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SYCP1

Synaptonemal complex protein 1 · UniProt Q15431

Length
976 aa
Mass
114.2 kDa
Annotated
2026-06-10
24 papers in source corpus 11 papers cited in narrative 11 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

SYCP1 is the core transverse filament protein of the meiotic synaptonemal complex, where it self-assembles into a zipper-like lattice that physically links homologous chromosomes during prophase I (PMID:29915389, PMID:15937223). The building block is an obligate tetramer composed of an N-terminal four-helical bundle that bifurcates into two elongated C-terminal antiparallel dimeric coiled-coils (PMID:29915389, PMID:27548613); this unit polymerizes through two self-assembly interfaces—N-terminal head-to-head contacts at the midline and C-terminal back-to-back contacts on the chromosome axis—to generate the supramolecular lattice that spans the synaptic space (PMID:29915389). The N-terminal head-to-head interface (residue L106) is essential in vivo: its disruption abolishes synapsis, prevents crossover formation, and arrests meiosis even though homologs still align and recruit low levels of SC proteins (PMID:37862414). SYCP1 acts upstream of central element assembly, recruiting SYCE1 and SYCE2 to the central element (PMID:15944401), and its lattice is remodeled by SYCE3, which converts tetramers into 2:1 SYCP1-SYCE3 heterotrimers, dismantles the original interfaces, and rebuilds an integrated scaffold that tethers SYCP1 dimers and recruits the SYCE1-SIX6OS1 and SYCE2-TEX12 complexes for long-range synapsis (PMID:36635604). Loss of SYCP1 leaves axial element formation and homolog alignment intact but blocks synapsis, leading to persistent recombination intermediates, absence of crossover markers (MLH1/MLH3), failed XY body assembly, infertility, and—across species—defective chromosome segregation (PMID:15937223, PMID:40911633). SYCP1 transcription is restricted to meiosis through a compact, sex-specifically regulated promoter active in pachytene spermatocytes but not in female meiosis (PMID:10096061). A homozygous C-tail-truncating frameshift in human SYCP1 is associated with severe oligozoospermia (PMID:35377450).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1999 Medium

    Before its mechanism was known, it was unclear how SYCP1 expression is confined to meiotic cells; promoter dissection established that a compact cis-regulatory module enforces stage- and sex-specific transcription.

    Evidence transgenic reporter assays with Sycp1 5' deletion constructs in mice

    PMID:10096061

    Open questions at the time
    • trans-acting factors driving pachytene-specific expression not identified
    • basis for absence of activity in female meiosis unresolved
  2. 2005 High

    The in vivo requirement for the transverse filament was undefined; knockout showed SYCP1 is dispensable for axial elements and homolog alignment but essential for synapsis, crossover maturation, and XY body formation.

    Evidence Sycp1-/- mouse knockout with immunofluorescence for recombination and crossover markers

    PMID:15937223

    Open questions at the time
    • molecular link between synapsis and crossover designation not defined
    • does not establish how transverse filaments are nucleated
  3. 2005 Medium

    It was unknown how central element proteins reach the SC midline; SYCP1 was placed upstream of central element assembly by recruiting SYCE1 and SYCE2.

    Evidence co-immunoprecipitation and localization analysis in Sycp1 mutant context

    PMID:15944401

    Open questions at the time
    • structural basis of SYCP1-SYCE interactions not resolved
    • reciprocal validation limited to a single lab
  4. 2016 High

    The orientation of the transverse filament was unknown; the C-terminal coiled-coil was shown to form asymmetric antiparallel dimers, providing the structural basis for filament polarity.

    Evidence X-ray crystallography with solution biophysics of the SYCP1 C-terminal domain

    PMID:27548613

    Open questions at the time
    • full-length assembly architecture not captured
    • in vivo relevance of dimer geometry not directly tested
  5. 2018 High

    How SYCP1 builds a lattice was unresolved; structural and biophysical work defined the obligate tetramer and two self-assembly interfaces that generate the zipper-like supramolecular lattice.

    Evidence X-ray crystallography and biophysical reconstitution in vitro

    PMID:29915389

    Open questions at the time
    • in vitro lattice formed without chromosome axis or partner proteins
    • regulation of assembly timing in vivo not addressed
  6. 2023 High

    Whether a specific assembly interface was functionally required in vivo was untested; knock-in mutation of the N-terminal head-to-head site (L106E) abolished synapsis and crossovers, validating the structural model genetically.

