Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Quantitative Proteomic Analysis of Human Airway Cilia Identifies Previously Uncharacterized Proteins of High Abundance.
-
CFAP61 was identified in human airway ciliary axonemes by quantitative LC/MS proteomics.
"...Quantitative Proteomic Analysis of Human Airway Cilia Identifies Previously Uncharacterized Proteins of High Abundance..."
CFAP61 is required for sperm flagellum formation and male fertility in human and mouse.
-
CFAP61 is a conserved CSC component. A splice variant causes MMAF in human. Cfap61 knockout mice are infertile with impaired radial spoke assembly during spermiogenesis and subsequent axoneme instability.
"...CFAP61 is a conserved component of the calmodulin- and radial spoke-associated complex (CSC) of cilia... the assembly of radial spoke components is impaired. As spermiogenesis progresses, the axoneme in Cfap61-/- cells becomes unstable and scatters, and the distribution of intraflagellar transport proteins is disrupted..."
-
CFAP61 interacts with the CSC, radial spoke stalk, and head proteins including CFAP91, RSPH3A, ROPN1, ROPN1L, RSPH9, DYNLT1, DYNC1I2, TUBB3, and IFT proteins.
"...CFAP61 interacts with the CSC, radial spoke stalk and head..."
-
This study reveals an organ-specific mechanism of axoneme stabilization. Cfap61 knockout mice show infertility but not other PCD symptoms.
"...We generated Cfap61 knockout mice that recapitulate the infertility phenotype of the human CFAP61 mutation, but without other symptoms usually observed in PCD..."
Biallelic Variants in CFAP61 Cause Multiple Morphological Abnormalities of the Flagella and Male Infertility.
-
Biallelic CFAP61 variants (frameshift p.I151Nfs*4 and nonsense p.R283*) cause MMAF with severely disorganized axonemes in three Pakistani families with 11 infertile males.
"...variants, c.451_452del (p.I151Nfs*4) in family 1 and c.847C > T (p.R283*) in family 2 and 3, were identified recessively co-segregating with the MMAF phenotype. Transmission electron microscopy analyses revealed severe disorganized axonemal ultrastructures, and missings of central pair, RSs, and inner dynein arms were also observed..."
-
Both CFAP61 and CFAP251 proteins are absent from patient sperm tails, indicating loss of the entire CSC complex.
"...CFAP61 and CFAP251 signals were absent from sperm tails of the patients, which suggested the loss of functional CSC in sperm flagella..."
Absence of murine CFAP61 causes male infertility due to multiple morphological abnormalities of the flagella.
-
Cfap61 knockout mice show MMAF with short, coiled, and irregular flagella. Cfap61 localizes first to the neck, then to the midpiece of mature sperm.
"...Cfap61 is initially localized at the neck of sperm, where it potentially functions in flagellum formation, and is later localized to the midpiece of the sperm..."
Axonemal structures reveal mechanoregulatory and disease mechanisms.
-
In the human respiratory-cilia axoneme, the full-length RS3 is built on a base of CFAP61, CFAP91 and CFAP251; CFAP91 links the RS3 subunits CFAP251 and CFAP61, defining the architecture of the calmodulin- and spoke-associated complex within the axoneme.
"...a full-length RS3, which we show is built on a base of CFAP61, CFAP91 and CFAP251... then links the RS3 subunits CFAP251 and CFAP61..."
Biallelic CFAP61 variants cause male infertility in humans and mice with severe oligoasthenoteratozoospermia.
-
Additional CFAP61 pathogenic variants (R552C, D971N, splice site, G556R) identified in OAT patients with MMAF, absence of central pair, and mitochondrial sheath malformation.
"...CONCLUSIONS: Our findings indicate that CFAP61 is essential for spermatogenesis and that biallelic CFAP61 variants lead to male infertility in humans and mice with OAT..."
The CSC proteins FAP61 and FAP251 build the basal substructures of radial spoke 3 in cilia.
-
In Tetrahymena, FAP61 is required for RS3 stem assembly. FAP61-null cilia have missing or incomplete RS3 while RS1 and RS2 are unaffected. Loss reduces cell swimming and alters ciliary waveform.
"...loss of either FAP61 or FAP251 reduces cell swimming and affects the ciliary waveform and that RS3 is either missing or incomplete, whereas RS1 and RS2 are unaffected. Specifically, FAP251-null cilia lack an arch-like density at the RS3 base, whereas FAP61-null cilia lack an adjacent portion of the RS3 stem region..."
The CSC connects three major axonemal complexes involved in dynein regulation.
-
The CSC connects RS2, the N-DRC, and RS3 stand-in (RS3S) in Chlamydomonas, providing a structural link for signal transduction from radial spokes to dynein motors.
"...the CSC connects three major axonemal complexes involved in dynein regulation: RS2, the nexin-dynein regulatory complex (N-DRC), and RS3S..."
The CSC is required for complete radial spoke assembly and wild-type ciliary motility.
-
The CSC was first characterized as a calmodulin- and spoke-associated complex in Chlamydomonas. It is required for RS2 assembly and modulates dynein activity.
"...We previously identified a CaM and Spoke associated Complex (CSC) and provided evidence that this complex mediates regulatory signals between the radial spokes and dynein arms... the CSC is required for spoke assembly and wild-type motility..."
Cfap91-Dependent Stability of the RS2 and RS3 Base Proteins and Adjacent Inner Dynein Arms in Tetrahymena Cilia.
-
Cfap91 is required for stable docking of RS3 and RS2 base proteins. Loss of Cfap91 causes significant reduction of Cfap61 and Cfap251 levels at the axoneme.
"...The localization studies confirmed that the level of RS3-specific proteins, Cfap61 and Cfap251, as well as RS2-associated Cfap206, are significantly diminished in Tetrahymena CFAP91-KO cells..."
CFAP61 knockdown aggravates male infertility by inhibiting testosterone secretion by Leydig cells via the MAPK/COX-2 pathway.
-
In vitro knockdown of CFAP61 in Leydig cells reduced testosterone secretion via MAPK/COX-2 pathway activation. Physiological relevance is uncertain.
"...CFAP61 knockdown reduced the Leydig cell viability and testosterone secretion and enhanced apoptosis..."
Falcon deep research report for CFAP61
-
Falcon research supports CFAP61 as a non-enzymatic axonemal CSC/radial-spoke structural factor needed for sperm flagellum assembly, radial spoke assembly, and sperm motility.
"CFAP61 is best supported as a structural/assembly and stabilization factor for the sperm flagellar axoneme, acting through the CSC-radial spoke system."