NCU04637 encodes the Neurospora crassa ortholog of yeast Rvs167, an amphiphysin-like BAR adaptor with an N-terminal BAR domain, a central proline/alanine-rich disordered linker and a C-terminal SH3 domain. By analogy with Rvs167-subfamily proteins it forms a heterodimer with an Rvs161-type BAR protein (amph-1/NCU01069 in Neurospora), binds membranes at the neck of clathrin/actin-dependent endocytic invaginations at cortical actin patches, and promotes vesicle scission, with the SH3 domain recruiting partners such as the dynamin-like Vps1. In Neurospora, loss of rvs-167 reduces endocytic uptake of the antifungal peptide PAF26.
Summary: Cytoplasm is correct (the protein acts on the cytoplasmic face of the plasma membrane at endocytic sites) but is far less specific than the actin cortical patch localization this gene already carries.
Reason: InterPro2GO mapping from the generic BAR domain. Rvs167-subfamily (PTHR47174:SF1) proteins localize to cortical actin patches, the fungal endocytic sites; GO:0030479 actin cortical patch is a part_of descendant of cytoplasm (via cell cortex) and is already annotated to this gene by IBA, so the general term should be replaced by it.
Summary: Endocytosis is the core conserved process of Rvs167-subfamily amphiphysins; in Neurospora itself, deletion of rvs-167 reduces endocytic uptake of the peptide PAF26.
Reason: NCU04637 is the only N. crassa member of PANTHER PTHR47174:SF1, the Rvs167 subfamily that contains budding-yeast RVS167 and Candida RVS167, inside the PTN002932529 clade where PAINT placed endocytosis. In yeast, Rvs161/Rvs167 act at the scission step of endocytosis. Direct Neurospora evidence (abstract only) shows that an rvs-167 deletion mutant has reduced endocytic internalization of PAF26; because NCU04637 is the sole SF1 protein in the genome, that RVS-167 is presumably this gene. Fission-yeast Hob1 is also in SF1 and is dispensable for endocytosis, which is a lineage-specific loss rather than a reason to doubt the filamentous-fungal protein given the Neurospora data.
Supporting Evidence:
file:NEUCR/NCU04637/NCU04637-uniprot.txt
DR PANTHER; PTHR47174:SF1; REDUCED VIABILITY UPON STARVATION PROTEIN 167; 1.
Summary: Same claim as the IBA endocytosis row, from the InterPro BIN3/RVS161-like (IPR046982) mapping.
Reason: Consistent with the IBA row: Rvs167-subfamily placement, the yeast scission phenotype and the Neurospora rvs-167 deletion phenotype all support participation in endocytosis.
Supporting Evidence:
file:NEUCR/NCU04637/NCU04637-uniprot.txt
DR PANTHER; PTHR47174:SF1; REDUCED VIABILITY UPON STARVATION PROTEIN 167; 1.
Summary: The yeast Rvs161-Rvs167 heterodimer binds liposomes; the contributes_to qualifier correctly reflects that the activity is a property of the heterodimeric BAR module.
Reason: Lipid (membrane) binding by the BAR-domain heterodimer is the biochemical basis of Rvs function, demonstrated for purified yeast Rvs161-Rvs167. NCU04637 retains the BAR domain (residues 17-269, CDD BAR_Rvs167p) and has a Rvs161-like partner in the genome (amph-1/NCU01069, PTHR47174:SF3). No specific lipid species is established, so the general term is as precise as the evidence allows.
Supporting Evidence:
file:NEUCR/NCU04637/NCU04637-uniprot.txt
DR PANTHER; PTHR47174:SF1; REDUCED VIABILITY UPON STARVATION PROTEIN 167; 1.
Rvs161 consists solely of a BAR domain, whereas Rvs167 is composed of a BAR domain followed by a region rich in glycine, proline, and alanine (GPA), and an SH3 (Src-homology 3) domain at its C-terminus
Summary: Actin cytoskeleton is correct but general; the more specific actin cortical patch is supported and already annotated.