    Evidence mouse knock-in point mutants with molecular dynamics and immunofluorescence

    PMID:37862414

    Open questions at the time
    • contribution of the C-terminal back-to-back interface in vivo not isolated here
    • residual low-level recruitment of SC proteins unexplained
  7. 2023 High

    How the SYCP1 lattice matures into a central-element-bearing SC was unknown; SYCE3 was shown to remodel SYCP1 tetramers into heterotrimers, rebuild the lattice, and recruit central element complexes.

    Evidence biochemical reconstitution, separation-of-function mouse mutagenesis, structural and biophysical analyses

    PMID:36635604

    Open questions at the time
    • kinetics of the tetramer-to-heterotrimer transition in vivo not measured
    • interplay with axial element proteins not addressed
  8. 2021 Medium

    The conservation of SYCP1 function and its role relative to DSB formation was tested in zebrafish, showing it is dispensable for DSB formation but required for complete homolog pairing.

    Evidence sycp1 premature-stop zebrafish mutant with recombination/axis marker immunofluorescence

    PMID:33842489

    Open questions at the time
    • molecular mechanism of pairing defect not defined
    • single-lab characterization
  9. 2025 Medium

    The downstream consequence of synapsis failure for segregation fidelity was quantified; zebrafish sycp1 mutants showed sex-dimorphic outcomes with male sterility and maternally transmitted aneuploidy.

    Evidence sycp1 mutant zebrafish cytological staging plus progeny viability and aneuploidy assays

    PMID:40911633

    Open questions at the time
    • basis for sexual dimorphism in fertility not defined
    • mechanism linking failed synapsis to univalent formation not resolved
  10. 2022 Low

    Clinical relevance in humans was probed; a C-tail-truncating frameshift was associated with severe oligozoospermia and impaired DSB repair signatures.

    Evidence whole-exome sequencing with HADDOCK modelling, γH2AX immunodetection, DNA fragmentation index

    PMID:35377450

    Open questions at the time
    • no functional rescue or in vitro reconstitution of the variant
    • causality inferred from a single individual and computational modelling
    • DNA-binding deficit predicted but not biochemically validated
  11. 2025 Low

    A non-meiotic role was proposed; in cancer cells aberrantly re-expressed SYCP1 was reported to bind chromatin and regulate DNA-repair transcriptional programs.

    Evidence ChIP-seq, proteomics, knockdown functional and drug-sensitivity assays (preprint)

    PMID:bio_10.1101_2025.09.18.677087

    Open questions at the time
    • preprint, not peer-reviewed
    • primarily correlative genomics without biochemical reconstitution
    • direct chromatin-binding mechanism for a coiled-coil filament protein unestablished

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the SYCP1-SYCE3 mature scaffold integrates with axial/lateral element proteins to convert synapsis into spatially regulated crossover designation remains unresolved.
  • no mechanistic link from lattice architecture to crossover positioning
  • in vivo dynamics of lattice remodeling unmeasured
  • any non-meiotic function remains unvalidated by peer review

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005694 chromosome 2
Pathway
R-HSA-1474165 Reproduction 2 R-HSA-1640170 Cell Cycle 2
Partners
SYCE1SYCE2SYCE3
Complex memberships
synaptonemal complex (transverse filament)synaptonemal complex central element

