gas7a encodes a Takifugu rubripes ortholog of growth arrest-specific protein 7 (GAS7), a member of the PANTHER GAS7 subfamily (PTHR23065:SF57) of F-BAR (FCH-BAR) domain proteins. This 401-residue gene model is the longest of three alternative transcript products of the fugu gas7a gene. It consists of a poorly conserved N-terminal segment, a WW-FCH linker and a complete F-BAR domain (residues 121-381), with no SH3 domain and no canonical WW motif. F-BAR domains form dimers that bind acidic phospholipids on the cytoplasmic face of the plasma membrane; in mammalian GAS7 the F-BAR domain assembles into two-dimensional sheets on flat plasma membrane, for example at macrophage phagocytic cups. In mammals GAS7 is expressed mainly in neurons, where it promotes neurite outgrowth and membrane protrusion, partly by recruiting N-WASP and the Arp2/3 complex through its WW domain. The fugu protein has not been studied experimentally; its expected roles, as a cytoplasmic and plasma-membrane-associated F-BAR scaffold that contributes to neuron projection morphogenesis, are inferred from subfamily membership and conserved domain architecture.
Summary: Soluble pool of a peripheral-membrane F-BAR protein. Correct but not informative beyond the plasma membrane association.
Reason: The TreeGrafter row comes from the eukaryote-wide PAINT IBD node PTN002747256, seeded by many F-BAR family members, and fits the cytoplasmic localization recorded for human GAS7. F-BAR proteins are cytosolic and associate peripherally with membranes. No more specific soluble compartment is supported, so the term stays, but the functional site is the cytoplasmic face of the plasma membrane.
Propagation Review
Root cause:NO FAILURE NON CORE
Sources checked:
PANTHER:PTN002747256SUPPORTS TRANSFER
Eukaryote-level IBD for cytoplasm; the target sits inside this node via PTHR23065:SF57.
Supporting Evidence:
file:TAKRU/A0A674PKV4/A0A674PKV4-uniprot.txt
DR PANTHER; PTHR23065:SF57; GROWTH ARREST-SPECIFIC PROTEIN 7; 1.
Summary: Core location. The GAS7 F-BAR domain assembles on the plasma membrane, and the fugu model has a complete F-BAR domain.
Reason: Inherited from the eukaryote-wide PAINT node PTN002747256. In mouse GAS7, F-BAR sheets on the plasma membrane were shown directly, and mutating the F-BAR loops abolished membrane localization. A0A674PKV4 keeps the full F-BAR domain (PROSITE PS51741, residues 121-381) and the GAS7-specific F-BAR signature (IPR037957), so the membrane-binding module is conserved.
Summary: Inherited from a Bilateria PAINT node defined by the FCHO muniscins. No GAS7 ortholog has been shown to localize to clathrin-coated pits, and GAS7 lacks the FCHO modules that target clathrin foci.
Reason: All four clathrin-related TreeGrafter rows match the IBD set of PTN000552124 (taxon Bilateria), whose seeds are only FCHO1 (O14526), FCHO2 (Q0JRZ9, MGI:3505790) and C. elegans fcho-1. The PAINT curator separately placed GAS7-derived terms (neuron projection morphogenesis, seeded by mouse Gas7) on the chordate GAS7 node PTN001890901 and did not add clathrin terms there. FCHO targeting to clathrin foci depends partly on its C-terminal muHD, and its AP2 activation depends on a linker motif. GAS7, including this 401-residue fugu model, ends about 20 residues after the F-BAR domain and has neither element. Experimentally, GAS7 forms sheets on flat membranes, unlike the curvature-coupled assemblies at clathrin-coated pits. The term is therefore a likely over-propagation into a lineage that diverged from the node's defining function. It is not shown to be false, so this is not a REMOVE.
Propagation Review
Root cause:PROPAGATION BAD
Failure modes:FUNCTIONAL DIVERGENCE
Sources checked:
PANTHER:PTN000552124SUPPORTS SOURCE BUT NOT TARGET
Bilateria IBD seeded only by FCHO1/FCHO2/fcho-1. The GAS7 descendants lack the muHD and AP2-activating linker the seed function depends on.
Summary: Same FCHO-defined Bilateria node as the clathrin-coated pit row (seeded only by FCHO2 Q0JRZ9). Not supported for the GAS7 lineage.
Reason: PTN000552124 carries this term with FCHO2 as its only seed. GAS7 lacks the FCHO C-terminal muHD and AP2-binding linker, and no study places GAS7 on clathrin-coated vesicles. Marked as over-annotation, consistent with the other clathrin-related rows from the same node.
Propagation Review
Root cause:PROPAGATION BAD
Failure modes:FUNCTIONAL DIVERGENCE
Sources checked:
PANTHER:PTN000552124SUPPORTS SOURCE BUT NOT TARGET
FCHO2-seeded clathrin-coated vesicle IBD; not applicable to the GAS7 subfamily.
Summary: Clathrin coat assembly is the defining FCHO activity, carried out through AP2 activation by the FCHO linker and Eps15/intersectin recruitment by the muHD. GAS7 has neither module.
