ARMC2 is an armadillo-repeat protein required for normal sperm axoneme assembly and organization. Loss of ARMC2 disrupts sperm flagellar structure, with prominent central-pair defects, and biallelic human variants cause autosomal recessive spermatogenic failure 38 with severe asthenoteratozoospermia. The algal ortholog transports radial-spoke precursors as an intraflagellar-transport cargo adaptor; the corresponding mammalian binding mechanism remains unresolved. In mice, ARMC2 loss also alters tracheal and oviductal motile cilia: tracheal axonemal ultrastructure is disrupted, whereas oviductal ultrastructure is largely preserved despite altered ciliary length, beat frequency and transport.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:24407287 Promyelocytic leukemia protein interacts with the apoptosis-... | UNDECIDED | Summary: The specific ARMC2–PYCARD interaction remains unverified. Reason: The exact ARMC2–PYCARD experiment or supporting table in PMID:24407287 has not been recovered. Keep the original IPI assertion and named partner unresolved until that source-specific assay can be inspected; the available abstract and figure captions do not settle this pair. Supporting Evidence: file:human/ARMC2/ARMC2-notes.md The specific ARMC2–PYCARD experiment or supporting table has not been recovered. |
| GO:0007288 sperm axoneme assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Inherited sperm-axoneme assembly function agrees with human and mouse phenotypes. Reason: The PAINT assertion through PANTHER:PTN002724716 is consistent with the human genetic and mouse disruption evidence in PMID:30686508. ARMC2 supports assembly or stability of the sperm axoneme; precise cargo contacts are a separate mechanistic question. Target self-inclusion is legitimate descendant experimental grounding, not circularity. The full ancestral-node placement was not independently reconstructed. Supporting Evidence: PMID:30686508 Immunostaining experiments in AMRC2-mutated individuals and mutant mice evidenced the absence of the axonemal central pair complex (CPC) proteins SPAG6 and SPEF2, whereas the other tested axonemal and peri-axonemal components were present, suggesting that ARMC2 is involved in CPC assembly and/or stability. |
| GO:0007288 sperm axoneme assembly | IEA GO_REF:0000107 | ACCEPT | Summary: The mouse-ortholog transfer is consistent with established human sperm-axoneme defects. Reason: Ensembl Compara transfers the function from mouse Q3URY6/ENSMUSP00000093397. Human and mouse ARMC2 deficiency both produce severe sperm flagellar defects in PMID:30686508, supporting conservation of this process. This supports the existing process assertion without assigning the entire algal radial-spoke transport mechanism to human ARMC2. Supporting Evidence: PMID:30686508 Immunostaining experiments in AMRC2-mutated individuals and mutant mice evidenced the absence of the axonemal central pair complex (CPC) proteins SPAG6 and SPEF2, whereas the other tested axonemal and peri-axonemal components were present, suggesting that ARMC2 is involved in CPC assembly and/or stability. |
| GO:0007288 sperm axoneme assembly | IMP PMID:30686508 Bi-allelic Mutations in ARMC2 Lead to Severe Astheno-Teratoz... | ACCEPT | Summary: Human ARMC2 deficiency establishes an essential sperm-axoneme assembly role. Reason: PMID:30686508 links biallelic human variants to abnormal sperm flagella and reproduces the phenotype in mouse. The original human ultrastructure and marker results support central-pair assembly or stability, although detailed studies used one affected individual. The established assembly annotation is retained; marker loss does not locate ARMC2 itself within the central pair. Supporting Evidence: PMID:30686508 Immunostaining experiments in AMRC2-mutated individuals and mutant mice evidenced the absence of the axonemal central pair complex (CPC) proteins SPAG6 and SPEF2, whereas the other tested axonemal and peri-axonemal components were present, suggesting that ARMC2 is involved in CPC assembly and/or stability. |
| GO:0044782 cilium organization | IBA GO_REF:0000033 | ACCEPT | Summary: Broad cilium organization is consistent with the conserved axonemal role. Reason: The PAINT assertion through PANTHER:PTN001085472 agrees with sperm flagellar organization in PMID:30686508 and the broader mouse ciliary phenotype in PMID:42272638. Chlamydomonas experiments in PMID:34982025 identify a radial-spoke transport role, but the equivalent mammalian molecular interaction remains unresolved. No human multisystem disease or additional developmental process is inferred. Self-inclusion among PAINT descendants is not circular support. Supporting Evidence: PMID:42272638 We also found that tracheal cilia were significantly shorter in Armc2-KO mice. |
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Download this section (compressed HTML)Q: Does mammalian ARMC2 directly couple radial-spoke precursors to intraflagellar transport, and which cargo and train contacts distinguish this role from secondary central-pair destabilization?
Experiment: Tag endogenous ARMC2 and selected radial-spoke precursors in differentiating mammalian multiciliated cells; combine live cotransport measurements with interface perturbation, rescue and biochemical interaction tests. Distinguish direct transport effects from later central-pair loss.
Hypothesis: Mammalian ARMC2 supports radial-spoke cargo delivery during cilium assembly.
Type: Live imaging and interaction analysis
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