Affinage

S100A16

Protein S100-A16 · UniProt Q96FQ6

Length
103 aa
Mass
11.8 kDa
Annotated
2026-06-10
56 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

S100A16 is a homodimeric EF-hand calcium-binding protein that senses Ca²⁺ exclusively through the C-terminal EF-hand of each subunit—the N-terminal site being non-functional owing to loss of the conserved glutamate ligand—and translates this into Ca²⁺-dependent conformational change, subcellular redistribution, and target engagement that collectively drive differentiation, metabolic, and pro-metastatic programs (PMID:17030513, PMID:21046186). Unlike most S100 proteins, Ca²⁺ binding produces only a minor structural rearrangement because strong hydrophobic helix 3–4 interactions stabilize the closed conformation, yet human S100A16 still forms a Ca²⁺-induced hydrophobic patch for target recognition (PMID:17030513, PMID:21046186), and it accumulates in nucleoli, translocating to the cytoplasm or nucleus upon Ca²⁺ stimulation (PMID:17030513, PMID:21266506). A recurrent mechanistic theme is inhibition of the tumor suppressor p53: S100A16 binds p53 and represses its transcriptional output, promoting adipogenesis and, through p53 degradation and downstream CXCR4/ERK/AKT signaling, hepatic stellate cell activation and liver fibrosis in transgenic and knockout mouse models (PMID:21266506, PMID:35914619). S100A16 controls lipid metabolism and stress responses through calmodulin binding and activation of the CaM/CAMKK2/AMPK axis (PMID:31069793, PMID:39613175), and engages the ER chaperone GRP78 to competitively displace IRE1α, triggering IRE1α/XBP1-mediated ER stress in a Ca²⁺-dependent manner (PMID:34645789). In cancer and fibrosis it drives epithelial–mesenchymal transition and invasion via multiple effectors—myosin-9-dependent cytoskeletal reorganization (PMID:32094322), and ubiquitin-mediated turnover of negative regulators, facilitating HRD1-mediated degradation of GSK3β and CK1α to activate Wnt/β-catenin signaling (PMID:35279748). In metastatic breast cancer it localizes to nucleoli and associates with RNA Polymerase I (RPA194) at rDNA loci to support rRNA synthesis, EMT, and metastasis (PMID:40846689). S100A16 is itself stabilized by its paralog S100A14 through a post-translational, non-transcriptional mechanism, with the S100A14/S100A16 complex amplifying p53 suppression (PMID:24086685, PMID:41799516), and its transcription is governed by TFAP2B and NF-κB/p65 (PMID:38710691, PMID:39613175).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 2006 High

    Established S100A16 as a genuine EF-hand Ca²⁺ sensor and defined the structural basis of its binding, answering whether and how this S100 family member responds to calcium.

    Evidence Flow dialysis Ca²⁺ binding, Trp fluorescence, and live-cell localization of recombinant human/mouse protein in glioblastoma cells

    PMID:17030513

    Open questions at the time
    • Did not identify physiological Ca²⁺-dependent target proteins
    • Functional consequence of nucleolar-to-cytoplasmic translocation unknown
  2. 2010 High

    Resolved why S100A16 behaves atypically among S100 proteins by showing Ca²⁺ binding causes only minimal conformational change, refining the structural model.

    Evidence X-ray crystallography and NMR solution structures of apo and Ca²⁺-bound homodimer

    PMID:21046186

    Open questions at the time
    • Structural basis of specific target recognition not resolved
    • No co-structure with a partner protein
  3. 2011 High

    Connected S100A16 to adipogenesis and identified p53 as a direct binding partner whose activity it represses, providing the first molecular partner and a tumor-suppressor link.

    Evidence 3T3-L1 differentiation with reciprocal overexpression/knockdown, p53 Co-IP, and Ca²⁺-ionophore-induced nuclear exclusion

    PMID:21266506

    Open questions at the time
    • Binding interface and Ca²⁺-dependence of p53 interaction not mapped
    • Mechanism by which binding represses p53 transcriptional output unclear
  4. 2013 Medium

    Showed S100A16 reciprocally controls the adipogenic/osteogenic fate switch in mesenchymal stem cells through ERK1/2 and JNK signaling, extending its role to lineage commitment.

    Evidence BM-MSC differentiation, PPARγ/RUNX2 promoter luciferase, and phospho-MAPK Western blots

    PMID:23526364

    Open questions at the time
    • Direct molecular link between S100A16 and MAPK activation not established
    • No in vivo skeletal phenotype tested
  5. 2013 High

    Identified the paralog S100A14 as a direct interactor that post-transcriptionally stabilizes S100A16, revealing a regulatory dimerization mechanism.

    Evidence Yeast two-hybrid, Co-IP, co-IF, and cycloheximide chase across multiple cell lines

    PMID:24086685

    Open questions at the time
    • Degradation pathway (non-proteasomal, non-lysosomal) not identified
    • Functional consequence of the complex not yet defined here
  6. 2014 Medium

    Placed S100A16 upstream of EMT transcription factors in breast cancer, defining a pro-invasive transcriptional program.

