Affinage

SEMG2

Semenogelin-2 · UniProt Q02383

Length
582 aa
Mass
65.4 kDa
Annotated
2026-04-28
98 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SEMG2 encodes semenogelin II, the major structural protein of the semen coagulum that chelates Zn²⁺ with high affinity to regulate PSA (KLK3) proteolytic activity and semen liquefaction (PMID:15563730, PMID:17253189). In neuroendocrine cells, the orthologous protein secretogranin II (SgII) is sorted into large dense-core vesicles via N- and C-terminal α-helical targeting domains and undergoes Ca²⁺/pH-dependent liquid–liquid phase separation that determines granule size and quantal neurotransmitter release (PMID:18299326, PMID:35896896, PMID:1918927). SgII expression is transcriptionally controlled by CREB and AP-1/c-Jun, is required for neuronal differentiation and survival, and is proteolytically processed to bioactive peptides—secretoneurin and EM66—that activate ERK/PKA/cAMP and EGFR/IR/IGF-1R–PI3K–AKT–mTOR signaling cascades to regulate LH secretion, cardiomyocyte protection, and angiogenesis (PMID:10648883, PMID:18239671, PMID:21521715, PMID:39549871). SEMG2 also interacts with the glycolytic enzymes PKM2 and LDHA, augmenting their activity and cellular energy metabolism in cancer cells (PMID:33311447).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1991 High

    Establishing where SgII resides within secretory neurons resolved a fundamental sorting question: SgII localizes exclusively to the matrix of large dense-core vesicles and is segregated from small synaptic vesicle markers at the trans-Golgi network.

    Evidence Immunogold and immunoperoxidase double-labeling electron microscopy in hypothalamic neurons

    PMID:1918927

    Open questions at the time
    • Identity of sorting receptor or aggregation mechanism at TGN unknown
    • Whether SgII localization differs across neuroendocrine cell types not tested
  2. 1994 High

    Cell-free reconstitution defined the energy and cofactor requirements for SgII transport through the regulated secretory pathway, showing ATP, GTP, cytosolic proteins, and organelle pH gradients are needed for immature granule formation, while lumenal Ca²⁺ is dispensable for sorting but required for prohormone processing.

    Evidence Semi-intact PC12 cell reconstitution with pharmacological inhibitors (GTPγS, AlF₃, BFA, monensin) and [³⁵S]sulfate-labeled SgII

    PMID:7962053

    Open questions at the time
    • Specific GTPase identity not determined
    • Whether SgII itself drives granule budding or is a passive cargo unclear
  3. 1996 Medium

    Genomic sequencing of the semenogelin locus established that SEMG1 and SEMG2 arose by tandem duplication ~61 Mya mediated by L1 element recombination, providing the evolutionary framework for their overlapping but distinct functions.

    Evidence Sequencing of 15.7 kb genomic locus and comparative sequence analysis

    PMID:8654389

    Open questions at the time
    • Selective pressures driving sequence divergence between SEMG1 and SEMG2 not addressed
    • Functional divergence not experimentally tested
  4. 1998 High

    Two discoveries in 1998 advanced understanding of SgII processing and granule maturation: homotypic fusion of immature secretory granules containing SgII as substrate was reconstituted and shown to require NSF, and the SgII-derived bioactive peptide EM66 was identified in human adrenal chromaffin cells.

    Evidence Cell-free ISG fusion assay with PC2-mediated SgII cleavage readout; RIA/HPLC characterization of EM66 in adrenal extracts

    PMID:9709974 PMID:9864358

    Open questions at the time
    • Biological function of EM66 unknown at this stage
    • SNARE complex composition for ISG fusion not identified
  5. 2000 Medium

    Identification of a functional CRE in the SgII promoter and demonstration that CREB overexpression drives up to 8-fold transcriptional activation established the core transcriptional control mechanism for neuroendocrine SgII expression.

    Evidence Luciferase reporter assays with promoter constructs and CREB overexpression across neuroblastoma lines

    PMID:10648883

    Open questions at the time
    • Chromatin context and epigenetic regulation not explored
    • Whether CREB is sufficient in non-neuroendocrine cells not tested
  6. 2002 Medium

    Detection of SEMG2 transcripts and protein in diverse non-genital tissues including trachea, kidney, prostate basal cells, skeletal muscle, and CNS expanded the gene's functional context beyond seminal plasma.

