Affinage

TERB2

Telomere repeats-binding bouquet formation protein 2 · UniProt Q8NHR7

Length
220 aa
Mass
25.3 kDa
Annotated
2026-06-10
9 papers in source corpus 5 papers cited in narrative 5 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/5 claims corpus-supported (80%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TERB2 is a central bridging subunit of the meiotic telomere complex that tethers chromosome ends to the inner nuclear membrane to enable the chromosome movements required for homologous pairing and synapsis during meiotic prophase I (PMID:30718482). It forms a 2:2 hetero-tetramer with MAJIN that binds telomeric DNA strongly and is anchored through flexible linkers to the inner nuclear membrane, while simultaneously engaging TERB1 in a 1:1 complex via TERB1's dedicated T2B domain (PMID:30559341, PMID:29141207). Through these two interfaces TERB2 nucleates the TERB1-TERB2-MAJIN assembly, which is sequentially recruited to telomeres by TRF1; TRF1 is later displaced during pachytene so that the complex binds telomeric DNA directly to form a mature attachment plate (PMID:30559341, PMID:29141207). Specific disruption of either the TERB1-TERB2 or TERB2-MAJIN interaction abolishes telomere attachment to the nuclear envelope and causes aberrant pairing and disordered synapsis, establishing TERB2's bridging role as essential to the tethering network (PMID:30718482). Attachment to the LINC complex is achieved through a SUN1-MAJIN interaction that is stabilized by SPDYA-CDK2 activity (PMID:33015044).

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 2017 High

    Established how the telomere-tethering complex is recruited to chromosome ends, defining the assembly order and the TERB1 domain required to engage TERB2.

    Evidence Germ-cell-specific TRF1 knockout mouse with domain mapping, co-immunoprecipitation, and meiotic immunofluorescence

    PMID:29141207

    Open questions at the time
    • Did not resolve the atomic basis of the TERB1-TERB2 or TERB2-MAJIN interfaces
    • Mechanism of TRF1 displacement during pachytene not defined
  2. 2018 High

    Resolved the architecture of the attachment plate, showing TERB2-MAJIN forms a DNA-binding 2:2 tetramer membrane-anchored via flexible linkers and that TRF1 is handed off to allow direct telomeric DNA binding.

    Evidence Crystal structure with X-ray/light scattering, structured illumination microscopy, and biochemical binding assays

    PMID:30559341

    Open questions at the time
    • Trigger for TRF1 displacement during pachytene unresolved
    • Stoichiometry of the full TERB1-TERB2-MAJIN assembly at telomeres in vivo not directly visualized
  3. 2019 High

    Demonstrated genetically that TERB2 is the obligate bridging subunit, since disrupting either of its two interfaces independently abolishes nuclear-envelope tethering and disrupts pairing/synapsis.

    Evidence Crystal structures of human TERB1-TERB2 and TERB2-MAJIN plus interface-specific knock-in mice and cytological meiotic analysis

    PMID:30718482

    Open questions at the time
    • Does not address how the bridge integrates with cytoskeletal force generation
    • Quantitative contribution of each interface to attachment-plate stability not separated
  4. 2020 Medium

    Connected the telomere complex to the LINC machinery, identifying SUN1-MAJIN as the key NE interface and implicating CDK2 activity in stabilizing it.

    Evidence Co-immunoprecipitation, binding-site mapping, and CDK2 inhibitor treatment

    PMID:33015044

    Open questions at the time
    • No mutagenesis reconstitution to confirm the CDK2 phosphosite
    • Single-lab pharmacological perturbation without genetic validation
    • Direct phosphorylation of MAJIN/SUN1 by CDK2 not demonstrated
  5. 2022 High

    Separated the tethering function from a downstream chromosome-maintenance role, showing the TERB1 MYB domain is dispensable for localization but governs telomeric cohesin and axial element remodeling.

