Affinage

SYMPK

Symplekin · UniProt Q92797

Length
1274 aa
Mass
141.1 kDa
Annotated
2026-06-10
56 papers in source corpus 3 papers cited in narrative 3 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SYMPK (Symplekin) is a scaffold protein that supports germ cell development and pluripotency through context-specific protein interactions and RNA processing (PMID:34434935, PMID:30801858, PMID:41520922). In male germ cells, SYMPK is required for meiotic progression: its loss disrupts homologous chromosome synapsis, DNA double-strand break repair, and meiotic recombination, and it regulates alternative splicing of pre-mRNAs including Sun1 in spermatogenic cells (PMID:34434935). In embryonic stem cells, SYMPK binds the pluripotency factor Oct4 directly through its DUF3453 domain, acting upstream of Oct4-dependent transcriptional programs to promote self-renewal and colony formation (PMID:30801858). During female meiosis, SYMPK localizes dynamically to spindle microtubules after germinal vesicle breakdown and scaffolds the spindle regulators KIF20A and NUMA1, with its loss causing metaphase I arrest, disorganized spindle architecture, destabilized kinetochore-microtubule attachments, persistent spindle assembly checkpoint activation, and complete female infertility (PMID:41520922). Beyond these contexts, the structural and biochemical basis of SYMPK scaffolding has not been further characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 3 steps
  1. 2019 Medium

    Established that SYMPK acts beyond RNA processing as a direct partner of a pluripotency factor, linking it to stem cell self-renewal.

    Evidence Co-immunoprecipitation, CRISPR/Cas9 and domain deletion, and teratoma/chimeric mouse assays in mouse ESCs

    PMID:30801858

    Open questions at the time
    • Structural basis of the DUF3453-Oct4 interaction not resolved
    • Reciprocal validation of the interaction and direct transcriptional targets not defined
    • Whether RNA-processing function contributes to the ESC phenotype unaddressed
  2. 2021 Medium

    Defined an in vivo requirement for SYMPK in male meiosis and tied its function to alternative splicing of meiotic transcripts.

    Evidence Germ cell-specific conditional knockout mice with RNA-Seq and immunofluorescence for synapsis and DSB markers

    PMID:34434935

    Open questions at the time
    • Direct splicing mechanism on Sun1 and other targets not biochemically reconstituted
    • Causal link between specific mis-splicing events and synapsis/recombination defects not established
    • Protein partners mediating the splicing role in spermatocytes not identified
  3. 2026 Medium

    Revealed a non-RNA scaffolding role for SYMPK at the acentrosomal meiotic spindle, coordinating spindle regulators required for chromosome segregation fidelity.

    Evidence Oocyte-specific conditional knockout with live imaging, chromosome spreads, pharmacologic SAC inhibition, and IP-MS identification of KIF20A and NUMA1

    PMID:41520922

    Open questions at the time
    • Whether SYMPK directly binds KIF20A and NUMA1 versus indirectly is unresolved by IP-MS alone
    • Mechanism by which SYMPK is recruited to spindle microtubules unknown
    • Relationship between the spindle scaffolding role and SYMPK's polyadenylation/splicing functions undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single scaffold protein switches between RNA-processing, transcription factor binding, and spindle organization across cell types remains unresolved.
  • No unifying structural or biochemical model linking the distinct activities
  • Domain requirements for the spindle and splicing roles not mapped
  • Direct versus scaffold-mediated nature of most interactions unconfirmed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 2
Pathway
R-HSA-1474165 Reproduction 2
Partners
KIF20ANUMA1POU5F1

