Affinage

CNTROB

Centrobin · UniProt Q8N137

Round 2 corrected
Length
903 aa
Mass
101.3 kDa
Annotated
2026-04-28
50 papers in source corpus 5 papers cited in narrative 5 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Centrobin (CNTROB) is a daughter centriole-associated protein that functions in centriole duplication, elongation, and stability, and is a positive regulator of primary ciliogenesis and spermatid head–tail coupling. It directly binds tubulin in an hSAS-6-dependent manner to promote centriole assembly and structural integrity, and its C-terminal domain, which also interacts with CP110, is required for axonemal extension during ciliogenesis (PMID:21576394, PMID:29440264). Phosphorylation by the mitotic kinase Nek2 mobilizes centrobin to cytoplasmic microtubules, where it promotes microtubule stabilization and proper spindle assembly (PMID:17535851). During spermiogenesis, centrobin localizes to the manchette and acroplaxome marginal ring, interacts with keratin 5 intermediate filaments, and is essential for maintaining the head–tail coupling apparatus; its loss causes spermatid decapitation and male infertility (PMID:19710508).

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 2005 High

    Identification of centrobin as the first marker of the daughter centriole and demonstration that it is required for centriole duplication resolved the question of whether centriole biogenesis depends on a centriole-intrinsic asymmetric factor.

    Evidence siRNA knockdown and immunofluorescence in cultured human cells

    PMID:16275750

    Open questions at the time
    • Mechanism by which centrobin promotes duplication was unknown
    • Direct molecular binding partners were not identified
    • Whether centrobin functions beyond centriole duplication was untested
  2. 2007 High

    Establishing Nek2 as a kinase that phosphorylates centrobin and regulates its redistribution to microtubules showed how centrobin activity is controlled during the cell cycle and linked it to microtubule stabilization and spindle assembly.

    Evidence In vitro kinase assay, co-immunoprecipitation, siRNA knockdown with immunofluorescence in human cells

    PMID:17535851

    Open questions at the time
    • Specific phosphorylation sites and their individual contributions were not mapped
    • Whether Nek2-dependent regulation is relevant in non-mitotic contexts was unknown
  3. 2009 High

    Characterization of the rat hd mutant revealed that centrobin is required in spermiogenesis for acroplaxome marginal ring integrity and centrosome–nucleus attachment via interaction with keratin 5, expanding centrobin's roles beyond centriole duplication to specialized cytoskeletal scaffolding.

    Evidence Genetic mapping of endogenous retroviral insertion, immunofluorescence, co-immunoprecipitation, and electron microscopy in rat hd mutant

    PMID:19710508

    Open questions at the time
    • Whether the spermiogenesis phenotype is entirely cell-autonomous was not resolved
    • Structural basis of the centrobin–keratin 5 interaction was not determined
  4. 2011 High

    Demonstration that centrobin directly binds tubulin and that this interaction is required for centriole elongation and stability — recruited via hSAS-6 but independent of CPAP/CP110 — defined the molecular basis of centrobin's role in centriole biogenesis.

    Evidence In vitro binding assays, mutagenesis, siRNA knockdown, immunofluorescence, and electron microscopy in human cells

    PMID:21576394

    Open questions at the time
    • Structural details of the centrobin–tubulin interface were not resolved
    • How centrobin cooperates with CPAP downstream of initial recruitment was unclear
  5. 2018 High

    CRISPR knockout and zebrafish depletion established centrobin as a positive regulator of primary ciliogenesis, showing its C-terminal domain (which binds CP110 and tubulin) is required for axonemal extension after centriole docking, and linking centrobin loss to ciliopathy-like phenotypes in vivo.

    Evidence CRISPR knockout in hTERT-RPE1 cells, electron microscopy, co-immunoprecipitation, zebrafish morpholino knockdown

    PMID:29440264

    Open questions at the time
    • Mechanism by which centrobin promotes CP110 removal or axoneme nucleation is unknown
    • Whether centrobin mutations cause human ciliopathies has not been demonstrated
    • Relative contributions of the tubulin-binding versus CP110-binding activities of the C-terminal domain to ciliogenesis are unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown how centrobin's multiple functions — centriole duplication, microtubule stabilization, spermatid coupling, and ciliogenesis — are differentially regulated in distinct cellular contexts, and no high-resolution structure of centrobin or its complexes has been determined.
  • No atomic-resolution structure of centrobin or centrobin–tubulin complex
  • Context-dependent regulation distinguishing centrobin's roles in mitotic versus ciliated versus spermatogenic cells is unexplored
  • No confirmed human disease-causing mutations in CNTROB

