Affinage

TERB1

Telomere repeats-binding bouquet formation protein 1 · UniProt Q8NA31

Length
727 aa
Mass
83.1 kDa
Annotated
2026-06-10
11 papers in source corpus 8 papers cited in narrative 8 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TERB1 (CCDC79) is a meiosis-specific telomere protein that serves as the central scaffold tethering telomeres to the nuclear envelope to drive chromosome movement, homologous pairing, and synapsis during meiotic prophase I (PMID:24413433). It localizes to telomeres from leptotene to diplotene and engages the canonical telomeric protein TRF1 through a dedicated TRF1-binding motif, whose interaction with the TRFH domain of TRF1 is defined at atomic resolution (PMID:24413433, PMID:29083416). TERB1 is organized into separable functional modules: the TRF1-binding motif, a TERB2-binding (T2B) domain that recruits the TERB2-MAJIN subcomplex for nuclear-envelope attachment, and an MYB-like domain dedicated to cohesin recruitment (PMID:29141207). Within the assembled complex, TRF1 directs sequential recruitment of TERB1→TERB2→MAJIN, and the MAJIN-TERB2-TERB1 module first captures telomere-bound TRF1 and then displaces it during pachytene, taking over direct telomeric DNA binding to form a mature attachment plate (PMID:29141207, PMID:30559341). The MYB domain has lost canonical DNA-binding activity and instead enriches cohesin at telomeres and remodels axial elements at the early-to-late pachytene transition, conferring structural rigidity that suppresses telomere erosion without affecting pairing or fertility (PMID:35081355). This nuclear-envelope tethering pathway operates cooperatively with, but separably from, the SUN-KASH LINC complex route to stably anchor telomeres (PMID:30718482). Disruption of TERB1 abolishes meiotic chromosomal movement and impairs pairing and synapsis, causing infertility, with the requirement conserved in fish meiosis (PMID:24413433, PMID:38809870).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2014 High

    Established TERB1 as a meiosis-specific telomere factor that physically links telomeres to the nuclear envelope and is essential for the chromosome movements underlying pairing and synapsis.

    Evidence Mouse knockout with reciprocal Co-IP, telomere DNA-binding and localization assays, genetic epistasis

    PMID:24413433

    Open questions at the time
    • Domain-level basis for TRF1 binding, NE attachment, and cohesin recruitment not yet resolved
    • Order of complex assembly undefined
  2. 2014 High

    Defined TERB1's place in the telomere-NE attachment hierarchy, showing it loads onto telomeres independently of SUN1 but depends on cohesin (SMC1B) for stable association.

    Evidence Immunofluorescence in SUN1-deficient and SMC1B-deficient spermatocytes

    PMID:24885367

    Open questions at the time
    • Did not resolve direct versus indirect dependence on cohesin
    • Molecular interactions not tested
  3. 2017 High

    Provided the structural basis of the TERB1-TRF1 interaction and demonstrated its specific in vivo requirement for meiotic telomere function.

    Evidence Crystal structure of TERB1 TBM with the TRF1 TRFH domain plus interaction-disrupting knock-in mouse, IF and FISH

    PMID:29083416

    Open questions at the time
    • Why disruption causes male-only infertility unexplained
    • Mechanism of PAR/X-Y pairing failure not resolved
  4. 2017 High

    Dissected TERB1 into separable functional domains and placed TRF1 at the top of a sequential TERB1-TERB2-MAJIN assembly pathway.

    Evidence Germ-cell TRF1 conditional knockout, domain-specific TERB1 mutants, Co-IP and IF

    PMID:29141207

    Open questions at the time
    • Structural mechanism of TERB2/MAJIN engagement not yet shown
    • Function of MYB-domain cohesin recruitment not phenotypically isolated
  5. 2018 High

    Solved the MAJIN-TERB2 architecture and proposed a handover model in which the complex first recruits TRF1 then displaces it to bind telomeric DNA directly at a mature attachment plate.

