SYCE3

id: A1L190
gene_symbol: SYCE3
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  SYCE3 (Synaptonemal complex central element protein 3) is a major component of the transverse central element
  of synaptonemal complexes (SCs), formed between homologous chromosomes during meiotic prophase. SYCE3 is an
  88 amino acid protein with a coiled-coil domain (residues 7-75) that forms homodimers and can self-assemble
  into higher-order homooligomers through staggered lateral interactions (mediated by W41/Y44) and end-on
  interactions (domain swapping via an open loop conformation). The core function of SYCE3 is to actively
  remodel the SYCP1 tetramer lattice during early synapsis: SYCE3 binds to SYCP1 tetramers and converts them
  to 2:1 SYCP1-SYCE3 heterotrimers, disrupting the tetramer interface. SYCE3 self-assembly then establishes a
  new integrated SYCP1-SYCE3 lattice by providing 'tetramer-like' interfaces between SYCE3-bound SYCP1 dimers.
  SYCE3 also recruits downstream central element complexes SYCE1-SIX6OS1 and SYCE2-TEX12, and promotes fibrous
  assembly of SYCE2-TEX12. Mouse Syce3 knockouts and Syce3WY/WY mutants are infertile with defective SC assembly,
  confirming the essential role of SYCE3's self-assembly in meiotic chromosome synapsis.
existing_annotations:
- term:
    id: GO:0000801
    label: central element
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      SYCE3 localization to the central element of the synaptonemal complex is strongly supported by structural
      and biochemical evidence. SYCE3 forms 2:1 heterotrimers with SYCP1 and integrates into the central element
      to establish the mature SC structure [PMID:36635604].
    action: ACCEPT
    reason: >-
      Central element localization is a core function of SYCE3. The IBA annotation is based on phylogenetic
      inference (including mouse ortholog MGI:MGI:1922709) and is fully consistent with direct biochemical and
      structural evidence from PMID:36635604 and PMID:31023827.
    supported_by:
      - reference_id: PMID:36635604
        supporting_text: "SYCE3 remodels and integrates into the SYCP1 lattice, establishing binding sites that cooperativity recruit SYCE1-SIX6OS1 and SYCE2-TEX12"
      - reference_id: PMID:31023827
        supporting_text: "SYCE3 adopts a dimeric four-helical bundle structure that acts as the building block for concentration-dependent self-assembly into a series of discrete higher-order oligomers"
- term:
    id: GO:0007130
    label: synaptonemal complex assembly
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      SYCE3 is required for synaptonemal complex assembly, and plays an active role in remodeling the SYCP1
      lattice to form the mature SC structure. This is a core function well-supported by mouse knockout studies
      and biochemical analyses [PMID:36635604].
    action: ACCEPT
    reason: >-
      Synaptonemal complex assembly is the primary biological process function of SYCE3. The IBA annotation
      accurately captures SYCE3's essential role in SC formation, supported by mouse Syce3-/- and Syce3WY/WY
      mutant phenotypes showing defective SC assembly and meiotic arrest.
    supported_by:
      - reference_id: PMID:36635604
        supporting_text: "SYCE3 has an essential role in actively remodelling SYCP1 tetramer lattices during the early stages of synapsis"
      - reference_id: PMID:36635604
        supporting_text: "SYCE3 remodels SYCP1 tetramer lattices into integrated SYCP1-SYCE3 lattices that support full SC maturation"
- term:
    id: GO:0007131
    label: reciprocal meiotic recombination
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      While SYCE3 is required for proper SC formation which is necessary for meiotic recombination, the role
      in reciprocal recombination is indirect. SYCE3's primary function is in structural remodeling of the SC
      lattice, not direct participation in recombination.
    action: KEEP_AS_NON_CORE
    reason: >-
      Reciprocal meiotic recombination is a downstream consequence of SYCE3's role in SC assembly. The SC
      provides the structural framework for DSB repair and crossover formation, but SYCE3 itself is not directly
      involved in the recombination machinery. This annotation reflects the phenotypic consequence rather than
      the direct molecular function.
