Affinage

SEMG1

Semenogelin-1 · UniProt P04279

Length
462 aa
Mass
52.1 kDa
Annotated
2026-04-28
19 papers in source corpus 6 papers cited in narrative 6 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SEMG1 is a seminal plasma protein that inhibits sperm hyperactivation by suppressing CatSper calcium channel currents through two distinct functional domains (Q32-V118 and R98-S220), which differ in their capacity to bind the sperm surface protein EPPIN [PMID:bio_10.1101_2025.09.05.674523]. Its transcription is driven by a core promoter flanked by GATA-1 binding domains and is responsive to IL-4 and IL-6 (PMID:18602691), while post-transcriptionally miR-525-3p represses SEMG1 by targeting its 3'-UTR (PMID:30575326). In cancer cells, SEMG1 physically associates with the glycolytic enzymes PKM2 and LDHA, increasing their protein levels and enzymatic activities to enhance glycolysis, mitochondrial membrane potential, and ROS production (PMID:33311447).

Mechanistic history

Synthesis pass · year-by-year structured walk · 4 steps
  1. 2008 Medium

    Defining how SEMG1 transcription is controlled revealed a core promoter between two GATA-1 sites that is necessary and sufficient for basal activity and is induced by IL-4/IL-6, establishing SEMG1 as a cytokine-responsive gene.

    Evidence Promoter deletion/reporter assays in myeloma cells

    PMID:18602691

    Open questions at the time
    • Whether GATA-1 itself binds and drives the promoter was not confirmed by ChIP or EMSA
    • Relevance of IL-4/IL-6 responsiveness outside myeloma cells is untested
    • Upstream signaling pathways linking cytokine receptors to SEMG1 promoter are unknown
  2. 2018 Medium

    Identifying miR-525-3p as a direct post-transcriptional repressor of SEMG1 established a regulatory layer that could modulate SEMG1 protein levels in spermatozoa independently of transcription.

    Evidence Luciferase reporter assay confirming miR-525-3p binding to SEMG1 3'-UTR; Western blot and qPCR

    PMID:30575326

    Open questions at the time
    • Physiological consequences of miR-525-3p–mediated SEMG1 repression on sperm function are not demonstrated
    • Whether other miRNAs also regulate SEMG1 is unexplored
    • Single-lab finding without independent replication
  3. 2020 Medium

    Demonstrating that SEMG1 physically binds PKM2 and LDHA and enhances their enzymatic activities revealed an unexpected metabolic function for this seminal protein in cancer cells, linking it to glycolysis and mitochondrial energetics.

    Evidence Pull-down/LC-MS/MS identification of PKM2 and LDHA; enzymatic activity assays; mitochondrial membrane potential measurements in cancer cells

    PMID:33311447

    Open questions at the time
    • Structural basis of SEMG1–PKM2/LDHA interaction is unknown
    • Whether this metabolic role operates in normal seminal or spermatogenic physiology is untested
    • Reciprocal co-immunoprecipitation was not reported
  4. 2025 Medium

    Electrophysiological demonstration that SEMG1 directly suppresses CatSper channel currents, together with domain mapping showing two functionally distinct inhibitory regions with differential EPPIN binding, established a molecular mechanism for SEMG1's role in regulating sperm capacitation.

    Evidence Patch-clamp electrophysiology of CatSper currents; recombinant truncation mutant assays; sperm motility/hyperactivation assays; EPPIN-binding assays (preprint)

    PMID:bio_10.1101_2025.09.05.674523

    Open questions at the time
    • Preprint not yet peer-reviewed
    • Whether SEMG1 binds CatSper directly or acts through an intermediary is not resolved
    • In vivo relevance in fertilization has not been tested with knockout models

Open questions

Synthesis pass · forward-looking unresolved questions
  • The relationship between SEMG1's sperm-regulatory function (CatSper inhibition) and its cancer-associated metabolic function (PKM2/LDHA activation) remains mechanistically unconnected, and whether these reflect context-dependent activities of distinct domains is unknown.
  • No structural model of SEMG1 exists to unify its multi-domain activities
  • No animal knockout or knockin model has been reported
  • Whether SEMG1's anti-apoptotic effect in spermatogonia is mediated through metabolic or CatSper-related pathways is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 2
Localization
GO:0005576 extracellular region 1
Pathway
R-HSA-1430728 Metabolism 1 R-HSA-1474165 Reproduction 1
Partners
CATSPER1EPPINLDHAPKM2

