Affinage

FAM3A

Protein FAM3A · UniProt P98173

Length
230 aa
Mass
25.2 kDa
Annotated
2026-06-09
36 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FAM3A is a mitochondrial matrix protein that drives ATP-dependent signaling to govern cellular metabolism, survival, and proliferation across hepatic, pancreatic, vascular, muscle, and neuronal tissues (PMID:24806753, PMID:36470472). Within the mitochondrial matrix it physically interacts with F1-ATP synthase to directly stimulate ATP synthesis, and the resulting ATP is released extracellularly—in hepatocytes through the HSF1-regulated, ATP-permeable channel PANX1—to act in an autocrine/paracrine manner (PMID:36470472, PMID:38937853). Released ATP engages P2 purinergic receptors (including P2Y1), triggering PLC/IP3R-mediated Ca2+ elevation and calmodulin activation that drives PI3K-p110α/Akt signaling independently of insulin (PMID:24806753, PMID:24857820). Downstream of this ATP-P2-Akt axis, FAM3A feeds multiple transcriptional programs: a CREB-FOXD3 loop that reinforces ATP synthase assembly (PMID:36470472), a calmodulin-FOXA2 axis driving CPT2-dependent fatty acid oxidation and PDX1 transcription (PMID:35995281, PMID:31944392), and CREB-driven VEGFA expression for angiogenesis (PMID:31000420). Functionally, FAM3A suppresses hepatic gluconeogenesis and lipogenesis (PMID:24806753, PMID:38937853), promotes β-cell insulin secretion and survival (PMID:31944392), regulates pancreatic α-cell proglucagon processing via an Nr4a2-FOXA2-PCSK1 axis (PMID:39362520), drives muscle stem cell myogenic commitment through oxidative phosphorylation (PMID:30996264), controls VSMC phenotype and blood pressure (PMID:32279581, PMID:37660071), and protects diverse cell types from oxidative, ischemic, and ER stress by preserving ATP, limiting ROS, and engaging Akt/NRF2 survival signaling (PMID:28562339, PMID:38875957, PMID:26492522). FAM3A transcription is activated by PPARγ, HNF4α, C/EBPβ, STAT3, HSF1, KLF4, and Hoxa13, and is repressed post-transcriptionally by miR-423-5p (PMID:23562554, PMID:27688071, PMID:30996264, PMID:32279581, PMID:40015605, PMID:28411267).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2012 Medium

    Established a transcriptional activator and a regulatory non-coding RNA circuit controlling FAM3A in neurons, linking it to ischemic neuronal apoptosis before its biochemical role was clear.

    Evidence Hoxa13 promoter-binding assay and Snhg8/miR-384 gain/loss-of-function in an in vivo cerebral ischemia mouse model

    PMID:31165722

    Open questions at the time
    • Did not define FAM3A's molecular activity downstream of transcription
    • Promoter binding not extended to direct biochemical FAM3A function
  2. 2013 High

    Identified the first direct transcriptional activator of FAM3A, placing it downstream of nuclear receptor signaling.

    Evidence Luciferase reporter, ChIP, and PPRE site-directed mutagenesis with PPARγ agonist/antagonist in human cells

    PMID:23562554

    Open questions at the time
    • Did not establish FAM3A's downstream effector mechanism
    • Physiological context of PPARγ-FAM3A axis not tested in vivo here
  3. 2014 High

    Defined FAM3A's core mechanism—mitochondrial ATP production and release activating an extracellular P2 receptor-Ca2+-CaM-PI3K/Akt cascade to suppress hepatic gluconeogenesis and lipogenesis insulin-independently.

    Evidence Subcellular fractionation, KD/OE, orthogonal pharmacological inhibition of P2/PLC/IP3R/CaM, and db/db and HFD mouse models

    PMID:24806753

    Open questions at the time
    • Did not identify how FAM3A mechanistically stimulates ATP synthesis
    • ATP release conduit not yet identified
  4. 2014 High

    Showed the same mitochondrial ATP-P2 receptor mechanism operates in vascular smooth muscle, where it drives proliferation/migration via P2Y1-Akt and ERK1/2, generalizing FAM3A beyond liver.