    Evidence MCF-7 overexpression with Notch1 siRNA rescue and EMT marker analysis

    PMID:25287362

    Open questions at the time
    • Mechanism by which S100A16 upregulates Notch1/ZEB unknown
    • Single cell line
  7. 2016 Medium

    Extended S100A16 pro-tumor signaling to prostate cancer via AKT/ERK activation and cell-cycle inhibitor downregulation.

    Evidence DU-145 overexpression/knockdown with LY294002 and PD98059 pharmacological epistasis

    PMID:27240591

    Open questions at the time
    • No direct binding partner upstream of AKT/ERK identified
    • Single cell line
  8. 2018 Medium

    Demonstrated intercellular transfer of S100A16 via exosomes confers apoptosis resistance through mitochondrial PHB-1, introducing a non-cell-autonomous mechanism.

    Evidence HBMEC-to-SCLC exosome transfer, JC-1 membrane-potential assay, and PHB-1 siRNA epistasis

    PMID:30183374

    Open questions at the time
    • Direct S100A16-PHB-1 binding not shown
    • Mechanism of nuclear translocation upon transfer unclear
  9. 2019 Medium

    Identified calmodulin as a binding partner linking S100A16 to the CaM/CAMKK2/AMPK pathway controlling hepatic lipid metabolism in vivo.

    Evidence S100A16 transgenic/knockout mice on HFD, CaM Co-IP, RNA-seq

    PMID:31069793

    Open questions at the time
    • Ca²⁺-dependence of CaM interaction not formally tested here
    • Direct effect on AMPK vs indirect not separated
  10. 2020 Medium

    Identified myosin-9 as a Ca²⁺/TGF-β-induced interactor driving cytoskeletal reorganization and EMT in renal fibrosis, linking S100A16 to fibrotic disease.

    Evidence Mass spectrometry interactome, UUO mouse model with transgenic/knockout mice, HK-2 functional assays

    PMID:32094322

    Open questions at the time
    • Binding interface with myosin-9 not mapped
    • Whether myosin-9 binding is direct not biochemically proven
  11. 2020 Medium

    Showed S100A16 drives PDAC metastasis through TWIST1 and STAT3, generalizing its EMT-promoting role to pancreatic cancer.

    Evidence Loss/gain-of-function in vitro and xenograft with TCGA correlation

    PMID:33359364

    Open questions at the time
    • No direct molecular partner linking S100A16 to STAT3
    • Mechanism of TWIST1 induction unknown
  12. 2021 High

    Defined a Ca²⁺-dependent ER stress mechanism in which S100A16 binds GRP78 and competitively displaces IRE1α to activate IRE1α/XBP1 signaling.

    Evidence Reciprocal Co-IP, IF colocalization, competitive binding, BAPTA-AM Ca²⁺ chelation in HK-2 cells

    PMID:34645789

    Open questions at the time
    • Stoichiometry of GRP78 displacement not quantified
    • Whether mechanism operates outside renal cells untested
  13. 2021 Medium

    Linked S100A16 to FGF19-dependent AKT/ERK signaling driving pancreatic cancer proliferation and survival.

    Evidence Knockdown/overexpression, cell-cycle and apoptosis assays, in vivo metastasis model

    PMID:33389337

    Open questions at the time
    • Mechanism connecting S100A16 to FGF19 unclear
    • No direct binding partner identified
  14. 2021 Medium

    Identified ZO-2 as a degradation target, showing S100A16 promotes gastric cancer invasion by ubiquitin-mediated turnover of a tight-junction regulator.

    Evidence Proteomic interactome, functional assays, ZO-2 ubiquitination Western blot

    PMID:34650982

    Open questions at the time
    • E3 ligase mediating ZO-2 ubiquitination not identified
    • Direct vs indirect role of S100A16 in degradation unclear
  15. 2021 Medium

    Established an NF-κB-driven transcriptional axis upstream of S100A16 suppressed by ADAMTS19 in gastric cancer.

    Evidence Co-IP, dual-luciferase reporter, and S100A16 rescue epistasis

    PMID:33921267

    Open questions at the time
    • Direct p65 binding to S100A16 promoter assumed not fully mapped
    • Single cancer context
  16. 2022 High

    Resolved how S100A16 activates Wnt/β-catenin by facilitating HRD1-mediated ubiquitination and degradation of GSK3β and CK1α, providing a defined enzymatic mechanism in kidney injury.

    Evidence S100A16 knockout/overexpression mice and NRK-49F cells, IRI model, ubiquitination assay, ICG-001 Wnt inhibitor

    PMID:35279748

    Open questions at the time
    • Whether S100A16 directly scaffolds HRD1 onto substrates not biochemically shown
    • Ca²⁺-dependence of this mechanism untested
  17. 2022 High

    Mechanistically tied S100A16-mediated p53 degradation to CXCR4/ERK/AKT signaling in hepatic stellate cell activation and liver fibrosis with strong in vivo support.

    Evidence Transgenic and knockout mice across fibrosis models, p53 Co-IP, RNA-seq

    PMID:35914619

    Open questions at the time
    • E3 ligase for p53 degradation not identified
    • Direct CXCR4 regulation mechanism not mapped
  18. 2024 Medium

    Identified TFAP2B as a direct transcription factor for S100A16 and integrated HIF-1α/HRD1 regulation into the renal hypoxia pathway.

