FGG

UniProt ID: P02679
Organism: Homo sapiens
Review Status: DRAFT
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Gene Description

FGG encodes the gamma subunit of fibrinogen, a secreted complex containing two alpha, two beta and two gamma chains. Gamma interfaces contribute to assembly and, after thrombin acts on the other chains, recognize exposed fibrin knobs to support the extracellular clot network. Gamma-containing fibrinogen also bridges activated platelets. Receptor-recognition regions contribute to contextual endothelial adhesion and signaling. Alternative C termini distinguish gamma-A from the longer gamma-B (gamma-prime) product; experimental fragments, multimerized preparations and clinical splice mutants do not establish equal activity of these natural products. Pathogenic FGG variants can impair assembly, secretion or clot properties, producing quantitative or qualitative fibrinogen disorders.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005102 signaling receptor binding
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: Gamma contributes an ICAM-1-recognition region in fibrinogen.
Reason: PMID7822297 explicitly maps receptor recognition to gamma117–133 in its abstract. Independently read PMID10903502 adhesion/survival experiments use this peptide and ICAM-1 controls. The same molecular claim is supported, without inferring the contact site from the InterPro match alone or making isolated gamma a general growth factor. Complete PMID7822297 Methods were unavailable. GO:0005102 and GO:0050839 are not ancestors of one another in the saved typed ontology. The former records recognition of a signaling receptor, supported by the ICAM-1/ERK context; the latter records the adhesion-molecule class. Both are non-core, with no duplicate core function.
Supporting Evidence:
GO_REF:0000002
file:human/FGG/FGG-source-provenance.yaml
GO:0005102 signaling receptor binding
IPI
PMID:7822297
Structural recognition of a novel fibrinogen gamma chain seq...
KEEP AS NON CORE
Summary: Gamma contributes an ICAM-1-recognition region in fibrinogen.
Reason: PMID7822297 explicitly maps receptor recognition to gamma117–133 in its abstract. Independently read PMID10903502 adhesion/survival experiments use this peptide and ICAM-1 controls. The same molecular claim is supported, without inferring the contact site from the InterPro match alone or making isolated gamma a general growth factor. Complete PMID7822297 Methods were unavailable. GO:0005102 and GO:0050839 are not ancestors of one another in the saved typed ontology. The former records recognition of a signaling receptor, supported by the ICAM-1/ERK context; the latter records the adhesion-molecule class. Both are non-core, with no duplicate core function.
Supporting Evidence:
file:human/FGG/FGG-source-provenance.yaml
GO:0005198 structural molecule activity
IDA
PMID:8910396
The role of betagamma and alphagamma complexes in the assemb...
ACCEPT
Summary: Gamma supplies structural interfaces for fibrinogen assembly and fibrin formation.
Reason: Actual PMID8910396 Results follow human alpha-gamma and beta-gamma assembly intermediates in BHK recipients. Human gamma-fragment binding and structure independently establish polymerization contacts. Structural molecule activity covers complex assembly as well as the extracellular polymer; gamma is neither thrombin nor the factor XIII crosslinking enzyme.
GO:0005201 extracellular matrix structural constituent
HDA
PMID:28344315
Proteomic characterization of human multiple myeloma bone ma...
UNDECIDED
Summary: FGG has a supported matrix structural role; the source-specific extension remains unverified.
Reason: Human gamma-fragment/pocket work establishes fibrin structural participation, and independent FGG proteomic joins support matrix association. The generic GO:0005201 claim is therefore supported and remains non-core in the other rows. This raw annotation additionally asserts occurs_in(UBERON:0002371); its exact specimen-specific FGG table was not recovered. UNDECIDED applies to that complete extended assertion, not to the established generic function. The original extension is restored as source metadata; no absence or wrong-gene inference is made.
Supporting Evidence:
file:human/FGG/FGG-source-provenance.yaml
GO:0005201 extracellular matrix structural constituent
RCA
PMID:25037231
Extracellular matrix signatures of human primary metastatic ...
KEEP AS NON CORE
Summary: FGG is detected in matrix preparations and contributes to fibrin structure.
Reason: The exact FGG target is present in the original supplement. Matrisome classification alone is not a mechanical assay; independent human gamma-fragment/pocket work supports fibrin structural participation. Retain the matrix-specific annotation without duplicating the broader structural core, which also covers fibrinogen assembly.
Supporting Evidence:
file:human/FGG/FGG-source-provenance.yaml
GO:0005201 extracellular matrix structural constituent
RCA
PMID:28327460
Comprehensive proteomic characterization of stem cell-derive...
UNDECIDED
Summary: FGG has a supported matrix structural role; the source-specific extension remains unverified.
Reason: Human gamma-fragment/pocket work establishes fibrin structural participation, and independent FGG proteomic joins support matrix association. The generic GO:0005201 claim is therefore supported and remains non-core in the other rows. This raw annotation additionally asserts occurs_in(CL:0002540); its exact specimen-specific FGG table was not recovered. UNDECIDED applies to that complete extended assertion, not to the established generic function. The original extension is restored as source metadata; no absence or wrong-gene inference is made.
Supporting Evidence:
file:human/FGG/FGG-source-provenance.yaml
GO:0005201 extracellular matrix structural constituent
RCA
PMID:28675934
Characterization of the Extracellular Matrix of Normal and D...
KEEP AS NON CORE
Summary: FGG is detected in matrix preparations and contributes to fibrin structure.
Reason: The exact FGG target is present in the original supplement. Matrisome classification alone is not a mechanical assay; independent human gamma-fragment/pocket work supports fibrin structural participation. Retain the matrix-specific annotation without duplicating the broader structural core, which also covers fibrinogen assembly.
Supporting Evidence:
file:human/FGG/FGG-source-provenance.yaml
GO:0005515 protein binding
IPI
PMID:10788510
The fibronectin-binding MSCRAMM FnbpA of Staphylococcus aure...
MODIFY
Summary: Gamma binds bacterial cell-surface adhesion molecules.
Reason: The PMID:10788510 abstract identifies the tested MSCRAMMs as microbial surface proteins mediating adherence to host matrix. It directly localizes recombinant FnBPA recognition to the gamma C terminus, reports binding measurements and competition with ClfA. GO:0050839 describes binding to a cell adhesion molecule, so it captures the verified partner class more specifically than generic protein binding. This assigns the binding activity to FGG, not microbial adhesin activity. Complete strain/construct Methods and accession-specific mapping were not recovered; the original IPI partner identifiers are preserved with curator deference. No natural-isoform specificity is inferred from the peptide.
