Affinage

S100A6

Protein S100-A6 · UniProt P06703

Length
90 aa
Mass
10.2 kDa
Annotated
2026-06-10
100 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

S100A6 (calcyclin) is a small, homodimeric EF-hand protein that binds two Ca2+ per monomer with low affinity and positive cooperativity, undergoing a Ca2+-induced conformational change that shifts buried aromatic residues into a less polar environment and creates target-binding surfaces, while remaining functionally distinct from calmodulin (it does not activate calmodulin-dependent enzymes) (PMID:8204608, PMID:1898017). Through this Ca2+-switch it engages a panel of intracellular partners: CacyBP/SIP, whose binding occurs at a discrete site mapped by NMR with ~1 μM affinity and which links S100A6 to β-catenin/Tcf-LEF signaling and proliferation control (PMID:10884380, PMID:8973570, PMID:22295074); the CacyBP yeast homolog Sgt1, where S100A6 binding blocks casein kinase II phosphorylation (PMID:12746458); p53, which it binds Ca2+-dependently to enhance nuclear accumulation and transcriptional activity under stress (PMID:18765292); the TPR-domain proteins Hop and kinesin light chain, where binding disrupts Hop–Hsp70/Hsp90 chaperone assembly and displaces JIP-1 from KLC (PMID:18669640); and annexin 2, whose membrane localization S100A6 promotes to drive cancer cell motility (PMID:19724273). S100A6 supports cell cycle progression and represses senescence, with its loss causing G0/G1 or G2/M arrest, reduced CDK1 and cyclins, and suppression of antiproliferative STAT1 signaling (PMID:20013795, PMID:23095053, PMID:27386938); its trafficking and migratory functions depend on the actin/microfilament cytoskeleton (PMID:12118070, PMID:12577318). Its expression is induced through multiple stress-responsive transcription factors—NF-κB downstream of TNF-α (PMID:18753141), Nrf2 via an antioxidant response element under oxidative stress (PMID:15878395), c-Myc (PMID:34060533), and ΔNp63 in keratinocyte differentiation (PMID:25450463). Extracellularly, S100A6 signals through the C1/C2 immunoglobulin domains of RAGE to activate JNK-dependent apoptosis (PMID:17726019), and RAGE engagement also underlies its activity as a hepatokine that suppresses glucose-stimulated insulin secretion via diminished mitochondrial respiration (PMID:35899967) and its promotion of VEGF-D–driven lymphangiogenesis via NF-κB (PMID:38350547). Additional roles include cardiomyocyte protection through calcineurin and improved calcium handling (PMID:28174168), maintenance of hematopoietic stem cell self-renewal through an Akt–Hsp90–mitochondrial calcium axis (PMID:32555370), and competition with zinc for Aβ to reduce amyloid plaque burden (PMID:31440382).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1991 Medium

    Establishing that S100A6 is a genuine Ca2+-binding protein with its own target spectrum, rather than a calmodulin mimic, defined it as a distinct calcium effector.

    Evidence Ca2+-dependent affinity chromatography and calmodulin-dependent enzyme assays on S100A6 purified from rabbit lung, plus serum-stimulation Northern/run-off analysis in smooth muscle cells

    PMID:1757477 PMID:1898017

    Open questions at the time
    • The identity of the 50 kDa cytosolic binding partner was not resolved
    • The post-transcriptional mechanism controlling cell-cycle-coupled mRNA levels was not defined
  2. 1994 High

    Quantitative biophysics established the Ca2+-binding stoichiometry, affinity, cooperativity, and conformational switch that mechanistically underlies S100A6 target engagement.

    Evidence Flow dialysis, fluorescence and UV difference spectroscopy, and ultracentrifugation on recombinant S100A6

    PMID:8204608

    Open questions at the time
    • The low Ca2+ affinity (sub-millimolar) leaves the physiological trigger concentration unclear
    • No target was bound in this study to link the conformational change to function
  3. 2003 High

    Identification of the CacyBP/SIP family (p30, CacyBP, Sgt1) as Ca2+-regulated S100A6 partners with mapped binding domains gave the protein a defined intracellular effector pathway.

    Evidence Gel overlay, affinity purification, NMR chemical-shift perturbation, deletion mutagenesis, cross-linking, and CK II kinase assays

    PMID:10884380 PMID:12746458 PMID:8973570

    Open questions at the time
    • The downstream consequence of inhibiting Sgt1 phosphorylation for substrate ubiquitination was not established in these studies
    • Binding was characterized in vitro and in cell extracts, not in a reconstituted ubiquitination system
  4. 2008 High

    S100A6 was shown to be a Ca2+-dependent regulator of p53 activity and of TPR-domain proteins, broadening its mechanism from a single-target protein to a hub disrupting chaperone and cargo-adaptor complexes.

    Evidence Affinity chromatography, co-IP, EMSA, luciferase reporters, GST pulldowns, and ionomycin stimulation across HEp-2 and Cos-7 cells

    PMID:18669640 PMID:18765292

    Open questions at the time
    • How p53 enhancement reconciles with the separate report that S100A6 limits p53 phosphorylation in cardiomyocytes was not resolved
    • Physiological contexts where Hop/KLC disruption matters were not defined
  5. 2008 High

    Defining NF-κB (TNF-α), Nrf2/ARE (oxidative stress), c-Myc, and ΔNp63 as upstream regulators placed S100A6 within stress- and differentiation-responsive transcriptional programs.

