK cells and resolves beta-gamma intermediates and assembled fibrinogen. Adding beta chain to preformed alpha-gamma intermediates produces assembled and secreted complexes, including after inhibition of new protein synthesis. The beta chain provides part of the structure being assembled; no enzyme activity or independent processing function is inferred. Supporting Evidence: |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | UNDECIDED | Summary: The exosome-specific FGB target record remains unresolved. Reason: The genuine full PMID:23533145 cache describes human urinary vesicle proteomics, but the exact supplemental FGB row was not recovered. The source also acknowledges that some identified proteins can have soluble forms. Without its target/sample join, neither independent extracellular localization nor another vesicle study verifies this HDA assertion. Retain uncertainty without inferring FGB absence or vesicle topology. Supporting Evidence: |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | IDA PMID:10903502 Fibrinogen interactions with ICAM-1 (CD54) regulate endothel... | KEEP AS NON CORE | Summary: Assembled fibrinogen supports endothelial ERK activation. Reason: PMID:10903502 measures ERK responses to human fibrinogen with receptor-recognition controls. The complex acts as an extracellular ligand, with a gamma-chain peptide reproducing key effects. Retain the structural beta-subunit contribution as a contextual non-core process; this does not assign kinase activity or an autonomous beta-chain signaling site. Supporting Evidence: |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | IDA PMID:19193866 Fibrinogen-induced endothelin-1 production from endothelial ... | KEEP AS NON CORE | Summary: Fibrinogen exposure increases endothelial ERK1/2 activation. Reason: PMID:19193866 exposes rat heart microvascular endothelial cells to human fibrinogen and measures ERK phosphorylation and receptor/pathway controls. These are positive ligand-dependent responses of the assembled protein. Retain the beta-subunit contribution as non-core, without claiming that FGB operates the secretion machinery, phosphorylates ERK, or itself becomes the secreted peptide hormone. The target ligand and recipient-cell species are distinct. Supporting Evidence: |
| GO:0070527 platelet aggregation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: FGB contributes to platelet aggregation as a fibrinogen subunit. Reason: The literal positive IBD and actual target ancestry agree at PTN002709771. PMID:6281794 finds that intact fibrinogen supports aggregation, while isolated reduced/carboxymethylated beta chain does not. The latter distinguishes autonomous chain activity from the structural contribution of beta within the intact ligand; it does not establish loss of the complex-level function. Retain the inherited aggregation assertion as a contextual, non-core complex effect. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002709771 SUPPORTS TRANSFER The preserved positive IBD term/node/donors match the literal TSV. Actual version-19 topology places the exact human 491-residue MSA sequence beneath this node; current family normal identifiers remain unchanged. The reason states the biological and product scope. |
| GO:0070527 platelet aggregation | IDA PMID:6281794 gamma and alpha chains of human fibrinogen possess sites rea... | KEEP AS NON CORE | Summary: The fibrinogen complex supports platelet aggregation; isolated beta chain was inactive in this assay. Reason: PMID:6281794 compares human intact fibrinogen with reduced/carboxymethylated isolated chains using human platelets. Intact fibrinogen promotes aggregation, while the beta-chain preparation does not; alpha and gamma preparations give positive responses. Retain only the contextual structural contribution of beta chain within intact fibrinogen, supported by its demonstrated complex assembly in PMID:8910396. This is not evidence that isolated beta chain directly bridges or stimulates platelets, and the modified-chain result is not generalized to every assembled state. |
| GO:0071347 cellular response to interleukin-1 | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Rat Fgb transcription responds to interleukin-1 in the inspected cellular study. Reason: PMID:17521427 detects an Fgb expression response to interleukin-1 and a stronger combined response with leptin in rat RINm5F cells. The ortholog transfer retains a contextual expression-response assertion. It does not show that FGB mediates interleukin-1 signal transduction, and the human transcriptional response was not measured. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P14480 SUPPORTS TRANSFER Rat P14480 carries the PMID:17521427 interleukin-1 expression-response annotation; no signaling-effector role is inferred. ensembl:ENSRNOP00000050663 SUPPORTS TRANSFER The actual Ensembl protein lookup and human-to-donor one-to-one orthology record were verified. Orthology does not itself verify the source experiment or a human tissue-specific response. |
