Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Combined Automated Annotation using Multiple IEA Methods
Identification and characterization of a set of conserved and new regulators of cytoskeletal organization, cell morphology and migration.
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CFAP410 depletion alters cortical actin organization in PC3 cells; the available text does not establish CFAP410 plasma-membrane localization.
"C21orf2cortical actin 55%NPNPNPNP"
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The GFP localization assay identifies a restricted set of proteins that does not include CFAP410.
"To investigate how overexpression of selected PMMs affected cell morphology and cytoskeletal organisation and to determine their localization, cDNAs for ARC, FAM40A, FAM40B, FMNL3 and ZRANB1 were cloned downstream of GFP and transfected into PC3 cells (Figure 8A)."
A proteome-scale map of the human interactome network.
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Systematic interactome mapping is the source of the generic CFAP410 protein-binding annotation; no specific CFAP410 activity is established.
"By systematically screening half of the interactome space with minimal
inspection bias, we more than doubled the number of high-quality binary PPIs
available from the literature."
An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes.
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CFAP410 localizes to basal bodies and associates with NEK1; disease variants impair this association.
"C21orf2 localises to the basal body in mIMCD3 and hTERT-RPE1 cells and to the base of the connecting cilium in mouse photoreceptors"
The NEK1 interactor, C21ORF2, is required for efficient DNA damage repair.
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CFAP410 depletion impairs homologous recombination, while the protein remains cytoplasmic.
"Knockdown of both C21ORF2 and NEK1 resulted in defective HR repair, as shown by significantly decreased percentages of GFP-positive (HR-repaired) cells"
C21orf2 is mutated in recessive early-onset retinal dystrophy with macular staphyloma and encodes a protein that localises to the photoreceptor primary cilium.
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Retinal immunohistochemistry identifies CFAP410 in photoreceptor ciliary structures.
"Immunohistochemical studies in human, pig and mouse retinas localised C21orf2
protein to the ciliary structures of the photoreceptor cell (the daughter basal
body, the centriole adjacent to the basal body, and the connecting cilium)."
Identification of Novel Mutations in the LRR-Cap Domain of C21orf2 in Japanese Patients With Retinitis Pigmentosa and Cone-Rod Dystrophy.
Immunochemical characterization of a novel mitochondrially located protein encoded by a nuclear gene within the DFNB8/10 critical region on 21q22.3.
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Antibody staining and a mitochondrial dye supported an early mitochondrial localization.
"Immunofluorescence studies and co-staining with a
mitochondrial-specific dye suggest the subcellular localization of the protein
to mitochondria."
Functional characterization of C21ORF2 association with the NEK1 kinase mutated in human in diseases.
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Human CFAP410 knockout causes a primary-ciliogenesis defect.
"Here, we show that ARPE-19 cells lacking C21ORF2, like cells lacking NEK1, also show major defects in ciliogenesis."
C21ORF2 mutations point towards primary cilia dysfunction in amyotrophic lateral sclerosis.
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CFAP410 depletion perturbs ciliary IFT88 distribution; this does not by itself establish an IFT motor or cargo-adapter activity.
"In cells with reduced levels of C21ORF2, IFT88 accumulates primarily at the tip of the cilium and forms a ‘bulb’ phenotype"
The C-terminus of CFAP410 forms a tetrameric helical bundle that is essential for its localization to the basal body.
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CFAP410 CTDs, including human CFAP410, form tetrameric helical bundles; functional localization assays were performed in T. brucei.
"The crystal
structures reveal that the three proteins all adopt the same conformation as a
tetrameric helical bundle."
CFAP410 has a bimodular architecture with a conserved surface patch on its N-terminal leucine-rich repeat motif for binding interaction partners.
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The N-terminal interaction domain was structurally characterized in T. brucei; the human CFAP410–NEK1 interface in this study is a computational model.
"We carried out structural modelling using AlphaFold-multimer for the complex of HsCFAP410-NTD (aa1-150) and HsNEK1-CTD (aa1208-1286)."
ALS-associated C21ORF2 variant disrupts DNA damage repair, mitochondrial metabolism, neuronal excitability and NEK1 levels in human motor neurons.
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ALS-associated V58L affects mitochondrial respiratory reserve in human motor-neuron cultures; this phenotype does not identify a mitochondrial catalytic function of CFAP410.
"Analysis of mitochondrial activity using the Seahorse XF analysis system showed a decrease in maximum respiration and spare respiratory capacity in C21ORF2-V58L MNs as compared to control cultures"
Falcon literature research report for human CFAP410
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The research synthesis agrees with primary evidence for CFAP410-NEK1 association in ciliogenesis and homologous recombination; specific scaffold or kinase-activator functions remain unproven.
"The complex is required for efficient primary-cilium formation and homologous-recombination DNA repair."
Axial Spondylometaphyseal Dysplasia Is Caused by C21orf2 Mutations.
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Human CFAP410-EGFP expressed in mouse photoreceptors localizes to connecting cilia and is spatially separated from a mitochondrial marker.
"We stained mitochondria by Kusabira-Orange fused with mitochondria localizing signal and found that subcellular distribution of the C21orf2-EGFP fusion protein was complementary to that of mitochondria (Fig 6O–6Q)."
Focused Primary-Evidence Audit: Human CFAP410 (O43822) Subcellular Localization for GO Curation
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The targeted provider audit corroborates the absence of a CFAP410 localization assay in the Bai2011 paper/supplementary materials; this does not demonstrate that CFAP410 can never associate with the plasma membrane.
"No supplementary file reports any GFP or antibody localization of C21orf2/CFAP410 or any plasma-membrane assay of it."