Evidence

Reading pass · 3 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2021 SYMPK functions as a scaffold protein required for meiotic progression in male germ cells; germ cell-specific knockout in mice causes spermatocyte defects in homologous chromosome synapsis, DNA double-strand break repair, and meiotic recombination. SYMPK also regulates alternative splicing in spermatogenic cells, including proper splicing of Sun1 pre-mRNA. Conditional knockout mice (cKO) with Ddx4-Cre and Stra8-Cre drivers; RNA-Seq analysis; immunofluorescence for synapsis and DSB markers Frontiers in cell and developmental biology Medium 34434935
2019 SYMPK interacts directly with the pluripotency factor Oct4 via its DUF3453 domain in mouse embryonic stem cells; this interaction promotes ESC self-renewal, colony formation, and pluripotency. Deletion of DUF3453 impairs colony formation, placing SYMPK upstream of Oct4-dependent transcriptional programs. Co-immunoprecipitation; CRISPR/Cas9 deletion; overexpression; teratoma and chimeric mouse assays; domain deletion analysis Stem cells (Dayton, Ohio) Medium 30801858
2026 SYMPK dynamically localizes to spindle microtubules during oocyte meiotic maturation following germinal vesicle breakdown. Oocyte-specific Sympk knockout causes complete female infertility, metaphase I arrest, disorganized spindle architecture, and destabilized kinetochore-microtubule attachments with persistent spindle assembly checkpoint (SAC) activation. Mechanistically, immunoprecipitation-mass spectrometry revealed that SYMPK interacts with spindle regulators KIF20A and NUMA1 in MI oocytes and is required for their proper spindle localization. Oocyte-specific conditional knockout mice; live imaging; immunofluorescence; chromosome spreads; pharmacologic SAC inhibition; immunoprecipitation-mass spectrometry Journal of genetics and genomics Medium 41520922