    Evidence Fractionation, reciprocal OE/KD, suramin/P2Y1 siRNA/PI3K inhibitors, and rat carotid balloon injury model

    PMID:24857820

    Open questions at the time
    • Branch point between Akt and ERK1/2 downstream of P2Y1 not resolved
    • No direct ATP synthase interaction shown
  5. 2015 Medium

    Extended FAM3A's cytoprotective function to neurons, linking ATP preservation and ROS reduction to PI3K/Akt-dependent survival under oxidative stress.

    Evidence Subcellular localization, lentiviral OE, selective PI3K/Akt vs MEK/ERK inhibitors, apoptosis and cytochrome c assays in HT22 cells

    PMID:26492522

    Open questions at the time
    • No rescue with reconstituted protein
    • Mechanism of ROS reduction not defined
  6. 2016 Medium

    Added C/EBPβ as a direct FAM3A activator and uncovered ER-stress protection via a CHOP-Wnt axis, broadening transcriptional control and stress-protective scope.

    Evidence Luciferase/EMSA/mutagenesis (C/EBPβ); tunicamycin model with CHOP siRNA and isolated-mitochondria assays in HT22 cells

    PMID:26939760 PMID:27688071

    Open questions at the time
    • How FAM3A modulates Wnt/CHOP signaling biochemically is unresolved
    • C/EBPβ regulation not tested in vivo
  7. 2017 High

    Identified miR-423-5p (driven by NFE2) as a direct post-transcriptional repressor of FAM3A, providing a mechanism for FAM3A downregulation in obesity, and extended the ATP-Akt axis to adipogenesis and liver ischemia protection.

    Evidence Luciferase miRNA targeting + in vivo miR-423-5p/NFE2 manipulation; P2-inhibitor adipogenesis assays; FAM3A KO + rosiglitazone IRI model

    PMID:28411267 PMID:28515350 PMID:28562339

    Open questions at the time
    • Tissue-specificity of miR-423-5p regulation incompletely mapped
    • Opposite metabolic outcomes (adipogenesis vs gluconeogenesis suppression) not reconciled mechanistically
  8. 2017 Medium

    Defined a neuronal Ca2+-homeostasis mechanism in which FAM3A disrupts STIM1-Orai1 and dampens store-operated Ca2+ entry to reduce apoptosis.

    Evidence STIM1/Orai1 co-IP, Ca2+ imaging, SOCE assays, and surface receptor blots in glutamate-injured PC12 cells

    PMID:29241198

    Open questions at the time
    • Single co-IP without reciprocal/structural validation
    • Relationship between this Ca2+ effect and the mitochondrial ATP role unclear
  9. 2019 High

    Established FAM3A as a STAT3-induced secreted factor promoting oxidative phosphorylation and myogenic commitment, and traced an endothelial CREB-VEGFA angiogenic program.

    Evidence Stat3 ablation + recombinant Fam3a rescue, Seahorse, Fam3a KO mice; endothelial OE/KD with hind-limb ischemia model and VEGFA promoter ChIP

    PMID:30996264 PMID:31000420

    Open questions at the time
    • Reconciliation of mitochondrial vs secreted-cytokine modes of action not addressed
    • Receptor mediating any secreted FAM3A action unidentified
  10. 2020 High

    Mapped tissue-specific transcriptional inputs and effector programs: HSF1-driven FAM3A in VSMC hypertension, HNF4α-driven hepatic FAM3A, and a β-cell CaM-FOXA2-PDX1 axis controlling insulin secretion.

    Evidence VSMC- and β-cell-specific Fam3a KO mice, HSF1 ChIP/inhibitor, doxepin/HNF4α translocation, FOXA2 ChIP on PDX1 promoter, Ang II and GTT models

    PMID:31944392 PMID:32279581 PMID:32312868

    Open questions at the time
    • How a single mitochondrial protein produces tissue-divergent transcriptional outputs not unified
    • Direct ATP synthase engagement still inferred, not shown
  11. 2022 High

    Resolved FAM3A's biochemical mechanism by demonstrating direct physical interaction with F1-ATP synthase to stimulate ATP synthesis, and uncovered a CREB-FOXD3 feed-forward loop reinforcing ATP synthase assembly, plus a CaM-FOXA2-CPT2 fatty-acid-oxidation arm.