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 Human SYCP1 has an obligate tetrameric structure in which an N-terminal four-helical bundle bifurcates into two elongated C-terminal dimeric coiled-coils. This building block assembles into a zipper-like lattice through two self-assembly sites: N-terminal sites undergo cooperative head-to-head assembly in the midline, while C-terminal sites interact back-to-back on the chromosome axis, generating a supramolecular lattice that mediates meiotic chromosome synapsis. X-ray crystallography and biophysical studies (in vitro) Nature structural & molecular biology High 29915389
2016 The C-terminal coiled-coil domain of SYCP1 forms asymmetric, anti-parallel dimers in solution, revealing the structural basis of the transverse filament orientation at the synaptonemal complex. X-ray crystallography and solution biophysics PloS one High 27548613
2023 SYCE3 binds SYCP1 tetramers and induces a conformational change into 2:1 SYCP1-SYCE3 heterotrimers, removing SYCP1 assembly interfaces and disrupting the SYCP1 lattice. SYCE3 then establishes a new lattice by self-assembly that mimics the disrupted interface, tethering SYCP1 dimers and recruiting CE complexes SYCE1-SIX6OS1 and SYCE2-TEX12 to achieve long-range synapsis. Biochemical reconstitution, separation-of-function mutagenesis in mice, structural and biophysical analyses Nature structural & molecular biology High 36635604
2023 SYCP1's N-terminal head-to-head assembly interface (involving residue L106) is essential for meiotic chromosome synapsis in vivo; the L106E mutation abolishes synapsis, prevents crossover formation, and causes meiotic arrest, while homologs still align and recruit low levels of SYCP1 and other SC proteins. Mouse knock-in mutagenesis (L106E and L102E point mutants), molecular dynamics simulations, immunofluorescence Science advances High 37862414
2005 Sycp1 knockout mice are infertile; Sycp1−/− spermatocytes form normal axial elements and homologous alignment occurs, but synapsis fails. Early/intermediate recombination intermediates (RAD51/DMC1, RPA, MSH4 foci) appear in normal numbers but persist, MLH1/MLH3 foci (crossover markers) are absent, crossovers are rare, and the XY body does not form, demonstrating that SYCP1/transverse filaments coordinate crossover formation and XY body assembly. Gene knockout (Sycp1−/− mice), immunofluorescence for recombination markers (γH2AX, RAD51, DMC1, RPA, MSH4, MLH1, MLH3), cytological analysis Genes & development High 15937223
2005 Two central element proteins, SYCE1 and CESC1 (SYCE2), interact with the transverse filament protein SYCP1 and their localization to the central element depends on recruitment by SYCP1, placing SYCP1 upstream of central element assembly. Co-immunoprecipitation, immunofluorescence localization in Sycp1 mutant context, microarray-guided candidate identification Journal of cell science Medium 15944401
2021 In zebrafish, Sycp1 is not required for subtelomeric DNA double-strand break formation (γH2AX, Dmc1/Rad51, RPA signals appear normally near telomeres in sycp1 mutants), but is required for complete homolog pairing/alignment in late zygonema/pachynema. sycp1 premature-stop zebrafish mutant, immunofluorescence for γH2AX, Dmc1/Rad51, RPA, Hormad1, Iho1 Frontiers in cell and developmental biology Medium 33842489
2025 In zebrafish sycp1 mutants, chromosomes undergo early prophase co-alignment but fail to synapse; sycp1 mutant males are sterile with spermatocytes arresting at metaphase I/II, while sycp1 mutant females are fertile but produce a higher proportion of malformed progeny correlating with increased univalent formation, and offspring from mutant females show widespread somatic mosaic aneuploidy, indicating SYCP1-dependent synapsis is required for faithful chromosome segregation. sycp1 mutant zebrafish analysis, cytological staging, progeny viability and aneuploidy assays PLoS genetics Medium 40911633
2025 In breast and other cancer cells, SYCP1 is aberrantly re-expressed and binds chromatin at regulatory elements, controlling transcriptional programs governing genome maintenance (including CCNB1, PCNA, RAD51C, H2AX). SYCP1 interfaces with chromatin remodeling complexes and transcription factors SP1 and SP2, modulating their genomic occupancy. Loss of SYCP1 impairs DNA repair kinetics, attenuates proliferation and migration, and increases sensitivity to cisplatin and gemcitabine. Integrative genomics (ChIP-seq), proteomics, siRNA/shRNA knockdown with proliferation/migration/DNA-repair assays, drug sensitivity assays bioRxivpreprint Low bio_10.1101_2025.09.18.677087
1999 A short fragment of the Sycp1 promoter (nucleotides −54 to +102) is sufficient for stage-specific expression in pachytene spermatocytes in transgenic mice, with upstream enhancer elements between −54 and −260 quantitatively regulating expression; however, none of these male-active promoter sequences drove expression during female meiosis, demonstrating sex-specific transcriptional regulation. Transgenic reporter assay in mice with Sycp1 5′ upstream deletion constructs Mechanisms of development Medium 10096061
2022 A homozygous frameshift mutation in human SYCP1 (c.2892delA; p.K967Nfs*1) truncating the C-tail region is associated with severe oligozoospermia; HADDOCK modelling indicated decreased ability of the truncated protein to bind DNA, and immunodetection revealed persistent γH2AX signals and ~40% DNA fragmentation index in mutant semen cells, suggesting impaired DSB repair due to SYCP1 loss. Whole-exome sequencing, Sanger validation, HADDOCK structural modelling, γH2AX immunodetection, DNA fragmentation index measurement Molecular human reproduction Low 35377450