    Evidence RT-PCR and immunohistochemistry across human tissues

    PMID:12200457

    Open questions at the time
    • Functional role in non-reproductive tissues unknown
    • Whether protein in non-genital tissues is full-length or processed not determined
  7. 2005 High

    Quantitative characterization of SEMG2 as a high-affinity Zn²⁺ chelator (≥10 sites, Kd ~5 µM) that reactivates Zn²⁺-inhibited PSA established the self-regulating proteolytic system governing semen coagulum liquefaction.

    Evidence Radioligand blotting, zinc fluorophore titration, NMR, and chromogenic PSA activity assays

    PMID:15563730

    Open questions at the time
    • In vivo kinetics of Zn²⁺ redistribution during liquefaction not measured
    • Structural basis of multi-site Zn²⁺ binding not resolved
  8. 2007 Medium

    Discovery that SEMG2 forms a ternary complex with PSA and protein C inhibitor modulated by Zn²⁺, pH, and glycosaminoglycans extended the regulatory model to include serpins in semen coagulum dynamics.

    Evidence Biochemical complex formation assays with ionic/pH modulation

    PMID:17253189

    Open questions at the time
    • Stoichiometry and affinity of ternary complex not quantified
    • In vivo relevance of PCI regulation of PSA-SEMG2 axis not validated
  9. 2008 High

    Two 2008 studies defined sorting signals and transcriptional regulation: N-terminal (25–41) and C-terminal (334–348) α-helical domains are each sufficient for dense-core granule targeting, and AP-1/c-Jun acting through the CRE is required for SgII expression, neuronal differentiation, and NO resistance.

    Evidence Chimeric SgII-GFP truncation analysis with regulated secretion assays; dominant-negative c-Jun, RNAi, and stable rescue experiments

    PMID:18239671 PMID:18299326

    Open questions at the time
    • Whether the two sorting signals act cooperatively or redundantly in vivo unresolved
    • Direct AP-1 ChIP on endogenous SgII promoter not performed
  10. 2011 Medium

    Secretoneurin was shown to stimulate LH release via a PKC–MEK–ERK and PKA/cAMP pathway independent of GnRH receptor, establishing it as an autonomous gonadotroph signaling peptide.

    Evidence RIA, ERK phosphorylation, cAMP measurement, and pharmacological inhibition in LβT2 gonadotroph cells

    PMID:21521715

    Open questions at the time
    • Secretoneurin receptor identity unknown
    • Physiological relevance in vivo not demonstrated
  11. 2012 Medium

    Secretoneurin was found to reduce myocardial ischemia-reperfusion injury and cardiomyocyte apoptosis by ~30% through rapid ERK1/2 and STAT3 phosphorylation, extending SgII-derived peptide signaling to cardioprotection.

    Evidence Post-MI mouse model, cardiomyocyte stimulation, apoptosis quantification, phosphorylation western blots

    PMID:22655045

    Open questions at the time
    • Receptor mediating secretoneurin cardioprotection not identified
    • Downstream transcriptional targets of ERK/STAT3 not characterized
  12. 2020 Medium

    Identification of PKM2 and LDHA as direct SEMG2-binding partners that are functionally activated by SEMG2 expression revealed an unexpected link between semenogelins and glycolytic metabolism in cancer cells.

    Evidence Pull-down/LC-MS/MS, enzymatic activity assays, Seahorse metabolic assays in cancer cells

    PMID:33311447

    Open questions at the time
    • Binding interface not mapped
    • Whether interaction is direct or scaffolded not distinguished
    • Relevance outside cancer cell context untested
  13. 2022 High

    Demonstration that SgII undergoes Ca²⁺-induced liquid–liquid phase separation that recruits lipids and determines LDCV size and quantal release provided a biophysical mechanism for how granin aggregation drives granule biogenesis.

    Evidence In vitro LLPS reconstitution, lipid recruitment, SgII knockdown with amperometry and LDCV size measurement, rescue with LLPS-competent truncations

    PMID:35896896

    Open questions at the time
    • Whether other granins cooperate with SgII in LLPS in vivo not resolved
    • Structural determinants of LLPS capacity beyond truncation not mapped
  14. 2024 Medium

    Secretoneurin was shown to promote pathological retinal neovascularization through activation of EGFR, IR, and IGF-1R followed by PI3K–AKT–mTOR signaling, identifying the first receptor-level targets for this peptide.