    Evidence Promoter deletion, EMSA, ChIP, DNA affinity chromatography, and reporter assays in cardiomyocytes, keratinocytes, and cell lines

    PMID:15878395 PMID:18753141 PMID:25450463 PMID:34060533

    Open questions at the time
    • The integration of these inputs in a single cell type was not addressed
    • Whether these regulators act combinatorially on the promoter is unknown
  6. 2009 High

    Linking S100A6 to annexin 2 membrane localization connected its Ca2+-binding activity to cancer cell motility via a defined cytoskeletal/membrane mechanism.

    Evidence Proteomic identification, reciprocal co-IP, co-immunofluorescence, siRNA, and motility assays in pancreatic cancer cells

    PMID:19724273

    Open questions at the time
    • The structural basis of the annexin 2 interaction was not mapped
    • Whether the interaction is direct was not established by reconstitution
  7. 2012 Medium

    Loss-of-function studies established S100A6 as a positive regulator of cell cycle progression that opposes senescence, identifying CDK1/cyclin and STAT1 nodes.

    Evidence Stable siRNA/RNAi, flow cytometry cell cycle analysis, β-galactosidase assays, Western blotting, and transcriptomics in fibroblasts and endothelial cells

    PMID:20013795 PMID:23095053 PMID:27386938

    Open questions at the time
    • The direct molecular link between S100A6 and CDK1 levels was not defined
    • Whether STAT1 suppression is a direct or indirect effect was not resolved
  8. 2012 High

    Biophysical aggregation studies revealed that S100A6 itself forms cytotoxic oligomers and seeds SOD1 aggregation, with Ca2+ as a protective conformational switch.

    Evidence Thioflavin-T kinetics, electron microscopy, FT-IR, seeding assays, and cell viability measurements

    PMID:23076148

    Open questions at the time
    • Whether S100A6 fibrillation occurs at physiological pH in vivo was not addressed
    • The cellular relevance of SOD1 seeding was not demonstrated in vivo
  9. 2019 Medium

    Extracellular S100A6 was shown to act as a zinc competitor that reduces Aβ plaque burden, defining a protective extracellular role distinct from RAGE signaling.

    Evidence Incubation of recombinant S100A6 with APP/PS1 brain sections, co-culture, plaque/zinc quantification, and viability assays

    PMID:31440382

    Open questions at the time
    • The effect was ex vivo/in vitro and not tested by systemic delivery in vivo
    • Whether endogenous S100A6 reaches relevant extracellular concentrations in brain is unknown
  10. 2024 High

    Tissue-level studies established physiological extracellular RAGE-dependent roles for S100A6 as a hepatokine suppressing insulin secretion and as a tumor-secreted lymphangiogenic factor.

    Evidence KO/depletion and overexpression in mouse HSCs, liver, and tumor models with Seahorse, GSIS, RAGE/NF-κB pathway, and VEGF-D readouts plus human sample validation

    PMID:32555370 PMID:35899967 PMID:38350547

    Open questions at the time
    • Whether the same RAGE-coupled mechanism operates across these tissues was not directly compared
    • The molecular basis linking RAGE to mitochondrial respiration was not fully dissected