Source papers

Stage 0 corpus · 56 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 The MC-Fold and MC-Sym pipeline infers RNA structure from sequence data. Nature 623 18322526
1987 Promoters in the nodulation region of the Rhizobium leguminosarum Sym plasmid pRL1JI. Plant molecular biology 572 24276795
2013 SyM-BBB: a microfluidic Blood Brain Barrier model. Lab on a chip 243 23344641
2000 Poliovirus RNA-dependent RNA polymerase (3D(pol)). Assembly of stable, elongation-competent complexes by using a symmetrical primer-template substrate (sym/sub). The Journal of biological chemistry 124 10681506
1993 Molecular cloning and characterization of a sym plasmid locus that regulates cultivar-specific nodulation of soybean by Rhizobium fredii USDA257. Molecular microbiology 99 8412662
1987 Induction of the nodA promoter of Rhizobium leguminosarum Sym plasmid pRL1JI by plant flavanones and flavones. Journal of bacteriology 94 3539915
1997 (2S,4R)-4-methylglutamic acid (SYM 2081): a selective, high-affinity ligand for kainate receptors. The Journal of pharmacology and experimental therapeutics 93 8996224
2008 Divergence of evolutionary ways among common sym genes: CASTOR and CCaMK show functional conservation between two symbiosis systems and constitute the root of a common signaling pathway. Plant & cell physiology 74 18852152
1987 Genes for the catabolism and synthesis of an opine-like compound in Rhizobium meliloti are closely linked and on the Sym plasmid. Proceedings of the National Academy of Sciences of the United States of America 67 16593802
1998 The methylglutamate, SYM 2081, is a potent and highly selective agonist at kainate receptors. The Journal of pharmacology and experimental therapeutics 53 9580595
2001 The complete nucleotide sequence of a plant root-inducing (Ri) plasmid indicates its chimeric structure and evolutionary relationship between tumor-inducing (Ti) and symbiotic (Sym) plasmids in Rhizobiaceae. Journal of molecular biology 52 11273700
2010 Evolution and multifarious horizontal transfer of an alternative biosynthetic pathway for the alternative polyamine sym-homospermidine. The Journal of biological chemistry 47 20194510
1989 nodO, a new nod gene of the Rhizobium leguminosarum biovar viciae sym plasmid pRL1JI, encodes a secreted protein. Journal of bacteriology 45 2687250
1983 Sym plasmid transfer to various symbiotic mutants of Rhizobium trifolii, R. leguminosarum, and R. meliloti. Journal of bacteriology 44 6315675
1999 Functional overlap between the mec-8 gene and five sym genes in Caenorhabditis elegans. Genetics 42 10471705
1997 Sequential functioning of Sym-13 and Sym-31, two genes affecting symbiosome development in root nodules of pea (Pisum sativum L.). Molecular & general genetics : MGG 36 9197420
2000 SYM-2081 a kainate receptor antagonist reduces allodynia and hyperalgesia in a freeze injury model of neuropathic pain. Brain research 33 10700603
1989 Additional nodulation genes on the Sym plasmid of Rhizobium leguminosarum biovar viciae. Plant molecular biology 32 2562395
1997 A Rhizobium leguminosarum biovar trifolii locus not localized on the sym plasmid hinders effective nodulation on plants of the pea cross-inoculation group. Molecular plant-microbe interactions : MPMI 31 9304865
1990 sym 13-A Gene Conditioning Ineffective Nodulation in Pisum sativum. Plant physiology 30 16667870
1989 Transcription of rhiA, a gene on a Rhizobium leguminosarum bv. viciae Sym plasmid, requires rhiR and is repressed by flavanoids that induce nod genes. Molecular microbiology 25 2716520
1992 Transconjugants of Agrobacterium radiobacter harbouring sym genes of Rhizobium galegae can form an effective symbiosis with Medicago sativa. FEMS microbiology letters 24 1499987
1991 Light Microscopy Study of Nodule Initiation in Pisum sativum L. cv Sparkle and in Its Low-Nodulating Mutant E2 (sym 5). Plant physiology 22 16668510
1988 Hepatocyte initiation during continuous administration of diethylnitrosamine and 1,2-sym-dimethylhydrazine. Cancer research 22 2892585
2011 NMR structure of a 4 x 4 nucleotide RNA internal loop from an R2 retrotransposon: identification of a three purine-purine sheared pair motif and comparison to MC-SYM predictions. RNA (New York, N.Y.) 20 21778280
2004 The identities of sym-2, sym-3 and sym-4, three genes that are synthetically lethal with mec-8 in Caenorhabditis elegans. Genetics 19 15579686
1988 Detection and subcellular localization of two Sym plasmid-dependent proteins of Rhizobium leguminosarum biovar viciae. Journal of bacteriology 18 3410833
1985 Expression of a Rhizobium phaseoli Sym plasmid in R. trifolii and Agrobacterium tumefaciens: incompatibility with a R. trifolii Sym plasmid. Plasmid 18 2994130