    Evidence ChIP and luciferase reporter assays, S100A16 knockout NRK-52E cells, H/R model

    PMID:38710691

    Open questions at the time
    • Relative contribution of TFAP2B vs NF-κB in different tissues unclear
    • Single experimental system
  19. 2024 Medium

    Showed VDAC1/NF-κB-driven S100A16 transcription and CaM/CAMKK2/AMPK activation contribute to myocardial ischemia/reperfusion injury, defining a cardiac stress axis.

    Evidence Cardiac I/R and H/R models, adenoviral inhibition, promoter binding and CaM Co-IP

    PMID:39613175

    Open questions at the time
    • Direct VDAC1-S100A16 relationship not established
    • Ca²⁺-dependence of CaM interaction in cardiac context not isolated
  20. 2024 Medium

    Revealed an RNA-regulatory function in which S100A16 binds the MOV10 helicase to stabilize ITGA3 mRNA and promote lung adenocarcinoma malignancy.

    Evidence Co-IP, RIP, actinomycin D mRNA stability assay, knockdown/overexpression rescue

    PMID:39450567

    Open questions at the time
    • Direct vs indirect MOV10 binding not fully resolved
    • Whether S100A16 itself binds RNA untested
  21. 2025 High

    Defined a nucleolar function: S100A16 associates with RNA Polymerase I (RPA194) at rDNA loci to drive rRNA synthesis and support breast cancer metastasis, explaining its long-observed nucleolar localization.

    Evidence Nucleolar proteomics, ChIP-MS at rDNA loci, loss-of-function in vitro and in vivo metastasis assays

    PMID:40846689

    Open questions at the time
    • How S100A16 is recruited to rDNA not defined
    • Ca²⁺-dependence of RNA Pol I association untested
  22. 2025 Medium

    Connected S100A16 to RPN2/STAT3/GSK3β-dependent β-catenin nuclear translocation driving cervical cancer migration.

    Evidence siRNA knockdown, RNA-seq, nuclear/cytosolic fractionation, RPN2 rescue

    PMID:40907797

    Open questions at the time
    • Direct partner linking S100A16 to RPN2 expression unknown
    • Single cancer type
  23. 2026 Medium

    Confirmed the S100A14/S100A16 complex amplifies p53 suppression through post-translational stabilization of S100A16, unifying paralog interaction with p53 regulation.

    Evidence Co-IP, CHX chase, dual-luciferase p53 activity assay, S100A14 knockdown

    PMID:41799516

    Open questions at the time
    • Identity of the stabilizing post-translational modification unknown
    • Stoichiometry of the complex on p53 not defined
  24. 2026 Medium

    Showed CRYAB K92 lactylation enhances S100A16 transcription and stability and strengthens CRYAB-S100A16 binding, embedding S100A16 in a glycolysis-fibrosis RAGE feedback loop.

    Evidence Mass spectrometry, K92R lactylation-blocking mutant, Co-IP, promoter assay, fibrosis assays

    PMID:42098255

    Open questions at the time
    • Direct RAGE binding by S100A16 not shown
    • Single disease context
  25. 2026 Medium

    Characterized Ca²⁺-sensitive S100A16 interactions with saturated short-chain phospholipids and cholesterol-rich membrane domains, suggesting a membrane-association function.

    Evidence Langmuir monolayer biophysical assays with defined lipid compositions

    PMID:42203137

    Open questions at the time
    • Single in vitro biophysical method
    • Membrane association not validated in cells

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single small Ca²⁺ sensor with minimal Ca²⁺-induced conformational change selects among its many reported partners (p53, CaM, GRP78, myosin-9, MOV10, RNA Pol I) in different cell types, and whether a unifying biochemical rule governs target choice, remains unresolved.
  • No co-structure of S100A16 with any partner
  • Ca²⁺-dependence not uniformly tested across interactions
  • Tissue-specific determinants of partner selection unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0140096 catalytic activity, acting on a protein 2 GO:0008092 cytoskeletal protein binding 1 GO:0008289 lipid binding 1
Localization
GO:0005634 nucleus 2 GO:0005730 nucleolus 2 GO:0005829 cytosol 2 GO:0005783 endoplasmic reticulum 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1266738 Developmental Biology 2 R-HSA-1643685 Disease 2 R-HSA-8953897 Cellular responses to stimuli 2 R-HSA-74160 Gene expression (Transcription) 1
Partners
CALM1CRYABDEPDC1HSPA5MOV10MYH9S100A14TP53
Complex memberships
S100A14/S100A16 complex