    Evidence OIR mouse model, SgII knockdown, receptor activation assays, PI3K–AKT–mTOR phosphorylation analysis

    PMID:39549871

    Open questions at the time
    • Whether secretoneurin binds these receptors directly or acts via co-receptor/ligand release not determined
    • Applicability beyond retinal vasculature not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The identity of a specific cell-surface receptor for secretoneurin remains unknown, as does the structural basis for SEMG2 multi-site Zn²⁺ binding and the physiological function of SEMG2 in non-reproductive tissues where it is expressed.
  • No dedicated secretoneurin receptor cloned or identified
  • No crystal or cryo-EM structure of SEMG2 or SgII available
  • Functional significance in trachea, kidney, and CNS unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 2
Localization
GO:0031410 cytoplasmic vesicle 5 GO:0005576 extracellular region 4 GO:0005794 Golgi apparatus 3
Pathway
R-HSA-5653656 Vesicle-mediated transport 5 R-HSA-162582 Signal Transduction 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-1430728 Metabolism 1
Partners
EGFRIGF1RKLK3LDHANSFPKMSERPINA5
Complex memberships
PSA-PCI-SEMG2 ternary complex

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 Semenogelin II (SEMG2) binds Zn²⁺ with high affinity (stoichiometry ≥10 mol/mol, average Kd ~5 µM per site) and activates PSA (prostate-specific antigen) that is inhibited by Zn²⁺, establishing SEMG2 as the major Zn²⁺ chelator in semen that regulates PSA proteolytic activity in a self-regulating system. Radioligand blotting, zinc fluorophore chelator titration, NMR analysis, chromogenic substrate PSA activity assay The Biochemical journal High 15563730
2007 SEMG2 forms a ternary complex with PSA (prostate-specific antigen) and protein C inhibitor (PCI) in seminal plasma; Sg-II binding to PSA and PCI is modulated by pH, ionic strength, heparin, dextran sulfate, divalent cations, and particularly Zn²⁺, indicating Sg-II regulates PSA-catalyzed degradation of the semen coagulum. Biochemical characterization of complex formation, modulation by ions and pH Seminars in thrombosis and hemostasis Medium 17253189
2008 SEMG2 is sorted into dense-core granules (DCGs) via saturable sorting machinery at the trans-Golgi/trans-Golgi network, with N-terminal (residues 25–41) and C-terminal (residues 334–348) alpha-helical domains acting as sufficient, independent DCG-targeting sorting signals in sympathoadrenal cells. Chimeric SgII-GFP/SEAP fusion proteins, 3D deconvolution fluorescence microscopy, secretagogue-stimulated release assays, truncation analysis, Golgi-retained mutant The Journal of biological chemistry High 18299326
2022 SgII undergoes pH-dependent polymerization and Ca²⁺-induced liquid-liquid phase separation (LLPS) in vitro and in vivo; Ca²⁺-induced SgII phase droplets recruit bio-lipids mimicking LDCV biogenesis, and SgII knockdown reduces LDCV size and quantal neurotransmitter release, rescued differentially by SgII truncations with varying LLPS capacity. In vitro phase separation assay, Ca²⁺-induced droplet formation, lipid recruitment reconstitution, SgII knockdown, amperometry for quantal release, LDCV size measurement Advanced science (Weinheim, Baden-Wurttemberg, Germany) High 35896896
1994 Transport of SgII via the regulated secretory pathway (immature granule formation and exocytosis) requires ATP, GTP, and cytosolic proteins; it is inhibited by GTPγS, AlF₃, and BFA during granule formation but GTPγS stimulates exocytosis after granule formation. SgII is sorted ~4-fold more efficiently than glycosaminoglycan chains from the TGN, and disruption of organelle pH gradients blocks both constitutive and regulated transport. Lumenal Ca²⁺ is required for prohormone processing but not for SgII sorting into immature granules. Semi-intact PC12 cell reconstitution assay, [³⁵S]sulfate labeling, pharmacological inhibitors of vesicular transport The Journal of cell biology High 7962053