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 3
Localization
GO:0005815 microtubule organizing center 5 GO:0005856 cytoskeleton 2 GO:0005929 cilium 1
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-1640170 Cell Cycle 2
Partners
CP110KRT5NEK2SASS6TUBA1A

Evidence

Reading pass · 5 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 Centrobin (CNTROB) was identified as a centriole-associated protein that asymmetrically localizes to the daughter centriole. siRNA-mediated silencing of centrobin inhibited centriole duplication, resulting in centrosomes with one or no centriole, and impaired cytokinesis, demonstrating that centrobin is required for centriole duplication. siRNA knockdown, immunofluorescence microscopy, cell cycle analysis The Journal of cell biology High 16275750
2007 Centrobin (NIP2/centrobin) was identified as a novel substrate of the mitotic kinase Nek2. Centrobin localizes to the daughter centriole and associates with stable cytoplasmic microtubules. Phosphorylation by Nek2 disperses centrobin aggregates and promotes its association with microtubules. Knockdown of centrobin caused reduced microtubule organizing activity, cell shrinkage, defective spindle assembly, and abnormal nuclear morphology, indicating a role in microtubule stabilization. Co-immunoprecipitation, kinase assay, siRNA knockdown, immunofluorescence microscopy Journal of cell science High 17535851
2009 In rats, an endogenous retroviral insertion into intron 10 of Cntrob disrupts normal splicing and produces a truncated centrobin protein. During spermiogenesis, centrobin localizes to the manchette, centrosome, and marginal ring of the acroplaxome, where it interacts with keratin 5-containing intermediate filaments. Loss of centrobin function causes defective acroplaxome marginal ring assembly and detachment of the centrosome from the nucleus, disrupting the head-tail coupling apparatus and causing spermatid decapitation, leading to male infertility. Genetic mapping, RT-PCR, immunofluorescence, co-immunoprecipitation, electron microscopy in rat hd mutant Biology of reproduction High 19710508
2011 Centrobin directly interacts with tubulin, and this interaction is required for centriole elongation and stability. Centrobin is recruited to the centriole biogenesis site via tubulin interaction in an hSAS-6-dependent but CPAP/CP110-independent manner. Disruption of the centrobin-tubulin interaction destabilized existing centrioles and CPAP-induced procentriole-like structures. In vitro binding assay (direct interaction), mutagenesis, siRNA knockdown, immunofluorescence, electron microscopy The Journal of cell biology High 21576394
2018 Genome editing (CRISPR) of CNTROB in hTERT-RPE1 cells showed that centrobin primarily localizes to daughter centrioles but also associates with mother centrioles upon serum starvation. Centrobin loss abrogated primary ciliation; ultrastructural analysis revealed defective axonemal extension after mother centriole docking. A C-terminal portion of centrobin that interacts with CP110 and tubulin is required for ciliogenesis. Depletion of centrobin in zebrafish caused microcephaly, body curvature, and laterality defects consistent with ciliary dysfunction, identifying centrobin as a positive regulator of vertebrate ciliogenesis. CRISPR knockout, monoclonal antibody localization, electron microscopy, Co-immunoprecipitation, zebrafish morpholino knockdown The Journal of cell biology High 29440264