    supported_by:
      - reference_id: PMID:36635604
        supporting_text: "The mature SC structure then provides the necessary three-dimensional framework for DSB repair and crossover formation"
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      Nuclear localization is consistent with SYCE3's function in the synaptonemal complex, which assembles
      in the nucleus during meiotic prophase.
    action: ACCEPT
    reason: >-
      Nuclear localization is accurate and expected for a synaptonemal complex component. While this is a
      general localization term, it is correctly annotated and does not represent over-annotation.
    supported_by:
      - reference_id: PMID:36635604
        supporting_text: "a supramolecular protein structure, the synaptonemal complex (SC), which binds homologous chromosomes together"
- term:
    id: GO:0005694
    label: chromosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      Chromosome localization is accurate for SYCE3, which localizes to chromosomes as part of the synaptonemal
      complex. The more specific term GO:0000801 (central element) better captures SYCE3's precise localization.
    action: ACCEPT
    reason: >-
      Chromosome localization is correct and represents a broader cellular component term that encompasses
      SYCE3's more specific localization to the central element. Both annotations are valid at different
      levels of specificity.
    supported_by:
      - reference_id: PMID:36635604
        supporting_text: "a supramolecular protein structure, the synaptonemal complex (SC), which binds homologous chromosomes together"
- term:
    id: GO:0007130
    label: synaptonemal complex assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      Duplicate annotation for synaptonemal complex assembly with IEA evidence. This is consistent with
      the IBA annotation and experimentally validated function.
    action: ACCEPT
    reason: >-
      While this is a duplicate of the IBA annotation with different evidence, both are valid. The IEA
      annotation provides computational support for the experimentally-verified core function.
    supported_by:
      - reference_id: PMID:36635604
        supporting_text: "SYCE3 has an essential role in actively remodelling SYCP1 tetramer lattices during the early stages of synapsis"
- term:
    id: GO:0007131
    label: reciprocal meiotic recombination
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      Duplicate IEA annotation for reciprocal meiotic recombination. As with the IBA annotation, this
      represents a downstream consequence of SYCE3's role in SC assembly.
    action: KEEP_AS_NON_CORE
    reason: >-
      Consistent with the IBA annotation review - recombination is downstream of SYCE3's core SC assembly
      function. The annotation is not incorrect but reflects phenotypic consequence rather than direct function.
- term:
    id: GO:0007283
    label: spermatogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      SYCE3 is required for male fertility and normal testis development, as shown by mouse knockout studies.
      However, this is a downstream phenotypic consequence of defective meiosis rather than a direct function.
    action: KEEP_AS_NON_CORE
    reason: >-
      Spermatogenesis is affected in Syce3-/- and Syce3WY/WY mice, but this is due to meiotic arrest caused
      by defective SC assembly. SYCE3's direct function is in SC structural remodeling, not spermatogenesis
      per se. The annotation captures a phenotypic consequence rather than core function.
    supported_by:
      - reference_id: PMID:36635604
        supporting_text: "resultant chromosome asynapsis, spermatocyte death and infertility in males"
      - reference_id: PMID:36635604
        supporting_text: "Syce3WY/WY and Syce3Δ/Δ homozygotes exhibited severely reduced testis weights and epididymal sperm counts"
- term:
    id: GO:0051301
    label: cell division
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      This annotation is derived from UniProt keyword mapping. While SYCE3 functions during meiotic cell
      division, the term 'cell division' is too general and does not accurately capture SYCE3's specific
      role in synaptonemal complex assembly.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Cell division is an overly broad term for SYCE3. SYCE3 functions specifically in meiotic chromosome
      synapsis during meiotic prophase I, not in cell division generally. The more specific terms
      (GO:0007130 synaptonemal complex assembly, GO:0051321 meiotic cell cycle) are more appropriate.