Proposed replacements: cell adhesion molecule binding
Supporting Evidence:
GO:0005515 protein binding
IPI
PMID:10788510
The fibronectin-binding MSCRAMM FnbpA of Staphylococcus aure...
MODIFY
Summary: Gamma binds bacterial cell-surface adhesion molecules.
Reason: The PMID:10788510 abstract identifies the tested MSCRAMMs as microbial surface proteins mediating adherence to host matrix. It directly localizes recombinant FnBPA recognition to the gamma C terminus, reports binding measurements and competition with ClfA. GO:0050839 describes binding to a cell adhesion molecule, so it captures the verified partner class more specifically than generic protein binding. This assigns the binding activity to FGG, not microbial adhesin activity. Complete strain/construct Methods and accession-specific mapping were not recovered; the original IPI partner identifiers are preserved with curator deference. No natural-isoform specificity is inferred from the peptide.
Proposed replacements: cell adhesion molecule binding
Supporting Evidence:
GO:0005515 protein binding
IPI
PMID:21546586
Role of Mycoplasma pneumoniae glyceraldehyde-3-phosphate deh...
UNDECIDED
Summary: The gamma-chain assignment in the GAPDH-binding experiment remains unverified.
Reason: The abstract reports microbial GAPDH binding to human fibrinogen in a Western-blot assay but does not resolve the FGG band or construct. The relevant original result was unavailable. Whole-fibrinogen recognition is positive context, not proof of isolated gamma binding.
Supporting Evidence:
GO:0005515 protein binding
IPI
PMID:26627825
Extracellular Fibrinogen-binding Protein (Efb) from Staphylo...
KEEP AS NON CORE
Summary: FGG is recovered in the Efb affinity-capture experiment.
Reason: Actual Results and Table 1 identify FIBG_HUMAN in platelet-lysate capture with added fibrinogen, at enrichment 1.40 relative to bead control. This supports association in the tested mixture, not purified gamma affinity or transfer of the microbial protein activities to FGG. No more informative host MF is established by this capture alone.
Supporting Evidence:
GO:0005576 extracellular region
EXP
PMID:10074346
Conformational changes in fragments D and double-D from huma...
ACCEPT
Summary: Human fibrin(ogen) fragments contain extracellular gamma chains.
Reason: The source abstracts describe human D/double-D structures. The complete originals were unavailable, but independently read human plasma structure and human-chain assembly/secretion experiments establish the identical generic extracellular location. No unexamined source-specific conformational result is asserted.
GO:0005576 extracellular region
EXP
PMID:19296670
Crystal structure of human fibrinogen.
ACCEPT
Summary: Human plasma fibrinogen contains the extracellular gamma subunit.
Reason: Actual Methods purify human plasma fibrinogen and the structure resolves gamma-containing D regions and coiled coils. Partial alpha-chain proteolysis and minor fibrinopeptide cleavage limit claims of a wholly intact native preparation, not the extracellular location.
Supporting Evidence:
GO:0005576 extracellular region
EXP
PMID:9628725
Crystal structure of fragment double-D from human fibrin wit...
ACCEPT
Summary: Human fibrin(ogen) fragments contain extracellular gamma chains.
Reason: The source abstracts describe human D/double-D structures. The complete originals were unavailable, but independently read human plasma structure and human-chain assembly/secretion experiments establish the identical generic extracellular location. No unexamined source-specific conformational result is asserted.
GO:0005576 extracellular region
HDA
PMID:16502470
Human colostrum: identification of minor proteins in the aqu...
UNDECIDED
Summary: Extracellular FGG is established; the colostrum-specific source assertion remains unverified.
Reason: Human plasma structure and chain assembly/secretion experiments establish the generic extracellular location. This raw HDA annotation additionally asserts part_of(UBERON:0001914) in the colostrum survey, whose exact FGG target table remains inaccessible. UNDECIDED concerns that complete specimen-specific assertion, not whether FGG can occur extracellularly. The original extension is restored as source metadata; another extracellular preparation does not independently verify the colostrum assignment.
Supporting Evidence:
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
IDA
PMID:6777381
Ca2+-mediated association of glycoprotein G (thrombinsensiti...
ACCEPT
Summary: Released platelet fibrin(ogen) is extracellular.
Reason: Actual Results distinguish soluble release from calcium-dependent surface retention and identify fibrin-chain bands in human platelets. This is complex-level evidence, not a membrane-spanning gamma protein or an isoform-resolved assay.
Supporting Evidence:
GO:0005576 extracellular region
IEA
GO_REF:0000044
ACCEPT
Summary: FGG is a secreted component of extracellular fibrinogen.
Reason: The literal UniProt Secreted location and mapping agree with human plasma purification and human-chain assembly/secretion experiments. Precursor processing does not imply identical activity of every splice form.
Supporting Evidence:
GO_REF:0000044
file:human/FGG/FGG-uniprot.txt
GO:0005576 extracellular region
TAS
Reactome:R-HSA-114560
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-114560 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-114560
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-140840
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-140840 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-140840
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-140842
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-140842 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-140842
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-140851
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-140851 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-140851
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-166072
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-166072 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-166072
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-166082
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-166082 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-166082
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-166091
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-166091 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-166091
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-166119
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-166119 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-166119
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-166284