    Evidence Terb1 MYB-domain point mutant knock-in mice with immunofluorescence, cohesin ChIP, and chromosome spread analysis

    PMID:35081355

    Open questions at the time
    • Concerns TERB1 rather than TERB2 directly
    • Mechanism linking MYB domain to cohesin enrichment not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How cytoskeletal forces transmitted through the LINC complex are coupled to the TERB2-anchored attachment plate to drive telomere-led chromosome movement remains unresolved.
  • No reconstitution of force transmission from cytoskeleton through SUN1-MAJIN to TERB2
  • Regulation of the TRF1-to-telomeric-DNA handoff at the molecular level unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 2 GO:0003677 DNA binding 1
Localization
GO:0000228 nuclear chromosome 2 GO:0005635 nuclear envelope 2
Pathway
R-HSA-1474165 Reproduction 2
Partners
MAJINSUN1TERB1TRF1
Complex memberships
LINC complexTERB1-TERB2-MAJIN (meiotic telomere complex)

Evidence

Reading pass · 5 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 Crystal structure of MAJIN-TERB2 revealed a 2:2 hetero-tetramer that binds strongly to DNA and is tethered through long flexible linkers to the inner nuclear membrane and two TRF1-binding 1:1 TERB2-TERB1 complexes. The MAJIN-TERB2-TERB1 complex recruits telomere-bound TRF1, which is then displaced during pachytene, allowing MAJIN-TERB2-TERB1 to bind telomeric DNA directly and form a mature attachment plate. Crystal structure determination, X-ray scattering, light scattering, structured illumination microscopy, biochemical binding assays Nature communications High 30559341
2019 Crystal structures of human TERB1-TERB2 and TERB2-MAJIN subcomplexes were determined. Specific disruption of the TERB1-TERB2 interaction or the TERB2-MAJIN interaction in mouse Terb2 abolishes telomere attachment to the nuclear envelope, causing aberrant homologous pairing and disordered synapsis, establishing that TERB2 acts as a bridging subunit in the TERB1-TERB2-MAJIN tethering network. Crystal structure determination, knock-in mouse with targeted disruption of specific protein-protein interaction interfaces, cytological analysis of meiotic chromosomes Nature communications High 30718482
2017 TERB1 contains a distinct TERB2-binding (T2B) domain that is dispensable for TRF1-TERB1 interaction but essential for the TERB1-TERB2 interaction and telomere attachment to the nuclear envelope. TRF1 directs the sequential assembly of TERB1-TERB2-MAJIN; loss of TRF1 in germ cells prevents TERB2-MAJIN recruitment to telomeres. Germ-cell-specific TRF1 knockout mouse, domain-mapping experiments, co-immunoprecipitation, immunofluorescence of meiotic chromosomes Cell reports High 29141207
2020 SUN1 interacts with MAJIN (more strongly than with TERB1) at its N-terminal domain; SPDYA recruits CDK2 to SUN1 via the Ringo domain; CDK2 inhibition decreases the SUN1-MAJIN interaction, suggesting CDK2-mediated phosphorylation promotes the telomere-NE attachment mediated by the TTM complex. Co-immunoprecipitation, binding-site mapping, CDK2 inhibitor treatment Frontiers in cell and developmental biology Medium 33015044
2022 The TERB1 MYB domain is dispensable for telomere localization of TERB1 and the downstream TERB2-MAJIN complex, and for homologous pairing; instead, it regulates cohesin enrichment at telomeres and promotes axial element remodeling in the early-to-late pachytene transition, suppressing telomere erosion. Terb1 point mutant knock-in mice lacking MYB domain, immunofluorescence, cohesin ChIP, chromosome spread analysis Cell reports High 35081355

Source papers

Stage 0 corpus · 9 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 The meiotic TERB1-TERB2-MAJIN complex tethers telomeres to the nuclear envelope. Nature communications 41 30718482
2020 Disruption of human meiotic telomere complex genes TERB1, TERB2 and MAJIN in men with non-obstructive azoospermia. Human genetics 37 33211200
2018 Structural basis of meiotic telomere attachment to the nuclear envelope by MAJIN-TERB2-TERB1. Nature communications 33 30559341
2017 Distinct TERB1 Domains Regulate Different Protein Interactions in Meiotic Telomere Movement. Cell reports 30 29141207
2020 The TERB1-TERB2-MAJIN complex of mouse meiotic telomeres dates back to the common ancestor of metazoans. BMC evolutionary biology 17 32408858
2020 Tethering of Telomeres to the Nuclear Envelope Is Mediated by SUN1-MAJIN and Possibly Promoted by SPDYA-CDK2 During Meiosis. Frontiers in cell and developmental biology 15 33015044
2022 The TERB1 MYB domain suppresses telomere erosion in meiotic prophase I. Cell reports 10 35081355
2022 Computational Analysis of the Potential Impact of MTC Complex Missenses SNPs Associated with Male Infertility. BioMed research international 4 35342767
2024 Telomeric function and regulation during male meiosis in mice and humans. Andrology 2 38511802

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