1998 Homotypic fusion of immature secretory granules (ISGs) containing SgII as substrate with ISGs containing the prohormone convertase PC2 was reconstituted in a cell-free assay; fusion is ISG-specific (not ISG-MSG), temperature-dependent, requires ATP, GTP, and cytosolic proteins including NSF. Cell-free ISG fusion assay, [³⁵S]sulfate-labeled SgII as substrate, PC2-mediated cleavage product quantification, NSF requirement tested The Journal of cell biology High 9864358
1998 Posttranslational processing of SgII generates the conserved 66-amino acid peptide EM66 in human adrenal chromaffin cells (both adult medulla and fetal adrenal gland), demonstrated by RIA and HPLC matching recombinant EM66. Recombinant protein generation, polyclonal antibody development, immunohistochemistry, RIA, HPLC fractionation of adrenal extracts The Journal of clinical endocrinology and metabolism Medium 9709974
2008 SgII is a key AP-1-regulated gene: NO upregulates SgII mRNA via a CRE in the SgII promoter dependent on c-Jun; dominant-negative c-Jun (TAM67) suppresses SgII expression, impairs neuronal differentiation and sensitizes cells to NO-induced apoptosis; stable SgII re-expression in TAM67 cells restores differentiation and NO resistance; RNAi knockdown of SgII abolishes neuronal differentiation and confers NO sensitivity. Dominant-negative c-Jun expression, RNAi knockdown, stable transfection rescue, luciferase reporter with CRE mutation, apoptosis assay, neuronal differentiation assay Cell death and differentiation High 18239671
2011 The SgII-derived peptide secretoneurin (SN) stimulates LH release and production in mouse LβT2 gonadotroph cells, activates ERK via PKC and MEK, increases cAMP levels, but does not activate the GnRH receptor, indicating SN signals through PKA/cAMP-ERK pathway independently of GnRH receptor. Radioimmunoassay, real-time RT-PCR, ERK phosphorylation western blot, pharmacological inhibition (PD-98059, bisindolylmaleimide), cAMP measurement American journal of physiology. Endocrinology and metabolism Medium 21521715
2012 SgII expression is induced in failing myocardium by TGF-β and norepinephrine; the SgII-derived fragment secretoneurin reduces myocardial ischemia-reperfusion injury and cardiomyocyte apoptosis by ~30% and rapidly increases ERK1/2 and STAT3 phosphorylation in cardiomyocytes. Post-MI mouse model, in vitro cardiomyocyte stimulation, ischemia-reperfusion injury assay, apoptosis quantification, western blot for ERK1/2 and STAT3 phosphorylation PloS one Medium 22655045
2004 GnRH-stimulated secretion of LH is closely correlated with co-secretion of SgII (but not CgA) from LβT2 gonadotroph cells in a regulated, granin-dependent pathway; activin stimulates FSH secretion through a constitutive, granin-independent pathway. LβT2 cell culture, RIA for LH and FSH, western blot and ELISA for SgII and CgA, GnRH pulse regimes, activin treatment Journal of molecular endocrinology Medium 15072552
1991 By immunoelectron microscopy, SgII localizes exclusively to the matrix of large dense-core vesicles (LDCVs) in hypothalamic neurons; SgII and synaptophysin (a small synaptic vesicle marker) are segregated from each other upon exit from the trans-Golgi network and follow distinct membrane traffic pathways. Immunoperoxidase and immunogold electron microscopy, double labeling with anti-SgII and anti-synaptophysin The journal of histochemistry and cytochemistry High 1918927
1992 SgII and prolactin are co-released in parallel from GH4C1 pituitary cells under basal and stimulated conditions (high K⁺, BAY K8644, 8-bromo-cAMP, phorbol ester, TRH); sulfation of SgII is not essential for normal packaging, processing, or regulated secretion. [³⁵S]SO₄ and ³⁵S-methionine metabolic labeling, secretagogue stimulation, chlorate inhibition of sulfation, immunoblotting Endocrinology Medium 1597152