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple intracellular partner interactions, extracellular RAGE signaling, transcriptional inputs, and aggregation propensity are integrated into a unified, context-specific function for S100A6 remains unresolved.
  • No structural model reconciles the competing partner-binding surfaces in a cellular context
  • The determinants directing S100A6 to intracellular versus secreted roles are unknown
  • Whether the pro-apoptotic and pro-survival activities reflect cell-type-specific partner availability is undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0048018 receptor ligand activity 3 GO:0008092 cytoskeletal protein binding 2 GO:0140096 catalytic activity, acting on a protein 1 GO:0140313 molecular sequestering activity 1
Localization
GO:0005576 extracellular region 4 GO:0005829 cytosol 3 GO:0005856 cytoskeleton 3 GO:0005634 nucleus 1
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-8953897 Cellular responses to stimuli 2
Partners
ANXA2CACYBPKLC1RAGES100BSGT1STIP1TP53
Complex memberships
S100A6 homodimerS100B–S100A6 heterocomplex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 S100A6 interacts specifically with the C1 and C2 extracellular immunoglobulin domains of RAGE (distinct from S100B which binds V and C1 domains), and extracellular S100A6 triggers apoptosis in SH-SY5Y neuroblastoma cells via activation of JNK (not PI3K/AKT or NF-κB), in a RAGE-dependent manner. In vitro binding assay with individual RAGE domain constructs, cell-based assay with ROS measurement, pathway inhibitor studies, and RAGE-blocking experiments in SH-SY5Y cells The Journal of biological chemistry Medium 17726019
2008 S100A6 interacts with p53 in a calcium-dependent manner (shown by affinity chromatography and co-immunoprecipitation), enhances p53 transcriptional activity and nuclear accumulation under stress without affecting p53 DNA binding (by EMSA), and its presence increases cell susceptibility to hydrogen peroxide-induced apoptosis. Affinity chromatography, co-immunoprecipitation, EMSA, siRNA knockdown in HEp-2 cells, luciferase reporter assay, immunofluorescence for p53 localization The international journal of biochemistry & cell biology Medium 18765292
2008 S100A6 is induced by TNF-α via an NF-κB–dependent mechanism (p65 binds an NF-κB site at -460/-451 in the S100A6 promoter as shown by EMSA and ChIP); S100A6 limits TNF-α-induced cardiomyocyte apoptosis by interfering with p53 phosphorylation. Luciferase reporter assay, EMSA, chromatin immunoprecipitation (ChIP), siRNA knockdown, gene transfer overexpression in rat neonatal cardiac myocytes The Journal of biological chemistry High 18753141
2000 S100A6 and S100A11 are specific target proteins for S100B; Ca2+/Zn2+ stabilizes S100B–S100A6 heterocomplexes; the C-terminal residues Phe87/Phe88 of S100B are required for interaction with S100A6 (but not for S100B homodimerization); interaction confirmed in U373 astrocytoma cells by co-immunoprecipitation. Yeast two-hybrid screen, co-immunoprecipitation, site-directed mutagenesis of S100B (Phe87/88), deletion analysis The Journal of biological chemistry High 10913138
2003 S100A6 binds Sgt1 (yeast homologue of CacyBP/SIP) in a calcium-regulated manner via Sgt1's C-terminal 71 residues; S100A6 does not affect Skp1–Sgt1 binding; S100A6 inhibits casein kinase II–mediated phosphorylation of the S100A6-binding domain of Sgt1; interaction confirmed by co-immunoprecipitation from HEp-2 cell extracts. Affinity chromatography, chemical cross-linking, co-immunoprecipitation, kinase phosphorylation assay with CK II The Journal of biological chemistry High 12746458
2000 The S100A6-binding domain of CacyBP (residues 178–229) is necessary and sufficient for calcium-dependent binding to S100A6 with a Kd ~1 μM; NMR analysis revealed that CacyBP binding occurs at a discrete site on 15N-labeled S100A6. Limited proteolysis, deletion mutagenesis, fluorescence spectroscopy (Kd determination), NMR chemical shift perturbation The Journal of biological chemistry High 10884380
2008 S100A6 binds the TPR domain of Hop (Hsp70/Hsp90-organizing protein) and of kinesin light chain (KLC) in a Ca2+-dependent manner; this binding inhibits Hop–Hsp70 and Hop–Hsp90 interactions and displaces JIP-1 from KLC in vitro and in ionomycin-stimulated Cos-7 cells. GST pulldown, co-immunoprecipitation, in vitro binding inhibition assays, ionomycin stimulation of Cos-7 cells The Journal of biological chemistry High 18669640
2009 S100A6 binds annexin 2 in pancreatic cancer cells (confirmed by reciprocal immunoprecipitation); S100A6 promotes membrane localization of annexin 2; siRNA depletion of S100A6 reduces membrane annexin 2 levels and markedly reduces pancreatic cancer cell motility. Immunoprecipitation + 2D-gel electrophoresis + mass spectrometry, reciprocal co-immunoprecipitation, co-immunofluorescence, siRNA knockdown, Boyden chamber and wound healing motility assays British journal of cancer High 19724273
1994 Recombinant S100A6 (CACY) binds 2 Ca2+ per monomer with low affinity (K0.5 = 0.32 mM), shows positive cooperativity (nH = 1.33), and Ca2+ binding induces a conformational change shifting Tyr to a less polar environment; Mg2+ does not affect Ca2+ binding or fluorescence properties; S100A6 forms homodimers but not heterodimers with CAPL in vitro. Flow dialysis calcium binding assay, fluorescence spectroscopy, UV difference spectroscopy, gel filtration/analytical ultracentrifugation Biochemistry High 8204608