    Evidence Co-IP (FAM3A-F1-ATPS), FOXD3 KO/KD, CREB inhibition, RNA-seq; FOXA2 ChIP on CPT2 promoter with FAM3A KO + imipramine HFD models

    PMID:35995281 PMID:36470472

    Open questions at the time
    • Structural basis of FAM3A-F1-ATPS interaction unknown
    • Stoichiometry and direct catalytic effect on ATP synthase not quantified
  12. 2023 Medium

    Defined non-ATP regulatory outputs in vasculature—FAM3A induces KLF4 ubiquitination to maintain VSMC differentiation and attenuate aneurysm—and a KLF4 feedback loop activating FAM3A, alongside cardiomyocyte mitochondrial dynamics via Opa1.

    Evidence AAA models with KLF4 ubiquitination/nuclear-localization assays; KLF4 ChIP/luciferase; Fam3a-/- MI model with Seahorse, TEM, mPTP and Opa1 analysis

    PMID:37014466 PMID:37660071 PMID:40015605

    Open questions at the time
    • Whether KLF4 ubiquitination is ATP-dependent or a distinct activity unclear
    • Mechanism linking FAM3A to Opa1 not defined
  13. 2024 High

    Identified PANX1 as the HSF1-induced conduit for FAM3A-driven ATP release in hepatocytes, defined a NRF2-dependent anti-pyroptotic mechanism, and uncovered an α-cell Nr4a2-FOXA2-PCSK1 axis shifting proglucagon processing toward GLP-1.

    Evidence Co-IP/MS, PANX1 KO and hepatic OE/KD with metabolic tests; FAM3A KO/OE renal I/R with NRF2 epistasis and GSDMD/Caspase-1 assays; α-cell-specific Fam3a KO with Pcsk1 luciferase and Nr4a2-FOXA2 co-IP

    PMID:38875957 PMID:38937853 PMID:39362520

    Open questions at the time
    • Whether PANX1 is the universal ATP conduit across all FAM3A-expressing tissues untested
    • How FAM3A loss elevates Nr4a2 mechanistically unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis and stoichiometry of FAM3A's interaction with F1-ATP synthase, and how a single mitochondrial protein generates tissue-divergent transcriptional and non-ATP (KLF4 ubiquitination, STIM1-Orai1) outputs, remain unresolved.
  • No structural model of FAM3A or its ATP synthase complex
  • Mechanism by which a matrix protein controls cytoplasmic/nuclear events beyond ATP release is unclear
  • Whether secreted and mitochondrial FAM3A pools are functionally distinct is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 2 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005739 mitochondrion 5 GO:0005576 extracellular region 1
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 3 R-HSA-8953897 Cellular responses to stimuli 3
Partners
ATP5F1 (F1-ATP SYNTHASE)FOXA2FOXD3KLF4NR4A2PANX1