- term:
    id: GO:0051321
    label: meiotic cell cycle
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      SYCE3 functions during the meiotic cell cycle, specifically during prophase I when the synaptonemal
      complex assembles. This annotation is accurate but less specific than 'synaptonemal complex assembly'.
    action: ACCEPT
    reason: >-
      Meiotic cell cycle is an appropriate general biological process term for SYCE3. The annotation correctly
      places SYCE3 in the meiotic context without being overly specific or overly general. It complements
      the more specific SC assembly annotation.
    supported_by:
      - reference_id: PMID:36635604
        supporting_text: "In meiosis, haploid germ cells are formed through the segregation of homologous chromosomes following their genetic exchange by crossing over"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  review:
    summary: >-
      This annotation derives from high-throughput interactome mapping (HI-II-14). The specific interactors
      detected (HAUS1, BLOC1S6) are not related to SYCE3's known core function in synaptonemal complex
      assembly. These may represent non-specific or false positive interactions from the Y2H screen.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput interactome studies often detect interactions that are not functionally relevant.
      SYCE3's characterized protein interactions are with SC components (SYCP1, SYCE1-SIX6OS1, SYCE2-TEX12).
      The 'protein binding' term is uninformative without specifying the biologically relevant binding partners.
      The detected interactions (HAUS1, BLOC1S6) lack validation in the context of SYCE3's meiotic function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  review:
    summary: >-
      This annotation derives from a study examining missense variant effects on protein-protein interactions.
      SYCE3-HAUS1 interaction was tested but this interaction is not relevant to SYCE3's known SC function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Same rationale as PMID:25416956 annotation. The 'protein binding' term from high-throughput studies
      does not provide insight into SYCE3's core molecular function. SYCE3's functionally relevant interactions
      are with SC components, not HAUS1.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  review:
    summary: >-
      This annotation derives from the HuRI reference interactome map. Detected interactions include PKN1,
      KRT79, and SGF29, none of which are known SC components or have demonstrated functional relevance
      to SYCE3's meiotic function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput binary interactome mapping may detect non-functional or context-inappropriate
      interactions. SYCE3's expression is largely restricted to meiotic cells, and interactions with
      PKN1, KRT79, or SGF29 have no established biological relevance. The annotation does not inform
      SYCE3's core function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  review:
    summary: >-
      This annotation derives from a neurodegenerative disease-focused interactome study. Detected interactions
      include HTT (huntingtin), KLF11, NUP58, WFS1, and PRPS1. These are unlikely to be physiologically
      relevant given SYCE3's meiosis-specific function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The neurodegenerative disease interactome study detected SYCE3 interactions that have no biological
      relevance to its meiotic function. SYCE3 is testis-enriched and functions specifically in meiotic
      prophase. Interactions with proteins like HTT or WFS1 are likely Y2H artifacts. The generic 'protein
      binding' term provides no useful functional information.
- term:
    id: GO:0000801
    label: central element
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      Central element localization inferred by Ensembl Compara orthology transfer from mouse. This is
      consistent with experimental evidence and other annotations.
    action: ACCEPT
    reason: >-
      This IEA annotation is redundant with the IBA annotation but correctly assigns SYCE3 to the central
      element based on orthology to the well-characterized mouse protein (B5KM66). The annotation is
      accurate for SYCE3's core cellular localization.
- term:
    id: GO:0000794
    label: condensed nuclear chromosome
  evidence_type: NAS
  original_reference_id: PMID:27142324
  review:
    summary: >-
      This annotation from ComplexPortal is based on a review article (Cahoon & Hawley 2016) that discusses
      SC regulation generally but does not provide SYCE3-specific evidence for localization to condensed
      chromosomes. The synaptonemal complex assembles during meiotic prophase I when chromosomes are not
      yet fully condensed, making this term potentially misleading.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      PMID:27142324 is a review article that discusses SC assembly and regulation but does not contain
      SYCE3-specific experimental data. The term 'condensed nuclear chromosome' is imprecise for SYCE3
      because the synaptonemal complex assembles during prophase I when chromosomes are in an extended,
      partially condensed state rather than fully condensed. The more accurate localization terms
      (GO:0000801 central element, GO:0000795 synaptonemal complex) are already annotated with better
      evidence. The NAS evidence from a general review does not support this annotation.
