Affinage

CETN1

Centrin-1 · UniProt Q12798

Length
172 aa
Mass
19.6 kDa
Annotated
2026-06-09
54 papers in source corpus 8 papers cited in narrative 8 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CETN1 is a calcium-binding centrin-family protein that supports centrosome/ciliary architecture and cell division, with specialized roles in photoreceptor and germ-cell biology (PMID:10486202, PMID:36048845). In adult male mice it is an intronless, retroposon-derived gene expressed exclusively in testis from postnatal day 14 onward, and in somatic and cancer cells its expression is silenced by promoter DNA methylation, reversible by 5'-AZA-2'-deoxycytidine (PMID:10486202, PMID:24252580). In photoreceptors CETN1 localizes to the connecting cilium and binds with high affinity to the Gtβγ subunit of transducin, positioning it within a centrin-transducin complex linked to transducin translocation through the cilium (PMID:15347651); it cannot fully substitute for CETN2 and CETN3, since in Cetn2/Cetn3 double-knockout retina CETN1 collapses to the connecting-cilium mid-segment and the axoneme is destabilized (PMID:30647131). A missense variant (p.Met72Thr) produces multipolar cells, fragmented mitotic nuclei, and disrupted ciliary disassembly dynamics, establishing a direct requirement in cell division and ciliary function (PMID:36048845). During spermatogenesis CETN1 localizes to the post-acrosomal region along manchette microtubule tracks (PMID:31651332). Its C-terminal calcium-binding domain mediates targeting to cone-cell lipid droplets in cooperation with the dynein adaptor isoform SPDL1-L (PMID:37699389).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 1999 Medium

    Establishing whether CETN1 was a distinct, regulated centrin gene defined it as an intronless, testis-restricted retroposon derived from CETN2 — explaining why its tissue distribution differs sharply from ubiquitous centrins.

    Evidence Genomic structure, RT-PCR, Northern blot, FISH, and phylogenetic analysis in mouse

    PMID:10486202

    Open questions at the time
    • Function in testis not directly tested
    • No protein-level interaction or localization data in this study
  2. 2004 Medium

    Identifying a high-affinity CETN1 partner addressed what centrins do at the photoreceptor cilium, placing CETN1 in a centrin-transducin complex relevant to G-protein translocation.

    Evidence Binding assays and immunofluorescence comparing four centrin isoforms in mammalian photoreceptors

    PMID:15347651

    Open questions at the time
    • Regulation of transducin translocation inferred, not directly demonstrated
    • Calcium-dependence of the interaction not resolved
  3. 2013 Medium

    Testing why CETN1 is absent from somatic/cancer cells showed its expression is gated by promoter DNA methylation, and yeast complementation showed it does not replace CDC31/centrin function.

    Evidence qPCR with 5'-AZA-2'-deoxycytidine and TSA treatment, plus yeast complementation assay

    PMID:24252580

    Open questions at the time
    • Endogenous methylation in normal vs tumor tissue not mapped
    • Functional consequence of re-expression untested
  4. 2014 Low

    Knockdown probed whether CETN1 contributes to tumor cell behavior, linking its loss to reduced proliferation, growth, metastasis, and altered cell cycle.

    Evidence Lentiviral shRNA knockdown with MTS, flow-cytometry cell-cycle analysis, and Western blot in breast cancer cells

    PMID:25261648

    Open questions at the time
    • Single knockdown approach without rescue
    • No mechanistic pathway placement
    • Off-target effects not excluded
  5. 2019 Low

    Localization during spermatogenesis addressed where CETN1 acts in germ cells, placing it at the post-acrosomal region along manchette microtubules and correlating its loss with sperm deformity.

    Evidence Western blot, IHC, immunofluorescence, and LC-MS/MS proteomics in mouse and human sperm

    PMID:31651332

    Open questions at the time
    • Functional role inferred from correlation, not loss-of-function
    • Mechanism linking CETN1 to manchette function unknown
  6. 2019 Medium

    Removing the other centrins tested CETN1's capacity to compensate, showing it redistributes to the connecting-cilium mid-segment and cannot prevent axonemal destabilization.

    Evidence Cetn2-/-;Cetn3GT/GT double-knockout mice with ERG, immunofluorescence, and electron microscopy

    PMID:30647131

    Open questions at the time
    • CETN1-specific contribution not isolated by its own knockout
    • Molecular basis of redistribution unknown
  7. 2023 Medium

    A disease-associated variant directly demonstrated CETN1's requirement in mitosis and ciliary disassembly, moving it from correlative to causal in cell division and cilium dynamics.

