Affinage

CABCOCO1

Ciliary-associated calcium-binding coiled-coil protein 1 · UniProt Q8IVU9

Length
208 aa
Mass
23.9 kDa
Annotated
2026-06-09
62 papers in source corpus 3 papers cited in narrative 3 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CABCOCO1 is a calcium-binding protein that functions in sperm flagellum formation during spermiogenesis (PMID:26990073, PMID:37601242). It exhibits direct calcium-binding activity and undergoes a developmentally programmed relocalization, concentrating around centrioles and co-localizing with pericentrin in spermatids before redistributing to the sperm flagellum; in species retaining the proximal centriole it localizes to both the basal body and the flagellum (PMID:26990073). At the axoneme, CABCOCO1 physically interacts with the radial-spoke-associated protein CCDC189 and engages the radial-spoke-specific protein RSPH1 and intraflagellar transport proteins, with CCDC189 required to maintain CABCOCO1 protein levels (PMID:37601242). Loss of CABCOCO1 causes multiple morphological abnormalities of the sperm flagella (MMAF), establishing it as essential for normal flagellar architecture (PMID:37601242). Beyond its role in sperm flagellum assembly, no further mechanistic detail has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 3 steps
  1. 2016 Medium

    Established CABCOCO1 as a genuine calcium-binding protein with a spermatogenic localization pattern, raising the question of how a calcium sensor participates in centriole and flagellum biology.

    Evidence In vitro calcium-binding assays (Stains-all, ruthenium red, terbium binding) on recombinant protein plus immunohistochemical localization across spermatogenic stages

    PMID:26990073

    Open questions at the time
    • Functional consequence of calcium binding not tested
    • Single lab, single study without loss-of-function validation
    • Molecular partners at the centriole or flagellum not identified
  2. 2023 High

    Defined CABCOCO1's molecular context at the axoneme and its functional requirement, showing it acts within the radial-spoke/IFT machinery and is needed for sperm flagellum integrity.

    Evidence Reciprocal Co-IP with mass spectrometry, Cabcoco1 knockout mouse with MMAF readout, and immunoelectron microscopy in mouse

    PMID:37601242

    Open questions at the time
    • Mechanism by which CABCOCO1 contributes to radial spoke or IFT function not resolved
    • Whether the interaction with RSPH1 and IFT proteins is direct or bridged by CCDC189 not determined
    • Role of calcium binding in the CCDC189 interaction not addressed
  3. 2025 Low

    Raised a possible role in left-right axis determination beyond the sperm flagellum, linking CABCOCO1 variants to laterality defects.

    Evidence Whole-exome sequencing of congenital heart disease patients with situs ambiguus

    PMID:40467998

    Open questions at the time
    • Variant association only; no functional experiment performed on CABCOCO1 in this context
    • Causality and ciliary mechanism in laterality not demonstrated
    • No link drawn to motile cilia of the embryonic node

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CABCOCO1's calcium-binding activity is mechanistically coupled to radial-spoke/IFT function and flagellar assembly remains unresolved.
  • No structural model of CABCOCO1 or its complexes
  • Calcium-dependence of partner interactions untested
  • Role outside spermatogenesis (e.g., motile cilia in laterality) unconfirmed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0005929 cilium 2 GO:0005815 microtubule organizing center 1 GO:0005829 cytosol 1
Partners
CCDC189RSPH1

Evidence

Reading pass · 3 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 CABCOCO1 (calcium-binding coiled-coil protein 1) is a novel protein with demonstrated calcium-binding activity, localized in the sperm flagellum. Recombinant CABCOCO1 showed calcium-binding activity via Stains-all, ruthenium red staining, and direct terbium-binding measurement. Immunohistochemical analyses showed localization in spermatogenic cells, initially in the cytoplasm of spermatocytes, concentrated around centrioles of spermatids, co-localizing with the centrosomal protein pericentrin. During spermiogenesis, CABCOCO1 relocalized from the centrosome to the sperm flagellum. In porcine sperm (where the proximal centriole is retained), CABCOCO1 localized to both the basal body and flagellum. In vitro calcium-binding assay (Stains-all, ruthenium red, terbium binding of recombinant protein); immunohistochemistry; subcellular fractionation/localization Molecular reproduction and development Medium 26990073
2023 CABCOCO1 physically interacts with CCDC189, a radial-spoke-associated protein of the sperm axoneme. CCDC189 was localized to the radial spoke of the first peripheral microtubule doublet by immunoelectron microscopy. Co-immunoprecipitation and mass spectrometry identified CABCOCO1 as a CCDC189-interacting protein. Inactivation of Cabcoco1 caused malformation of sperm flagella (MMAF phenotype). Inactivation of CCDC189 caused downregulation of CABCOCO1 protein expression. Both CCDC189 and CABCOCO1 were found to interact with the radial-spoke-specific protein RSPH1 and intraflagellar transport proteins. Co-immunoprecipitation, mass spectrometry, Cabcoco1 knockout mouse (loss-of-function with MMAF phenotype readout), immunoelectron microscopy, immunoblotting National science review High 37601242
2025 C10ORF107 (CABCOCO1) was identified as a candidate gene variant in patients with congenital heart disease presenting with laterality defects (situs ambiguus), suggesting a role in left-right axis determination, potentially through ciliary function. Whole-exome sequencing of CHD patients with laterality defects Journal of human genetics Low 40467998