1996 S100A6 (calcyclin) interacts with a novel 30 kDa target protein (p30, later identified as CacyBP) in a Ca2+-dependent manner with higher affinity than annexin II or GAPDH; p30 was purified from Ehrlich ascites tumor cells and found in mouse brain and spleen. Gel overlay with 125I-labeled calcyclin, Ca2+-dependent affinity chromatography, Phenyl-Sepharose and CM-cellulose chromatography, partial amino acid sequencing The Biochemical journal Medium 8973570
1991 S100A6 (calcyclin/2A9 product) purified from rabbit lung binds 2 Ca2+ per mole, does not activate calmodulin-dependent enzymes (CaM kinase II, MLCK, phosphodiesterase), and interacts in a Ca2+-dependent manner with a 50 kDa cytosolic binding protein present in lung, intestine, and spleen. Ca2+-dependent affinity chromatography (W-77 Sepharose), UV difference spectroscopy, equilibrium dialysis, calmodulin-dependent enzyme activity assays Archives of biochemistry and biophysics Medium 1898017
2002 S100A6 translocation in endothelial cells in response to increased intracellular calcium is dependent on actin stress fibers (distinct from S100A13 which uses the Golgi-ER pathway), implicating actin cytoskeleton in S100A6 intracellular trafficking. Live cell imaging/immunofluorescence of S100A6 translocation, cytoskeletal disruption experiments, comparison with S100A13 in angiotensin II–stimulated endothelial cells Journal of cell science Medium 12118070
2003 Antisense-mediated reduction of S100A6 in pulmonary fibroblasts inhibits serum- and mechanical strain-induced cell proliferation, causes flattened cell morphology, and disrupts tropomyosin-labeled microfilament organization without reducing tropomyosin protein levels. Antisense RNA stable expression, proliferation assay, immunofluorescence of tropomyosin/microfilaments, cell morphology analysis Journal of cellular biochemistry Medium 12577318
2004 The S100A6 gene promoter contains a functional antioxidant response element (ARE) at -290/-281 that overlaps an E-box; oxidative stress agents (cadmium ions) activate S100A6 transcription via this ARE; Nrf2 transcription factor binds to this ARE region as shown by DNA affinity chromatography and EMSA; mutation of ARE inhibits cadmium-stimulated promoter activity. Luciferase reporter assay, RT-PCR, Northern blot, EMSA, site-directed mutation of ARE, DNA affinity chromatography + Western blot for Nrf2 Biochimica et biophysica acta High 15878395
2010 S100A6 deficiency (stable siRNA knockdown) in NIH 3T3 fibroblasts causes G0/G1 cell cycle arrest unresponsive to serum, senescence-like morphological and biochemical changes (elevated β-galactosidase, gelatinase activity), disrupted actin cytoskeleton, and impaired cell adhesion and migration. Stable siRNA expression, cell cycle analysis by flow cytometry, β-galactosidase senescence assay, gelatinase assay, phalloidin staining, adhesion and migration assays Journal of cellular biochemistry Medium 20013795
2012 S100A6 depletion by RNAi in primary human endothelial cells causes G2/M cell cycle arrest, decreases CDK1 and phospho-CDK1 levels, reduces cyclin A1 (CCNA1) and cyclin B (CCNB1) gene expression, and induces β-galactosidase expression (senescence marker). RNAi knockdown, flow cytometry cell cycle analysis, Western blotting, qRT-PCR, β-galactosidase staining The FEBS journal Medium 23095053
2016 S100A6 suppresses antiproliferative STAT1 signaling in endothelial cells; S100A6 silencing combined with VEGFA stimulation revealed interferon-inducible transmembrane protein 1 and PIAS proteins as key components linking S100A6 to STAT1 suppression. siRNA knockdown in human endothelial cells, gene expression time-series analysis, bioinformatic pathway modeling, experimental validation of STAT1 pathway components Arteriosclerosis, thrombosis, and vascular biology Medium 27386938
2012 S100A6 forms amyloid fibrils under acidic conditions; Ca2+ inhibits fibrillation (promoting anti-parallel β-sheet conformations that repress fibril formation) by a mechanism reversible upon chelation; S100A6 oligomers (not fibrils) are cytotoxic (reducing cell viability ~40%); native S100A6 seeds SOD1 aggregation, shortening its nucleation phase. Thioflavin-T kinetics, electron microscopy, FT-IR spectroscopy, cell viability assay, seeding aggregation kinetics with SOD1, computational aggregation prediction The Journal of biological chemistry High 23076148
2017 S100A6 overexpression in rat neonatal cardiomyocytes improves calcium transients and protects against hypoxia-reoxygenation-induced apoptosis via enhanced calcineurin activity; in vivo S100A6 gene therapy (via ultrasound-targeted microbubble destruction) reduced infarct size and improved left ventricular systolic function after ischemia-reperfusion. S100A6 overexpression and siRNA knockdown in cardiomyocytes, calcium transient imaging, calcineurin activity assay, in vivo gene delivery + coronary ligation/reperfusion model in Fischer-344 rats Journal of the American Heart Association Medium 28174168