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-166284 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-166284
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-166286
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-166286 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-166286
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-166362
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-166362 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-166362
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-166363
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-166363 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-166363
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-216069
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-216069 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-216069
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-216082
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-216082 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-216082
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-2201316
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-2201316 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-2201316
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-2201322
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-2201322 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-2201322
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-2262775
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-2262775 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-2262775
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-2262777
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-2262777 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-2262777
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-2559414
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-2559414 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-2559414
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-354066
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-354066 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-354066
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-354073
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-354073 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-354073
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-354087
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-354087 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-354087
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-354124
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-354124 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-354124
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-354149
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-354149 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-354149
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-354165
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-354165 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-354165
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-372693
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-372693 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-372693
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-372697
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-372697 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-372697
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-372705
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-372705 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-372705
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-377640
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-377640 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-377640
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-377641
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-377641 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-377641
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-377643
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-377643 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-377643
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-377644
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-377644 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-377644
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-429415
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-429415 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-429415
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-429441
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-429441 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-429441
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-481007
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-481007 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-481007
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-5602353
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-5602353 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-5602353
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-5602383
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-5602383 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-5602383
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-5602606
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-5602606 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-5602606
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-8870678
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-8870678 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-8870678
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-937022
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-937022 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-937022
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-937059
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-937059 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-937059
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-937079
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-937079 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-937079
file:human/FGG/FGG-source-provenance.yaml
GO:0005576 extracellular region
TAS
Reactome:R-HSA-9936699
ACCEPT
Summary: FGG is modeled in the extracellular region component of this event.
Reason: The actual Reactome:R-HSA-9936699 component route reaches human P02679 entity 140585, modeled residues 27–453, in extracellular region. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B.
Supporting Evidence:
Reactome:R-HSA-9936699
file:human/FGG/FGG-source-provenance.yaml
GO:0005577 fibrinogen complex
IDA
PMID:16846481
The fibrinogen Aalpha R16C mutation results in fibrinolytic ...
ACCEPT
Summary: Gamma is a constituent of the fibrinogen complex.