Source papers

Stage 0 corpus · 62 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Maternal HIV-1 viral load and vertical transmission of infection: the Ariel Project for the prevention of HIV transmission from mother to infant. Nature medicine 145 9142125
2007 Identification of in vivo-expressed immunogenic proteins by serological proteome analysis of the Bacillus anthracis secretome. Infection and immunity 88 17353282
1999 Chitinase secretion by encysting Entamoeba invadens and transfected Entamoeba histolytica trophozoites: localization of secretory vesicles, endoplasmic reticulum, and Golgi apparatus. Infection and immunity 82 10338523
2002 High RhoA activity maintains the undifferentiated mesenchymal cell phenotype, whereas RhoA down-regulation by laminin-2 induces smooth muscle myogenesis. The Journal of cell biology 69 11877460
2011 Common variants in or near FGF5, CYP17A1 and MTHFR genes are associated with blood pressure and hypertension in Chinese Hans. Journal of hypertension 68 20852445
2019 The enhancer RNA ARIEL activates the oncogenic transcriptional program in T-cell acute lymphoblastic leukemia. Blood 61 31076442
2006 Stability of thermostable alkaline protease from Bacillus licheniformis RP1 in commercial solid laundry detergent formulations. Microbiological research 55 16872818
2001 Studies on carboxymethyl cellulase produced by an alkalothermophilic actinomycete. Bioresource technology 44 11272024
2013 Production, purification and characterization of a novel thermotolerant endoglucanase (CMCase) from Bacillus strain isolated from cow dung. SpringerPlus 38 23519129
2013 Detergent compatible alkaline lipase produced by marine Bacillus smithii BTMS 11. World journal of microbiology & biotechnology 34 23443894
2016 Enhancement of Alkaline Protease Activity and Stability via Covalent Immobilization onto Hollow Core-Mesoporous Shell Silica Nanospheres. International journal of molecular sciences 32 26840303
2006 Characterization of a novel virus causing a lethal disease in carp and koi. Microbiology and molecular biology reviews : MMBR 30 16524920
2011 Toxicity assessment of a common laundry detergent using the freshwater flagellate Euglena gracilis. Chemosphere 28 21601907
2020 Bacillus sp. CSK2 produced thermostable alkaline keratinase using agro-wastes: keratinolytic enzyme characterization. BMC biotechnology 25 33317483
2015 Purification and characterization of halo-alkali-thermophilic protease from Halobacterium sp. strain HP25 isolated from raw salt, Lake Qarun, Fayoum, Egypt. Extremophiles : life under extreme conditions 25 25982741
2003 The thyrotropin receptor mutation database: update 2003. Thyroid : official journal of the American Thyroid Association 25 14751032
2020 lncRNA-DNA hybrids regulate distant genes. EMBO reports 24 32078233
2018 Striatin is a novel modulator of cell adhesion. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 22 30592649
2019 Transcriptomic analysis reveals novel downstream regulatory motifs and highly transcribed virulence factor genes of Entamoeba histolytica. BMC genomics 21 30866809
2005 Protein promiscuity: drug resistance and native functions--HIV-1 case. Journal of biomolecular structure & dynamics 20 15842167
1999 DNA sequences corresponding to the ariel gene family of Entamoeba histolytica are not present in E. dispar. Parasitology research 20 10431751
2009 Evolutionary history of Ramphastos toucans: molecular phylogenetics, temporal diversification, and biogeography. Molecular phylogenetics and evolution 19 19699308
1998 A new gene family (ariel) encodes asparagine-rich Entamoeba histolytica antigens, which resemble the amebic vaccine candidate serine-rich E. histolytica protein. Infection and immunity 18 9423879
2019 Characterisation of Streptomyces violascens OC125-8 lipase for oily wastewater treatment. 3 Biotech 16 30622843
2015 Characterization of Sphingomonas sp. JB13 exo-inulinase: a novel detergent-, salt-, and protease-tolerant exo-inulinase. Extremophiles : life under extreme conditions 16 25575614
2023 CCDC189 affects sperm flagellum formation by interacting with CABCOCO1. National science review 15 37601242
2011 Myofibrillar myopathy caused by a mutation in the motor domain of mouse MyHC IIb. Human molecular genetics 15 22199023
2007 Nicotinic acetylcholine receptor expression by directionally selective ganglion cells. Visual neuroscience 15 17686198
2004 MLA-sensitive cholinergic receptors involved in the detection of complex moving stimuli in retina. Visual neuroscience 14 15733341
2023 Butterfly classification and species discovery using genomics. The taxonomic report of the International Lepidoptera Survey 13 39867748
2012 Producing pronouns and definite noun phrases: do speakers use the addressee's discourse model? Cognitive science 13 22671693