2019 Extracellular S100A6 competes with zinc ions for binding to Aβ, reducing amyloid plaque burden in APP/PS1 mouse brain sections; exogenous S100A6 decreased plaque-associated zinc content and protected COS-7 cells against zinc toxicity. In vitro incubation of brain sections with recombinant S100A6, co-culture with S100A6-expressing cells, Aβ plaque quantification, zinc chelator (clioquinol) control experiments, cell viability assay Aging and disease Medium 31440382
2020 S100A6 knockout in mouse hematopoietic stem cells (HSCs) reduces self-renewal and regenerative capacity, decreases phospho-Akt and Hsp90 levels, impairs mitochondrial respiratory capacity and mitochondrial calcium buffering; Akt activator SC79 rescues intracellular/mitochondrial calcium levels and colony-forming and Hsp90 activity. S100A6 KO mouse model, flow cytometry, transcriptomics, proteomics, Seahorse mitochondrial assay, calcium imaging, pharmacological Akt activation rescue experiments Leukemia High 32555370
2013 S100A6 overexpression in HCC cells causes down-regulation of E-cadherin, nuclear accumulation of β-catenin, and promotes proliferation and migration via activation of the PI3K/AKT pathway; intracellular (not extracellular) S100A6 is sufficient to rescue proliferation and migration defects after S100A6 silencing. siRNA knockdown, recombinant S100A6 with cell-penetrating peptide re-expression, Western blotting for E-cadherin/β-catenin, PI3K inhibitor (LY294002) treatment, proliferation and migration assays Journal of molecular medicine Medium 24281831
2013 S100A6 promotes colorectal carcinoma cell proliferation via ERK pathway and migration via p38 MAPK pathway; ERK inhibitor partially attenuates S100A6-induced proliferation and p38 inhibitor suppresses S100A6-induced migration. Adenoviral overexpression, recombinant S100A6 protein treatment, RNAi knockdown, kinase inhibitors (ERK, p38), in vitro proliferation/migration assays, nude mouse xenograft International journal of oncology Medium 24378749
2022 Liver-derived S100A6 (a hepatokine) inhibits glucose-stimulated insulin secretion (GSIS) from β cells via activation of RAGE and diminution of mitochondrial respiration; hepatic S100A6 transcription is driven by ChREBP; ectopic hepatic ChREBP overexpression suppresses GSIS in an S100A6-dependent manner; depletion of hepatic S100A6 improves GSIS and glycemia in mice. High-fat diet mouse model, hepatic S100A6 depletion (siRNA/KO), GSIS assay, RAGE pathway assay, Seahorse mitochondrial respiration, ChREBP overexpression in liver, human NAFLD patient serum measurements Diabetes High 35899967
2024 Secreted S100A6 from tumor cells promotes lymphangiogenesis in human lymphatic endothelial cells (HLECs) by upregulating VEGF-D expression and secretion via the RAGE/NF-κB/VEGF-D signaling pathway, thereby driving lymph node metastasis of liver cancer. Single-cell RNA-seq analysis, HLEC co-culture experiments, S100A6 overexpression/knockdown, RAGE/NF-κB pathway inhibition, VEGF-D ELISA, in vivo lymphatic metastasis model Cancer letters Medium 38350547
1991 S100A6 (2A9/calcyclin) mRNA is low in quiescent vascular smooth muscle cells and increases 2–4 h after serum re-addition (cell cycle entry); this regulation occurs post-transcriptionally as no change in transcription rate was detected by nuclear run-off assay. Northern blotting, serum deprivation/re-addition synchronization, nuclear run-off transcription assay Journal of cellular biochemistry Medium 1757477
2021 c-Myc directly binds the S100A6 promoter to activate S100A6 transcription in keratinocytes; high-glucose-induced c-Myc upregulates S100A6 to inhibit HaCaT keratinocyte differentiation via WNT/β-catenin pathway; knockdown of S100A6 rescues the differentiation dysfunction caused by c-Myc overexpression or high glucose. ChIP assay, luciferase reporter assay, siRNA knockdown, overexpression, Western blotting for differentiation markers, organotypic culture Frontiers in endocrinology Medium 34060533
2012 S100A6 interaction with wild-type CacyBP/SIP (but not with a truncated mutant lacking the S100-binding domain) negatively regulates CacyBP/SIP-mediated inhibition of gastric cancer cell proliferation and tumorigenesis; S100A6 binding to CacyBP/SIP modulates β-catenin protein expression and Tcf/LEF transcriptional activation. Co-immunoprecipitation of endogenous S100A6 with CacyBP/SIP, truncation mutant expression, MTT/FACS/clonogenic assay, tumor xenograft PloS one Medium 22295074
2014 S100A6 overexpression in keratinocytes suppresses loricrin expression, accelerates proliferation, and blocks epidermal differentiation in organotypic culture; S100A6 expression is regulated during differentiation via ΔNp63 and retinoic acid (not by DNA methylation) as shown by bisulfite treatment, luciferase assay, and ChIP. Stable knockdown and overexpression in HaCaT cells, organotypic (3D) culture, bisulfite sequencing, luciferase reporter, ChIP for ΔNp63, retinoic acid treatment The international journal of biochemistry & cell biology Medium 25450463
2019 S100A6 promotes B lymphocyte infiltration through the blood-brain barrier endothelial layer; recombinant S100A6 protein treatment of an in vitro transendothelial migration model significantly increased B cell penetration, partially recapitulating the effect of autoimmune encephalitis serum. In vitro leukocyte transendothelial migration assay, recombinant S100A6 protein treatment, genome-wide DNA methylation assay, qPCR Frontiers in genetics Low 31850060