- term:
    id: GO:0000795
    label: synaptonemal complex
  evidence_type: NAS
  original_reference_id: PMID:27142324
  review:
    summary: >-
      SYCE3 is indeed a component of the synaptonemal complex. This annotation is accurate but the evidence
      code (NAS from review article) is suboptimal. Better evidence exists from PMID:36635604 and PMID:31023827.
    action: ACCEPT
    reason: >-
      Synaptonemal complex localization is well-established for SYCE3 through extensive biochemical and
      structural studies. While the NAS evidence from a review is weak, the annotation itself is correct.
      SYCE3 integrates into the SC by forming heterotrimers with SYCP1.
    additional_reference_ids:
      - PMID:36635604
      - PMID:31023827
    supported_by:
      - reference_id: PMID:36635604
        supporting_text: "SYCE3 remodels and integrates into the SYCP1 lattice, establishing binding sites that cooperativity recruit SYCE1-SIX6OS1 and SYCE2-TEX12"
- term:
    id: GO:0007129
    label: homologous chromosome pairing at meiosis
  evidence_type: NAS
  original_reference_id: PMID:27142324
  review:
    summary: >-
      SYCE3 contributes to chromosome synapsis through its role in SC assembly, but 'homologous chromosome
      pairing' is an upstream process that precedes SC formation. Pairing is established by recombination
      intermediates before SYCE3 acts.
    action: KEEP_AS_NON_CORE
    reason: >-
      Homologous chromosome pairing is established by recombination-mediated alignments before SC assembly.
      SYCE3's role is in converting these initial alignments into mature synapsis through SYCP1 lattice
      remodeling. While SYCE3 loss affects overall pairing success, the primary defect is in synapsis
      progression rather than initial pairing.
    supported_by:
      - reference_id: PMID:36635604
        supporting_text: "SC assembly is directed by the inter-homologue alignments established at recombination intermediates formed at sites of induced double-strand breaks"
- term:
    id: GO:0007131
    label: reciprocal meiotic recombination
  evidence_type: NAS
  original_reference_id: PMID:27142324
  review:
    summary: >-
      Duplicate annotation for reciprocal meiotic recombination with NAS evidence from review article.
      Same assessment as IBA and IEA annotations.
    action: KEEP_AS_NON_CORE
    reason: >-
      As noted for other evidence types, recombination is downstream of SYCE3's core function in SC
      structural assembly. This is a phenotypic consequence annotation.
- term:
    id: GO:0035825
    label: homologous recombination
  evidence_type: NAS
  original_reference_id: PMID:27142324
  review:
    summary: >-
      Homologous recombination is a very broad term that encompasses both mitotic and meiotic recombination.
      For SYCE3, the more specific term GO:0007131 (reciprocal meiotic recombination) is more appropriate.
    action: MODIFY
    reason: >-
      'Homologous recombination' is too general for SYCE3, which functions specifically in meiosis.
      The term does not distinguish meiotic from mitotic recombination. If an annotation to recombination
      is retained, GO:0007131 (reciprocal meiotic recombination) is more appropriate, though this is
      still a downstream consequence of SC assembly.
    proposed_replacement_terms:
      - id: GO:0007131
        label: reciprocal meiotic recombination
- term:
    id: GO:0000801
    label: central element
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: >-
      Central element localization transferred by sequence similarity from mouse ortholog (UniProtKB:B5KM66).
      This is well-supported by direct experimental evidence.
    action: ACCEPT
    reason: >-
      ISS annotation based on mouse ortholog is accurate. Mouse Syce3 has been extensively characterized
      biochemically and genetically, confirming central element localization. Human SYCE3 shares the
      same domain architecture and is expected to have identical localization.
    supported_by:
      - reference_id: PMID:36635604
        supporting_text: "SYCE3 remodels and integrates into the SYCP1 lattice, establishing binding sites that cooperativity recruit SYCE1-SIX6OS1 and SYCE2-TEX12"
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: >-
      Nuclear localization transferred from mouse ortholog. This is accurate and consistent with SYCE3's
      function in the synaptonemal complex.
    action: ACCEPT
    reason: >-
      Nuclear localization is expected for a synaptonemal complex component. The ISS annotation from
      mouse ortholog is reliable given the high conservation of SC components.