    Evidence Exome sequencing, biophysical characterization, mitosis imaging, ciliary disassembly assays, and reporter assays of a 5' UTR variant

    PMID:36048845

    Open questions at the time
    • Mechanism by which p.Met72Thr causes multipolarity not defined
    • In vivo phenotype of the variant not established
  8. 2023 Medium

    Domain-deletion experiments defined how CETN1 reaches a non-ciliary target, showing its C-terminal calcium-binding domain and the dynein adaptor SPDL1-L drive lipid-droplet localization in cone cells.

    Evidence Transgenic overexpression, truncation mutants, live imaging, and co-localization in chicken cone cells

    PMID:37699389

    Open questions at the time
    • Direct CETN1-SPDL1-L interaction not biochemically resolved
    • Functional purpose of centrin at lipid droplets unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown how CETN1's calcium-binding activity is coupled to its distinct roles across the connecting cilium, mitotic apparatus, manchette, and lipid droplets, and whether a single biochemical activity underlies these.
  • No unifying biochemical mechanism established
  • No CETN1-specific knockout phenotype reported
  • Calcium-dependence of partner binding not characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005929 cilium 2 GO:0005811 lipid droplet 1 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-1640170 Cell Cycle 1
Partners
GNB1SPDL1

Evidence

Reading pass · 8 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Mouse Cetn1 is an intronless gene located on chromosome 18A2 encoding a 172-amino-acid centrosome protein with all structural features of centrin; it is expressed exclusively in the testis of adult male mice, first appearing at postnatal day 14 and reaching adult levels by day 17, consistent with its origin as a retroposon derived from Cetn2. Genomic structure analysis, RT-PCR, Northern blot, chromosome localization (FISH), phylogenetic analysis Genomics Medium 10486202
2004 CETN1 (Cen1) and CETN2 (Cen2) localize to the connecting cilium of mammalian photoreceptor cells and bind with high affinity to the Gtβγ heterodimer of the visual G-protein transducin, suggesting participation in a centrin-transducin complex that may regulate transducin translocation through the photoreceptor cilium. Interaction assays (binding assays), immunofluorescence subcellular localization, comparison of four centrin isoforms The Journal of biological chemistry Medium 15347651
2013 CETN1 expression in cancer cell lines is regulated by promoter methylation: treatment with the DNA demethylation agent 5'-AZA-2'-deoxycytidine restored CETN1 expression in cell lines where it was virtually absent, whereas histone deacetylase inhibitor trichostatin-A alone had no effect. Additionally, neither CETN1 nor CETN2 could compensate for loss of the yeast CDC31/centrin in yeast complementation assays. qPCR, 5'-AZA-2'-deoxycytidine and TSA treatment, yeast complementation assay Biomarker research Medium 24252580
2019 CETN1 localizes in the post-acrosomal region of spermatid heads parallel to the microtubule tracks of the manchette structure during spermatogenesis, and in mature sperm is confined to the post-acrosomal region of the sperm head. Reduced CETN1 abundance is associated with sperm deformity in obese mice and men. Western blot, immunohistochemistry, immunofluorescence, proteomic LC-MS/MS analysis Reproductive biology and endocrinology Low 31651332
2023 A CETN1 missense variant p.Met72Thr causes multipolar cells, fragmented nuclei during mitosis leading to cell death, and significantly perturbed ciliary disassembly dynamics, establishing that CETN1 is required for proper cell division and ciliary function. A 5' UTR variant (rs367716858) eliminates a methylation site and increases reporter gene expression in vitro. Exome sequencing, biophysical characterization, cell biology assays (mitosis imaging, ciliary disassembly dynamics), reporter gene assay Human molecular genetics Medium 36048845
2019 In Cetn2−/−;Cetn3GT/GT double-knockout mice, CETN1 was condensed to the mid-segment of the connecting cilium (CC) rather than its normal distribution, and the CC/axoneme structure was destabilized with radial expansion of the axoneme at the distal end, demonstrating that CETN1 cannot fully compensate for loss of CETN2 and CETN3 in the photoreceptor connecting cilium. Mouse double-knockout (Cetn2−/−;Cetn3GT/GT), electroretinography, immunofluorescence, ultrastructural analysis (electron microscopy) The Journal of biological chemistry Medium 30647131
2023 Overexpression of a truncated CETN1 (lacking part of its C-terminal calcium-binding domain) abrogates the apical localization of the single lipid droplet in chicken cone cells, while full-length centrins target to cone cell lipid droplets via their C-terminal calcium-binding domains and do so with the help of SPDL1-L, a novel isoform of the kinetochore-associated dynein adaptor SPDL1. Transgenic overexpression, truncation/domain mutant analysis, live imaging, co-localization studies in chicken cone cells Developmental cell Medium 37699389
2014 Knockdown of CETN1 by lentivirus-shRNA significantly inhibited breast cancer cell proliferation, growth, and metastasis, and caused changes in cell cycle progression. Lentivirus-shRNA knockdown, MTS proliferation assay, cell cycle analysis (flow cytometry), Western blot Journal of B.U.ON. Low 25261648