Reason: Inherited from PTN000552124, seeded by human FCHO1 and FCHO2. FCHO proteins act in coat assembly as allosteric activators of AP2, using a linker motif that GAS7 does not have. Nothing shows GAS7 doing any of the work of clathrin coat assembly. By the participation test, the step is performed by the FCHO/AP2 machinery, not by GAS7.
Propagation Review
Root cause:PROPAGATION BAD
Failure modes:FUNCTIONAL DIVERGENCE
Sources checked:
PANTHER:PTN000552124SUPPORTS SOURCE BUT NOT TARGET
FCHO1/FCHO2-seeded coat-assembly IBD; the molecular basis (AP2-activating linker, muHD) is absent from GAS7.
Summary: The best-supported GAS7 process, placed by PAINT on the chordate GAS7 node and seeded by mouse Gas7 neurite-outgrowth experiments.
Reason: The row matches the IBD on PTN001890901 (Chordata), seeded by mouse Gas7 (MGI:1202388). The fugu protein is in the same PANTHER subfamily (PTHR23065:SF57) as mouse Gas7. In mouse, knockdown impaired Purkinje neurite outgrowth, overexpression promoted neurite-like outgrowth, and Gas7 contributes to membrane protrusions by recruiting N-WASP/Arp2/3. One caveat: this gene model lacks a canonical WW motif, so the WW-dependent N-WASP route cannot be assumed. The F-BAR membrane-scaffold contribution remains, and other fugu gas7a transcripts or the gas7b paralog may supply the WW-containing forms.
Propagation Review
Root cause:NO FAILURE CORE
Sources checked:
PANTHER:PTN001890901SUPPORTS TRANSFER
Chordate GAS7-lineage IBD seeded by mouse Gas7; the target is a descendant in the same subfamily.
MGI:MGI:1202388SUPPORTS TRANSFER
Mouse Gas7 neurite-outgrowth experiments ground the node.
Summary: Inherited from the FCHO-defined Bilateria node. The GAS7 experimental literature describes a role in phagocytosis and protrusion, not in clathrin-mediated endocytosis.
Reason: PTN000552124 carries this term with seeds FCHO1, FCHO2 and C. elegans fcho-1. No GAS7 seed contributes, and the PAINT curator did not add endocytic terms to the GAS7-specific node PTN001890901. The mouse GAS7 study contrasts phagocytosis with clathrin-mediated endocytosis and finds GAS7 sheets on flat membranes. Consistent with the other clathrin rows, this is likely over-propagation into a diverged lineage.
Propagation Review
Root cause:PROPAGATION BAD
Failure modes:FUNCTIONAL DIVERGENCE
Sources checked:
PANTHER:PTN000552124SUPPORTS SOURCE BUT NOT TARGET
FCHO-seeded clathrin-dependent endocytosis IBD; no GAS7 evidence and the FCHO-specific modules are absent.
Phagocytosis is a process that internalizes larger, micron-sized particles than those internalized by other endocytic pathways, such as clathrin-mediated endocytosis
any mu-homology domain (muHD) or AP-2-activating linker of the FCHO1/FCHO2 muniscins.
Core Functions
F-BAR domain-mediated association with the cytoplasmic face of the plasma membrane, acting as a membrane scaffold that contributes to neuron projection morphogenesis, as for the mammalian GAS7 orthologs in the same PANTHER subfamily
Q: PAINT node PTN000552124 propagates clathrin-coated pit, clathrin-coated vesicle, clathrin coat assembly and clathrin-dependent endocytosis from FCHO1/FCHO2 to the GAS7 subfamily, which lacks the muHD and AP2-activating linker. Should these IBDs be moved to an FCHO-only node?
Q: Do any fugu gas7a or gas7b transcripts encode the WW (and SH3) modules that mammalian GAS7b/c use to recruit N-WASP, or is this lineage F-BAR-only like mammalian GAS7d?
Suggested Experiments
Experiment: Express tagged fugu gas7a (A0A674PKV4) in cultured neurons or macrophages and test plasma membrane sheet assembly, colocalization with clathrin-coated pits, and effects on neurite outgrowth, compared with mouse GAS7b.
External Prediction Reviews
These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
Prediction method: ProtNLM2 Β· Version: UniProt 2024_06 pilot
Review rationale: Correct but not novel. The target carries the GAS7-specific F-BAR domain (residues 121-381) and sits in PANTHER subfamily PTHR23065:SF57, inside the PAINT node PTN002747256 whose IBD places cytoplasm across F-BAR proteins; F-BAR proteins are cytosolic and associate peripherally with membranes, as shown for GAS7 assembling on membranes during phagocytic-cup formation (PMID:31628328). The exact term GO:0005737 cytoplasm is already in GOA for this gene (TreeGrafter IEA), and the gene review keeps it as a correct, non-core localization; the functional site is the cytoplasmic face of the plasma membrane, which is also already annotated.
Supporting Evidence:
file:TAKRU/A0A674PKV4/A0A674PKV4-uniprot.txt: "ID A0A674PKV4_TAKRU Unreviewed; 401 AA. ... DR InterPro; IPR037957; GAS7_F-BAR. ... DR PANTHER; PTHR23065:SF57; GROWTH ARREST-SPECIFIC PROTEIN 7; 1. ... FT DOMAIN 121..381 ... FT /note="F-BAR""