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 S100B and S100A6 differentially modulate cell survival by interacting with distinct RAGE (receptor for advanced glycation end products) immunoglobulin domains. The Journal of biological chemistry 231 17726019
2000 Five members of a novel Ca(2+)-binding protein (CABP) subfamily with similarity to calmodulin. The Journal of biological chemistry 221 10625670
1997 Differential expression patterns of S100A2, S100A4 and S100A6 during progression of human malignant melanoma. International journal of cancer 149 9291441
2005 The role of S100A6 in pancreatic cancer development and its clinical implication as a diagnostic marker and therapeutic target. Clinical cancer research : an official journal of the American Association for Cancer Research 142 16278400
2009 S100A6 - new facts and features. Biochemical and biophysical research communications 125 19891957
1991 Calbindin-D28K (CaBP) levels and calcium currents in acutely dissociated epileptic neurons. Experimental brain research 121 1655508
2017 S100A6 protein: functional roles. Cellular and molecular life sciences : CMLS 117 28417162
2009 Progesterone receptor A (PRA) and PRB-independent effects of progesterone on gonadotropin-releasing hormone release. Endocrinology 99 19423765
2008 Reliable identification of mycobacterial species by PCR-restriction enzyme analysis (PRA)-hsp65 in a reference laboratory and elaboration of a sequence-based extended algorithm of PRA-hsp65 patterns. BMC microbiology 95 18366704
2008 S100A6 binds p53 and affects its activity. The international journal of biochemistry & cell biology 93 18765292
2003 Calcyclin (S100A6) regulates pulmonary fibroblast proliferation, morphology, and cytoskeletal organization in vitro. Journal of cellular biochemistry 92 12577318
2007 Progesterone receptor (PR) isoforms PRA and PRB differentially regulate expression of the breast cancer resistance protein in human placental choriocarcinoma BeWo cells. Molecular pharmacology 89 18042733
1992 S100 alpha, CAPL, and CACY: molecular cloning and expression analysis of three calcium-binding proteins from human heart. Biochemistry 89 1384693
2000 S100A6 and S100A11 are specific targets of the calcium- and zinc-binding S100B protein in vivo. The Journal of biological chemistry 80 10913138
2015 The Calcium-Binding Protein S100A6 Accelerates Human Osteosarcoma Growth by Promoting Cell Proliferation and Inhibiting Osteogenic Differentiation. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 79 26646427
2009 S100A6 binds to annexin 2 in pancreatic cancer cells and promotes pancreatic cancer cell motility. British journal of cancer 79 19724273
2000 Increased expression of S100A6 at the invading fronts of the primary lesion and liver metastasis in patients with colorectal adenocarcinoma. British journal of cancer 76 10952782
2008 Aliskiren fails to lower blood pressure in patients who have either low PRA levels or whose PRA falls insufficiently or reactively rises. American journal of hypertension 70 18802434
1996 p30, a novel protein target of mouse calcyclin (S100A6). The Biochemical journal 70 8973570
2000 Increased expression of S100A6 (Calcyclin), a calcium-binding protein of the S100 family, in human colorectal adenocarcinomas. Clinical cancer research : an official journal of the American Association for Cancer Research 68 10656447
2004 Astrocytic calcium/zinc binding protein S100A6 over expression in Alzheimer's disease and in PS1/APP transgenic mice models. Biochimica et biophysica acta 66 15590066
1988 Calbindin (CaBP 28 kDa) appearance and distribution during development of the mouse inner ear. Brain research 65 3260120
2005 Calcium-binding proteins annexin A2 and S100A6 are sensors of tubular injury and recovery in acute renal failure. Kidney international 62 16316344
2000 Differential expression of S100B and S100A6(1) in the human fetal and aged cerebral cortex. Brain research. Developmental brain research 61 10675765
1994 Purification and characterization of the recombinant human calcium-binding S100 proteins CAPL and CACY. Biochemistry 61 8204608
2020 Mesenchymal Stem Cell-Secreted Exosome Promotes Chemoresistance in Breast Cancer via Enhancing miR-21-5p-Mediated S100A6 Expression. Molecular therapy oncolytics 60 33294586
2003 Calcium-regulated interaction of Sgt1 with S100A6 (calcyclin) and other S100 proteins. The Journal of biological chemistry 60 12746458
1988 The rat vitamin-D-dependent calcium-binding protein (9-kDa CaBP) gene. Complete nucleotide sequence and structural organization. European journal of biochemistry 57 3345761
2008 Tumor expression of S100A6 correlates with survival of patients with stage I non-small-cell lung cancer. Lung cancer (Amsterdam, Netherlands) 53 18620780
2002 Expression of S100A6 and S100A4 in matched samples of human colorectal mucosa, primary colorectal adenocarcinomas and liver metastases. Oncology 52 12239456
2000 Calcyclin (S100A6) binding protein (CacyBP) is highly expressed in brain neurons. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 50 10950876
2000 Differential expression of the Ca2+ binding S100A6 protein in normal, preneoplastic and neoplastic colon mucosa. European journal of cancer (Oxford, England : 1990) 47 10885611
