CFAP47

Summary: Proteome-scale affinity purification-mass spectrometry (BioPlex 2.0) detected an association between CFAP47 and ubiquitin (UBB).

Reason: Generic protein binding is uninformative about CFAP47 function and no more specific molecular function follows from this evidence. Removal does not mean the reported interaction is false. Ubiquitin (UBB) co-purification in a proteome-scale AP-MS screen most likely reflects ubiquitinated bait or a contaminant rather than a defined CFAP47 activity.

Summary: A targeted interaction assay in the X-linked MMAF study (UniProt: interaction with CFAP65) detected an association between CFAP47 and CFAP65.

Reason: Unlike the two BioPlex rows, which come from proteome-scale AP-MS screens, this row reports a targeted CFAP47-CFAP65 interaction assay in the X-linked MMAF study. That study (PMID:33472045) is cached abstract-only here and the abstract does not describe the interaction, so the row's own source cannot be quoted; the quote below is from an independent study (PMID:37424856) that corroborates a physical CFAP47-CFAP65 interaction by co-immunoprecipitation. Removal does not mean the interaction is false: it fits the shared central-apparatus context (CFAP65 is a C2a component). The action is REMOVE because generic protein binding names no activity, and the specific molecular functions that CFAP47 does perform (structural constituent of cytoskeleton, microtubule binding) are proposed as NEW rows in this review from the in situ structure (PMID:40473901) rather than inferred from this binding pair.

Summary: Proteome-scale affinity purification-mass spectrometry (BioPlex 3.0) detected an association between CFAP47 and ubiquitin (UBB).

Reason: Generic protein binding is uninformative about CFAP47 function and no more specific molecular function follows from this evidence. Removal does not mean the reported interaction is false. Ubiquitin (UBB) co-purification in a proteome-scale AP-MS screen most likely reflects ubiquitinated bait or a contaminant rather than a defined CFAP47 activity.

Summary: Phylogenetic inference that CFAP47 family members localise to cilia, from a node (PTN002347368) that includes the Trypanosoma brucei ortholog.

Reason: True but uninformative. CFAP47 is a central-apparatus bridge protein of the motile axoneme (PMID:40473901), and this review proposes axonemal central apparatus (GO:1990716) as NEW, which entails cilium via axoneme. The deep node is consistent with the conserved central-apparatus role; no objection to the propagation itself.

Summary: CFAP47 is the core structural component of the bridge that tethers the C1 and C2 microtubules of the sperm central apparatus. Hemizygous CFAP47 variants cause MMAF in men, and Cfap47-deficient mouse sperm have a hollow central-apparatus bridge, reduced motility and abnormal flagellar morphology.

Reason: Core process. CFAP47 does part of the work of sperm axoneme assembly by contributing the structural bridge of the central apparatus (PMID:40473901), and loss-of-function in men and mice disrupts flagellar formation (PMID:33472045, PMID:40473901). For the IBA row, the PANTHER node (PTN001496298) covers the vertebrate CFAP47 orthologs, human CFAP47 sits inside it, and there is no evidence of loss; the target appearing in its own WITH/FROM reflects its own experimental annotation feeding the node placement.

Summary: Hemizygous deleterious CFAP47 variants and a whole-gene deletion cause MMAF in men, and Cfap47-mutated male mice are sterile with abnormal flagellar morphology. CFAP47 is the core structural component of the bridge that tethers the C1 and C2 microtubules of the sperm central apparatus. Hemizygous CFAP47 variants cause MMAF in men, and Cfap47-deficient mouse sperm have a hollow central-apparatus bridge, reduced motility and abnormal flagellar morphology.

Reason: Core process. CFAP47 does part of the work of sperm axoneme assembly by contributing the structural bridge of the central apparatus (PMID:40473901), and loss-of-function in men and mice disrupts flagellar formation (PMID:33472045, PMID:40473901). For the IBA row, the PANTHER node (PTN001496298) covers the vertebrate CFAP47 orthologs, human CFAP47 sits inside it, and there is no evidence of loss; the target appearing in its own WITH/FROM reflects its own experimental annotation feeding the node placement.

Summary: Phylogenetic inference of a role in cilium assembly.