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 Human and mouse recombinant S100A16 form homodimers that bind two Ca²⁺ ions exclusively via the C-terminal EF-hand of each subunit (the N-terminal EF-hand is non-functional due to absence of the conserved glutamate); Ca²⁺ binding induces conformational changes detected by Trp fluorescence, and only human S100A16 forms a hydrophobic patch upon Ca²⁺ binding (implicated in target protein recognition). In glioblastoma cells, S100A16 accumulates in nucleoli and translocates to the cytoplasm upon Ca²⁺ stimulation. Flow dialysis (Ca²⁺ binding), Trp fluorescence spectroscopy, in situ hybridization, immunohistochemistry, immunofluorescence in live cells The Journal of biological chemistry High 17030513
2010 NMR and crystal structures of human S100A16 homodimer in apo and Ca²⁺-bound forms show that Ca²⁺ binding produces only minor conformational rearrangement (unlike most S100 proteins), attributed to the absence of the glutamate Ca²⁺ ligand in the N-domain EF-hand and to unusually strong hydrophobic interactions between helices 3 and 4 that stabilize the 'closed' form even after Ca²⁺ binding. X-ray crystallography and NMR solution structure determination Journal of biological inorganic chemistry High 21046186
2011 S100A16 promotes adipogenesis in 3T3-L1 preadipocytes: overexpression markedly enhances adipocyte differentiation and proliferation, while RNAi knockdown inhibits both. S100A16 physically interacts with tumor suppressor p53 (co-immunoprecipitation), and S100A16 overexpression inhibits p53-responsive gene expression while knockdown activates them. Elevated intracellular Ca²⁺ causes nuclear exclusion of S100A16. Overexpression also reduces insulin-stimulated glucose uptake and AKT phosphorylation. 3T3-L1 differentiation assay, RNAi knockdown, overexpression, co-immunoprecipitation, Western blot, calcium ionophore treatment Endocrinology High 21266506
2013 S100A16 inhibits osteogenesis and stimulates adipogenesis in bone marrow-derived mesenchymal stem cells: S100A16 overexpression increases PPARγ promoter luciferase activity and decreases RUNX2 promoter activity, while knockdown has opposite effects. ERK1/2 phosphorylation is involved in osteogenesis regulation whereas JNK phosphorylation is involved in adipogenesis downstream of S100A16. BM-MSC differentiation assay, Oil Red O and Alizarin Red S staining, promoter luciferase assay, Western blot for ERK1/2 and JNK phosphorylation, transgenic/knockout mouse-derived cells Molecular biology reports Medium 23526364
2013 S100A14 physically interacts with S100A16 (identified by yeast two-hybrid, confirmed by co-immunoprecipitation and co-immunofluorescence). S100A14 overexpression upregulates S100A16 protein without increasing its mRNA, indicating post-transcriptional regulation, whereas S100A16 overexpression does not reciprocally upregulate S100A14 (unidirectional regulation). S100A14/S100A16 degradation is independent of classical proteasomal and lysosomal pathways. Yeast two-hybrid screen, co-immunoprecipitation, double immunofluorescence, cycloheximide chase, retroviral overexpression and knockdown, RT-PCR PloS one High 24086685
2014 S100A16 overexpression in MCF-7 breast cancer cells upregulates Notch1, ZEB1, and ZEB2 transcription factors, leading to repression of E-cadherin and β-catenin and induction of N-cadherin and vimentin (EMT). Notch1-specific siRNA knockdown reverses EMT induced by S100A16 overexpression, placing Notch1 downstream of S100A16 in this pathway. Overexpression in MCF-7 cells, siRNA knockdown of Notch1, Western blot, migration/invasion assays, colony formation Journal of biomedical science Medium 25287362
2016 S100A16 overexpression in DU-145 prostate cancer cells activates AKT and ERK signaling and downregulates p21 and p27. Pharmacological inhibition of AKT (LY294002) or ERK (PD98059) suppresses S100A16-induced clone formation and invasion, placing AKT and ERK downstream of S100A16. Stable overexpression and shRNA knockdown, Western blot, transwell/wound healing assays, pharmacological inhibitors Tumour biology Medium 27240591
2018 Brain microvascular endothelial cell (HBMEC) exosomes transfer S100A16 to SCLC cells, causing S100A16 translocation from cytoplasm to nucleus. Elevated S100A16 prevents loss of mitochondrial membrane potential (Δψm) and enhances resistance to apoptosis. This protective effect depends on prohibitin-1 (PHB-1) in the mitochondrial inner membrane, as PHB-1 siRNA delivery into S100A16-overexpressing cells weakens the protective effect. Exosome isolation by ultracentrifugation, GW4869 inhibitor treatment, Western blot, immunofluorescence, Annexin V/PI apoptosis assay, JC-1 mitochondrial membrane potential assay, PHB-1 siRNA knockdown FASEB journal Medium 30183374
2019 S100A16 interacts with calmodulin (CaM) and regulates hepatic lipid metabolism via the CaM/CAMKK2/AMPK signaling pathway. S100A16 transgenic mice show more severe fatty liver on HFD, while knockdown mice show attenuated steatosis. Overexpression of S100A16 inhibits degradation of 11β-HSD1, a downstream effector of S100A16-induced adipogenesis. Transgenic and knockout mouse models, HFD feeding, co-immunoprecipitation (S100A16-CaM interaction), Western blot, RNA sequencing, Oil Red O staining Journal of cellular physiology Medium 31069793