- term:
    id: GO:0005694
    label: chromosome
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: >-
      Chromosome localization transferred from mouse ortholog. Accurate but less specific than central
      element localization.
    action: ACCEPT
    reason: >-
      Chromosome localization is accurate and represents a broader cellular component that includes the
      synaptonemal complex central element where SYCE3 resides.
- term:
    id: GO:0007130
    label: synaptonemal complex assembly
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: >-
      SC assembly function transferred from mouse ortholog. This is the core biological process function
      of SYCE3 and is well-supported by mouse genetic studies.
    action: ACCEPT
    reason: >-
      Mouse Syce3-/- and Syce3WY/WY studies in PMID:36635604 provide direct genetic evidence for SYCE3's
      essential role in SC assembly. The ISS annotation correctly captures this core function.
    supported_by:
      - reference_id: PMID:36635604
        supporting_text: "Syce3WY/WY and Syce3Δ/Δ homozygotes... with testis histology indicating a severe block in meiosis"
- term:
    id: GO:0007131
    label: reciprocal meiotic recombination
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: >-
      Reciprocal meiotic recombination function transferred from mouse ortholog. This represents a
      downstream consequence of SYCE3's SC assembly function.
    action: KEEP_AS_NON_CORE
    reason: >-
      Same rationale as other recombination annotations - SYCE3's direct function is in SC structural
      remodeling, with recombination affected as a downstream consequence of SC defects.
- term:
    id: GO:0007283
    label: spermatogenesis
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: >-
      Spermatogenesis annotation transferred from mouse ortholog. Mouse Syce3 knockouts show male
      infertility, but this is a downstream phenotype of meiotic arrest.
    action: KEEP_AS_NON_CORE
    reason: >-
      Spermatogenesis defects in Syce3 mutant mice result from meiotic arrest at pachytene, not from
      a direct role in spermatogenesis per se. SYCE3 functions in meiotic chromosome synapsis; the
      spermatogenesis defect is a phenotypic consequence.
    supported_by:
      - reference_id: PMID:36635604
        supporting_text: "severely reduced testis weights and epididymal sperm counts, with testis histology indicating a severe block in meiosis"
- term:
    id: GO:0005198
    label: structural molecule activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: >-
      SYCE3 is a structural component of the synaptonemal complex central element that forms 2:1
      heterotrimers with SYCP1 and self-assembles to create an integrated SYCP1-SYCE3 lattice. Its
      primary molecular function is providing structural support for SC assembly and maturation,
      consistent with structural molecule activity [PMID:36635604, PMID:31023827].
    action: NEW
    reason: >-
      SYCE3's core molecular function is as a structural scaffold protein in the synaptonemal complex.
      It forms the central element by remodeling SYCP1 tetramers and self-assembling into higher-order
      structures. This structural role is well-characterized biochemically and structurally (crystal
      structure PDB 6H86) but is not currently annotated with a molecular function term. The existing
      annotations focus on biological process and cellular component aspects; GO:0005198 captures the
      essential molecular function of SYCE3 as a structural protein.
    supported_by:
      - reference_id: PMID:36635604
        supporting_text: "SYCE3 remodels and integrates into the SYCP1 lattice, establishing binding sites that cooperativity recruit SYCE1-SIX6OS1 and SYCE2-TEX12"
      - reference_id: PMID:31023827
        supporting_text: "SYCE3 adopts a dimeric four-helical bundle structure that acts as the building block for concentration-dependent self-assembly into a series of discrete higher-order oligomers"
references:
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings:
    - statement: High-throughput Y2H interactome mapping that detected SYCE3 interactions with HAUS1 and BLOC1S6. These interactions lack validation in the context of SYCE3's meiotic function.