Source papers

Stage 0 corpus · 50 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2006 A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. Cell 610 16713569
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2013 Protein interaction network of the mammalian Hippo pathway reveals mechanisms of kinase-phosphatase interactions. Science signaling 383 24255178
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2004 Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation. Nature biotechnology 266 15146197
2011 Novel asymmetrically localizing components of human centrosomes identified by complementary proteomics methods. The EMBO journal 265 21399614
2014 Proximity biotinylation and affinity purification are complementary approaches for the interactome mapping of chromatin-associated protein complexes. Journal of proteomics 215 25281560
2015 A deep proteomics perspective on CRM1-mediated nuclear export and nucleocytoplasmic partitioning. eLife 198 26673895
2011 Protein interactome reveals converging molecular pathways among autism disorders. Science translational medicine 180 21653829
2014 Proximity interactions among centrosome components identify regulators of centriole duplication. Current biology : CB 162 24613305
2000 Secreted lipases of Candida albicans: cloning, characterisation and expression analysis of a new gene family with at least ten members. Archives of microbiology 152 11131027
2005 Centrobin: a novel daughter centriole-associated protein that is required for centriole duplication. The Journal of cell biology 122 16275750
2007 Toward a confocal subcellular atlas of the human proteome. Molecular & cellular proteomics : MCP 114 18029348
2002 The Chediak-Higashi protein interacts with SNARE complex and signal transduction proteins. Molecular medicine (Cambridge, Mass.) 102 11984006
2017 Mammalian APE1 controls miRNA processing and its interactome is linked to cancer RNA metabolism. Nature communications 99 28986522
2020 Targeting TRIM37-driven centrosome dysfunction in 17q23-amplified breast cancer. Nature 93 32908313
2004 Large-scale cDNA transfection screening for genes related to cancer development and progression. Proceedings of the National Academy of Sciences of the United States of America 82 15498874
2007 Characterization of NIP2/centrobin, a novel substrate of Nek2, and its potential role in microtubule stabilization. Journal of cell science 74 17535851
2016 Phenotypic and Interaction Profiling of the Human Phosphatases Identifies Diverse Mitotic Regulators. Cell reports 72 27880917
2005 Identification and characterisation of LIP7 and LIP8 genes encoding two extracellular triacylglycerol lipases in the yeast Yarrowia lipolytica. Fungal genetics and biology : FG & B 67 15707847
2016 Dynamic Protein Interactions of the Polycomb Repressive Complex 2 during Differentiation of Pluripotent Cells. Molecular & cellular proteomics : MCP 64 27634302
2016 CEP295 interacts with microtubules and is required for centriole elongation. Journal of cell science 63 27185865
2007 Lipase 8 affects the pathogenesis of Candida albicans. Infection and immunity 63 17646357
2009 Rat hd mutation reveals an essential role of centrobin in spermatid head shaping and assembly of the head-tail coupling apparatus. Biology of reproduction 62 19710508
2011 Centrobin-tubulin interaction is required for centriole elongation and stability. The Journal of cell biology 57 21576394
2020 Identification of a lipase gene with a role in tomato fruit short-chain fatty acid-derived flavor volatiles by genome-wide association. The Plant journal : for cell and molecular biology 47 32786123
2021 Metabolic engineering of Saccharomyces cerevisiae for production of β-carotene from hydrophobic substrates. FEMS yeast research 31 33332529
2012 Extracellular expression and characterization of thermostable lipases, LIP8, LIP14 and LIP18, from Yarrowia lipolytica. Biotechnology letters 28 22639089
2022 The diagnostic yield, candidate genes, and pitfalls for a genetic study of intellectual disability in 118 middle eastern families. Scientific reports 27 36344539
2018 Centrobin controls primary ciliogenesis in vertebrates. The Journal of cell biology 25 29440264
2014 Modulation of induced cytotoxicity of doxorubicin by using apoferritin and liposomal cages. International journal of molecular sciences 25 25514405
2010 Surface display of active lipases Lip7 and Lip8 from Yarrowia lipolytica on Saccharomyces cerevisiae. Applied microbiology and biotechnology 18 20676630
2009 A novel active endogenous retrovirus family contributes to genome variability in rat inbred strains. Genome research 15 19887576
2004 Cloning, expression, and characterization of a lipolytic enzyme gene (lip8) from Pseudomonas aeruginosa LST-03. Journal of molecular microbiology and biotechnology 14 15383719
2014 Biochemical characterization of Yarrowia lipolytica LIP8, a secreted lipase with a cleavable C-terminal region. Biochimica et biophysica acta 4 25449652
2023 Using multi-tissue transcriptome-wide association study to identify candidate susceptibility genes for respiratory infectious diseases. Frontiers in genetics 3 37020999
2016 [Mutations in genes affecting fertility of men - current routine laboratory genetic diagnostics and searching for more DNA segments and genes influencing spermatogenesis]. Ceska gynekologie 2 27918162
2025 A missense mutation in TCFL5 is associated with male infertility due to oligoasthenoteratozoospermia. Molecular genetics and genomics : MGG 1 40711600
2018 Expression, purification, crystallization, and diffraction analysis of a selenomethionyl lipase Lip8 from Yarrowia lipolytica. Preparative biochemistry & biotechnology 1 27380164
2025 Genetic architecture of the tomato fruit lipidome. PNAS nexus 0 41522695
2011 [Methylation profiling of the cell cycle regulating genes in placenta of human embryos with chromosomal mosaicism]. Molekuliarnaia biologiia 0 21634119