Reason: The source abstracts describe purified/expressed human fibrinogen, including gamma variants where relevant. Complete source-specific assays were unavailable. Independent human-chain assembly and plasma structure establish this identical generic membership claim; variant mechanisms or natural-splice activity are not inferred from membership.
GO:0005577 fibrinogen complex
IDA
PMID:18676163
Congenital hypofibrinogenemia: characterization of two misse...
ACCEPT
Summary: Gamma is a constituent of the fibrinogen complex.
Reason: The source abstracts describe purified/expressed human fibrinogen, including gamma variants where relevant. Complete source-specific assays were unavailable. Independent human-chain assembly and plasma structure establish this identical generic membership claim; variant mechanisms or natural-splice activity are not inferred from membership.
GO:0005577 fibrinogen complex
IDA
PMID:6451630
Localization of a fibrin polymerization site.
ACCEPT
Summary: A gamma-derived polymerization fragment is isolated from human fibrinogen.
Reason: The actual fragment-D study identifies a gamma-derived peptide and its recognition of fibrin-related fragments. This establishes complex membership; the experimental fragment is not a natural splice product.
Supporting Evidence:
GO:0005577 fibrinogen complex
IDA
PMID:8470043
Paris I dysfibrinogenemia: a point mutation in intron 8 resu...
ACCEPT
Summary: Gamma is a constituent of the fibrinogen complex.
Reason: The source abstracts describe purified/expressed human fibrinogen, including gamma variants where relevant. Complete source-specific assays were unavailable. Independent human-chain assembly and plasma structure establish this identical generic membership claim; variant mechanisms or natural-splice activity are not inferred from membership.
GO:0005577 fibrinogen complex
IDA
PMID:8910396
The role of betagamma and alphagamma complexes in the assemb...
ACCEPT
Summary: Gamma-containing intermediates assemble into human fibrinogen.
Reason: Actual Results follow alpha-gamma/beta-gamma intermediates and full assembly after supplying the missing chain. The human-chain fusion experiments use hamster BHK recipients; human hepatocyte-derived observations are a separate context.
Supporting Evidence:
GO:0005577 fibrinogen complex
IEA
GO_REF:0000120
ACCEPT
Summary: Electronic complex membership agrees with human assembly evidence.
Reason: The actual ARBA00086903 FunFam/Primates branch and InterPro IPR012290 target mapping were verified. Human gamma-containing intermediates and plasma fibrinogen independently corroborate membership; the mappings are not new experiments.
Supporting Evidence:
GO_REF:0000120
file:human/FGG/FGG-source-provenance.yaml
GO:0005788 endoplasmic reticulum lumen
TAS
Reactome:R-HSA-8952289
KEEP AS NON CORE
Summary: FGG is modeled in the endoplasmic reticulum lumen component of this event.
Reason: The actual Reactome:R-HSA-8952289 component route reaches human P02679 entity 8956692, 8956993, modeled residues 27–453, in endoplasmic reticulum lumen. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B. FGG is modeled as a FAM20C substrate, not the kinase.
Supporting Evidence:
Reactome:R-HSA-8952289
file:human/FGG/FGG-source-provenance.yaml
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-114560
KEEP AS NON CORE
Summary: FGG is modeled in the plasma membrane component of this event.
Reason: The actual Reactome:R-HSA-114560 component route reaches human P02679 entity 140918, modeled residues 27–453, in plasma membrane. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B. Plasma membrane here denotes extracellularly associated fibrin in an integrin complex, not a transmembrane gamma chain.
Supporting Evidence:
Reactome:R-HSA-114560
file:human/FGG/FGG-source-provenance.yaml
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-9921091
KEEP AS NON CORE
Summary: FGG is modeled in the plasma membrane component of this event.
Reason: The actual Reactome:R-HSA-9921091 component route reaches human P02679 entity 140918, modeled residues 27–453, in plasma membrane. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B. Plasma membrane here denotes extracellularly associated fibrin in an integrin complex, not a transmembrane gamma chain.
Supporting Evidence:
Reactome:R-HSA-9921091
file:human/FGG/FGG-source-provenance.yaml
GO:0007160 cell-matrix adhesion
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: Cell-matrix adhesion is a positive inherited and contextual gamma role.
Reason: The positive IBD at PTN009036378 is on the target path to PTN002499052; the MSA exactly matches canonical human FGG. Self-WITH is legitimate descendant evidence. Gamma-region/ICAM-1 substrate-adhesion assays corroborate the contextual role, retained outside the principal hemostatic core.
Supporting Evidence:
GO_REF:0000033
file:human/FGG/FGG-source-provenance.yaml
GO:0007160 cell-matrix adhesion
IDA
PMID:10903502
Fibrinogen interactions with ICAM-1 (CD54) regulate endothel...
KEEP AS NON CORE
Summary: Fibrinogen and its gamma-region peptide support endothelial adhesion.
Reason: Actual adhesion Methods, Table 1 and Results use fibrinogen substrates and gamma117–133 with ICAM-1 controls. This supports the tested matrix-adhesion context, not autonomous gamma activity in every tissue or exclusive ICAM-1 use.
Supporting Evidence:
GO:0007596 blood coagulation
IEA
GO_REF:0000002
TOO GENERAL
Summary: The positive broad hemostatic mapping is less informative than retained specific processes.
Reason: Actual typed GO ancestry places platelet aggregation below platelet activation/blood coagulation and fibrin clot formation below blood coagulation. Gamma bridging and pocket evidence support the retained specific processes. This is ontology refinement, not rejection of hemostatic participation or assignment of protease activity.
Supporting Evidence:
GO_REF:0000002
file:human/FGG/FGG-source-provenance.yaml
GO:0009306 protein secretion
IMP
PMID:18676163
Congenital hypofibrinogenemia: characterization of two misse...
UNDECIDED
Summary: The secretion-specific interpretation of the gamma variant remains unresolved.
Reason: The abstract explicitly reports gammaAsn345Ser impairing hexamer secretion, distinct from alphaCys45Phe assembly failure. Full expression experiments were unavailable. A defect in assembly/quality control of secreted cargo does not by itself distinguish direct participation in secretion. Preserve the IMP assertion pending the relevant full result.
Supporting Evidence:
GO:0009897 external side of plasma membrane
IDA
PMID:6777381
Ca2+-mediated association of glycoprotein G (thrombinsensiti...
KEEP AS NON CORE
Summary: Fibrin-chain material associates with activated human platelet surfaces.
Reason: Actual surface-iodination Results and Figure 3 caption identify fibrin-chain bands after activation, with calcium-dependent extracellular retention. This supports complex surface association, not gamma membrane insertion or isoform-specific topology.
Supporting Evidence:
GO:0009897 external side of plasma membrane
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: The external platelet-surface mapping has matching human evidence.