- id: PMID:27142324
  title: Regulating the construction and demolition of the synaptonemal complex.
  findings:
    - statement: Review article providing general overview of SC assembly and regulation. Does not contain SYCE3-specific experimental data. Used as reference for ComplexPortal annotations.
- id: PMID:31023827
  title: A molecular model for self-assembly of the synaptonemal complex protein SYCE3.
  findings:
    - statement: Determined crystal structure of SYCE3 showing dimeric four-helical bundle (PDB 6H86)
      supporting_text: "SYCE3 adopts a dimeric four-helical bundle structure that acts as the building block for concentration-dependent self-assembly into a series of discrete higher-order oligomers"
      reference_section_type: ABSTRACT
      full_text_unavailable: false
    - statement: Identified SYCE3 self-assembly mechanism through staggered lateral and end-on interactions
      supporting_text: "This is achieved through staggered lateral interactions between self-assembly surfaces of SYCE3 dimers and through end-on interactions that likely occur through intermolecular domain swapping between dimer folds"
      reference_section_type: ABSTRACT
      full_text_unavailable: false
    - statement: Key residues W41 and Y44 mediate lateral self-assembly; P53 affects oligomerization
      supporting_text: "mutation of Trp-41 and Tyr-44 residues to glutamate completely inhibited SYCE3 self-assembly, as determined by SEC-MALS, leaving a nonassembled 21-kDa dimer"
      reference_section_type: RESULTS
      full_text_unavailable: false
    - statement: SYCE3 forms dimers, tetramers, and higher-order oligomers (up to dodecamers)
      supporting_text: "SYCE3 assembly, particularly favoring formation of dodecamers of three laterally associated end-on tetramers"
      reference_section_type: ABSTRACT
      full_text_unavailable: false
- id: PMID:31515488
  title: Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
  findings:
    - statement: High-throughput study of missense SNV effects on protein interactions. SYCE3-HAUS1 interaction tested.
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings:
    - statement: HuRI reference interactome detected SYCE3 interactions with PKN1, KRT79, SGF29. These lack biological validation for SYCE3's meiotic function.
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings:
    - statement: Neurodegenerative disease interactome study detected SYCE3 interactions with HTT, KLF11, NUP58, WFS1, PRPS1. These are unlikely to be physiologically relevant for SYCE3's meiotic function.
- id: PMID:36635604
  title: Structural maturation of SYCP1-mediated meiotic chromosome synapsis by SYCE3.
  findings:
    - statement: SYCE3 actively remodels SYCP1 tetramer lattice during early synapsis, not just stabilizes it
      supporting_text: "SYCE3 has an essential role in actively remodelling SYCP1 tetramer lattices during the early stages of synapsis"
      reference_section_type: ABSTRACT
      full_text_unavailable: false
    - statement: SYCE3 binds SYCP1 tetrameric core (alphaNcore) with approximately 170 nM affinity
      supporting_text: "indicated a binding affinity of 170 ± 30 nM"
      reference_section_type: RESULTS
      full_text_unavailable: false
    - statement: SYCE3 binding converts SYCP1 tetramers to 2:1 SYCP1-SYCE3 heterotrimers
      supporting_text: "SYCP1 tetramers undergo conformational change into 2:1 heterotrimers on SYCE3 binding, removing their assembly interfaces and disrupting the SYCP1 lattice"
      reference_section_type: ABSTRACT
      full_text_unavailable: false
    - statement: SYCE3 self-assembly provides tetramer-like interfaces for integrated SYCP1-SYCE3 lattice
      supporting_text: "SYCE3 then establishes a new lattice by its self-assembly mimicking the role of the disrupted interface in tethering together SYCP1 dimers"
      reference_section_type: ABSTRACT
      full_text_unavailable: false
    - statement: SYCE3 W41E/Y44E mutation blocks lateral self-assembly and integrated lattice formation