2012 Bioprocessing of "Hair Waste" by Paecilomyces lilacinus as a Source of a Bleach-Stable, Alkaline, and Thermostable Keratinase with Potential Application as a Laundry Detergent Additive: Characterization and Wash Performance Analysis. Biotechnology research international 13 23365760
1991 Effects of synaptic drugs on turtle optokinetic nystagmus and the spike responses of the basal optic nucleus. Visual neuroscience 13 1764413
2020 Exoproduction and characterization of a detergent-stable alkaline keratinase from Arthrobacter sp. KFS-1. Biochimie 12 32835736
2012 Biodegradation of a keratin waste and the concomitant production of detergent stable serine proteases from Paecilomyces lilacinus. Applied biochemistry and biotechnology 11 22447221
2012 Chronic toxicity of a laundry detergent to the freshwater flagellate Euglena gracilis. Ecotoxicology (London, England) 11 22644093
2018 Isolated populations of Ixodes lividus ticks in the Czech Republic and Belgium host genetically homogeneous Rickettsia vini. Ticks and tick-borne diseases 10 29373306
2021 Taxon-Specific Proteins of the Pathogenic Entamoeba Species E. histolytica and E. nuttalli. Frontiers in cellular and infection microbiology 9 33816346
2021 Chryseobacterium aquifrigidense FANN1 Produced Detergent-Stable Metallokeratinase and Amino Acids Through the Abasement of Chicken Feathers. Frontiers in bioengineering and biotechnology 9 34422784
2018 Rickettsia fournieri sp. nov., a novel spotted fever group rickettsia from Argas lagenoplastis ticks in Australia. International journal of systematic and evolutionary microbiology 9 30307387
2016 CABCOCO1, a novel coiled-coil protein With calcium-binding activity, is localized in the sperm flagellum. Molecular reproduction and development 7 26990073
2011 Biochemical characterization of a novel thermostable xyloglucanase from an alkalothermophilic Thermomonospora sp. Extremophiles : life under extreme conditions 7 22120834
1975 Molecular genetics of avian proteins. XIII. Protein polymorphism in three species of Australian passerines. Australian journal of biological sciences 7 1225289
2023 Infrared Spectra of Small Radicals for Exoplanetary Spectroscopy: OH, NH, CN and CH: The State of Current Knowledge. Molecules (Basel, Switzerland) 6 37110598
2014 Proteomic analysis of the follicular fluid of Tianzhu white yak during diestrus. International journal of molecular sciences 6 24633201
2017 Gene-by-Psychosocial Factor Interactions Influence Diastolic Blood Pressure in European and African Ancestry Populations: Meta-Analysis of Four Cohort Studies. International journal of environmental research and public health 5 29258278
2014 Molecular characterization of the rare translocation t(3;10)(q26;q21) in an acute myeloid leukemia patient. Molecular cytogenetics 4 25071866
2021 Biochemical characterization, cytotoxic, antimutagenic, anticancer and molecular docking studies on Tecomella undulata. Saudi journal of biological sciences 3 35531249
2016 SHG10 keratinolytic alkaline protease from Bacillus licheniformis SHG10 DSM 28096: Robust stability and unusual non-cumbersome purification. Journal of basic microbiology 3 27334682
2024 iDISCO Tissue Clearing Whole-Brain and Light Sheet Microscopy for High-Throughput Imaging in a Mouse Model of Traumatic Brain Injury. Methods in molecular biology (Clifton, N.J.) 2 38427263
2010 Origin and timing of voltage-sensitive dye signals within layers of the turtle cerebellar cortex. Brain research 2 20707989
2025 Enhanced efficiency of virulent and temperate phage combination mediated through bacterial membrane vesicles. Journal of virology 1 41294326
2022 Molecular Mechanisms Responsible for In Vitro Cytotoxic Attributes of Conyza bonariensis Extract against Lymphoblastic Leukaemia Jurkat Cells. Anti-cancer agents in medicinal chemistry 1 34488604
2021 Rucabarib: A new lease of life for ovarian cancer patients. Journal of cancer research and therapeutics 1 34528576
2019 Finding ARIEL under the sea of T-ALL circuits. Blood 1 31320362
2007 Analysis of quantal size of voltage responses to retinal stimulation in the accessory optic system. Brain research 1 17543898
2025 The prevalence of laterality defects in patients with congenital heart disease. Journal of human genetics 0 40467998
2024 Transitions in development - an interview with Ariel Waisman. Development (Cambridge, England) 0 38885080
2023 Paracholeplasma manati sp. nov. isolated from Florida manatees (Trichechus manatus latirostris). International journal of systematic and evolutionary microbiology 0 37489952
2018 Inherited gynaecological cancers. Current opinion in oncology 0 30036195
2013 Expression of concern: Subfunctionalization reduces the fitness cost of gene duplication in humans by buffering dosage imbalances. BMC genomics 0 23594279
2013 Withdrawn: Supramolecular Evolution of Protein Organization. Annual review of genetics 0 23808343

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