    Evidence Crystal structure, X-ray scattering, biochemical DNA-binding assays, structured illumination microscopy

    PMID:30559341

    Open questions at the time
    • Trigger and timing of TRF1 displacement in vivo not defined
    • Stoichiometry at native telomeres not directly measured
  6. 2019 High

    Resolved the TERB1-TERB2 and TERB2-MAJIN interfaces and showed the TRF1-TERB1-TERB2-MAJIN pathway acts as a separate but cooperative route to the LINC complex for telomere-NE anchoring.

    Evidence Crystal structures, interaction-specific Terb2 knock-in mice, SUN1 depletion, chromosome spreading

    PMID:30718482

    Open questions at the time
    • Quantitative contribution of each pathway to force transmission unresolved
    • Crosstalk mechanism between the two routes unknown
  7. 2022 High

    Separated the MYB domain's role from telomere tethering, showing it has lost DNA binding and instead recruits cohesin to remodel axial elements and prevent telomere erosion.

    Evidence In vitro DNA-binding assay, MYB-domain point-mutant knock-in mouse, IF, telomere FISH, chromosome spreading

    PMID:35081355

    Open questions at the time
    • Direct cohesin-binding partner of the MYB domain not identified
    • Molecular basis of axial-element remodeling unresolved
  8. 2024 Medium

    Extended TERB1's requirement for synaptonemal complex completion and homolog arrangement to a non-mammalian vertebrate, revealing sexually dimorphic checkpoint responses to its loss.

    Evidence Medaka terb1 loss-of-function mutant, IF, FISH, cytological SC analysis

    PMID:38809870

    Open questions at the time
    • No molecular interaction data in fish
    • Basis of sexually dimorphic checkpoint not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the assembled attachment plate transduces cytoskeletal force and how TRF1 displacement is temporally controlled in vivo remain unresolved.
  • No direct measurement of force transmission through the TERB1 scaffold
  • In vivo trigger for the TRF1-to-MAJIN handover unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0003677 DNA binding 2
Localization
GO:0005635 nuclear envelope 3 GO:0005694 chromosome 3
Pathway
R-HSA-1474165 Reproduction 3 R-HSA-1640170 Cell Cycle 1
Partners
MAJINSMC1BSUN1TERB2TRF1
Complex memberships
LINC (SUN-KASH) complexTERB1-TERB2-MAJIN complex