      supporting_text: "The SYCE3 WY mutation separates the disruptive and integrative functions of SYCE3, triggering SYCP1 tetramer lattice disruption, whilst failing to form an integrated SYCP1-SYCE3 lattice"
      reference_section_type: RESULTS
      full_text_unavailable: false
    - statement: Syce3WY/WY mice are infertile with severely disrupted SYCP1 assemblies
      supporting_text: "Syce3WY/WY and Syce3Δ/Δ homozygotes exhibited severely reduced testis weights and epididymal sperm counts, with testis histology indicating a severe block in meiosis"
      reference_section_type: RESULTS
      full_text_unavailable: false
    - statement: Syce3 null mice retain SYCP1 tetramer lattices but cannot form mature SC
      supporting_text: "Syce3Δ/Δ captures the formation of SYCP1 tetramer lattices between axes, which cannot be remodelled in absence of SYCE3, so fail to develop into a mature SC"
      reference_section_type: RESULTS
      full_text_unavailable: false
    - statement: SYCE3 recruits SYCE1-SIX6OS1 and SYCE2-TEX12 complexes (micromolar affinity)
      supporting_text: "SYCE3 remodels and integrates into the SYCP1 lattice, establishing binding sites that cooperativity recruit SYCE1-SIX6OS1 and SYCE2-TEX12"
      reference_section_type: RESULTS
      full_text_unavailable: false
    - statement: SYCE3 promotes fibrous assembly of SYCE2-TEX12
      supporting_text: "SYCE3 promoted fibrous assembly of SYCE2-TEX12"
      reference_section_type: RESULTS
      full_text_unavailable: false
core_functions:
  - description: >-
      SYCE3 is a major structural component of the central element of the synaptonemal complex. It localizes
      to the central element by forming 2:1 heterotrimers with SYCP1 molecules that span between the central
      and lateral elements. SYCE3 is essential for SC assembly, functioning by actively remodeling the nascent
      SYCP1 tetramer lattice. SYCE3 binding disrupts SYCP1 tetramers and establishes a new integrated SYCP1-SYCE3
      lattice through its self-assembly. Mouse Syce3 knockouts show meiotic arrest with defective SC assembly.
      SYCE3 also recruits downstream central element complexes SYCE1-SIX6OS1 and SYCE2-TEX12 to the synaptonemal
      complex with micromolar affinity and promotes fibrous assembly of SYCE2-TEX12.
    supported_by:
      - reference_id: PMID:36635604
        supporting_text: "SYCE3 remodels and integrates into the SYCP1 lattice, establishing binding sites that cooperativity recruit SYCE1-SIX6OS1 and SYCE2-TEX12"
      - reference_id: PMID:31023827
        supporting_text: "SYCE3 adopts a dimeric four-helical bundle structure that acts as the building block for concentration-dependent self-assembly into a series of discrete higher-order oligomers"
    molecular_function:
      id: GO:0005198
      label: structural molecule activity
    directly_involved_in:
      - id: GO:0007130
        label: synaptonemal complex assembly
    locations:
      - id: GO:0000801
        label: central element
proposed_new_terms: []
suggested_questions:
  - question: What is the precise stoichiometry and structure of the integrated SYCP1-SYCE3 lattice in vivo? While in vitro studies show 2:1 SYCP1-SYCE3 heterotrimers and characterize their assembly, the precise structure of the integrated lattice in the native SC remains to be determined.
  - question: How does SYCE3 coordinate with other CE proteins temporally during synapsis? The hierarchical recruitment of SYCE1-SIX6OS1 and SYCE2-TEX12 by SYCE3 suggests temporal coordination, but the precise timing and regulatory mechanisms are unclear.
suggested_experiments:
  - description: Cryo-EM structure of SYCP1-SYCE3 lattice assemblies to determine the molecular architecture of the integrated SYCP1-SYCE3 lattice at near-atomic resolution
    hypothesis: The integrated SYCP1-SYCE3 lattice has a defined structural organization that can be visualized by cryo-EM
  - description: Live imaging of SC assembly with fluorescently tagged SYCE3 to determine the temporal dynamics of SYCE3 recruitment and SYCP1 lattice remodeling during synapsis
    hypothesis: SYCE3 recruitment occurs in a temporally regulated manner during early synapsis