Reason: ARBA00043397 matches FGG FunFam/Haplorrhini. Human surface iodination and calcium-dependent fibrin retention support gamma as a subunit of the extracellularly bound complex.
Supporting Evidence:
GO_REF:0000117
file:human/FGG/FGG-source-provenance.yaml
GO:0009986 cell surface
IDA
PMID:6777381
Ca2+-mediated association of glycoprotein G (thrombinsensiti...
KEEP AS NON CORE
Summary: Fibrin-chain material associates with activated human platelet surfaces.
Reason: Actual surface-iodination Results and Figure 3 caption identify fibrin-chain bands after activation, with calcium-dependent extracellular retention. This supports complex surface association, not gamma membrane insertion or isoform-specific topology.
Supporting Evidence:
GO:0030168 platelet activation
IEA
GO_REF:0000002
TOO GENERAL
Summary: The positive broad hemostatic mapping is less informative than retained specific processes.
Reason: Actual typed GO ancestry places platelet aggregation below platelet activation/blood coagulation and fibrin clot formation below blood coagulation. Gamma bridging and pocket evidence support the retained specific processes. This is ontology refinement, not rejection of hemostatic participation or assignment of protease activity.
Supporting Evidence:
GO_REF:0000002
file:human/FGG/FGG-source-provenance.yaml
GO:0031012 extracellular matrix
HDA
PMID:25037231
Extracellular matrix signatures of human primary metastatic ...
ACCEPT
Summary: FGG is measured in extracellular-matrix-enriched human tissue preparations.
Reason: Exact FGG/P02679 supplement rows establish association. Sample, accession-group and raw-to-seed joins are retained in the source provenance. Enrichment does not establish new mechanical activity or distinguish intact precursor, gamma-A and gamma-B.
Supporting Evidence:
file:human/FGG/FGG-source-provenance.yaml
GO:0031012 extracellular matrix
HDA
PMID:28327460
Comprehensive proteomic characterization of stem cell-derive...
UNDECIDED
Summary: FGG matrix association is established; the source-specific extension remains unverified.
Reason: Exact FGG/P02679 rows in the independent PMID:25037231 and PMID:28675934 supplements establish the generic extracellular-matrix association accepted elsewhere. This raw source annotation additionally asserts part_of(CL:0002540). Its own FGG target table and specimen-specific join remain unrecovered, so the complete extended assertion remains UNDECIDED. The original extension is restored as source metadata. This is not uncertainty about generic ECM association and does not assert absence from the unverified specimen.
Supporting Evidence:
file:human/FGG/FGG-source-provenance.yaml
GO:0031012 extracellular matrix
HDA
PMID:28344315
Proteomic characterization of human multiple myeloma bone ma...
UNDECIDED
Summary: FGG matrix association is established; the source-specific extension remains unverified.
Reason: Exact FGG/P02679 rows in the independent PMID:25037231 and PMID:28675934 supplements establish the generic extracellular-matrix association accepted elsewhere. This raw source annotation additionally asserts part_of(UBERON:0002371). Its own FGG target table and specimen-specific join remain unrecovered, so the complete extended assertion remains UNDECIDED. The original extension is restored as source metadata. This is not uncertainty about generic ECM association and does not assert absence from the unverified specimen.
Supporting Evidence:
file:human/FGG/FGG-source-provenance.yaml
GO:0031012 extracellular matrix
HDA
PMID:28675934
Characterization of the Extracellular Matrix of Normal and D...
ACCEPT
Summary: FGG is measured in extracellular-matrix-enriched human tissue preparations.
Reason: Exact FGG/P02679 supplement rows establish association. Sample, accession-group and raw-to-seed joins are retained in the source provenance. Enrichment does not establish new mechanical activity or distinguish intact precursor, gamma-A and gamma-B.
Supporting Evidence:
file:human/FGG/FGG-source-provenance.yaml
GO:0031012 extracellular matrix
IBA
GO_REF:0000033
ACCEPT
Summary: ECM localization has positive phylogenetic and human proteomic support.
Reason: PTN000441162 is ancestral to the exact human leaf. The current family table has the positive ECM IBD and no IRD records; the older API tree and exact sequence establish the persistent-node join. Human target tables corroborate association without using donor count as an evidence-quality proxy.
Supporting Evidence:
GO_REF:0000033
file:human/FGG/FGG-source-provenance.yaml
GO:0031091 platelet alpha granule
IDA
PMID:6777381
Ca2+-mediated association of glycoprotein G (thrombinsensiti...
KEEP AS NON CORE
Summary: Platelet fibrinogen is a releasable alpha-granule constituent.
Reason: The actual paper describes fibrinogen as alpha-granule cargo and follows its release and extracellular retention. It does not provide a gamma-specific intragranular image or splice comparison. The curated Reactome gamma-containing cargo supports the compartment, retained as a storage rather than principal structural-action location.
Supporting Evidence:
Reactome:R-HSA-481007
file:human/FGG/FGG-source-provenance.yaml
GO:0031093 platelet alpha granule lumen
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: The rule supports gamma-containing platelet granule cargo.
Reason: ARBA00084788 matches the target FunFam/Homo branch. Reactome represents P02679 in platelet alpha-granule lumen before release. This is positive electronic/pathway evidence with complex scope, not a new direct gamma localization assay.
Supporting Evidence:
GO_REF:0000117
Reactome:R-HSA-481007
file:human/FGG/FGG-source-provenance.yaml
GO:0031093 platelet alpha granule lumen
TAS
Reactome:R-HSA-481007
KEEP AS NON CORE
Summary: FGG is modeled in the platelet alpha granule lumen component of this event.
Reason: The actual Reactome:R-HSA-481007 component route reaches human P02679 entity 140922, modeled residues 27–453, in platelet alpha granule lumen. Exact edges are recorded in the source-provenance file. This establishes component localization, not an independent FGG catalytic/signaling claim for the event name or experimental resolution of gamma-A versus gamma-B. This is curated cargo localization, not a new gamma-specific granule image.
Supporting Evidence:
Reactome:R-HSA-481007
file:human/FGG/FGG-source-provenance.yaml
GO:0031639 plasminogen activation
IDA
PMID:16846481
The fibrinogen Aalpha R16C mutation results in fibrinolytic ...
UNDECIDED
Summary: The gamma-specific cofactor contribution remains unresolved in this source.
Reason: The PMID16846481 abstract studies purified fibrinogen with Aalpha R16C, reports normal plasminogen activation and delayed lysis attributed to altered clot properties. Full relevant assays were unavailable. This neither proves nor refutes gamma cofactor work. Being cleaved is insufficient, and alpha-C cofactor evidence from other papers is not transferred to gamma.
Supporting Evidence:
GO:0031639 plasminogen activation
IEA
GO_REF:0000117
UNDECIDED