Evidence

Reading pass · 8 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 TERB1 (CCDC79) is a meiosis-specific Myb-domain protein that localizes to telomeres in mouse germ cells, forms a heterocomplex with the canonical telomeric protein TRF1, and binds telomere repeat DNA. TERB1 promotes telomere association with the nuclear envelope and deposition of the SUN-KASH complex (which recruits cytoplasmic motor complexes), and also recruits cohesin to telomeres to develop structural rigidity. Disruption of Terb1 abolishes meiotic chromosomal movement and impairs homologous pairing and synapsis, causing infertility in both sexes. Mouse knockout, Co-immunoprecipitation, telomere DNA binding assay, immunofluorescence localization, genetic epistasis Nature cell biology High 24413433
2014 CCDC79 (TERB1) is a meiosis-specific protein that localizes to telomeres from leptotene to diplotene stages. CCDC79 associates with telomeres independently of SUN1-mediated nuclear envelope attachment (localization persists in SUN1-deficient spermatocytes), but is largely absent from telomeres that fail to connect to SUN1 in SMC1B-deficient spermatocytes. Immunofluorescence localization in wild-type and mutant (SUN1-deficient, SMC1B-deficient) spermatocytes BMC cell biology High 24885367
2017 Crystal structure of the TRF1-binding motif (TBM) of human TERB1 in complex with the TRFH domain of TRF1 was solved. A specific point mutation disrupting the TERB1-TRF1 interaction in mice causes infertility only in males, with arrest at the zygotene-early pachytene stage, mild telomere abnormalities on autosomes, and failure of X-Y chromosome pairing at the pseudoautosomal region (PAR) in pachytene. Crystal structure determination, point-mutant knock-in mouse, immunofluorescence, FISH Nature structural & molecular biology High 29083416
2017 TERB1 contains distinct functional domains: a TRF1-binding motif required for TRF1 interaction; a TERB2-binding (T2B) domain required for TERB1-TERB2 interaction and telomere attachment to the nuclear envelope (but dispensable for TRF1-TERB1 interaction); and an MYB-like domain required for cohesin recruitment at telomeres (but not for TERB2-MAJIN assembly). TRF1 directs the sequential assembly of TERB1-TERB2-MAJIN. Germ-cell-specific TRF1 knockout mouse, domain-specific TERB1 mutant analysis, Co-immunoprecipitation, immunofluorescence Cell reports High 29141207
2018 Crystal structure of the MAJIN-TERB2 complex (2:2 hetero-tetramer) was determined; MAJIN-TERB2 strongly binds DNA and is tethered via long flexible linkers to the inner nuclear membrane and to two TRF1-binding 1:1 TERB2-TERB1 complexes. Structured illumination microscopy and biochemical data revealed a telomere attachment mechanism in which MAJIN-TERB2-TERB1 first recruits telomere-bound TRF1, which is then displaced during pachytene, allowing MAJIN-TERB2-TERB1 to bind telomeric DNA and form a mature attachment plate. Crystal structure determination, X-ray scattering, biochemical DNA binding assays, structured illumination microscopy Nature communications High 30559341
2019 Crystal structures of human TERB1-TERB2 and TERB2-MAJIN subcomplexes were determined. Specific disruption of either the TERB1-TERB2 interaction or the TERB2-MAJIN interaction by point mutations in the mouse Terb2 gene abolishes telomere attachment to the nuclear envelope and causes aberrant homologous pairing and disordered synapsis. SUN1 depletion partially disrupts the telomere-NE connection, suggesting that the telomere-TRF1-TERB1-TERB2-MAJIN-NE pathway and the LINC complex pathway are two separate but cooperative routes for stable telomere-NE recruitment. Crystal structure determination, knock-in point mutant mice (Terb2 gene), SUN1 depletion, immunofluorescence, chromosome spreading Nature communications High 30718482
2022 The TERB1 MYB domain has lost its canonical DNA-binding activity. In Terb1 point-mutant mice lacking the functional MYB domain, telomere localization of TERB1 and the downstream TERB2-MAJIN complex, homologous pairing, and fertility are unaffected. Instead, the MYB domain is required for cohesin enrichment at telomeres and remodeling of axial elements at the early-to-late pachytene transition, thereby suppressing telomere erosion during meiotic prophase I. In vitro DNA-binding assay, Terb1 MYB-domain point-mutant knock-in mouse, immunofluorescence, telomere FISH, chromosome spreading Cell reports High 35081355
2024 In medaka (fish ortholog), loss of terb1 causes failure to complete synaptonemal complex formation despite initiation of lateral elements and fragmented transverse filaments, and results in aberrant homologous chromosome arrangement. The oogenesis-spermatogenesis checkpoint response to terb1 loss is sexually dimorphic: oogenesis arrests at zygotene-like stage while spermatogenesis continues to produce sperm-like cells with abnormal DNA content. Medaka terb1 mutant (loss-of-function), immunofluorescence, FISH, cytological analysis of SC Zoological science Medium 38809870

Source papers

Stage 0 corpus · 11 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 The TRF1-binding protein TERB1 promotes chromosome movement and telomere rigidity in meiosis. Nature cell biology 151 24413433
2019 The meiotic TERB1-TERB2-MAJIN complex tethers telomeres to the nuclear envelope. Nature communications 41 30718482
2017 Telomeric TERB1-TRF1 interaction is crucial for male meiosis. Nature structural & molecular biology 41 29083416
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
2014 Mouse CCDC79 (TERB1) is a meiosis-specific telomere associated protein. BMC cell biology 33 24885367
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
2022 The TERB1 MYB domain suppresses telomere erosion in meiotic prophase I. Cell reports 10 35081355
2024 A report of two homozygous TERB1 protein-truncating variants in two unrelated women with primary infertility. Journal of assisted reproduction and genetics 3 38277113
2024 Medaka Terb1 Mutant Displays Defects of Synaptonemal Complex Formation and Sexual Difference in Gametogenesis. Zoological science 1 38809870

Missed literature

Know a paper Affinage missed for TERB1? Flag it for the maintainers and the community.

No submissions yet.