Reason: True but uninformative: sperm axoneme assembly (GO:0007288), accepted in this review by IBA and IMP, is a descendant of cilium assembly. Outside sperm, CFAP47 variants in two PCD patients were associated with short, sparse respiratory cilia with an intact 9+2 structure (PMID:37723893), which does not establish a distinct general role in cilium assembly.

Summary: Immunofluorescence of control human sperm shows a CFAP47 signal at the head-tail junction; an independent study reports the same neck localisation.

Reason: Two independent immunofluorescence studies place a CFAP47 signal at the head-flagellum junction (PMID:33472045, abstract only, as curated; PMID:37723893). The structural data, however, place CFAP47 along the central apparatus of the axoneme (PMID:40473901), so the neck signal is likely a pool or an antibody-accessibility effect rather than the site of CFAP47's main function. Kept as a real but non-core observation.

Summary: In situ cryo-ET of mouse sperm resolves full-length CFAP47 as the core of the bridge connecting the C1 and C2 microtubules of the central apparatus.

Reason: Location of CFAP47's core function, not present in GOA. Mouse structural data (PMID:40473901) with conservation to human (human MMAF variants map onto the same structure), so the evidence is ISS from the mouse ortholog Cfap47 (MGI:MGI:3781475, the same donor GOA uses in the WITH/FROM of the CFAP47 IBA rows). part_of is used because CFAP47 is a structural subunit of the central apparatus, not merely located in it. Comparator check (QuickGO annotation search, exact term, run 2026-10-16): its bridge partner HYDIN, and SPAG16, SPAG17, CFAP65 and MYCBPAP each carry GO:1990716 in human GOA (IBA, ISS and/or IEA), so this is the convention for central-apparatus components.

Summary: In the in situ mouse sperm central-apparatus structure, CFAP47 is the core structural component of the bridge: its N-terminal domains bind C1, its central CFAP47-ring binds HYDIN, and its C-terminal region anchors to C2, so the CFAP47 chain tethers the two central microtubules. Cfap47-knockout sperm have a hollow bridge and weakened C1-C2 connections.

Reason: CFAP47 contributes the structural integrity of a cytoskeletal structure, which is what GO:0005200 describes: the resolved full-length model shows the CFAP47 molecule itself spanning and linking C1 and C2, and loss of CFAP47 removes the bridge density (including the SPAG6 proteins that depend on it) and weakens the C1-C2 linkage (PMID:40473901). This is the same call this repository made for CFAP43 (genes/human/CFAP43, NEW GO:0005200 enables, from a native axoneme structure), and CFAP47 has, if anything, the more detailed evidence: a domain-by-domain contact map. The structure is from mouse sperm, so the evidence code is ISS from mouse Cfap47 (MGI:MGI:3781475) rather than IDA; the human relevance is supported by human truncating variants that map onto the same structure and cause asthenozoospermia/MMAF. Comparator check (QuickGO, run 2026-10-16): no human central-apparatus protein (HYDIN, SPAG6, SPAG16, SPAG17, CFAP65, MYCBPAP, SPEF2, CFAP46, CFAP54, CFAP74) carries any MF other than protein binding or unrelated HDA/IBA terms, so GOA has no convention either way for central-apparatus scaffolds; the absence reflects missing structural curation, not a deliberate choice, and the CFAP43 precedent is followed. Enables, not contributes_to: the structural contribution is made by the CFAP47 molecule itself.

Summary: The mouse sperm in situ structure resolves direct CFAP47 contacts with both central microtubules: ASH1 and ASH4 bind protofilaments 13 and 1 of C1, and ASH20 binds protofilament 12 of C2.

Reason: Direct, domain-resolved binding of CFAP47 to the C1 and C2 microtubule lattices (PMID:40473901), which is the specific activity behind the structural tether role. Evidence code ISS from mouse Cfap47 (MGI:MGI:3781475), as for the other rows derived from this mouse structure. Comparator check (QuickGO exact GO:0008017, human, run 2026-10-16): other axonemal microtubule-associated proteins carry this term, including the central-pair protein SPEF1 (IBA, ISS), CFAP144 (IDA), CFAP100 (IMP), CFAP157 and SAXO1/SAXO2/SAXO6, so microtubule binding is the established MF for proteins that contact axonemal microtubules.