Reason: GO:0030479 actin cortical patch is an is_a descendant of actin cytoskeleton (via cortical actin cytoskeleton). Rvs167-family proteins localize specifically to cortical actin patches, and the gene already carries that term by IBA, so this broader node-level inference is refined to it.
Propagation Review
Root cause:NO FAILURE NON CORE
Failure modes:GRANULARITY MISMATCH
Sources checked:
PANTHER:PTN005335241SUPPORTS TRANSFER
Deep node spanning fungal Rvs proteins and metazoan Bin3; actin cytoskeleton is correct at that depth, and the fungal-specific refinement is actin cortical patch.
Summary: Rvs161 and Rvs167 localize to cortical actin patches, the endocytic sites of fungal cells.
Reason: The localization is experimentally established for yeast Rvs167 (SF1) and is the site where its endocytic scission function is executed. NCU04637 sits in the same subfamily with intact BAR and SH3 domains, and Neurospora hyphae have subapical endocytic actin patches, so the transfer is sound.
Supporting Evidence:
file:NEUCR/NCU04637/NCU04637-uniprot.txt
DR PANTHER; PTHR47174:SF1; REDUCED VIABILITY UPON STARVATION PROTEIN 167; 1.
Summary: Same localization claim as the IBA actin cortical patch row (here from an ARBA rule).
Reason: Consistent with the IBA row; the localization is supported by the Rvs167 subfamily placement and yeast localization data, not by the ARBA rule itself.
Supporting Evidence:
file:NEUCR/NCU04637/NCU04637-uniprot.txt
DR PANTHER; PTHR47174:SF1; REDUCED VIABILITY UPON STARVATION PROTEIN 167; 1.
Summary: Medial cortex is a fission-yeast structure (a cortical band over the nucleus that positions the contractile ring); the donors are S. pombe hob1 and hob3.
Reason: GO defines medial cortex as a medial cortical band overlaying the nucleus that acts as a landmark for contractile ring positioning, a feature of medially dividing uninucleate cells. The PTN002932538 node was seeded only by S. pombe Hob1 and Hob3. Neurospora hyphae are multinucleate and septate, without a nucleus-positioned medial cortical band, so this localization does not have a counterpart that can be transferred. Conserved patch localization is captured by GO:0030479.
Propagation Review
Root cause:TERM SCOPING PROBLEM
Failure modes:LINEAGE OR TAXON MISMATCH
Sources checked:
PANTHER:PTN002932538SUPPORTS SOURCE BUT NOT TARGET
Seeded by S. pombe Hob1 (SF1) and Hob3 (SF3) medial-cortex localization; the term describes fission-yeast cell geometry with no equivalent in multinucleate Neurospora hyphae.
Supporting Evidence:
file:NEUCR/NCU04637/NCU04637-uniprot.txt
DR PANTHER; PTHR47174:SF1; REDUCED VIABILITY UPON STARVATION PROTEIN 167; 1.
Summary: Mating projection tip is defined for pheromone-induced projections of unicellular fungi (S. cerevisiae shmoos); Neurospora is a filamentous fungus.
Reason: GO defines mating projection tip as the apex of the mating projection in unicellular fungi exposed to mating pheromone. The node was seeded by budding-yeast Rvs167 alone. Neurospora mates through trichogynes and conidial fusion rather than shmoos; whether NCU04637 concentrates at trichogyne or hyphal tips is unknown, and the term as defined does not apply to this organism.
Propagation Review
Root cause:TERM SCOPING PROBLEM
Failure modes:LINEAGE OR TAXON MISMATCH
Sources checked:
PANTHER:PTN002932538SUPPORTS SOURCE BUT NOT TARGET
Seeded by S. cerevisiae RVS167 shmoo-tip localization; the term is restricted to unicellular fungi by definition.
Supporting Evidence:
file:NEUCR/NCU04637/NCU04637-uniprot.txt
DR PANTHER; PTHR47174:SF1; REDUCED VIABILITY UPON STARVATION PROTEIN 167; 1.
Summary: Rvs mutants mislocalize actin patches, but this is a downstream consequence of losing a patch component rather than participation in moving or anchoring patches.