2008 S100A6 expression and function in human osteosarcoma. Clinical orthopaedics and related research 46 18612712
2017 Cardiac Overexpression of S100A6 Attenuates Cardiomyocyte Apoptosis and Reduces Infarct Size After Myocardial Ischemia-Reperfusion. Journal of the American Heart Association 45 28174168
2013 Increased expression of S100A6 promotes cell proliferation and migration in human hepatocellular carcinoma. Journal of molecular medicine (Berlin, Germany) 45 24281831
2012 The S100A6 calcium-binding protein regulates endothelial cell-cycle progression and senescence. The FEBS journal 45 23095053
2004 S100A6 (Calcyclin) is a prostate basal cell marker absent in prostate cancer and its precursors. British journal of cancer 45 15280928
1987 Analysis and in situ detection of cholecalcin messenger RNA (9000 Mr CaBP) in the uterus of the pregnant rat. Cell and tissue research 44 3829120
2010 S100A6 binding protein and Siah-1 interacting protein (CacyBP/SIP): spotlight on properties and cellular function. Amino acids 43 20182755
2008 Expression of S100A6 in cardiac myocytes limits apoptosis induced by tumor necrosis factor-alpha. The Journal of biological chemistry 43 18753141
2005 Expression of S100A2 and S100A6 in thyroid carcinomas. Histopathology 43 15842639
2009 Immunohistochemical expression of S100A6 in cellular neurothekeoma: clinicopathologic and immunohistochemical analysis of 31 cases. The American Journal of dermatopathology 42 19542912
1991 A calcium-binding protein from rabbit lung cytosol identified as the product of growth-regulated gene (2A9) and its binding proteins. Archives of biochemistry and biophysics 42 1898017
2000 Characterization of the interaction of calcyclin (S100A6) and calcyclin-binding protein. The Journal of biological chemistry 41 10884380
1987 Vitamin D-dependent calcium-binding proteins (CaBPs) in human fetuses: comparative distribution of 9K CaBP mRNA and 28K CaBP during development. Pediatric research 41 2437519
2008 Interactions of S100A2 and S100A6 with the tetratricopeptide repeat proteins, Hsp90/Hsp70-organizing protein and kinesin light chain. The Journal of biological chemistry 40 18669640
2013 S100A6 stimulates proliferation and migration of colorectal carcinoma cells through activation of the MAPK pathways. International journal of oncology 39 24378749
2004 Calcyclin (S100A6) expression is stimulated by agents evoking oxidative stress via the antioxidant response element. Biochimica et biophysica acta 39 15878395
2002 S100A13 and S100A6 exhibit distinct translocation pathways in endothelial cells. Journal of cell science 39 12118070
2023 S100A6: molecular function and biomarker role. Biomarker research 38 37670392
2018 Aqueous Extract of Mori Folium Exerts Bone Protective Effect Through Regulation of Calcium and Redox Homeostasis via PTH/VDR/CaBP and AGEs/RAGE/Nox4/NF-κB Signaling in Diabetic Rats. Frontiers in pharmacology 36 30459613
2014 Progestin and antiprogestin responsiveness in breast cancer is driven by the PRA/PRB ratio via AIB1 or SMRT recruitment to the CCND1 and MYC promoters. International journal of cancer 35 25363551
1997 Ca(2+)-binding proteins S100A6 and S100B in primary cutaneous melanoma. Journal of cutaneous pathology 35 9162739
2013 Genetic screening for PRA-associated mutations in multiple dog breeds shows that PRA is heterogeneous within and between breeds. Veterinary ophthalmology 33 24255994
1984 Membrane-associated vitamin D-induced calcium-binding protein (CaBP): quantification by a radioimmunoassay and evidence for a specific CaBP in purified intestinal brush borders. Endocrinology 33 6489266
2019 Glial S100A6 Degrades β-amyloid Aggregation through Targeting Competition with Zinc Ions. Aging and disease 32 31440382
2018 S100A6 promotes the proliferation and migration of cervical cancer cells via the PI3K/Akt signaling pathway. Oncology letters 32 29552203
2012 S100A6 amyloid fibril formation is calcium-modulated and enhances superoxide dismutase-1 (SOD1) aggregation. The Journal of biological chemistry 31 23076148
2020 S100A6 and Its Brain Ligands in Neurodegenerative Disorders. International journal of molecular sciences 30 32492924
2019 S100A6/miR193a regulates the proliferation, invasion, migration and angiogenesis of lung cancer cells through the P53 acetylation. American journal of translational research 30 31497188
2016 S100A6 promotes cell proliferation in human nasopharyngeal carcinoma via the p38/MAPK signaling pathway. Molecular carcinogenesis 30 27596819
2015 Diagnostic significance of S100A2 and S100A6 levels in sera of patients with non-small cell lung cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 30 26361956
2011 Specific expression of osteopontin and S100A6 in hepatocellular carcinoma. Surgery 30 21310450
2010 S100A6 (calcyclin) deficiency induces senescence-like changes in cell cycle, morphology and functional characteristics of mouse NIH 3T3 fibroblasts. Journal of cellular biochemistry 30 20013795
2007 Upregulated expression of S100A6 in human gastric cancer. Journal of digestive diseases 30 17970874