Summary: The rule match is genuine, but gamma-specific cofactor work remains unresolved.
Reason: Actual target conditions and GO outputs were verified, but they expose no gamma-specific primary cofactor assay. Gamma structural participation does not automatically establish plasminogen-activation cofactor activity. Preserve uncertainty rather than declaring the inference impossible or misattributed.
Supporting Evidence:
GO_REF:0000117
file:human/FGG/FGG-source-provenance.yaml
GO:0034116 positive regulation of heterotypic cell-cell adhesion
IDA
PMID:8100742
Fibrinogen mediates leukocyte adhesion to vascular endotheli...
UNDECIDED
Summary: The gamma contribution to the exact heterotypic-adhesion assay remains unresolved.
Reason: PMID8100742 supports fibrinogen-mediated leukocyte/endothelial bridging in its abstract, and the rule target match is genuine. Full gamma-specific assay/control evidence was unavailable. Other gamma/ICAM-1 recognition is positive context but does not reconstruct this particular experiment; no wrong-chain conclusion is inferred.
Supporting Evidence:
file:human/FGG/FGG-source-provenance.yaml
GO:0034116 positive regulation of heterotypic cell-cell adhesion
IEA
GO_REF:0000117
UNDECIDED
Summary: The gamma contribution to the exact heterotypic-adhesion assay remains unresolved.
Reason: PMID8100742 supports fibrinogen-mediated leukocyte/endothelial bridging in its abstract, and the rule target match is genuine. Full gamma-specific assay/control evidence was unavailable. Other gamma/ICAM-1 recognition is positive context but does not reconstruct this particular experiment; no wrong-chain conclusion is inferred.
Supporting Evidence:
GO_REF:0000117
file:human/FGG/FGG-source-provenance.yaml
GO:0042730 fibrinolysis
IDA
PMID:16846481
The fibrinogen Aalpha R16C mutation results in fibrinolytic ...
UNDECIDED
Summary: The gamma-specific cofactor contribution remains unresolved in this source.
Reason: The PMID16846481 abstract studies purified fibrinogen with Aalpha R16C, reports normal plasminogen activation and delayed lysis attributed to altered clot properties. Full relevant assays were unavailable. This neither proves nor refutes gamma cofactor work. Being cleaved is insufficient, and alpha-C cofactor evidence from other papers is not transferred to gamma.
Supporting Evidence:
GO:0042730 fibrinolysis
IEA
GO_REF:0000117
UNDECIDED
Summary: The rule match is genuine, but gamma-specific cofactor work remains unresolved.
Reason: Actual target conditions and GO outputs were verified, but they expose no gamma-specific primary cofactor assay. Gamma structural participation does not automatically establish plasminogen-activation cofactor activity. Preserve uncertainty rather than declaring the inference impossible or misattributed.
Supporting Evidence:
GO_REF:0000117
file:human/FGG/FGG-source-provenance.yaml
GO:0045907 positive regulation of vasoconstriction
IDA
PMID:15739255
Fibrinogen and fragment D-induced vascular constriction.
KEEP AS NON CORE
Summary: Human fibrinogen and fragment D promote vascular constriction in rat preparations.
Reason: Actual Methods, Results and Figures 6–8 use human fibrinogen/multichain fragment D in rat vessels with receptor/ligand-blocking and endothelin pharmacology. Gamma-region ICAM-1 recognition supports participation in the ligand complex, not an autonomous gamma vasoconstrictor or receptor-exclusive mechanism.
Supporting Evidence:
file:human/FGG/FGG-source-provenance.yaml
GO:0045907 positive regulation of vasoconstriction
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Human fibrinogen and fragment D promote vascular constriction in rat preparations.
Reason: Actual Methods, Results and Figures 6–8 use human fibrinogen/multichain fragment D in rat vessels with receptor/ligand-blocking and endothelin pharmacology. Gamma-region ICAM-1 recognition supports participation in the ligand complex, not an autonomous gamma vasoconstrictor or receptor-exclusive mechanism.
Supporting Evidence:
GO_REF:0000117
file:human/FGG/FGG-source-provenance.yaml
GO:0045921 positive regulation of exocytosis
IDA
PMID:19193866
Fibrinogen-induced endothelin-1 production from endothelial ...
KEEP AS NON CORE
Summary: Fibrinogen triggers endothelial secretory responses and ERK signaling in context.
Reason: Actual PMID19193866 uses human fibrinogen on rat heart microvascular endothelial cells, measuring conditioned-medium ET-1/vWF, WPB staining and ERK phosphorylation. ICAM-1/MEK perturbations support the response with partial-blockade/feedback limits. Gamma participates in the ligand complex and has an independently mapped receptor-recognition region; it is not secretory machinery or the peptide hormone.
Supporting Evidence:
file:human/FGG/FGG-source-provenance.yaml
GO:0050714 positive regulation of protein secretion
IDA
PMID:19193866
Fibrinogen-induced endothelin-1 production from endothelial ...
KEEP AS NON CORE
Summary: Fibrinogen triggers endothelial secretory responses and ERK signaling in context.
Reason: Actual PMID19193866 uses human fibrinogen on rat heart microvascular endothelial cells, measuring conditioned-medium ET-1/vWF, WPB staining and ERK phosphorylation. ICAM-1/MEK perturbations support the response with partial-blockade/feedback limits. Gamma participates in the ligand complex and has an independently mapped receptor-recognition region; it is not secretory machinery or the peptide hormone.
Supporting Evidence:
file:human/FGG/FGG-source-provenance.yaml
GO:0050839 cell adhesion molecule binding
IPI
PMID:7822297
Structural recognition of a novel fibrinogen gamma chain seq...
KEEP AS NON CORE
Summary: Gamma117–133 supports ICAM-1 recognition.
Reason: The source abstract explicitly identifies the gamma region and receptor binding/competition. Independently read gamma-peptide adhesion experiments corroborate the same molecular claim. The informative cell-adhesion binding term is contextual rather than a duplicate core; complete source Methods remain unavailable.
Supporting Evidence:
GO:0051258 protein polymerization
IEA
GO_REF:0000120
ACCEPT
Summary: Gamma-chain interfaces contribute to fibrin polymer assembly.
Reason: Actual ARBA/InterPro mappings agree with human gamma-derived peptide binding/inhibition and the recombinant gamma a-pocket structure. Gamma provides a recognition surface for exposed alpha-chain knobs; thrombin exposes the knobs and factor XIII catalyzes crosslinks.
Supporting Evidence:
GO_REF:0000120
file:human/FGG/FGG-source-provenance.yaml
GO:0051258 protein polymerization
IMP
PMID:12706644
Fibrinogen Magdeburg I: a novel variant of human fibrinogen ...
ACCEPT
Summary: Gamma-chain contacts contribute directly to fibrin polymerization.
Reason: Human gamma-fragment binding and inhibition experiments in PMID:6451630 and the gamma a-pocket structure in PMID:9207064 establish this gene-level polymerization role independently. Retain the existing IMP annotation with curator deference. The PMID:12706644 abstract concerns FGA Leu9Pro, delayed fibrinopeptide release and nearly normal fibrin-monomer aggregation; its full relevant assays remain unavailable. This decision neither reconstructs those experiments nor attributes the alpha-chain variant mechanism to gamma.