| GO:0072378 blood coagulation, fibrin clot formation | IBA GO_REF:0000033 | ACCEPT | Summary: FGB supplies structure to the fibrin clot. Reason: The actual 491-residue target sequence lies below IBD node PTN002709771, matching the preserved clot-formation annotation. Human-chain assembly, human fibrinogen structure and the curated fibrin-polymer reaction support beta-chain structural participation. Thrombin removes fibrinopeptide B and other proteins perform catalytic activation and cross-linking; the beta chain contributes the material assembled into fibrin rather than those enzymatic activities. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002709771 SUPPORTS TRANSFER The preserved positive IBD term/node/donors match the literal TSV. Actual version-19 topology places the exact human 491-residue MSA sequence beneath this node; current family normal identifiers remain unchanged. The reason states the biological and product scope. |
| GO:0072378 blood coagulation, fibrin clot formation | IDA PMID:16846481 The fibrinogen Aalpha R16C mutation results in fibrinolytic ... | ACCEPT | Summary: Beta chains contribute structure to fibrin clot formation. Reason: PMID:16846481 reports clot formation by purified human fibrinogen carrying an alpha-chain variant, but the full operative experiment was not recovered. Independent human-chain assembly and structural studies establish beta chain as a component of the fibrin-building complex. Retain this generic structural participation in clot formation without certifying the unavailable variant mechanism, assigning protease activity, or transferring the separate unresolved plasminogen-activation claim. |
| GO:0072562 blood microparticle | HDA PMID:22516433 Proteomic analysis of microvesicles from plasma of healthy d... | UNDECIDED | Summary: The blood-microparticle FGB target identification remains unresolved. Reason: The original metadata and abstract of PMID:22516433 were verified, but the operative source and exact FGB target table were not recovered. Other plasma or vesicle detections cannot substitute for this microparticle-specific HDA record. Retain uncertainty without interpreting failed access as negative evidence or assigning a processed-product location. Supporting Evidence: |
| GO:0072562 blood microparticle | IEA GO_REF:0000107 | UNDECIDED | Summary: The exact rat microparticle identification remains insufficiently inspected for transfer. Reason: The rat donor traces to PMID:22014850. Its verified abstract reports fibrinogen-beta enrichment in microparticles after experimental pulmonary embolism, and bounded publisher material confirms the study context. The operative target table and preparation controls were not recovered. Preserve the source-specific uncertainty rather than replacing it with an unrelated human detection or treating the absence of accessible detail as a negative localization result. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P14480 UNRESOLVED Rat P14480 carries the PMID:22014850 microparticle annotation; the exact target table and preparation evidence remain inaccessible. ensembl:ENSRNOP00000050663 SUPPORTS TRANSFER The actual Ensembl protein lookup and human-to-donor one-to-one orthology record were verified. Orthology does not itself verify the source experiment or a human tissue-specific response. |
| GO:0090277 positive regulation of peptide hormone secretion | IDA PMID:19193866 Fibrinogen-induced endothelin-1 production from endothelial ... | KEEP AS NON CORE | Summary: Fibrinogen stimulates endothelin-1 secretion in an endothelial assay. Reason: PMID:19193866 exposes rat heart microvascular endothelial cells to human fibrinogen and measures endothelin-1 release, with processing-enzyme and receptor/pathway controls. These are positive ligand-dependent responses of the assembled protein. Retain the beta-subunit contribution as non-core, without claiming that FGB operates the secretion machinery, phosphorylates ERK, or itself becomes the secreted peptide hormone. The target ligand and recipient-cell species are distinct. Supporting Evidence: |
| GO:0140149 non-collagenous component of interstitial matrix | TAS PMID:36399478 MatrisomeDB 2.0: 2023 updates to the ECM-protein knowledge d... | UNDECIDED | Summary: The exact non-collagenous interstitial-matrix target context remains unresolved. Reason: PMID:36399478 describes MatrisomeDB curation and data integration. The exact FGB target record underlying this interstitial-matrix assertion was not recovered. Plasma fibrinogen and fibrin-clot biology do not by themselves establish this specific tissue compartment. Preserve uncertainty without inferring an erroneous target assignment from incomplete database access. Supporting Evidence: |