Reason: The evidence for this term is phenotypic: Candida rvs167 deletion mutants fail to polarize actin patches. Rvs167 is itself a patch component acting at the scission step of endocytosis; patch depolarization in its absence is most simply explained as a secondary effect of defective endocytosis and patch turnover, not as Rvs167 performing patch transport or anchoring. Following the necessity-is-not-participation rule, this InterPro2GO process is treated as an over-annotation; the conserved roles are captured by endocytosis and actin cortical patch.
The rvs161Delta mutant was more defective in endocytosis and morphogenesis than rvs167Delta, but both were strongly defective in polarizing actin patches.
Summary: Purified Rvs161-Rvs167 tubulates liposomes, and in vivo the Rvs heterodimer coats the tubular neck of the endocytic invagination.
Reason: Tubulation is demonstrated in vitro for the yeast heterodimer and fits its in vivo position on the invagination neck, but the in vivo role emphasised by live-cell data is stabilisation of the invagination and promotion of scission rather than generation of plasma membrane tubules per se. The term is retained as a mechanistic facet of the endocytic function, not as a separate core process.
Supporting Evidence:
file:NEUCR/NCU04637/NCU04637-uniprot.txt
DR PANTHER; PTHR47174:SF1; REDUCED VIABILITY UPON STARVATION PROTEIN 167; 1.
Summary: Rvs167-subfamily proteins form an obligate BAR heterodimer with Rvs161-type proteins; N. crassa encodes both partners.
Reason: The Rvs161-Rvs167 heterodimer is biochemically established in yeast (purified complex binds liposomes and disassembles Vps1 oligomers). NCU04637 is the N. crassa SF1 (Rvs167) member and amph-1/NCU01069 is the SF3 (Rvs161/BIN3) member, and deletion of either rvs-161 or rvs-167 in Neurospora produces the same endocytic uptake defect, consistent with conservation of the heterodimer. The complex term is named for yeast but its definition is generic.
Supporting Evidence:
file:NEUCR/NCU04637/NCU04637-uniprot.txt
DR PANTHER; PTHR47174:SF1; REDUCED VIABILITY UPON STARVATION PROTEIN 167; 1.
Q: Does NCU04637 localize to the subapical endocytic collar of actin patches in growing Neurospora hyphae, and does its recruitment depend on amph-1 (NCU01069)?
Q: Is the Vps1-binding function of the Rvs167 SH3 domain conserved for the Neurospora dynamin-like Vps1 ortholog?
Suggested Experiments
Experiment: Image an endogenously tagged NCU04637-GFP alongside an actin patch marker (e.g. fimbrin or Abp1) and an endocytic coat marker in wild type and amph-1 deletion hyphae, measuring patch lifetime and inward movement to test for a scission defect.
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.
The single emitted GO prediction, cytoplasm, is correct for this Rvs167-subfamily BAR adaptor and already annotated to the gene (CNN), which also carries the more specific actin cortical patch.
Review rationale: Cytoplasm is correct and already annotated to the gene, which also carries the more specific actin cortical patch localization. PANTHER places the target in the Rvs167 subfamily (PTHR47174:SF1), and its BAR-plus-SH3 architecture matches the characterized yeast endocytic adaptor Rvs167, which localizes to cortical actin patches at endocytic sites on the cytoplasmic face of the plasma membrane. The gene already carries cytoplasm (InterPro2GO IEA) and the more specific actin cortical patch (IBA, accepted in the gene review), which is a part_of descendant of cytoplasm via cell cortex; the gene review refines the cytoplasm row to that term. The ProtNLM2 string match points to medial cortex, a fission-yeast-specific term the gene review marks over-annotated, but the emitted cytoplasm term does not depend on it.
PMID:20610658: "In growing yeast cells, Rvs161 and Rvs167 localize to cortical actin patches, which are sites of endocytosis"
PMID:20610658: "Rvs161 consists solely of a BAR domain, whereas Rvs167 is composed of a BAR domain followed by a region rich in glycine, proline, and alanine (GPA), and an SH3 (Src-homology 3) domain at its C-terminus"