1992 Granulogenesis in GH4C1 cells is preceded by increased expression of SgII (and CgB), their condensation in the Golgi, and their co-aggregation with prolactin in vitro under high Ca²⁺/low pH conditions resembling the trans-Golgi environment, suggesting SgII participates in regulated secretory granule formation. Hormone treatment (estradiol, insulin, EGF), immunocytochemistry with anti-MG-160 Golgi marker, Northern blot, in vitro aggregation assay under low pH/high Ca²⁺ Endocrinology Medium 1612012
2000 The human SgII gene promoter contains a TATA box and a CRE (cyclic AMP response element) that confer neuroendocrine cell type-specific expression; SgII promoter activity correlates with CREB levels and overexpression of CREB increases SgII promoter activity up to 8-fold, establishing CREB as a key transcriptional activator of SgII. Promoter isolation, luciferase reporter transfection assays, CREB overexpression, comparison across neuroblastoma cell lines with varying SgII/CREB levels Brain research. Molecular brain research Medium 10648883
2014 Forced expression of SgII in LNCaP prostate cancer cells triggers formation of secretory granule-like structures competent for hormone storage and regulated release, implementing a regulated secretory pathway; androgen deprivation-induced neuroendocrine differentiation is associated with induction of SgII expression and SgII promotes cancer cell proliferation. SgII forced expression in LNCaP cells, immunocytochemistry for secretory granule markers, regulated secretion assay, proliferation assay, IHC on patient biopsies European journal of cancer Medium 25307750
2020 SEMG2 (and SEMG1) interact with the glycolytic enzymes pyruvate kinase M2 (PKM2) and lactate dehydrogenase A (LDHA) by pull-down/LC-MS/MS, and their expression increases protein levels and enzymatic activity of both PKM2 and LDHA, as well as mitochondrial membrane potential, glycolysis, respiration, and ROS production in cancer cells. Pull-down assay followed by LC-MS/MS mass spectrometry, western blot for PKM2/LDHA, enzymatic activity assays, Seahorse metabolic assay, mitochondrial membrane potential measurement Cell death & disease Medium 33311447
2002 SEMG2 transcripts are expressed in multiple non-genital tissues beyond seminal vesicles, including vas deferens, prostate, epididymis, trachea, bronchi, kidney, and testis; immunohistochemistry shows SEMG2 protein in basal cell layers of prostate, trachea and bronchi epithelium (in contrast to luminal cells in seminal vesicle and vas deferens), and in skeletal muscle and scattered CNS cells. RT-PCR, immunohistochemistry with antibodies recognizing SgI and SgII Molecular human reproduction Medium 12200457
1996 The two semenogelin genes (SEMG1 and SEMG2) evolved by duplication of an ~8 kb DNA segment approximately 61 million years ago, likely by recombination between L1 elements; they are separated by 11,616 bp of intergenic DNA containing >40% repetitive sequences. DNA sequencing of 15.7 kb semenogelin gene locus, comparative sequence analysis European journal of biochemistry Medium 8654389
2024 SgII is overexpressed in the retina in oxygen-induced retinopathy (OIR); SgII knockdown alleviates pathological retinal neovascularization but has no effect on embryonic physiological vasculature. The SgII-derived peptide secretoneurin (SN) promotes angiogenesis via activation of EGFR, IR, and IGF-1R, followed by PI3K-AKT-mTOR signaling phosphorylation. OIR mouse model, SgII knockdown, in vitro and in vivo angiogenesis assays, receptor activation assays (EGFR, IR, IGF-1R), PI3K-AKT-mTOR phosphorylation western blot Experimental eye research Medium 39549871