Source papers

Stage 0 corpus · 24 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Mouse Sycp1 functions in synaptonemal complex assembly, meiotic recombination, and XY body formation. Genes & development 381 15937223
2005 Two novel proteins recruited by synaptonemal complex protein 1 (SYCP1) are at the centre of meiosis. Journal of cell science 164 15944401
2018 Structural basis of meiotic chromosome synapsis through SYCP1 self-assembly. Nature structural & molecular biology 63 29915389
2019 Production, purification, and in vivo evaluation of a novel multiepitope peptide vaccine consisted of immunodominant epitopes of SYCP1 and ACRBP antigens as a prophylactic melanoma vaccine. International immunopharmacology 56 31499268
2006 Structural components of the synaptonemal complex, SYCP1 and SYCP3, in the medaka fish Oryzias latipes. Experimental cell research 55 16764855
1999 Temporal and spatial control of the Sycp1 gene transcription in the mouse meiosis: regulatory elements active in the male are not sufficient for expression in the female gonad. Mechanisms of development 36 10096061
1992 Effect of induced molting on B cell and CT4 and CT8 T cell numbers in spleens and peripheral blood of White Leghorn hens. Poultry science 33 1361673
2020 Efficacy of co-immunization with the DNA and peptide vaccines containing SYCP1 and ACRBP epitopes in a murine triple-negative breast cancer model. Human vaccines & immunotherapeutics 32 32497486
2005 Identification of an epitope derived from the cancer testis antigen HOM-TES-14/SCP1 and presented by dendritic cells to circulating CD4+ T cells. Blood 32 16030183
2023 Structural maturation of SYCP1-mediated meiotic chromosome synapsis by SYCE3. Nature structural & molecular biology 22 36635604
2020 LncRNA-Gm2044 is transcriptionally activated by A-MYB and regulates Sycp1 expression as a miR-335-3p sponge in mouse spermatocyte-derived GC-2spd(ts) cells. Differentiation; research in biological diversity 18 32585553
2023 SYCP1 head-to-head assembly is required for chromosome synapsis in mouse meiosis. Science advances 16 37862414
1990 Characterization of suppressor T cells for antibody production by chicken spleen cells. I. Antigen-induced suppressor cells are CT8+, TcR1+ (gamma delta) T cells. Immunology 16 2149122
2022 A rare frameshift mutation in SYCP1 is associated with human male infertility. Molecular human reproduction 15 35377450
2021 Sycp1 Is Not Required for Subtelomeric DNA Double-Strand Breaks but Is Required for Homologous Alignment in Zebrafish Spermatocytes. Frontiers in cell and developmental biology 15 33842489
1997 The Sycp1 loci of the mouse genome: successive retropositions of a meiotic gene during the recent evolution of the genus. Genomics 14 9286707
2016 Crystal Structure of C-Terminal Coiled-Coil Domain of SYCP1 Reveals Non-Canonical Anti-Parallel Dimeric Structure of Transverse Filament at the Synaptonemal Complex. PloS one 10 27548613
2006 The Sycp1-Cre transgenic mouse and male germ cell inhibition of NF-kappa b. Journal of andrology 10 16775250
1990 Characterization of suppressor T cells for antibody production by chicken spleen cells. II. Comparison of CT8+ cells from concanavalin A-injected normal and bursa cell-injected agammaglobulinaemic chickens. Immunology 8 2149123
2024 Differential expression and regulation of ADAD1, DMRTC2, PRSS54, SYCE1, SYCP1, TEX101, TEX48, and TMPRSS12 gene profiles in colon cancer tissues and their in vitro response to epigenetic drugs. PloS one 5 39208330
2018 Amphioxus SYCP1: a case of retrogene replacement and co-option of regulatory elements adjacent to the ParaHox cluster. Development genes and evolution 2 29297095
2002 [CG17604 gene from Drosophila melanogaster--possible functional homolog of the yeast ZIP1 and SCP1 (SYCP1) mammalian genes, coding for synaptonemal complex proteins]. Genetika 2 11852789
1991 Suppressor cells for antibody production in vivo, induced by bursa cell injection into agammaglobulinemic chickens, belong to A CT4-, CT8+, TCRI- subset of T cells. Developmental and comparative immunology 2 1828774
2025 Distinct cellular and reproductive consequences of meiotic chromosome synapsis defects in syce2 and sycp1 mutant zebrafish. PLoS genetics 1 40911633

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