2020 S100A16 interacts with myosin-9 (identified by mass spectrometry and confirmed functionally) in response to increased Ca²⁺ and TGF-β stimulation, promoting cytoskeleton (F-actin) reorganization and EMT progression in renal tubular epithelial cells. S100A16 overexpression in HK-2 cells increases N-cadherin and vimentin and decreases E-cadherin, and is associated with renal tubulointerstitial fibrosis in both UUO mouse model and patient biopsies. Mass spectrometry (binding partner identification), immunohistochemistry, UUO mouse model with S100A16 transgenic/heterozygous knockout mice, overexpression and knockdown in HK-2 cells, Western blot, F-actin staining Cell death & disease Medium 32094322
2020 S100A16 induces EMT in PDAC cells and promotes metastasis via upregulation of TWIST1 and activation of the STAT3 signaling pathway, as shown by in vitro and in vivo experiments. siRNA knockdown, overexpression, Western blot, in vivo xenograft, TCGA correlation analysis Biochemical pharmacology Medium 33359364
2021 S100A16 physically interacts with GRP78 in the endoplasmic reticulum of HK-2 cells (co-immunoprecipitation, immunofluorescence colocalization). S100A16 overexpression causes GRP78 to relocalize from ER to cytoplasm and competitively displaces IRE1α from GRP78, leading to IRE1α phosphorylation and XBP1 splicing (ER stress activation). Calcium chelation with BAPTA-AM blocks both the cytoplasmic colocalization and the upregulation of ER stress markers. Co-immunoprecipitation, immunofluorescence, lentiviral overexpression, BAPTA-AM chelation, Western blot for ER stress markers Cell death & disease High 34645789
2021 S100A16 promotes pancreatic cancer cell proliferation, migration, and invasion via FGF19-dependent activation of AKT and ERK1/2 signaling. S100A16 knockdown induces G2/M cell cycle arrest and apoptosis. Knockdown and overexpression, in vitro proliferation/migration/invasion assays, in vivo metastasis model, Western blot Cell biology and toxicology Medium 33389337
2021 S100A16 promotes gastric cancer cell invasion and EMT via ubiquitination and degradation of ZO-2 (Zonula Occludens-2), a tight junction regulator, identified by proteomic analysis and validated by functional assays. Proteomics/mass spectrometry (interactome), overexpression and knockdown, functional invasion/migration assays, Western blot for ZO-2 ubiquitination Frontiers in cell and developmental biology Medium 34650982
2021 ADAMTS19 binds cytoplasmic p65 and decreases nuclear phospho-p65 (NF-κB), thereby suppressing S100A16 transcription. S100A16 acts downstream of ADAMTS19 to promote gastric cancer cell migration and invasion, and rescue of S100A16 reverses the suppression caused by ADAMTS19 overexpression. Co-immunoprecipitation, immunofluorescence, dual-luciferase reporter assay, gain/loss-of-function, transwell assay Biomolecules Medium 33921267
2022 S100A16 promotes Wnt/β-catenin signaling activation in renal interstitial fibroblasts during acute kidney injury by facilitating HRD1 (E3 ubiquitin ligase)-mediated ubiquitination and degradation of GSK3β and CK1α (negative regulators of β-catenin). S100A16 knockout in mice subjected to ischemia-reperfusion injury impedes Wnt/β-catenin activation and restores HGF expression. S100A16 knockout and overexpression in mice and NRK-49F cells, IRI model, Western blot, ubiquitination assay, ICG-001 Wnt inhibitor Cellular and molecular life sciences High 35279748
2022 S100A16 binds to p53 protein, inducing its degradation; this augments CXCR4 expression, which activates ERK1/2 and AKT signaling, promoting hepatic stellate cell activation and liver fibrosis. S100a16 transgenic mice develop spontaneous liver fibrosis while S100a16 knockout mice are protected. HSC isolation, S100a16 knockout and transgenic mice, multiple fibrosis models, transcriptome sequencing (RNA-seq), co-immunoprecipitation (S100A16-p53), Western blot Metabolism: clinical and experimental High 35914619
2024 TFAP2B acts as a transcription factor for S100A16 (confirmed by ChIP and luciferase reporter assay). HIF-1α transcriptionally regulates HRD1 (confirmed by ChIP and luciferase reporter assay) within the S100A16→HRD1→GSK3β/CK1α pathway in renal hypoxia injury. S100A16 deletion attenuates HIF-1α upregulation during IRI. ChIP assay, luciferase reporter assay, S100A16 knockout rat cell line (NRK-52E), hypoxia/reoxygenation model, Western blot Cell death & disease Medium 38710691
2024 During myocardial ischemia/reperfusion injury, VDAC1 upregulation activates NF-κB/p65, which binds to the S100A16 promoter to drive S100A16 transcription. S100A16 then interacts with calmodulin (CaM) in response to elevated Ca²⁺ to activate the CAMKK2/AMPK pathway, contributing to inflammation and ROS production. Adenovirus-mediated S100A16 inhibition improves cardiac function and reduces infarct size. In vivo cardiac I/R model (ligation/release), H/R cell model, adenovirus-mediated S100A16 inhibition, ChIP-like and luciferase assays for NF-κB promoter binding, Western blot, co-immunoprecipitation (S100A16-CaM) European journal of pharmacology Medium 39613175
2024 S100A16 binds to MOV10 RNA helicase (co-immunoprecipitation) and positively modulates MOV10 expression in lung adenocarcinoma cells. MOV10 in turn stabilizes ITGA3 mRNA (RNA immunoprecipitation, actinomycin D mRNA stability assay), thereby regulating ECM-receptor interaction signaling and promoting malignant properties. MOV10 overexpression partially reverses the suppressive effects of S100A16 knockdown. Co-immunoprecipitation (S100A16-MOV10), RNA immunoprecipitation (MOV10-ITGA3 mRNA), actinomycin D mRNA stability assay, knockdown and overexpression, Western blot Molecular medicine reports Medium 39450567