Source papers

Stage 0 corpus · 54 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Mutations derepressing silent centromeric domains in fission yeast disrupt chromosome segregation. Genes & development 402 7851795
2013 Generation of mutant mice by pronuclear injection of circular plasmid expressing Cas9 and single guided RNA. Scientific reports 367 24284873
1994 Position effect variegation at fission yeast centromeres. Cell 293 8287474
2000 Distinct protein interaction domains and protein spreading in a complex centromere. Genes & development 211 10766735
2012 Repeatless and repeat-based centromeres in potato: implications for centromere evolution. The Plant cell 205 22968715
1989 Composite motifs and repeat symmetry in S. pombe centromeres: direct analysis by integration of NotI restriction sites. Cell 195 2541922
2006 Comparative genomic and phylogenetic analyses of calcium ATPases and calcium-regulated proteins in the apicomplexa. Molecular biology and evolution 127 16751258
1992 Replication forks pause at yeast centromeres. Molecular and cellular biology 127 1508202
1991 The chromatin structure of centromeres from fission yeast: differentiation of the central core that correlates with function. The Journal of cell biology 109 1988457
2011 Structure of MyTH4-FERM domains in myosin VIIa tail bound to cargo. Science (New York, N.Y.) 94 21311020
2005 Basal body duplication and maintenance require one member of the Tetrahymena thermophila centrin gene family. Molecular biology of the cell 84 15944224
1999 Testis-specific murine centrin, Cetn1: genomic characterization and evidence for retroposition of a gene encoding a centrosome protein. Genomics 70 10486202
2004 Differential expression and interaction with the visual G-protein transducin of centrin isoforms in mammalian photoreceptor cells. The Journal of biological chemistry 69 15347651
1991 Identification of DNA regions required for mitotic and meiotic functions within the centromere of Schizosaccharomyces pombe chromosome I. Molecular and cellular biology 69 2005906
2007 An RNA polymerase III-dependent heterochromatin barrier at fission yeast centromere 1. PloS one 51 17971862
1991 Clustered tRNA genes in Schizosaccharomyces pombe centromeric DNA sequence repeats. Proceedings of the National Academy of Sciences of the United States of America 51 1996332
2001 Fission yeast living mitosis visualized by GFP-tagged gene products. Micron (Oxford, England : 1993) 48 10900382
1987 Molecular cloning of chromosome I DNA from Saccharomyces cerevisiae: isolation and analysis of the CEN1-ADE1-CDC15 region. Molecular and cellular biology 47 3031471
2006 Centrin isoforms in mammals. Relation to calmodulin. Molecular biology reports 36 17089211
1997 The centromere enhancer mediates centromere activation in Schizosaccharomyces pombe. Molecular and cellular biology 36 9154829
2001 Only centromeres can supply the partition system required for ARS function in the yeast Yarrowia lipolytica. Journal of molecular biology 34 11124900
2011 The two domains of centrin have distinct basal body functions in Tetrahymena. Molecular biology of the cell 29 21562224
2019 Deletion of both centrin 2 (CETN2) and CETN3 destabilizes the distal connecting cilium of mouse photoreceptors. The Journal of biological chemistry 22 30647131
2012 High-resolution mapping and transcriptional activity analysis of chicken centromere sequences on giant lampbrush chromosomes. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 22 23143648
2008 Dissection of centromeric DNA from yeast Yarrowia lipolytica and identification of protein-binding site required for plasmid transmission. Journal of bioscience and bioengineering 22 18640595
2023 CRISPR/Cas9 mutants delineate roles of Populus FT and TFL1/CEN/BFT family members in growth, dormancy release and flowering. Tree physiology 21 36892416
2001 Characterization of the X-linked murine centrin Cetn2 gene. Gene 19 11250075
2017 Regulation of mitotic recombination between DNA repeats in centromeres. Nucleic acids research 18 28977643