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 miR-525-3p directly targets the 3'-UTR of SEMG1 mRNA and suppresses its expression, providing a post-transcriptional regulatory mechanism for SEMG1 levels in spermatozoa. Luciferase reporter assay confirming miR-525-3p binding to SEMG1 3'-UTR; Western blot and real-time PCR for expression quantification Andrology Medium 30575326
2008 The core promoter of SEMG1 spans the region between two putative GATA-1 binding domains, and this region is necessary and sufficient for basal promoter activity in myeloma cells; the promoter is responsive to IL-4 and IL-6. Promoter deletion/reporter assays in myeloma cells Leukemia research Medium 18602691
2020 SEMG1 physically associates with the glycolytic enzymes pyruvate kinase M2 (PKM2) and lactate dehydrogenase A (LDHA), and increases the protein levels and enzymatic activity of both, leading to enhanced glycolysis, mitochondrial membrane potential, respiration, and ROS production in cancer cells. Pull-down assay followed by LC-MS/MS mass spectrometry; enzymatic activity assays; mitochondrial membrane potential assay Cell death & disease Medium 33311447
2020 Silencing SEMG1 in GC-1 spg spermatogonia cells by siRNA promotes apoptosis, associated with increased caspase-3 and decreased BCL2 protein levels, without affecting cell cycle distribution. siRNA knockdown; flow cytometry for apoptosis; Western blot for caspase-3 and BCL2 Zhonghua nan ke xue = National journal of andrology Low 33377697
2024 SEMG1 overexpression in OSCC cells augments reactive oxygen species production, increases mitochondrial membrane potential, promotes S-phase entry, and correlates with expression of metabolic enzymes ENO1 and PKM2. Stable SEMG1 overexpression and shRNA knockdown in CAL27 cells; fluorescent dihydroethidium ROS assay; mitochondrial membrane potential assay; flow cytometry cell cycle analysis; immunohistochemistry and Western blot Oral diseases Low 39155514
2025 Recombinant SEMG1 inhibits sperm hyperactivation and progressive motility by suppressing CatSper calcium channel currents at physiologically relevant concentrations; two functional domains (Q32-V118 and R98-S220) within SEMG1 mediate this inhibition and differ in their EPPIN-binding capacities. Electrophysiological recordings of CatSper currents; truncated recombinant fragment assays; sperm motility/hyperactivation assays; EPPIN-binding assays bioRxivpreprint Medium bio_10.1101_2025.09.05.674523

Source papers

Stage 0 corpus · 19 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Exercise induced muscle damage and recovery assessed by means of linear and non-linear sEMG analysis and ultrasonography. Journal of electromyography and kinesiology : official journal of the International Society of Electrophysiological Kinesiology 39 11228421
2018 Expressions of miR-525-3p and its target gene SEMG1 in the spermatozoa of patients with asthenozoospermia. Andrology 28 30575326
2016 Evaluation of the Check-Points Check MDR CT103 and CT103 XL Microarray Kits by Use of Preparatory Rapid Cell Lysis. Journal of clinical microbiology 26 26888905
2020 SEMG1/2 augment energy metabolism of tumor cells. Cell death & disease 18 33311447
2019 Expression Analysis of the CRISP2, CATSPER1, PATE1 and SEMG1 in the Sperm of Men with Idiopathic Asthenozoospermia. Journal of reproduction & infertility 18 31058050
2013 SEMG1 may be the candidate gene for idiopathic asthenozoospermia. Andrologia 13 23289976
2008 Core promoter sequence of SEMG I spans between the two putative GATA-1 binding domains and is responsive to IL-4 and IL-6 in myeloma cells. Leukemia research 7 18602691
2019 Association of semenogelin (SEMG) gene variants in idiopathic male infertility in Chinese-Han population. Journal of toxicology and environmental health. Part A 6 31535590
2025 Motor control performance-related modulation of beta-band EEG-sEMG coherence differs between general and local muscular exercise-induced fatigue. European journal of applied physiology 5 39909897
2021 A novel energy-motion model for continuous sEMG decoding: from muscle energy to motor pattern. Journal of neural engineering 5 33022663
2025 High-Accuracy Lower-Limb Intent Recognition: A KPCA-ISSA-SVM Approach with sEMG-IMU Sensor Fusion. Biomimetics (Basel, Switzerland) 1 41002842
2022 An sEMG-Based Human-Exoskeleton Interface Fusing Convolutional Neural Networks With Hand-Crafted Features. Frontiers in neurorobotics 1 35845758
2009 SEMG-1 expression in early stage chronic lymphocytic leukemia. Cytotherapy 1 19241194
2003 Neuropathology considerations: clinical and SEMG/biofeedback applications. Applied psychophysiology and biofeedback 1 12827988
2026 Hydrogel-based electrodes for high-fidelity sEMG acquisition and robotic hand control. Microsystems & nanoengineering 0 41876445
2025 Facial expression recognition through muscle synergies and estimation of facial keypoint displacements through a skin-musculoskeletal model using facial sEMG signals. Frontiers in bioengineering and biotechnology 0 40013307
2025 Dynamic Changes in Mimic Muscle Tone During Early Orthodontic Treatment: An sEMG Study. Journal of clinical medicine 0 40725747
2024 The role of SEMG1 overexpression in OSCC tumorigenesis and its relation with metabolic molecules. Oral diseases 0 39155514
2020 [Effects of silencing the SEMG1 protein on the cycle and apoptosis of GC-1 spg cells]. Zhonghua nan ke xue = National journal of andrology 0 33377697