2025 S100A16 knockdown in HeLa and SiHa cervical cancer cells inhibits cell migration. S100A16 regulates RPN2 (ribophorin II) expression via phospho-STAT3, which in turn modulates phospho-GSK3β to activate β-catenin/TCF signaling. S100A16 silencing reduces nuclear translocation of β-catenin (shown by nuclear/cytosolic fractionation). RPN2 overexpression reverses the migration suppression caused by S100A16 knockdown. siRNA knockdown, RNA sequencing, nuclear/cytosolic fractionation, Western blot, overexpression rescue experiment, wound-healing migration assay Biochimica et biophysica acta. Molecular cell research Medium 40907797
2025 S100A16 is enriched in nucleoli of metastatic breast cancer cells (nucleolar proteomics). ChIP-MS shows S100A16 associates at rDNA loci with RPA194 (catalytic subunit of RNA Polymerase I). Loss of S100A16 disrupts RNA Polymerase I activation and rRNA synthesis, reverses EMT, inhibits invasion, and reduces metastatic incidence in animal models. Nucleolar proteomics, ChIP-MS (rDNA loci, RPA194), loss-of-function in vitro and in vivo metastasis assays, rRNA synthesis assay Cell death & disease High 40846689
2026 S100A14 physically interacts with S100A16 (confirmed by Co-IP), stabilizes S100A16 protein via post-translational modification without transcriptional regulation (CHX chase and mRNA analysis). The S100A14/S100A16 complex reduces p53 protein stability and inhibits p53 transcriptional activity and downstream p21 expression. Knockdown of S100A14 restores p53 function, consistent with the previously described S100A16-p53 interaction. Co-immunoprecipitation, CHX chase assay, dual-luciferase assay (p53 transcriptional activity), siRNA knockdown, Western blot Oncology research Medium 41799516
2026 CRYAB lysine 92 lactylation (CRYAB_K92la) enhances S100A16 transcription, stabilizes S100A16 protein by inhibiting its degradation, and strengthens CRYAB-S100A16 binding. Upregulated S100A16 activates RAGE signaling, which promotes lactate production, forming a glycolysis-fibrosis positive feedback loop in ligamentum flavum hypertrophy. Mass spectrometry (lactylation identification), CRYAB_K92R lactylation-blocking mutation, co-immunoprecipitation (CRYAB-S100A16), promoter assay (S100A16 transcription), Western blot, in vitro fibrosis assays Communications biology Medium 42098255
2026 S100A16 preferentially interacts with saturated phospholipids with short acyl chains and zwitterionic polar head groups, and with cholesterol-enriched membrane domains (lipid raft-like), as determined using Langmuir monolayer biophysical assays. These interactions are calcium-sensitive and suggest S100A16 associates with plasma membrane and nascent disk membranes in photoreceptor outer segments. Langmuir monolayer model, surface tensiometry Archives of biochemistry and biophysics Medium 42203137
2022 S100A16 knockdown in renal cancer cells inhibits proliferation and migration and reduces VEGF, VEGFR2, and phospho-AKT expression, implicating S100A16 in the VEGF/VEGFR2/PI3K-AKT signaling axis in renal cell carcinoma. siRNA knockdown, Western blot, CCK8, wound healing/transwell assays Contrast media & molecular imaging Low 36176934
2022 S100A16 knockdown in bladder cancer cells suppresses the AKT/Bcl-2 pathway to promote apoptosis and sensitizes cells to mitomycin C. The EMT-associated transcription factor Snail regulates S100A16 expression in resistant bladder cancer cells. Proteomics (LC-MS/MS) for initial identification, siRNA knockdown, Western blot, CCK8 viability assay Cancer management and research Low 31118765
2023 S100A16 deletion protects mice against alcoholic liver lipid accumulation and inflammation by upregulating mesencephalic astrocyte-derived neurotrophic factor (MANF), which inhibits ER stress signaling. MANF silencing suppressed the inhibitory effect of S100a16 knockout on ethanol-induced lipid droplet accumulation in primary hepatocytes. S100a16 knockout and transgenic mice, Gao-binge alcohol feeding model, MANF siRNA, Western blot, lipid staining, ELISA International journal of biological sciences Medium 37928262
2022 Co-silencing of S100A16 and HSP27 in placenta-derived multipotent stem cells (PDMCs) without chemical induction drives differentiation into functional astrocytes (confirmed by morphology, neural marker immunofluorescence, electrophysiology, and Ca²⁺ influx measurement), indicating S100A16 suppresses astrocyte differentiation. siRNA knockdown (combinatorial), immunofluorescence quantification, electrophysiology, Ca²⁺ influx assay, transcriptomic/proteomic cross-comparison Stem cell reviews and reports Medium 35061207
2023 S100A16 knockdown in nephroblastoma cells inhibits proliferation, invasion, migration, and angiogenesis. S100A16 physically interacts with DEPDC1 (co-immunoprecipitation), and DEPDC1 overexpression partially reverses the suppressive effects of S100A16 interference, including suppression of PI3K/Akt/mTOR pathway activation. Co-immunoprecipitation, siRNA knockdown, overexpression rescue, CCK8, Transwell, tube formation assay, Western blot Polish journal of pathology Low 37955537
2018 In cancer stem-like spheroids of Yumoto cervical carcinoma cells, S100A16 knockdown decreases Oct4 and Nanog mRNA and protein expression and reduces sphere size. S100A16 knockdown also restores p53 protein that was diminished during sphere formation. Proteasome inhibitor lactacystin decreases Oct4 and Nanog protein but does not affect S100A16 protein, indicating S100A16 maintains Oct4/Nanog via a proteasome-dependent mechanism without being itself a proteasomal target. Sphere formation assay, siRNA knockdown, RT-PCR, Western blot, proteasome inhibitor (lactacystin) treatment Oncology letters Low 29928366