GO:0051592 response to calcium ion
IDA
PMID:6777381
Ca2+-mediated association of glycoprotein G (thrombinsensiti...
KEEP AS NON CORE
Summary: Calcium affects fibrin association with activated platelet surfaces.
Reason: Actual human platelet Results separate calcium-dependent extracellular retention from soluble released material and identify fibrin chains. This supports a complex-level response, not gamma as a calcium sensor or intracellular signaling enzyme. Rule provenance is documented separately.
Supporting Evidence:
file:human/FGG/FGG-source-provenance.yaml
GO:0051592 response to calcium ion
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Calcium affects fibrin association with activated platelet surfaces.
Reason: Actual human platelet Results separate calcium-dependent extracellular retention from soluble released material and identify fibrin chains. This supports a complex-level response, not gamma as a calcium sensor or intracellular signaling enzyme. Rule provenance is documented separately.
Supporting Evidence:
GO_REF:0000117
file:human/FGG/FGG-source-provenance.yaml
GO:0065003 protein-containing complex assembly
IDA
PMID:8910396
The role of betagamma and alphagamma complexes in the assemb...
ACCEPT
Summary: Gamma-containing intermediates contribute structural interfaces to complex assembly.
Reason: Actual human-chain fusion experiments follow alpha-gamma/beta-gamma intermediates into full fibrinogen. This is structural participation rather than inference solely from a secretion defect or an assignment of catalytic assembly activity.
Supporting Evidence:
GO:0070062 extracellular exosome
HDA
PMID:19056867
Large-scale proteomics and phosphoproteomics of urinary exos...
KEEP AS NON CORE
Summary: FGG is detected in a urinary low-density membrane fraction.
Reason: Original Main Table 1 identifies FGG with one unique peptide and one spectrum. The fraction consists chiefly of exosomes, supporting the association-level annotation. It does not resolve vesicle topology, exclude co-isolated protein or prove a gamma-A-specific peptide from the database protein name.
Supporting Evidence:
file:human/FGG/FGG-source-provenance.yaml
GO:0070062 extracellular exosome
HDA
PMID:23533145
In-depth proteomic analyses of exosomes isolated from expres...
KEEP AS NON CORE
Summary: FGG has supported association with extracellular-exosome preparations.
Reason: Independent original Main Table 1 in PMID:19056867 identifies FGG in a human urinary low-density membrane fraction consisting chiefly of exosomes, with one unique peptide and one spectrum. Retain the existing generic vesicle-association claim with curator deference. The FGG supplementary row in PMID:23533145 remains unrecovered, so its prostatic-secretion sample assignment is not independently verified. Neither source establishes intravesicular topology, exclusion of co-isolated protein or a splice-specific peptide.
Supporting Evidence:
file:human/FGG/FGG-source-provenance.yaml
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: Gamma-region recognition supports contextual endothelial signaling and survival.
Reason: Actual PMID10903502 uses fibrinogen substrates, gamma117–133 peptide and ICAM-1 controls in TNF-alpha-exposed endothelial cells. ERK activation and reduced apoptosis support the tested downstream effects, not universal death-pathway inhibition or gamma kinase activity. Electronic mappings are not independent replicate experiments.
Supporting Evidence:
file:human/FGG/FGG-source-provenance.yaml
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 triggers endothelial secretory responses and ERK signaling in context.
Reason: Actual PMID19193866 uses human fibrinogen on rat heart microvascular endothelial cells, measuring conditioned-medium ET-1/vWF, WPB staining and ERK phosphorylation. ICAM-1/MEK perturbations support the response with partial-blockade/feedback limits. Gamma participates in the ligand complex and has an independently mapped receptor-recognition region; it is not secretory machinery or the peptide hormone.
Supporting Evidence:
file:human/FGG/FGG-source-provenance.yaml
GO:0070527 platelet aggregation
IBA
GO_REF:0000033
ACCEPT
Summary: Platelet aggregation has positive ancestry and human gamma-chain support.
Reason: The positive PTN002709696 IBD lies on the exact target path; self-WITH is expected target grounding. The ARBA match and human gamma preparation support bridging. The isolated chains form multimers; this is not a soluble-monomer or natural-splice comparison.
Supporting Evidence:
GO_REF:0000033
file:human/FGG/FGG-source-provenance.yaml
GO:0070527 platelet aggregation
IDA
PMID:6281794
gamma and alpha chains of human fibrinogen possess sites rea...
ACCEPT
Summary: Human gamma-chain preparations support platelet aggregation.
Reason: Actual Methods, Results, Tables 1–2 and Figure 1 distinguish ADP-stimulated platelets, gamma multimers and intact fibrinogen, with antibody inhibition. Gamma is strongly active in this preparation, alpha weaker and beta inactive. Multivalency/preparation limits preclude a monomer-agonist claim or equal activity of the two natural splice products.
Supporting Evidence:
GO:0070527 platelet aggregation
IEA
GO_REF:0000117
ACCEPT
Summary: Platelet aggregation has positive ancestry and human gamma-chain support.
Reason: The positive PTN002709696 IBD lies on the exact target path; self-WITH is expected target grounding. The ARBA match and human gamma preparation support bridging. The isolated chains form multimers; this is not a soluble-monomer or natural-splice comparison.
Supporting Evidence:
GO_REF:0000117
file:human/FGG/FGG-source-provenance.yaml
GO:0072378 blood coagulation, fibrin clot formation
IBA
GO_REF:0000033
ACCEPT
Summary: Gamma structural contacts contribute to fibrin clot formation.
Reason: The positive target-path IBD and actual ARBA match agree with human gamma-fragment binding and a-pocket structure. This is structural participation, not a process assignment solely because gamma is a substrate for another enzyme.
Supporting Evidence:
GO_REF:0000033
file:human/FGG/FGG-source-provenance.yaml
GO:0072378 blood coagulation, fibrin clot formation
IDA
PMID:16846481
The fibrinogen Aalpha R16C mutation results in fibrinolytic ...
ACCEPT
Summary: Gamma contributes to the fibrin structure formed by the tested complex.
Reason: The source abstract reports clot formation with purified alpha-variant fibrinogen. Independently read gamma-binding/structure experiments establish the same generic clot-formation role. Source-specific activation/lysis claims remain unresolved; the alpha variant is not relabeled a gamma mutation.
GO:0072378 blood coagulation, fibrin clot formation
IEA
GO_REF:0000117
ACCEPT
Summary: Gamma structural contacts contribute to fibrin clot formation.