Source papers

Stage 0 corpus · 98 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Rate of molecular evolution of the seminal protein gene SEMG2 correlates with levels of female promiscuity. Nature genetics 184 15531881
2003 The differential secretion of FSH and LH: regulation through genes, feedback and packaging. Reproduction (Cambridge, England). Supplement 122 14635955
1999 A regulated secretory pathway in cultured hippocampal astrocytes. The Journal of biological chemistry 122 10428831
1995 Calcitonin gene-related peptide: possible role in formation and maintenance of neuromuscular junctions. The Journal of neuroscience : the official journal of the Society for Neuroscience 103 7823160
2007 Sexual selection and the adaptive evolution of mammalian ejaculate proteins. Molecular biology and evolution 98 18032407
2002 Semenogelin I and II, the predominant human seminal plasma proteins, are also expressed in non-genital tissues. Molecular human reproduction 79 12200457
2002 Molecular epidemiology and phylogenetic analysis of Sapporo-like viruses. Archives of virology 77 12111418
2005 Semenogelins I and II bind zinc and regulate the activity of prostate-specific antigen. The Biochemical journal 75 15563730
2003 The chromogranins: their roles in secretion from neuroendocrine cells and as markers for neuroendocrine neoplasia. Endocrine pathology 69 12746559
1994 Transport via the regulated secretory pathway in semi-intact PC12 cells: role of intra-cisternal calcium and pH in the transport and sorting of secretogranin II. The Journal of cell biology 69 7962053
2003 Evidence for genetic linkage between the gene segments encoding NSP4 and VP6 proteins in common and reassortant human rotavirus strains. Journal of clinical microbiology 68 12904356
2007 Comparative sequence analyses reveal rapid and divergent evolutionary changes of the WFDC locus in the primate lineage. Genome research 63 17267810
1998 Homotypic fusion of immature secretory granules during maturation in a cell-free assay. The Journal of cell biology 59 9864358
2007 Differential dynamics of Rab3A and Rab27A on secretory granules. Journal of cell science 56 17311845
2015 Sudomotor innervation in transthyretin amyloid neuropathy: Pathology and functional correlates. Annals of neurology 51 25973863
2004 Eight-year survey of human rotavirus strains demonstrates circulation of unusual G and P types in Hungary. Journal of clinical microbiology 47 14715788
2008 Sorting of the neuroendocrine secretory protein Secretogranin II into the regulated secretory pathway: role of N- and C-terminal alpha-helical domains. The Journal of biological chemistry 46 18299326
1998 Identification of a novel secretogranin II-derived peptide (SgII(187-252)) in adult and fetal human adrenal glands using antibodies raised against the human recombinant peptide. The Journal of clinical endocrinology and metabolism 45 9709974
1991 Immunoreactivities for chromogranin A and B, and secretogranin II in the guinea pig entero-endocrine system: cellular distributions and intercellular heterogeneities. Cell and tissue research 45 1878943
2019 Skin nerve pathology: Biomarkers of premanifest and manifest amyloid neuropathy. Annals of neurology 43 30737830
2004 Differential secretion of gonadotrophins: investigation of the role of secretogranin II and chromogranin A in the release of LH and FSH in LbetaT2 cells. Journal of molecular endocrinology 42 15072552
2002 Influence of steroids and GnRH on biosynthesis and secretion of secretogranin II and chromogranin A in relation to LH release in LbetaT2 gonadotroph cells. The Journal of endocrinology 41 12208668
1994 Mapping the subgroup epitopes of rotavirus protein VP6. Virology 41 7522369
2020 Alterations in seminal plasma proteomic profile in men with primary and secondary infertility. Scientific reports 38 32372034
2007 Molecular characterization of G11P[25] and G3P[3] human rotavirus strains associated with asymptomatic infection in South India. Journal of medical virology 37 17854037
1992 Prolactin granulogenesis is associated with increased secretogranin expression and aggregation in the Golgi apparatus of GH4C1 cells. Endocrinology 37 1612012
1992 Differential regulation of chromogranin B/secretogranin I and secretogranin II by forskolin in PC12 cells. Brain research. Molecular brain research 36 1312201
2012 Secretogranin II; a protein increased in the myocardium and circulation in heart failure with cardioprotective properties. PloS one 34 22655045
1991 Estradiol negatively regulates secretogranin II and chromogranin A messenger ribonucleic acid levels in the female rat pituitary but not in the adrenal. Endocrinology 34 1935773
2015 Esophageal Cancer Epigenomics and Integrome Analysis of Genome-Wide Methylation and Expression in High Risk Northeast Indian Population. Omics : a journal of integrative biology 33 26496483
1992 Chromogranin A, chromogranin B and secretogranin II mRNAs in the pituitary and adrenal glands of various mammals. Regulation of chromogranin A, chromogranin B and secretogranin II mRNA levels by estrogen. Laboratory investigation; a journal of technical methods and pathology 31 1405495
2010 Co-purification of Mac-2 binding protein with galectin-3 and association with prostasomes in human semen. The Prostate 29 21031433