| GO:1900026 positive regulation of substrate adhesion-dependent cell spreading | NAS PMID:24041635 The role of fibrin matrices and tissue factor in early-term ... | UNDECIDED | Summary: The specific cell-spreading context remains incompletely accessible. Reason: PMID:24041635 reports early human trophoblast spreading on fibrin in its abstract. The operative Methods and figures were not recovered. Other fibrinogen adhesion assays do not establish the same target-cell response or isolate a beta-chain contribution. Retain source-specific uncertainty rather than generalizing the result from matrix presence alone. Supporting Evidence: |
| GO:1902042 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors | IDA PMID:10903502 Fibrinogen interactions with ICAM-1 (CD54) regulate endothel... | KEEP AS NON CORE | Summary: Fibrinogen supports survival of challenged endothelial cells. Reason: PMID:10903502 measures survival of TNF-alpha-treated endothelial cells on fibrinogen-containing substrates, with ICAM-1 recognition and ERK-pathway controls. Retain the supported negative regulation of extrinsic apoptotic signaling as a contextual effect of the assembled ligand. The gamma-chain peptide experiments do not isolate a beta-chain survival site, and FGB is not assigned an intrinsic apoptosis enzyme or universal cytoprotective activity. Supporting Evidence: |
| GO:1903561 extracellular vesicle | HDA PMID:24769233 Proteomic analysis of cerebrospinal fluid extracellular vesi... | KEEP AS NON CORE | Summary: FGB is detected in human cerebrospinal-fluid vesicle fractions. Reason: The official PMID:24769233 deposit PXD000608 identifies FGB in proteinGroups.txt line 692, group 703 (P02675;D6REL8). Both vesicle preparations have positive peptide/intensity measurements, with blank reverse, contaminant and site-only flags; soluble fractions are also positive. Retain the contextual extracellular-vesicle association as non-core. These processed protein-group data do not establish vesicle lumen versus external/co-isolated material, a natural splice, or measured free fibrinopeptide B. Supporting Evidence: |
| GO:2000352 negative regulation of endothelial cell apoptotic process | IDA PMID:10903502 Fibrinogen interactions with ICAM-1 (CD54) regulate endothel... | KEEP AS NON CORE | Summary: Fibrinogen supports survival of challenged endothelial cells. Reason: PMID:10903502 measures survival of TNF-alpha-treated endothelial cells on fibrinogen-containing substrates, with ICAM-1 recognition and ERK-pathway controls. Retain the supported negative regulation of endothelial apoptosis as a contextual effect of the assembled ligand. The gamma-chain peptide experiments do not isolate a beta-chain survival site, and FGB is not assigned an intrinsic apoptosis enzyme or universal cytoprotective activity. Supporting Evidence: |
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Download this section (compressed HTML)Q: Which receptor-binding and cell-response effects depend directly on beta-chain surfaces, and which arise through other chains of assembled fibrinogen?
Q: Do beta-chain structural changes alter fibrinolysis by changing fibrin architecture, by altering cofactor presentation elsewhere in the complex, or through a direct beta-chain contribution?
Q: Which extracellular-matrix and vesicle measurements resolve intact fibrinogen, mature beta chain or released fibrinopeptide B, and which reflect externally associated soluble material?
Experiment: Reconstitute sequence-verified human fibrinogen with targeted beta-chain changes and matched alpha/gamma chains. Measure assembly and fibrin architecture before receptor-binding or cell-response assays, with intact-complex and isolated-chain controls.
Hypothesis: Some apparent beta-chain effects may arise from altered complex assembly rather than an autonomous beta-chain ligand activity.
Type: Chain-resolved biochemical reconstitution
Experiment: Use cleavage-specific peptide measurements and appropriate fraction-purity controls to distinguish fibrinopeptide B, mature beta chain and intact fibrinogen in extracellular-matrix and vesicle preparations. Combine protease protection with measurements of soluble and surface-associated material.
Hypothesis: Parent-accession protein groups may combine processing states and extracellular associations that have distinct locations.
Type: Processed-product and compartment-resolved proteomics
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