Source papers

Stage 0 corpus · 56 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 Brain microvascular endothelial cell exosome-mediated S100A16 up-regulation confers small-cell lung cancer cell survival in brain. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 70 30183374
2006 S100A16, a novel calcium-binding protein of the EF-hand superfamily. The Journal of biological chemistry 68 17030513
2004 S100A16, a ubiquitously expressed EF-hand protein which is up-regulated in tumors. Biochemical and biophysical research communications 64 14684152
2014 Up-regulation of S100A16 expression promotes epithelial-mesenchymal transition via Notch1 pathway in breast cancer. Journal of biomedical science 48 25287362
2015 S100A16 promotes differentiation and contributes to a less aggressive tumor phenotype in oral squamous cell carcinoma. BMC cancer 46 26353754
2011 Identification of S100A16 as a novel adipogenesis promoting factor in 3T3-L1 cells. Endocrinology 46 21266506
2016 S100A16 promotes cell proliferation and metastasis via AKT and ERK cell signaling pathways in human prostate cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 44 27240591
2021 S100A16 promotes metastasis and progression of pancreatic cancer through FGF19-mediated AKT and ERK1/2 pathways. Cell biology and toxicology 42 33389337
2021 The interaction of S100A16 and GRP78 actives endoplasmic reticulum stress-mediated through the IRE1α/XBP1 pathway in renal tubulointerstitial fibrosis. Cell death & disease 33 34645789
2020 S100A16 induces epithelial-mesenchymal transition in human PDAC cells and is a new therapeutic target for pancreatic cancer treatment that synergizes with gemcitabine. Biochemical pharmacology 32 33359364
2013 S100A16 inhibits osteogenesis but stimulates adipogenesis. Molecular biology reports 31 23526364
2022 S100A16 promotes acute kidney injury by activating HRD1-induced ubiquitination and degradation of GSK3β and CK1α. Cellular and molecular life sciences : CMLS 28 35279748
2022 S100a16 deficiency prevents hepatic stellate cells activation and liver fibrosis via inhibiting CXCR4 expression. Metabolism: clinical and experimental 28 35914619
2019 MicroRNA-6884-5p Regulates the Proliferation, Invasion, and EMT of Gastric Cancer Cells by Directly Targeting S100A16. Oncology research 27 31796150
2020 S100A16 suppresses the proliferation, migration and invasion of colorectal cancer cells in part via the JNK/p38 MAPK pathway. Molecular medicine reports 26 33355370
2019 S100A16 regulated by Snail promotes the chemoresistance of nonmuscle invasive bladder cancer through the AKT/Bcl-2 pathway. Cancer management and research 23 31118765
2013 S100A14 interacts with S100A16 and regulates its expression in human cancer cells. PloS one 23 24086685
2021 ADAMTS19 Suppresses Cell Migration and Invasion by Targeting S100A16 via the NF-κB Pathway in Human Gastric Cancer. Biomolecules 22 33921267
2020 Interaction of calcium binding protein S100A16 with myosin-9 promotes cytoskeleton reorganization in renal tubulointerstitial fibrosis. Cell death & disease 22 32094322
2010 Structural characterization of human S100A16, a low-affinity calcium binder. Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry 22 21046186
2019 S100A16, a novel lipogenesis promoting factor in livers of mice and hepatocytes in vitro. Journal of cellular physiology 19 31069793
2021 Calcium Binding Protein S100A16 Expedites Proliferation, Invasion and Epithelial-Mesenchymal Transition Process in Gastric Cancer. Frontiers in cell and developmental biology 18 34650982
2018 S100A16 up-regulates Oct4 and Nanog expression in cancer stem-like cells of Yumoto human cervical carcinoma cells. Oncology letters 18 29928366
2014 Estrogen suppresses adipogenesis by inhibiting S100A16 expression. Journal of molecular endocrinology 17 24501224
2023 An Update on S100A16 in Human Cancer. Biomolecules 16 37509106
2024 HIF-1α participates in the regulation of S100A16-HRD1-GSK3β/CK1α pathway in renal hypoxia injury. Cell death & disease 14 38710691
2020 S100A16 Regulates HeLa Cell through the Phosphatidylinositol 3 Kinase (PI3K)/AKT Signaling Pathway. Medical science monitor : international medical journal of experimental and clinical research 14 31894756
2022 Calbindin S100A16 Promotes Renal Cell Carcinoma Progression and Angiogenesis via the VEGF/VEGFR2 Signaling Pathway. Contrast media & molecular imaging 13 36176934
2022 An inhibitor of BRD4, GNE987, inhibits the growth of glioblastoma cells by targeting C-Myc and S100A16. Cancer chemotherapy and pharmacology 13 36224471
2019 S100A16 suppresses the growth and survival of leukaemia cells and correlates with relapse and relapse free survival in adults with Philadelphia chromosome-negative B-cell acute lymphoblastic leukaemia. British journal of haematology 11 30916375