2008 Hominoid seminal protein evolution and ancestral mating behavior. American journal of primatology 29 18561295
1991 Differential expression of secretogranin II and chromogranin A genes in the female rat pituitary through sexual maturation and estrous cycle. Endocrinology 29 1999159
1993 Differentiation of human pituitary adenomas determines the pattern of chromogranin/secretogranin messenger ribonucleic acid expression. The Journal of clinical endocrinology and metabolism 28 7680355
1995 Neural and mesenchymal differentiations in Ewing's sarcoma cell lines. Morphological, immunophenotypic, molecular biological and cytogenetic evidence. International journal of cancer 27 7591294
1991 Subcellular localization of secretogranin II and synaptophysin by immunoelectron microscopy in differentiated hypothalamic neurons in culture. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 27 1918927
2008 Secretogranin II: a key AP-1-regulated protein that mediates neuronal differentiation and protection from nitric oxide-induced apoptosis of neuroblastoma cells. Cell death and differentiation 26 18239671
1992 Direct estradiol down-regulation of secretogranin II and chromogranin A mRNA levels in rat pituitary cells. Molecular and cellular endocrinology 26 1281127
1999 Coactivation of secretogranin-II and BDNF genes mediated by calcium signals in mouse cerebellar granule cells. Brain research. Molecular brain research 25 9878806
2011 Secretoneurin stimulates the production and release of luteinizing hormone in mouse L{beta}T2 gonadotropin cells. American journal of physiology. Endocrinology and metabolism 24 21521715
2007 The interaction among protein C inhibitor, prostate-specific antigen, and the semenogelin system. Seminars in thrombosis and hemostasis 23 17253189
2005 Proteolytic processing and differential distribution of secretogranin-II in goldfish. General and comparative endocrinology 23 16376889
1992 Prolactin and secretogranin-II, a marker for the regulated pathway, are secreted in parallel by pituitary GH4C1 cells. Endocrinology 23 1597152
2020 Genetically predicted circulating protein biomarkers and ovarian cancer risk. Gynecologic oncology 22 33246661
1992 Immunolocalization of secretogranin II, chromogranin A, and chromogranin B in differentiating human neuroblastoma cells. European journal of cell biology 21 1425774
1994 Transcriptional regulation of secretogranin II and chromogranin B by cyclic AMP in a rat pheochromocytoma cell line. Molecular pharmacology 19 7969075
2020 SEMG1/2 augment energy metabolism of tumor cells. Cell death & disease 18 33311447
2010 Converging pathways of chromogranin and amyloid metabolism in the brain. Journal of Alzheimer's disease : JAD 18 20413871
2008 Immunohistochemical staining of human islet cells with region-specific antibodies against secretogranins II and III. Journal of anatomy 18 18221483
2004 Seasonal cyclicity of secretogranin-II expression and its modulation by sex steroids and GnRH in the female goldfish pituitary. General and comparative endocrinology 18 15560866
2022 The Hippo Pathway Effectors YAP and TAZ Regulate LH Release by Pituitary Gonadotrope Cells in Mice. Endocrinology 17 34905605
1997 Secretogranin II (SgII) distribution and processing studies in human normal and adenomatous anterior pituitaries using new polyclonal antibodies. Regulatory peptides 17 9100282
2020 A 10-gene signature as a predictor of biochemical recurrence after radical prostatectomy in patients with prostate cancer and a Gleason score ≥7. Oncology letters 16 32782607
2010 Cellular expression and subcellular localization of secretogranin II in the mouse hippocampus and cerebellum. The European journal of neuroscience 16 21044184
1993 Secretogranin II: regulation of synthesis and post-translational proteolysis in bovine adrenal chromaffin cells. Journal of neuroendocrinology 16 8680438
2022 Tuning the Size of Large Dense-Core Vesicles and Quantal Neurotransmitter Release via Secretogranin II Liquid-Liquid Phase Separation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 15 35896896
2013 Effect of short- and long-term physical activities on circulating granin protein levels. Regulatory peptides 15 23816467
2018 Fecal chromogranins and secretogranins are linked to the fecal and mucosal intestinal bacterial composition of IBS patients and healthy subjects. Scientific reports 14 30429499
1993 Regulation of expression of secretogranin II mRNA in female rat pituitary and hypothalamus. Neuroendocrinology 14 8321414
2016 Clinical and Pathological Characteristics of Hypertensive and Normotensive Adrenal Pheochromocytomas. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association 13 27219882
2012 Birth-and-death of KLK3 and KLK2 in primates: evolution driven by reproductive biology. Genome biology and evolution 13 23204305
2009 Aspects of the neuroendocrine cerebellum: expression of secretogranin II, chromogranin A and chromogranin B in mouse cerebellar unipolar brush cells. Neuroscience 13 19217926
2000 Isolation and characterization of the human secretogranin II gene promoter. Brain research. Molecular brain research 13 10648883
1998 Immunocytochemical localization of chromogranin A and secretogranin II in female rat gonadotropes. Archives of histology and cytology 13 9650885