2000 A novel member of the Swi6p family of fission yeast chromo domain-containing proteins associates with the centromere in vivo and affects chromosome segregation. Molecular & general genetics : MGG 18 11129054
2019 Proteomic alterations underlie an association with teratozoospermia in obese mice sperm. Reproductive biology and endocrinology : RB&E 17 31651332
2005 Gene cloning of an endoglucanase from the basidiomycete Irpex lacteus and its cDNA expression in Saccharomyces cerevisiae. Bioscience, biotechnology, and biochemistry 17 16041128
2013 CETN1 is a cancer testis antigen with expression in prostate and pancreatic cancers. Biomarker research 15 24252580
2023 Exome sequencing and functional analyses revealed CETN1 variants leads to impaired cell division and male fertility. Human molecular genetics 12 36048845
1990 Molecular cloning of chromosome I DNA from Saccharomyces cerevisiae: isolation, characterization and regulation of the SPO7 sporulation gene. Gene 12 2253888
2019 Evaluation of novel highly specific antibodies to cancer testis antigen Centrin-1 for radioimmunoimaging and radioimmunotherapy of pancreatic cancer. Cancer medicine 11 31309741
2016 Novel Centromeric Loci of the Wine and Beer Yeast Dekkera bruxellensis CEN1 and CEN2. PloS one 11 27560164
2008 Interaction of APC/C-E3 ligase with Swi6/HP1 and Clr4/Suv39 in heterochromatin assembly in fission yeast. The Journal of biological chemistry 10 19117951
2014 Chromosome number reduction in Eremothecium coryli by two telomere-to-telomere fusions. Genome biology and evolution 9 24803574
2017 Do some epithelial ovarian cancers originate from a fallopian tube ciliate cell lineage? Medical hypotheses 8 28915954
2022 Changes in mechanical and bacterial properties of denture base resin following nanoceria incorporation with and without SBA-15 carriers. Journal of the mechanical behavior of biomedical materials 7 36543086
2017 TET3-mediated demethylation in tomato activates expression of a CETS gene that stimulates vegetative growth. Plant direct 6 31245668
1993 Distribution of bent DNA structures in the fission yeast centromere. Gene 6 8224870
2023 Centrins control chicken cone cell lipid droplet dynamics through lipid-droplet-localized SPDL1. Developmental cell 5 37699389
2018 Aberrant promoter methylation reduced the expression of protocadherin 17 in nasopharyngeal cancer. Biochemistry and cell biology = Biochimie et biologie cellulaire 5 30165032
2014 Knockdown of CETN1 inhibits breast cancer cells proliferation. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 5 25261648
2003 [Effects of two LMP1 variants on resistance of CNE1 cell strain to TGF-beta1]. Ai zheng = Aizheng = Chinese journal of cancer 5 14693046
1993 Sequence of a fission yeast gene encoding a protein with extensive homology to eukaryotic elongation factor-1 gamma. Gene 5 8244022
1994 Sequencing of chromosome I of Saccharomyces cerevisiae: analysis of the 42 kbp SPO7-CENI-CDC15 region. Yeast (Chichester, England) 4 7941740
2008 Isolation and characterization of the Cetn1 gene from tufted deer (Elaphodus cephalophus). Biochemical genetics 3 18751886
2021 Structural Abnormalities of Spermatozoa in Triploid Gynogenetic Crucian Carp (Carassius auratus). Frontiers in genetics 2 34868272
2013 [Expression of miR-143 in nasopharyngeal carcinoma cell lines and its effect on cell adhesion ability]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 1 23644125
2025 Intragenic overexpression of TONNEAU 1b enhances grain length and weight in durum wheat. Plant physiology and biochemistry : PPB 0 41475044
2024 Identification of potential differences in salivary proteomic profiles between estrus and diestrus stage of estrous cycle in dairy cows. Systems biology in reproductive medicine 0 39008339
2021 [The expression of clock gene CLOCK and its clinical significance in nasopharyngeal carcinoma]. Zhonghua zhong liu za zhi [Chinese journal of oncology] 0 34915633

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