Affinage

MAJIN

Membrane-anchored junction protein · UniProt Q3KP22

Length
176 aa
Mass
20.1 kDa
Annotated
2026-06-10
12 papers in source corpus 6 papers cited in narrative 6 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAJIN is a meiosis-specific inner nuclear membrane protein that physically tethers telomeres to the nuclear envelope to enable the chromosome movements underlying homolog pairing and recombination (PMID:26548954). As a putative transmembrane component of the inner nuclear membrane, MAJIN nucleates assembly of the meiotic telomere complex by sequestering TERB1 and TERB2 at the membrane, where the complex first forms a chimeric assembly with shelterin and then matures into a DNA-bound state by releasing shelterin in a CDK-phosphorylation-regulated 'telomere cap exchange' (PMID:26548954). Structurally, MAJIN and TERB2 form a 2:2 hetero-tetramer that binds DNA directly and is joined through long flexible linkers to TERB1, which engages telomere-bound TRF1; TRF1 is displaced during pachytene to allow the MAJIN-TERB2-TERB1 module to grip telomeric DNA and form a mature attachment plate (PMID:30559341). The direct TERB2-MAJIN protein-protein interaction is essential in vivo: disrupting this interface in mice abolishes telomere-nuclear envelope tethering and produces aberrant homolog pairing and disordered synapsis (PMID:30718482). Telomeric recruitment of the complex is directed by TRF1, since germ-cell TRF1 loss eliminates TERB1-TERB2-MAJIN telomere localization (PMID:29141207), and MAJIN connects this module to the LINC complex by binding directly to SUN1 at the nuclear envelope in a CDK2-promoted manner (PMID:33015044).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 2015 High

    Established MAJIN as a meiosis-specific INM protein and defined the core logic of meiotic telomere attachment, answering how telomeres become physically coupled to the nuclear envelope.

    Evidence Co-IP, knockout mouse germ-cell genetics, imaging, fractionation, and functional mutagenesis in mouse

    PMID:26548954

    Open questions at the time
    • Atomic basis of the MAJIN-TERB2 interaction not resolved
    • Molecular trigger and ordering of the shelterin-to-DNA cap exchange not fully defined
  2. 2017 High

    Showed that TRF1 directs telomeric assembly of the TERB1-TERB2-MAJIN complex and separated MAJIN/TERB2 from the cohesin-recruiting function, clarifying the division of labor within the complex.

    Evidence Germ-cell-specific TRF1 conditional knockout mice, Co-IP, and immunofluorescence

    PMID:29141207

    Open questions at the time
    • How TRF1 recruitment is handed off during cap exchange not mechanistically detailed
    • Does not address MAJIN membrane topology
  3. 2018 High

    Resolved the 2:2 MAJIN-TERB2 hetero-tetramer and its DNA-binding capacity, explaining structurally how the complex tethers via flexible linkers and grips telomeric DNA after TRF1 displacement.

    Evidence X-ray crystallography, X-ray scattering, structured illumination microscopy, and in vitro DNA-binding assays

    PMID:30559341

    Open questions at the time
    • Structure of full-length membrane-embedded MAJIN not determined
    • Conformational changes during cap exchange not captured
  4. 2019 High

    Demonstrated that the direct TERB2-MAJIN interface is genetically required for telomere-NE tethering and proper synapsis, converting the structural model into an in vivo functional requirement.

    Evidence Crystal structures of human TERB1-TERB2 and TERB2-MAJIN subcomplexes plus interface-disrupting knock-in mouse genetics with synapsis readouts

    PMID:30718482

    Open questions at the time
    • Quantitative contribution of MAJIN DNA-binding versus TERB2 binding to attachment strength not separated
  5. 2020 Medium

    Identified a direct MAJIN-SUN1 interaction at the nuclear envelope and its CDK2 dependence, providing the molecular link between the telomere complex and the LINC complex.

    Evidence Co-IP, GST pulldown, truncation-based binding-site mapping, and CDK2 inhibitor treatment

    PMID:33015044

    Open questions at the time
    • No structural validation of the SUN1-MAJIN interface
    • No in vivo genetic confirmation of the interaction's functional requirement
  6. 2022 Medium

    Distinguished the TERB1 MYB domain's role from MAJIN/TERB2 localization, showing that MYB DNA-binding is dispensable for TERB2-MAJIN telomere recruitment and instead controls cohesin and axial element remodeling.

