Affinage

TEX14

Inactive serine/threonine-protein kinase TEX14 · UniProt Q8IWB6

Length
1497 aa
Mass
167.9 kDa
Annotated
2026-04-28
16 papers in source corpus 11 papers cited in narrative 11 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TEX14 is a germ-cell intercellular bridge protein that converts the cytokinetic abscission machinery into a stable intercellular connection, and additionally functions at kinetochores during mitosis. TEX14 blocks abscission by binding CEP55 through a high-affinity AxGPPx3YxPP motif, competitively displacing ALIX and TSG101 from the midbody and thereby preventing ESCRT-mediated membrane scission; loss of TEX14 eliminates intercellular bridges and causes meiotic arrest and azoospermia in mice and humans (PMID:16549803, PMID:20176808, PMID:26392564, PMID:40492599). During mitosis in somatic cells, TEX14 is recruited to kinetochores by PLK1 in a CDK1-dependent manner, where it promotes outer kinetochore assembly and spindle assembly checkpoint function, and is subsequently degraded via APC/C(Cdc20) after PLK1-mediated phosphorylation to permit the metaphase-to-anaphase transition (PMID:22405274). Biallelic loss-of-function TEX14 mutations cause non-obstructive azoospermia in humans due to failed intercellular bridge assembly and meiotic arrest (PMID:40492599, PMID:41603674).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2003 Medium

    Initial cloning established TEX14 as a testis-specific gene encoding a large protein with ankyrin repeats, a kinase domain, and a leucine zipper, expressed predominantly in meiotic spermatocytes — defining TEX14 as a candidate male germ cell regulator.

    Evidence Sequence analysis, Northern blot, and in situ hybridization in mouse testis

    PMID:12711554

    Open questions at the time
    • Kinase activity of the predicted kinase domain has never been biochemically validated
    • Functional role of ankyrin repeats and leucine zipper not determined
  2. 2006 High

    Gene knockout resolved TEX14's essential cellular function: it is required for the formation of stable germ cell intercellular bridges, and its absence causes complete spermatogenic arrest and male sterility.

    Evidence Tex14 targeted knockout in mice with electron microscopy, immunofluorescence, and histology

    PMID:16549803

    Open questions at the time
    • Molecular mechanism by which TEX14 stabilizes bridges was unknown
    • Whether TEX14 has functions beyond bridge formation was untested
  3. 2008 High

    Extension to embryonic germ cells showed TEX14 is required for intercellular bridges in both sexes and identified KIF23/MKLP1 as a bridge component, yet female fertility is TEX14-independent — revealing sex-specific requirements for bridges.

    Evidence Tex14 knockout mice, KIF23 immunofluorescence and electron microscopy in embryonic gonads

    PMID:19020301

    Open questions at the time
    • Why female germ cells tolerate bridge loss remains unexplained
    • Full molecular composition of the intercellular bridge was unknown
  4. 2010 High

    The mechanism of bridge stabilization was elucidated: TEX14 binds CEP55 via a GPPX3Y motif and competitively prevents ALIX and TSG101 from localizing to the midbody, thereby blocking abscission and converting the cytokinetic machinery into a stable bridge.

    Evidence Biochemical enrichment of intercellular bridges, co-immunoprecipitation, competitive binding assays

    PMID:20176808

    Open questions at the time
    • Structural basis of the TEX14–CEP55 interaction was not yet resolved
    • Whether the kinase domain contributes to bridge function was unknown
  5. 2011 Medium

    A natural loss-of-function mutation in pig Tex14 independently confirmed the gene's essential role: a 51-bp insertion causing a premature stop led to absent TEX14 protein, early meiotic arrest, and azoospermia.

    Evidence Genome-wide SNP scan, candidate gene sequencing, RT-PCR, and Western blot in pig testis

    PMID:22136159

    Open questions at the time
    • Single breed/population studied
    • Whether heterozygous carriers have any subfertility phenotype is unknown
  6. 2012 High

    An unexpected somatic function was uncovered: TEX14 is recruited to kinetochores by PLK1/CDK1 during mitosis, where it promotes outer kinetochore assembly, kinetochore-microtubule attachment, and spindle assembly checkpoint activity; its subsequent PLK1-mediated phosphorylation triggers APC/C(Cdc20)-dependent degradation to allow anaphase onset.

    Evidence siRNA knockdown, phosphomutant analysis, kinetochore localization, and checkpoint assays in somatic cells

    PMID:22405274

    Open questions at the time
    • Relationship between kinetochore and intercellular bridge functions is not integrated
    • Direct kinase substrates or catalytic activity of TEX14 at kinetochores not demonstrated
    • Whether the kinetochore role is relevant in germ cells remains untested
  7. 2015 High

    Crystal structures of the CEP55-EABR–TEX14 peptide complex provided an atomic-resolution mechanism: TEX14 uses an AxGPPx3YxPP motif to bind CEP55 with high affinity and slow dissociation, cooperatively blocking ALIX recruitment at physiological concentrations.