2004 Endometrial expression of calbindin (CaBP)-d28k but not CaBP-d9k in primates implies evolutionary changes and functional redundancy of calbindins at implantation. Reproduction (Cambridge, England) 30 15454638
2011 Plasma renin activity (PRA) levels and antihypertensive drug use in a large healthcare system. American journal of hypertension 28 22158065
2005 S100A6 and CacyBP/SIP - two proteins discovered in ehrlich ascites tumor cells that are potentially involved in the degradation of beta-catenin. Chemotherapy 28 16340196
2016 Increased expression of S100A6 promotes cell proliferation in gastric cancer cells. Oncology letters 27 28123545
2012 S100A6 protein negatively regulates CacyBP/SIP-mediated inhibition of gastric cancer cell proliferation and tumorigenesis. PloS one 26 22295074
2001 S100A6 expression in fibrohistiocytic lesions. Journal of cutaneous pathology 26 11401666
2016 Expression and Localization of CaBP Ca2+ Binding Proteins in the Mouse Cochlea. PloS one 25 26809054
2020 S100A6 is a critical regulator of hematopoietic stem cells. Leukemia 24 32555370
2013 Progesterone receptor isoforms PRA and PRB differentially contribute to breast cancer cell migration through interaction with focal adhesion kinase complexes. Molecular biology of the cell 24 23485561
2013 Expression of TRPV6 and CaBP-D28k in the egg shell gland (uterus) during the oviposition cycle of the laying hen. British poultry science 24 23796121
2021 c-Myc Upregulated by High Glucose Inhibits HaCaT Differentiation by S100A6 Transcriptional Activation. Frontiers in endocrinology 23 34060533
2018 Therapeutic effects of recombinant human S100A6 and soluble receptor for advanced glycation end products(sRAGE) on CCl4-induced liver fibrosis in mice. European journal of pharmacology 23 29800549
2016 S100A6 Regulates Endothelial Cell Cycle Progression by Attenuating Antiproliferative Signal Transducers and Activators of Transcription 1 Signaling. Arteriosclerosis, thrombosis, and vascular biology 23 27386938
2015 Elevated S100A6 (Calcyclin) enhances tumorigenesis and suppresses CXCL14-induced apoptosis in clear cell renal cell carcinoma. Oncotarget 23 25760073
2009 Increased cytoplasmic S100A6 expression is associated with pulmonary adenocarcinoma progression. Pathology international 23 19712129
1985 Characterisation of rat 9-kDa cholecalcin (CaBP) messenger RNA using a complementary DNA. Absence of homology with 28-kDa cholecalcin mRNA. European journal of biochemistry 23 3838511
2017 S100A6 - focus on recent developments. Biological chemistry 22 28343163
2008 Expression of S100A6 protein in a broad spectrum of cutaneous tumors using tissue microarrays. Journal of cutaneous pathology 22 18201235
2024 S100A6 drives lymphatic metastasis of liver cancer via activation of the RAGE/NF-kB/VEGF-D pathway. Cancer letters 21 38350547
2023 S100A6 Protein-Expression and Function in Norm and Pathology. International journal of molecular sciences 20 36674873
2014 S100A6 expression in keratinocytes and its impact on epidermal differentiation. The international journal of biochemistry & cell biology 20 25450463
1995 Detection of HLA IgG antibodies by two enzyme-linked immunoassays, solubilized HLA class I and PRA-STAT. Comparison with the AHG PRA. Transplantation 20 8545895
2023 The Role of S100A6 in Human Diseases: Molecular Mechanisms and Therapeutic Potential. Biomolecules 19 37509175
2019 S100A6 Promotes B Lymphocyte Penetration Through the Blood-Brain Barrier in Autoimmune Encephalitis. Frontiers in genetics 19 31850060
1995 Distribution of OMP-, PGP 9.5- and CaBP-like immunoreactive chemoreceptor neurons in the developing human olfactory epithelium. Anatomy and embryology 19 7645757
2022 Liver-Derived S100A6 Propels β-Cell Dysfunction in NAFLD. Diabetes 18 35899967
2017 Stress-Dependent Changes in the CacyBP/SIP Interacting Protein S100A6 in the Mouse Brain. PloS one 18 28068373
2022 SNHG1 functions as an oncogenic lncRNA and promotes osteosarcoma progression by up-regulating S100A6 via miR-493-5p. Acta biochimica et biophysica Sinica 17 35130629
1995 Effects of presence of an egg and calcium deposition in the shell gland on levels of messenger ribonucleic acid of CaBP-D28K and of vitamin D3 receptor in the shell gland of the laying hen. General and comparative endocrinology 17 8536923
2021 Toxoplasma gondii SAG1 targeting host cell S100A6 for parasite invasion and host immunity. iScience 16 34950858
2017 Amlexanox Downregulates S100A6 to Sensitize KMT2A/AFF1-Positive Acute Lymphoblastic Leukemia to TNFα Treatment. Cancer research 16 28646023
2015 High-level S100A6 promotes metastasis and predicts the outcome of T1-T2 stage in clear cell renal cell carcinoma. Cell biochemistry and biophysics 16 25120023
2013 Aberrant expression of S100A6 and matrix metalloproteinase 9, but not S100A2, S100A4, and S100A7, is associated with epidermal carcinogenesis. Journal of dermatological science 16 23993025
1991 Regulation of expression of the growth-state-related genes 2F1 and 2A9 during entry of quiescent smooth muscle cells into the cell cycle. Journal of cellular biochemistry 16 1757477
2000 Regulation of cell specific expression of calcyclin (S100A6) in nerve cells and other tissues. Acta neurobiologiae experimentalis 15 11200185

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