Affinage

CETN2

Centrin-2 · UniProt P41208

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

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CETN2 is a ubiquitously expressed EF-hand calcium-binding protein that operates at the centriole/centrosome and within DNA damage recognition machinery (PMID:11250075). At ciliary structures, CETN2 acts redundantly with CETN3 to stabilize the photoreceptor connecting cilium axoneme: combined loss of both centrins, but neither alone, destabilizes the axoneme, shortens the connecting cilium, depletes SPATA7 from its distal region, misaligns outer segment discs, and drives retinal degeneration (PMID:30647131). In a distinct functional context, CETN2 forms a complex with the nucleotide excision repair initiator XPC, enhancing NER activity; this complex limits oxaliplatin-induced DNA damage and cytotoxicity, such that CETN2 depletion sensitizes hepatocellular carcinoma cells to oxaliplatin in an XPC-dependent manner (PMID:39945187). Beyond these centriolar, ciliary, and NER roles, no further mechanistic detail has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 3 steps
  1. 2001 Medium

    Established the basic identity and subcellular address of CETN2, defining it as a calcium-binding protein concentrated at the centriolar region rather than diffusely distributed.

    Evidence Immunofluorescence microscopy, Northern blot, RT-PCR and FISH for mouse CETN2 in NIH 3T3 cells and adult tissues

    PMID:11250075

    Open questions at the time
    • Calcium-dependent conformational or binding behavior not functionally tested
    • No interacting partners identified
    • Cellular consequence of CETN2 loss not addressed
  2. 2019 High

    Resolved why single centrin loss is phenotypically silent by showing CETN2 and CETN3 act redundantly to maintain photoreceptor connecting cilium architecture, linking centrin function to ciliary stability and retinal integrity.

    Evidence Cetn2/Cetn3 double-knockout mice analyzed by ERG, immunofluorescence, and electron microscopy ultrastructure

    PMID:30647131

    Open questions at the time
    • Molecular mechanism by which centrins stabilize the axoneme is undefined
    • Direct relationship between CETN2 and SPATA7 retention not established
    • Calcium dependence of the ciliary role not tested
  3. 2025 Medium

    Connected CETN2 to DNA repair by showing it complexes with XPC to promote NER, framing CETN2 as a determinant of chemotherapy response.

    Evidence Co-immunoprecipitation, siRNA knockdown, overexpression, and DNA damage/apoptosis assays with oxaliplatin in HCC cell lines, with XPC-knockdown rescue

    PMID:39945187

    Open questions at the time
    • Single-lab Co-IP without reciprocal validation or structural mapping of the CETN2-XPC interface
    • Step in NER that CETN2 facilitates is not pinpointed
    • Whether the centriolar pool and the NER pool of CETN2 are functionally distinct is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CETN2's calcium-binding activity mechanistically couples its centriolar/ciliary structural role to its NER function remains unresolved.
  • No structural model of CETN2 in either context
  • Calcium-dependence of any documented function untested
  • Integration of ciliary and DNA-repair roles unexplained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0005815 microtubule organizing center 1 GO:0005929 cilium 1
Pathway
R-HSA-73894 DNA Repair 1
Partners
CETN3XPC

Evidence

Reading pass · 3 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Mouse centrin 2 (CETN2) protein localizes to the region immediately surrounding the centrioles in the centrosome of NIH 3T3 cells, as demonstrated by immunofluorescence microscopy. CETN2 encodes a 172 amino acid EF-hand calcium-binding protein and is ubiquitously expressed in adult mouse tissues. Immunofluorescence microscopy, Northern blot, RT-PCR, FISH Gene Medium 11250075
2019 CETN2 and CETN3 cooperate to stabilize the photoreceptor connecting cilium (CC) axoneme structure; simultaneous deletion of both Cetn2 and Cetn3 in mice destabilizes the photoreceptor axoneme, reduces CC length, depletes SPATA7 from the distal CC, and causes radial expansion of the axoneme with misaligned outer segment discs, ultimately leading to retinal degeneration — whereas single knockouts of either gene alone do not affect photoreceptor function. Double-knockout mouse model (Cetn2-/-;Cetn3GT/GT), electroretinography (ERG), immunofluorescence, ultrastructural analysis (electron microscopy) The Journal of biological chemistry High 30647131
2025 CETN2 forms a complex with XPC (a key initiator of nucleotide excision repair, NER), enhancing NER activity and thereby reducing the cytotoxic efficacy of oxaliplatin in hepatocellular carcinoma (HCC) cells. siRNA-mediated knockdown of CETN2 increased oxaliplatin-induced cytotoxicity and apoptosis, while CETN2 overexpression inhibited oxaliplatin-induced DNA damage in a manner partially reversed by XPC knockdown. Co-immunoprecipitation (complex formation with XPC), siRNA knockdown, overexpression, cytotoxicity and apoptosis assays, DNA damage assays in HCC cell lines Carcinogenesis Medium 39945187

Source papers

Stage 0 corpus · 10 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Conjunctiva-associated lymphoid tissue (CALT) reactions to antiglaucoma prostaglandins with or without BAK-preservative in rabbit acute toxicity study. PloS one 32 22442734
1994 Sequence around the centromere of Saccharomyces cerevisiae chromosome II: similarity of CEN2 to CEN4. Yeast (Chichester, England) 25 8091860
2019 Deletion of both centrin 2 (CETN2) and CETN3 destabilizes the distal connecting cilium of mouse photoreceptors. The Journal of biological chemistry 22 30647131
1994 Conjunctival instillation of retinal antigens induces tolerance Does it invoke mucosal tolerance mediated via conjunctiva associated lymphoid tissues (CALT)? Ocular immunology and inflammation 21 22823013
2001 Characterization of the X-linked murine centrin Cetn2 gene. Gene 19 11250075
2020 Disease-Specific Expression of Conjunctiva Associated Lymphoid Tissue (CALT) in Mouse Models of Dry Eye Disease and Ocular Allergy. International journal of molecular sciences 16 33053795
1996 The effect of topical cyclosporin on conjunctiva-associated lymphoid tissue (CALT). Eye (London, England) 14 8944092
2016 Novel Centromeric Loci of the Wine and Beer Yeast Dekkera bruxellensis CEN1 and CEN2. PloS one 11 27560164
2011 Characterization of membranous (M) cells in normal feline conjunctiva-associated lymphoid tissue (CALT). Veterinary ophthalmology 7 21923825
2025 Role of the nucleotide excision repair function of CETN2 in the inhibition of the sensitivity of hepatocellular carcinoma cells to oxaliplatin. Carcinogenesis 1 39945187

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