Reason: The positive target-path IBD and actual ARBA match agree with human gamma-fragment binding and a-pocket structure. This is structural participation, not a process assignment solely because gamma is a substrate for another enzyme.
Supporting Evidence:
GO_REF:0000117
file:human/FGG/FGG-source-provenance.yaml
GO:0072378 blood coagulation, fibrin clot formation
IMP
PMID:11001902
Afibrinogenemia: first identification of a splicing mutation...
ACCEPT
Summary: Gamma-chain structural contacts contribute to fibrin clot formation.
Reason: Independent human gamma-fragment and a-pocket evidence establishes direct structural participation in fibrin formation. The original PMID:11001902 clinical/minigene Results support aberrant RNA and a predicted severe truncation with loss of circulating fibrinogen; the predicted protein was not directly demonstrated. Retain that disease-context evidence without treating necessity alone as the structural mechanism. The pathological/engineered truncation is not a natural splice product.
GO:0072562 blood microparticle
HDA
PMID:22516433
Proteomic analysis of microvesicles from plasma of healthy d...
UNDECIDED
Summary: The source-specific vesicle-associated target join remains unresolved.
Reason: The survey/sample context is accessible but its exact FGG peptide/protein table was not recovered. Positive detection in another publication does not verify this specimen-specific assertion; absence or misattribution is not inferred.
Supporting Evidence:
GO:0090277 positive regulation of peptide hormone secretion
IDA
PMID:19193866
Fibrinogen-induced endothelin-1 production from endothelial ...
KEEP AS NON CORE
Summary: Fibrinogen triggers endothelial secretory responses and ERK signaling in context.
Reason: Actual PMID19193866 uses human fibrinogen on rat heart microvascular endothelial cells, measuring conditioned-medium ET-1/vWF, WPB staining and ERK phosphorylation. ICAM-1/MEK perturbations support the response with partial-blockade/feedback limits. Gamma participates in the ligand complex and has an independently mapped receptor-recognition region; it is not secretory machinery or the peptide hormone.
Supporting Evidence:
file:human/FGG/FGG-source-provenance.yaml
GO:0090277 positive regulation of peptide hormone secretion
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Fibrinogen triggers endothelial secretory responses and ERK signaling in context.
Reason: Actual PMID19193866 uses human fibrinogen on rat heart microvascular endothelial cells, measuring conditioned-medium ET-1/vWF, WPB staining and ERK phosphorylation. ICAM-1/MEK perturbations support the response with partial-blockade/feedback limits. Gamma participates in the ligand complex and has an independently mapped receptor-recognition region; it is not secretory machinery or the peptide hormone.
Supporting Evidence:
GO_REF:0000117
file:human/FGG/FGG-source-provenance.yaml
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 MatrisomeDB interstitial-matrix assignment remains unresolved.
Reason: The database paper describes ECM integration, but the FGG-specific record for this finer subcompartment was not recovered. Human proteomics supports broad ECM association, not every tissue subcompartment. Preserve this TAS context pending its target record.
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 gamma role in trophoblast spreading remains unresolved.
Reason: The abstract reports primary human trophoblast responses to fibrin matrices and factor-XIII conditions. Full relevant results were unavailable and the abstract does not isolate gamma participation in the spreading response. General structure or other-cell adhesion assays do not settle this NAS context.
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: Gamma-region recognition supports contextual endothelial signaling and survival.
Reason: Actual PMID10903502 uses fibrinogen substrates, gamma117–133 peptide and ICAM-1 controls in TNF-alpha-exposed endothelial cells. ERK activation and reduced apoptosis support the tested downstream effects, not universal death-pathway inhibition or gamma kinase activity. Electronic mappings are not independent replicate experiments.
Supporting Evidence:
file:human/FGG/FGG-source-provenance.yaml
GO:1902042 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Gamma-region recognition supports contextual endothelial signaling and survival.
Reason: Actual PMID10903502 uses fibrinogen substrates, gamma117–133 peptide and ICAM-1 controls in TNF-alpha-exposed endothelial cells. ERK activation and reduced apoptosis support the tested downstream effects, not universal death-pathway inhibition or gamma kinase activity. Electronic mappings are not independent replicate experiments.
Supporting Evidence:
GO_REF:0000117
file:human/FGG/FGG-source-provenance.yaml
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: Gamma-region recognition supports contextual endothelial signaling and survival.
Reason: Actual PMID10903502 uses fibrinogen substrates, gamma117–133 peptide and ICAM-1 controls in TNF-alpha-exposed endothelial cells. ERK activation and reduced apoptosis support the tested downstream effects, not universal death-pathway inhibition or gamma kinase activity. Electronic mappings are not independent replicate experiments.
Supporting Evidence:
file:human/FGG/FGG-source-provenance.yaml
GO:2000352 negative regulation of endothelial cell apoptotic process
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Gamma-region recognition supports contextual endothelial signaling and survival.
Reason: Actual PMID10903502 uses fibrinogen substrates, gamma117–133 peptide and ICAM-1 controls in TNF-alpha-exposed endothelial cells. ERK activation and reduced apoptosis support the tested downstream effects, not universal death-pathway inhibition or gamma kinase activity. Electronic mappings are not independent replicate experiments.
Supporting Evidence:
GO_REF:0000117
file:human/FGG/FGG-source-provenance.yaml

Core Functions

Gamma interfaces assemble with alpha and beta chains into fibrinogen and provide the a-pocket recognizing exposed alpha-chain knobs during fibrin polymer formation. Gamma receptor contacts also support bridging of activated platelets. The isolated platelet-active preparation was multimeric; shared structural participation does not imply identical C-terminal ligand recognition by gamma-A and gamma-B. Proteolytic activation and covalent crosslinking are performed by other enzymes.

Supporting Evidence:

References

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Suggested Questions for Experts

Q: Which gamma-chain contacts, if any, directly contribute to the fibrin template for tPA-mediated plasminogen activation, independently of effects on fibrin assembly and lysis susceptibility?

πŸ“š Additional Documentation

Notes

(FGG-notes.md)

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Source Evidence

(FGG-source-evidence.md)

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πŸ“„ View Raw YAML

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