2019 S100A16-induced adipogenesis is associated with up-regulation of 11 β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Bioscience reports 11 31399502
2011 S100A16 mediation of weight gain attenuation induced by dietary calcium. Metabolism: clinical and experimental 9 21871643
2023 miR-508-5p serves as an anti-oncogene by targeting S100A16 to regulate AKT signaling and epithelial-mesenchymal transition process in lung adenocarcinoma cells. The American journal of the medical sciences 8 36967030
2023 S100a16 Deficiency Prevents Alcohol-induced Fatty Liver Injury via Inducing MANF Expression in Mice. International journal of biological sciences 8 37928262
2023 New progress with calcium-binding protein S100A16 in digestive system disease. Expert review of gastroenterology & hepatology 7 36718596
2023 S100A16 cooperates with DEPDC1 to promote the progression and angiogenesis of nephroblastoma through PI3K/Akt/mTOR pathway. Polish journal of pathology : official journal of the Polish Society of Pathologists 6 37955537
2023 Expression and gene regulatory network of S100A16 protein in cervical cancer cells based on data mining. BMC cancer 6 37978469
2021 Interference of S100A16 suppresses lipid accumulation and inflammation in high glucose-induced HK-2 cells. International urology and nephrology 6 33389513
2023 Circular ribonucleic acid circ-FADS2 promotes colorectal cancer cell proliferation and invasion by regulating miR-498/S100A16. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society 5 36696241
2024 Resistance to gemcitabine is mediated by the circ_0036627/miR-145/S100A16 axis in pancreatic cancer. Journal of cellular and molecular medicine 4 38924205
2024 Icariside II protects from marrow adipose tissue (MAT) expansion in estrogen-deficient mice by targeting S100A16. Journal of molecular endocrinology 4 39101576
2024 S100A16 stabilizes the ITGA3‑mediated ECM‑receptor interaction pathway to drive the malignant properties of lung adenocarcinoma cells via binding MOV10. Molecular medicine reports 4 39450567
2024 VDAC1-NF-κB/p65-mediated S100A16 contributes to myocardial ischemia/reperfusion injury by regulating oxidative stress and inflammatory response via calmodulin/CaMKK2/AMPK pathway. European journal of pharmacology 4 39613175
2022 Downregulated Calcium-Binding Protein S100A16 and HSP27 in Placenta-Derived Multipotent Cells Induce Functional Astrocyte Differentiation. Stem cell reviews and reports 4 35061207
2025 Correction: Jiang et al. ADAMTS19 Suppresses Cell Migration and Invasion by Targeting S100A16 via the NF-κB Pathway in Human Gastric Cancer. Biomolecules 2021, 11, 561. Biomolecules 3 41594721
2024 LncRNA PRKCA-AS1 promotes LUAD progression and function as a ceRNA to regulate S100A16 by sponging miR-508-5p. Journal of Cancer 3 38370382
2024 S100A16 is a potential target for reshaping the tumor microenvironment in the hypoxic context of liver cancer. International immunopharmacology 2 38733818
2024 SPDEF drives pancreatic adenocarcinoma progression via transcriptional upregulation of S100A16 and activation of the PI3K/AKT signaling pathway. Biomolecules & biomedicine 1 38520747
2026 Integrative single-cell and spatial transcriptomic reveals S100A16+ tumor endothelial cells drive angiogenesis and immunosuppression in hepatocellular carcinoma. Cancer letters 0 41722834
2026 S100A14 Facilitates Pancreatic Cancer Progression via S100A16-Mediated p53 Suppression. Oncology research 0 41799516
2026 Integrated bioinformatics and immunohistochemical analysis reveal that S100A16 is correlated with mutational burden, immune evasion, and P53 expression in gastric adenocarcinoma. International journal of clinical and experimental pathology 0 41868093
2026 CRYAB_K92 lactylation drives hypertrophy of the ligamentum flavum via an S100A16/RAGE-mediated glycolysis-fibrosis positive feedback loop. Communications biology 0 42098255
2026 Effect of calcium and cholesterol on membrane binding and localization of the S100A16 protein. Archives of biochemistry and biophysics 0 42203137
2025 Validation of S100A16 as an asthma biomarker and its role in IL-13-induced bronchial epithelial cell injury. Journal of thoracic disease 0 40688271
2025 Nucleolar proteomics identifies S100A16 as a key nucleolar protein driving breast cancer metastasis. Cell death & disease 0 40846689
2025 S100A16 knockdown reduces RPN2 expression and inhibits β-catenin/TCF signaling, leading to suppressed metastasis in cervical cancer cells. Biochimica et biophysica acta. Molecular cell research 0 40907797

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