1979 The use of sym-triazine trichloride in RNA-protein cross-linking studies with Escherichia coli ribosomal subunits. Molecular & general genetics : MGG 18 372742
2011 Treatment of fish parasites: 5. The effects of sym. triazinone (Toltrazuril) on fish parasitic ciliophora (Ichthyophthirius multifiliis FOUQUET, 1876, Apiosoma amoebea GRENFELL, 1884, Trichodina sp. EHRENBERG, 1831). European journal of protistology 15 23195567
1989 Localization and symbiotic function of a region on the Rhizobium leguminosarum Sym plasmid pRL1JI responsible for a secreted, flavonoid-inducible 50-kilodalton protein. Journal of bacteriology 15 2644226
2013 Biological activity of sym-triazines with acetylcholine-like substitutions as multitarget modulators of Alzheimer's disease. ACS chemical neuroscience 14 23472585
2009 C. elegans sym-1 is a downstream target of the hunchback-like-1 developmental timing transcription factor. Cell cycle (Georgetown, Tex.) 12 19923914
1984 Comparative studies of rabies and Sindbis virus replication in human neuroblastoma (SYM-I) cells that can produce interferon. The Journal of general virology 12 6208314
1980 Enzymic synthesis of sym-homospermidine in Lathyrus sativus (grass pea) seedlings. The Biochemical journal 10 7470060
2021 SYMPK Is Required for Meiosis and Involved in Alternative Splicing in Male Germ Cells. Frontiers in cell and developmental biology 9 34434935
2011 RNA2 of TRV SYM breaks the rules for tobravirus genome structure. Virus research 9 21798296
1997 Dimethyldioxirane converts benzene oxide/oxepin into (Z,Z)-muconaldehyde and sym-oxepin oxide: modeling the metabolism of benzene and its photooxidative degradation. Chemical research in toxicology 9 9437519
1994 Sequence and regulation of psrA, a gene on the Sym plasmid of Rhizobium leguminosarum biover phaseoli which inhibits transcription of the psi genes. Microbiology (Reading, England) 9 8012570
1992 Pleiotropic Effects of sym-17 : A Mutation in Pisum sativum L. cv Sparkle Causes Decreased Nodulation, Altered Root and Shoot Growth, and Increased Ethylene Production. Plant physiology 9 16653124
1985 Effect of Sym Plasmid Curing on Symbiotic Effectiveness in Rhizobium fredii. Applied and environmental microbiology 8 16346803
2015 A single sym plasmid type predominates across diverse chromosomal lineages of Cupriavidus nodule symbionts. Systematic and applied microbiology 7 26159623
1991 Distribution of O-acetyl groups in the exopolysaccharide synthesized by Rhizobium leguminosarum strains is not determined by the Sym plasmid. The Journal of biological chemistry 7 2033052
2020 The pseudogene problem and RT-qPCR data normalization; SYMPK: a suitable reference gene for papillary thyroid carcinoma. Scientific reports 6 33110161
2025 The IAA-Producing Rhizobacterium Bacillus sp. SYM-4 Promotes Maize Growth and Yield. Plants (Basel, Switzerland) 5 40508264
2015 Amino acids in sandal (Santalum album L) with special reference to cis-4-hydroxy-l-proline and sym. homospermidine. SpringerPlus 5 26435892
2023 Impacts of Natural Selection on Evolution of Core and Symbiotically Specialized (sym) Genes in the Polytypic Species Neorhizobium galegae. International journal of molecular sciences 3 38069024
2019 Interaction Between Sympk and Oct4 Promotes Mouse Embryonic Stem Cell Proliferation. Stem cells (Dayton, Ohio) 3 30801858
1988 Characterization of Sym plasmids of Rhizobium leguminosarum strains able to nodulate Pisum sativum cv Afghanistan. Plant molecular biology 3 24272399
1985 Inhibition of the activities of DNA primase-polymerase alpha complex from KB cells by hexasodium sym-bis(m-aminobenzoyl-m-amino-p-methylbenzoyl-1-naphthylamino-4 ,6,8-trisulfonate)carbamide. Nucleic acids symposium series 3 4088877
2021 sym-2 loss-of-function causes glutamatergic neurodegeneration after oxidative stress. microPublication biology 2 33554054
1990 An altered constitutive peptide in sym 5 mutants of Pisum sativum L. Plant molecular biology 2 1714314
2026 SYMPK interacts with KIF20A and NUMA1 to coordinate spindle organization and safeguard oocyte meiotic maturation. Journal of genetics and genomics = Yi chuan xue bao 1 41520922
2008 The function of three indigenous plasmids in Mesorhizobium huakuii 2020 and its symbiotic interaction with Sym pJB5JI of Rhizobium leguminosarum. Science in China. Series C, Life sciences 1 18368313
2025 A non-canonical fungal peroxisome PTS-1 signal, SYM, and its evolutionary aspects. Scientific reports 0 40750654
2023 A new metabolic pathway for sym-homospermidine synthesis in an extreme thermophile, Thermus thermophilus. The Journal of general and applied microbiology 0 37532583

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