2021 Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer's disease. Translational neurodegeneration 12 34565482
1994 Induction of secretogranin II mRNA by protein synthesis inhibitors in GH4C1 cells. The American journal of physiology 12 7977715
2018 Catestatin regulates vesicular quanta through modulation of cholinergic and peptidergic (PACAPergic) stimulation in PC12 cells. Cell and tissue research 11 30467710
2012 Differential expression and processing of secretogranin II in relation to the status of pheochromocytoma: implications for the production of the tumoral marker EM66. Journal of molecular endocrinology 11 22217803
1999 Granin proteins (chromogranin A and secretogranin II C23-3 and C26-3) in the intestine of reptiles. Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft 11 10363108
1992 Molecular approaches for the analysis of chromogranins and secretogranins. Diagnostic molecular pathology : the American journal of surgical pathology, part B 11 1342950
2014 Secretogranin II is overexpressed in advanced prostate cancer and promotes the neuroendocrine differentiation of prostate cancer cells. European journal of cancer (Oxford, England : 1990) 10 25307750
2005 Differential expression and processing of chromogranin A and secretogranin II in relation to the secretory status of endocrine cells. Endocrinology 10 16357044
2002 Neuroendocrine cell type-specific and inducible expression of chromogranin/secretogranin genes: crucial promoter motifs. Annals of the New York Academy of Sciences 10 12438085
2000 Differential onset of expression of mRNAs encoding proopiomelanocortin, prohormone convertases 1 and 2, and granin family members during Xenopus laevis development. Brain research. Molecular brain research 10 10648889
1992 Secretogranin II expression in Ewing's sarcomas and primitive neuroectodermal tumors. Diagnostic molecular pathology : the American journal of surgical pathology, part B 10 1342962
2021 Emerging roles of cancer-testis antigenes, semenogelin 1 and 2, in neoplastic cells. Cell death discovery 9 33966049
2000 Expression of the precursor of secretoneurin, secretogranin II, in the synovium of patients with rheumatoid arthritis and osteoarthritis. The Journal of rheumatology 9 11036828
1996 The structure of the semenogelin gene locus--nucleotide sequence of the intergenic and the flanking DNA. European journal of biochemistry 9 8654389
2007 A locus on chromosome 20 encompassing genes that are highly expressed in the epididymis. Asian journal of andrology 8 17589793
1995 Early detection of secretogranin-II (SgII) in the human fetal pituitary: immunocytochemical study using an antiserum raised against a human recombinant SgII. Endocrinology 8 7720657
2014 Co-storage and secretion of growth hormone and secretoneurin in retinal ganglion cells. General and comparative endocrinology 7 25435278
2006 The common marmoset (Callithrix jacchus) has two very similar semenogelin genes as the result of gene conversion. Biology of reproduction 7 17192513
2000 Genomic diversity of group A rotavirus RNA from children with acute diarrhoea in Chennai, south India. The Indian journal of medical research 7 10824467
2020 Cancer-testis antigens, semenogelins 1 and 2, exhibit different anti-proliferative effects on human lung adenocarcinoma cells. Cell death discovery 6 33101710
2019 Serum levels of chromogranins and secretogranins correlate with the progress and severity of Parkinson's disease. The Kaohsiung journal of medical sciences 6 30887724
2017 Mysterious inhibitory cell regulator investigated and found likely to be secretogranin II related. PeerJ 6 29043108
2000 Development and characterization of pituitary GH3 cell clones stably transfected with a human proinsulin cDNA. Cell transplantation 6 11202569
2011 Genes encoding WFDC- and Kunitz-type protease inhibitor domains: are they related? Biochemical Society transactions 5 21936822
2022 SGII: Systematic Identification of Essential lncRNAs in Mouse and Human Genome With lncRNA-Protein-Protein Heterogeneous Interaction Network. Frontiers in genetics 3 35386279
2022 Differential Expression of Secretogranins II and III in Canine Adrenal Chromaffin Cells and Pheochromocytomas. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 3 35400231
2020 Identification of the major rabbit and guinea pig semen coagulum proteins and description of the diversity of the REST gene locus in the mammalian clade Glires. PloS one 3 33052982
2018 Molecular evolution of the semenogelin 1 and 2 and mating system in gibbons. American journal of physical anthropology 3 30575018
2010 Regulation and distribution of squirrel monkey chorionic gonadotropin and secretogranin II in the pituitary. General and comparative endocrinology 3 21095191
2020 Reprogrammable fluorescence logic sensing for biomolecules via RNA-like coenzyme A-based coordination polymer. Biosensors & bioelectronics 2 32729525
2024 Investigating the effects of COVID-19 on sperm in male smokers: A prospective integrated proteomic and metabolomic study. Reproductive toxicology (Elmsford, N.Y.) 0 39406274
2024 SN promote retinal pathological neovascularization through activation of EGFR, IR and IGF-1R. Experimental eye research 0 39549871
2022 Re-Analysis of Published Datasets in Search of Novel Urogenital Diseases Biomarkers. Current protein & peptide science 0 36177616