    Evidence X-ray crystallography, quantitative binding and displacement assays, functional mutagenesis

    PMID:26392564

    Open questions at the time
    • Full-length TEX14 structure remains undetermined
    • Whether post-translational modifications regulate CEP55 binding in vivo is unknown
  8. 2019 Medium

    Upstream translational control of TEX14 was identified: the RNA-binding protein DAZL promotes TEX14 translation in germ cells via its 3ʹUTR, linking RNA regulatory programs to intercellular bridge assembly.

    Evidence Dazl hypomorph ovaries, immunostaining quantification, 3ʹUTR-luciferase reporter assays

    PMID:31659914

    Open questions at the time
    • Direct DAZL binding site on Tex14 mRNA not mapped
    • Whether other RNA-binding proteins co-regulate TEX14 translation is unknown
  9. 2025 Medium

    TEX14's abscission-blocking mechanism was shown to be exploitable therapeutically: partial peptides containing the GPPX3Y motif inhibit cancer cell proliferation and induce apoptosis by blocking abscission, with flanking residues modulating potency.

    Evidence Cancer cell proliferation and apoptosis assays with peptide variants

    PMID:41219627

    Open questions at the time
    • In vivo efficacy and pharmacokinetics not tested
    • Selectivity for cancer cells versus normal dividing cells not established
  10. 2025 Medium

    Human genetic validation was achieved: biallelic TEX14 mutations were shown to cause non-obstructive azoospermia with meiotic arrest and impaired intercellular bridge assembly in patient testis tissue, establishing TEX14 as a human male infertility gene.

    Evidence Exome sequencing, Sanger sequencing, Western blot and immunofluorescence on patient testicular biopsies; knock-in mouse model recapitulating phenotype

    PMID:40492599 PMID:41603674

    Open questions at the time
    • Number of reported families is small
    • Genotype-phenotype correlation across different mutation types is incomplete
    • Whether any TEX14 mutations cause oligozoospermia rather than complete azoospermia is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Whether TEX14 possesses catalytic kinase activity, how its kinetochore and intercellular bridge functions are coordinately regulated in germ cells, and the full proteomic composition and signaling functions of TEX14-dependent intercellular bridges remain unresolved.
  • No demonstration of TEX14 kinase activity despite a predicted kinase domain
  • Integration of kinetochore and bridge roles in meiotic cells not addressed
  • Functional significance of RNA-processing proteins enriched at intercellular bridges is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 2 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005829 cytosol 2 GO:0005694 chromosome 1
Pathway
R-HSA-1474165 Reproduction 4 R-HSA-1640170 Cell Cycle 1
Partners
CEP55DAZLKIF23PLK1
Complex memberships
intercellular bridge complex