    Evidence Terb1 MYB point-mutant knock-in mice with MAJIN/TERB2 localization, cohesin, synaptonemal, and telomere-length readouts

    PMID:35081355

    Open questions at the time
    • Single lab, single study
    • Does not define what within the complex independently anchors TERB2-MAJIN to telomeres after TRF1 handoff

Open questions

Synthesis pass · forward-looking unresolved questions
  • The precise molecular trigger that drives the shelterin-to-direct-DNA cap exchange and the force-transmission dynamics from SUN1/LINC through MAJIN to moving telomeres remain unresolved.
  • Real-time mechanics of cap exchange not visualized
  • In vivo necessity of the SUN1-MAJIN interface not genetically tested
  • Membrane topology of MAJIN not structurally confirmed

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 4
Pathway
R-HSA-1474165 Reproduction 2 R-HSA-1640170 Cell Cycle 1
Partners
SUN1TERB1TERB2TRF1
Complex memberships
LINC complex (via SUN1)TERB1-TERB2-MAJIN (TTM) complex

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 MAJIN is a putative transmembrane protein of the inner nuclear membrane (INM) that, together with TERB1 and TERB2, forms a meiotic telomere complex. TERB1/2-MAJIN initially assembles on the INM sequestered by MAJIN. In early meiosis, a chimeric complex of TERB1/2-MAJIN and shelterin is formed; during prophase this matures into DNA-bound TERB1/2-MAJIN by releasing shelterin ('telomere cap exchange'), creating a direct link between telomeric DNA and the INM. These processes are regulated by CDK-dependent phosphorylation and the DNA-binding activity of MAJIN. Co-immunoprecipitation, mouse germ-cell genetics (knockout mice), live-cell and immunofluorescence imaging, biochemical fractionation, functional mutagenesis Cell High 26548954
2018 Crystal structure of the MAJIN-TERB2 complex reveals 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 TERB2-TERB1 complexes. Structured illumination microscopy and biochemical studies show that MAJIN-TERB2-TERB1 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. X-ray crystallography, X-ray scattering, structured illumination microscopy, in vitro DNA-binding assays Nature communications High 30559341
2019 Crystal structures of human TERB1-TERB2 and TERB2-MAJIN subcomplexes were determined. Specific disruption of the TERB2-MAJIN interaction in mouse Terb2 knock-in mice abolishes telomere attachment to the nuclear envelope and causes aberrant homologous pairing and disordered synapsis, establishing that direct TERB2-MAJIN protein-protein interaction is required for meiotic telomere-NE tethering. X-ray crystallography, knock-in mouse genetics with point mutations disrupting TERB2-MAJIN interface, immunofluorescence for telomere attachment and synapsis Nature communications High 30718482
2017 TRF1 directs the assembly of TERB1-TERB2-MAJIN on telomeres in vivo; germ-cell-specific TRF1 knockout eliminates TERB1-TERB2-MAJIN telomere localization. TERB2 and MAJIN do not mediate cohesin recruitment at telomeres; that function is confined to the MYB-like domain of TERB1. Germ-cell-specific TRF1 conditional knockout mice, co-immunoprecipitation, immunofluorescence Cell reports High 29141207
2020 SUN1 interacts directly with MAJIN (and with TERB1) at the nuclear envelope; the SUN1-MAJIN interaction is stronger than the SUN1-TERB1 interaction. Both MAJIN and the CDK2-activator SPDYA bind to the N-terminal domain of SUN1 at overlapping sites. CDK2 inhibition decreases the SUN1-MAJIN interaction, suggesting CDK2-dependent phosphorylation promotes telomere-NE attachment via SUN1-MAJIN. Co-immunoprecipitation, GST pulldown, binding-site mapping with truncation constructs, CDK2 inhibitor treatment Frontiers in cell and developmental biology Medium 33015044
2022 The TERB1 MYB domain does not mediate telomere localization of the downstream TERB2-MAJIN complex; Terb1 point-mutant mice lacking MYB DNA-binding activity show normal TERB2-MAJIN telomere localization. Instead, the MYB domain regulates cohesin enrichment and axial element remodeling at telomeres in the early-to-late pachytene transition, suppressing telomere erosion. Terb1 point-mutant knock-in mice, immunofluorescence for TERB2/MAJIN localization, cohesin and synaptonemal complex markers, telomere length analysis Cell reports Medium 35081355

Source papers

Stage 0 corpus · 12 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 MAJIN Links Telomeric DNA to the Nuclear Membrane by Exchanging Telomere Cap. Cell 126 26548954
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
2021 CRISPR/Cas9-based genetic screen of SCNT-reprogramming resistant genes identifies critical genes for male germ cell development in mice. Scientific reports 19 34326397
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
2023 MJL-1 is a nuclear envelope protein required for homologous chromosome pairing and regulation of synapsis during meiosis in C. elegans. Science advances 10 36753547
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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