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 TEX14 is an essential structural component of germ cell intercellular bridges in male mice. In Tex14-/- mice, intercellular bridges are absent by electron microscopy, spermatogenesis arrests before completion of the first meiotic division, and male mice are sterile, demonstrating TEX14 is required for stable intercellular bridge formation. Targeted gene knockout, electron microscopy, immunofluorescence, histological analysis Proceedings of the National Academy of Sciences of the United States of America High 16549803
2008 TEX14 is an essential component of both male and female embryonic germ cell intercellular bridges. KIF23 (MKLP1) was identified as a component of intercellular bridges during spermatogenesis and in embryonic germ cells. In Tex14-null mice, embryonic intercellular bridges are absent between gonocytes and oogonia (confirmed by KIF23 immunofluorescence and EM), yet female mice remain fertile. Tex14 knockout mouse model, KIF23 immunofluorescence, electron microscopy Biology of reproduction High 19020301
2010 TEX14 blocks cytokinetic abscission by binding CEP55 via a conserved GPPX3Y motif, preventing ALIX and TSG101 from interacting with CEP55 and localizing to the midbody. CEP55 becomes a stable intercellular bridge component instead of a nidus for abscission. TEX14 was identified as part of a biochemically enriched intercellular bridge complex. Biochemical enrichment of intercellular bridges, co-immunoprecipitation, competitive binding assays, targeted knockout, immunofluorescence Molecular and cellular biology High 20176808
2012 TEX14 is recruited to kinetochores by PLK1 in a CDK1-dependent manner during early mitosis in somatic cells. TEX14 loss impairs outer kinetochore component localization, kinetochore-microtubule attachment, chromosome congression, and spindle assembly checkpoint function. PLK1-mediated phosphorylation of TEX14 during metaphase promotes APC/C(Cdc20)-mediated TEX14 degradation; blocking this phosphorylation retains TEX14 at kinetochores and delays metaphase-to-anaphase transition. siRNA knockdown, phosphorylation assays, kinetochore localization studies, chromosome segregation assays, inhibitor treatments Molecular cell High 22405274
2015 Crystal structures of the CEP55-EABR domain bound to TEX14 peptide reveal that TEX14 interacts via an AxGPPx3YxPP motif. TEX14 competitively displaces ALIX from CEP55-EABR with high affinity and a low dissociation rate, and increased local concentration of TEX14 cooperatively prevents ALIX from recruiting ESCRT complexes to the midbody. X-ray crystallography, binding affinity measurements, competitive binding/displacement assays, functional mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 26392564
2003 TEX14 encodes a 1450-amino-acid protein containing three ankyrin repeats, a protein kinase domain, and a leucine zipper dimerization motif, and is expressed specifically in the testis with highest levels in pachytene, diplotene, and meiotically dividing spermatocytes. Sequence analysis, Northern blot, in situ hybridization, 5'-RACE Gene expression patterns : GEP Medium 12711554
2019 DAZL, a germ cell RNA-binding protein, translationally regulates TEX14. In Dazl hypomorph ovaries, TEX14 protein is reduced ~59% without change in Tex14 mRNA, and TEX14 intercellular bridge foci are reduced in number and size. DAZL-dependent translational regulation of TEX14 was confirmed by 3'UTR-luciferase reporter assays. siRNA knockdown in fetal ovary cultures, immunostaining, 3'UTR-luciferase reporter assay FASEB journal : official publication of the Federation of American Societies for Experimental Biology Medium 31659914
2011 A 51-bp insertion within exon 27 of pig Tex14 causes differential splicing and a premature stop codon, resulting in markedly reduced Tex14 mRNA and absence of TEX14 protein in the testis, causing spermatogenic arrest at an early meiotic phase and azoospermia. Genome-wide SNP scan, candidate gene sequencing, RT-PCR, Western blot BMC genomics Medium 22136159
2025 Partial TEX14 peptides containing the GPPX3Y motif are sufficient to inhibit proliferation and induce apoptosis in cancer cells, functioning by blocking abscission; the amino acids surrounding the GPPX3Y motif modulate the efficiency of this inhibition. Cancer cell proliferation assays, apoptosis assays, peptide structure-activity studies Human cell Medium 41219627
2025 Compound heterozygous TEX14 mutations (p.S268C and p.R341*) in a human NOA patient disrupt TEX14 synthesis and cause meiotic arrest at the pachytene stage with impaired intercellular bridge assembly, confirming pathogenic biallelic TEX14 mutations as a cause of human azoospermia. Exome sequencing, Sanger sequencing, Western blot, immunofluorescence, testicular histology Clinical genetics Medium 40492599
2026 Loss-of-function frameshift mutations in TEX14 in humans cause meiotic arrest at the zygotene stage (rather than pachytene) due to complete failure of intercellular bridge formation. A knock-in mouse model recapitulated the human NOA phenotype. Mass spectrometry of purified intercellular bridges identified associated proteins predominantly involved in RNA processing and ribonucleoprotein complex biogenesis. Exome sequencing, knock-in mouse model, immunofluorescence, histology, mass spectrometry of purified ICBs Andrology Medium 41603674

Source papers

Stage 0 corpus · 16 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 TEX14 is essential for intercellular bridges and fertility in male mice. Proceedings of the National Academy of Sciences of the United States of America 221 16549803
2008 Mouse TEX14 is required for embryonic germ cell intercellular bridges but not female fertility. Biology of reproduction 88 19020301
2010 TEX14 interacts with CEP55 to block cell abscission. Molecular and cellular biology 68 20176808
2012 Tex14, a Plk1-regulated protein, is required for kinetochore-microtubule attachment and regulation of the spindle assembly checkpoint. Molecular cell 42 22405274
2003 Sequence and expression of testis-expressed gene 14 (Tex14): a gene encoding a protein kinase preferentially expressed during spermatogenesis. Gene expression patterns : GEP 32 12711554
2018 Expression analysis of genes encoding TEX11, TEX12, TEX14 and TEX15 in testis tissues of men with non-obstructive azoospermia. JBRA assisted reproduction 27 29932616
2015 Structural and biochemical insights into the role of testis-expressed gene 14 (TEX14) in forming the stable intercellular bridges of germ cells. Proceedings of the National Academy of Sciences of the United States of America 26 26392564
2021 Altered germline cyst formation and oogenesis in Tex14 mutant mice. Biology open 22 34156079
2011 An exonic insertion within Tex14 gene causes spermatogenic arrest in pigs. BMC genomics 22 22136159
2019 Dazl determines primordial follicle formation through the translational regulation of Tex14. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 13 31659914
2020 Spermatogonial asynchrony in Tex14 mutant mice lacking intercellular bridges. Reproduction (Cambridge, England) 9 32438343
2024 Correlation between TEX14 and ADAM17 expressions in colorectal cancer tissues of elderly patients and neoplasm staging, invasion, and metastasis. World journal of clinical cases 1 39188605
2026 Pathogenic TEX14 Variants Disrupt Intercellular Bridge Formation, Causing Meiotic Arrest and Non-Obstructive Azoospermia in Humans and Mice. Andrology 0 41603674
2025 A Novel Compound Heterozygous Mutation in TEX14 Causes Human Non-Obstructive Azoospermia by Disrupting the Assembly of Intercellular Bridges. Clinical genetics 0 40492599
2025 Partial TEX14 peptides inhibit proliferation of cancer cells and have potential as anti-tumour agents. Human cell 0 41219627
2023 Inhibition mechanism of testis-expressed gene 14 (TEX14) in cytokinetic abscission: Well-tempered metadynamics simulation studies. The Journal of chemical physics 0 37409705