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 FAM3A is localized in mitochondria, where it increases ATP production and secretion in hepatocytes. Released ATP activates P2 receptors, triggering PLC/IP3R-mediated Ca2+ elevation, which activates calmodulin (CaM), which in turn activates PI3K p110α/Akt signaling in an insulin-independent manner to suppress hepatic gluconeogenesis and lipogenesis. Subcellular fractionation, siRNA knockdown, adenoviral overexpression, pharmacological inhibition of P2 receptors/PLC/IP3R/CaM, in vivo mouse models (db/db, HFD) Hepatology High 24806753
2013 PPARγ directly binds a peroxisome proliferator response element (PPRE) at -1258/-1246 in the human FAM3A promoter to transcriptionally activate FAM3A expression; site-directed mutagenesis of this PPRE abolished the stimulatory effect. Luciferase reporter assay, chromatin immunoprecipitation (ChIP), site-directed mutagenesis, PPARγ agonist/antagonist treatment, PPARγ overexpression Biochimica et biophysica acta High 23562554
2014 FAM3A localizes to mitochondria in VSMCs and promotes ATP production and release. Released ATP activates the P2Y1 receptor to stimulate Akt (PI3K-dependent) and ERK1/2 (PI3K-independent) pathways, driving VSMC proliferation and migration. FAM3A overexpression exacerbates neointima formation after balloon injury in rat carotid artery. Subcellular fractionation, adenoviral overexpression, siRNA knockdown, P2 receptor antagonist suramin, P2Y1 siRNA knockdown, PI3K inhibitor, in vivo rat balloon injury model Journal of molecular and cellular cardiology High 24857820
2017 NFE2 transcriptionally induces miR-423-5p, which directly targets FAM3A mRNA to repress its expression, thereby suppressing the FAM3A-ATP-Akt pathway, promoting hepatic gluconeogenesis and lipogenesis under obese conditions. miRNA target site prediction + luciferase reporter, hepatic adenoviral miR-423-5p overexpression/inhibition, NFE2 overexpression, in vivo mouse models (db/db, HFD) Diabetes High 28411267
2019 Stat3 transcriptionally activates Fam3a in muscle stem cells; Fam3a is a secreted cytokine-like protein that promotes oxidative phosphorylation/mitochondrial respiration to drive myogenic commitment and skeletal muscle development. Recombinant Fam3a rescues mitochondrial respiration and myogenic commitment defects in Stat3-ablated muscle stem cells. Stat3 genetic ablation, recombinant Fam3a treatment in vitro and in vivo, Fam3a knockdown/KO in mice, Seahorse respirometry, myogenic differentiation assays Nature communications High 30996264
2017 FAM3A localized to mitochondria promotes ATP production in 3T3-L1 preadipocytes; released ATP activates P2 receptors to stimulate Akt phosphorylation, which enhances adipogenesis. P2 receptor inhibition blocks FAM3A-induced adipogenesis. Subcellular fractionation, adenoviral overexpression, siRNA knockdown, P2 receptor antagonist, ATP measurement, lipid staining Oncotarget Medium 28515350
2017 FAM3A protects against liver ischemia-reperfusion injury by activating Akt survival pathway (ATP-P2 receptor-dependent), repressing apoptosis, inflammation, and oxidative stress; PPARγ agonist rosiglitazone's hepatoprotective effects are dependent on FAM3A. FAM3A-deficient (KO) mice, rosiglitazone treatment, hepatocyte overexpression/deficiency, P2 receptor inhibition, in vivo IRI model Oncotarget Medium 28562339
2019 Endothelial FAM3A (mitochondrial) increases ATP production and secretion; extracellular ATP activates P2 receptors to elevate cytosolic Ca2+, which enhances CREB phosphorylation and CREB recruitment to the VEGFA promoter, thereby activating VEGFA transcription and promoting angiogenesis. Adenoviral and AAV-mediated overexpression/knockdown, tube formation/migration/proliferation assays, hind limb ischemia mouse model, intracellular Ca2+ imaging, ChIP/promoter analysis EBioMedicine Medium 31000420
2020 In VSMCs, Angiotensin II activates HSF1 (heat shock factor 1), which transcriptionally upregulates FAM3A expression; elevated FAM3A enhances ATP production and activates the ATP-P2 receptor pathway, promoting VSMC phenotypic switch from contractile to proliferative. VSMC-specific FAM3A deletion reduces vessel contractility, blood pressure, and attenuates Ang II-induced hypertension and cardiac hypertrophy in mice. VSMC-specific Fam3a conditional KO mice, Ang II infusion model, HSF1 ChIP/overexpression, HSF1 inhibitor treatment, spontaneously hypertensive rats Circulation research High 32279581
2020 FAM3A plays crucial roles in pancreatic β cells: it promotes ATP synthesis, elevates cytosolic Ca2+ to stimulate insulin secretion, and releases ATP extracellularly to activate CaM as a co-activator of FOXA2, stimulating PDX1 gene transcription. β cell-specific FAM3A KO mice display markedly blunted insulin secretion and glucose intolerance. β cell-specific FAM3A KO mice, islet-specific adenoviral overexpression, CaM inhibitor, FOXA2 ChIP on PDX1 promoter, Ca2+ measurement, glucose tolerance test FASEB journal High 31944392
2020 Doxepin stimulates the nuclear translocation of HNF4α, which then promotes FAM3A transcription in hepatocytes; FAM3A deficiency abolishes doxepin's effects on ATP production, Akt activation, gluconeogenesis suppression, and lipid reduction. Drug-repurposing screen, HNF4α nuclear translocation assay, FAM3A KO mice on HFD, in vivo metabolic phenotyping Diabetes Medium 32312868
2022 FAM3A localizes to the mitochondrial matrix where it physically interacts with F1-ATP synthase (F1-ATPS) to directly activate ATP synthesis; released ATP subsequently activates P2 receptor-Akt-CREB signaling to induce FOXD3 expression. FOXD3 synchronously stimulates transcription of ATP synthase subunit genes and assembly factors to increase ATP synthase assembly and capacity, constituting a positive regulatory loop. Subcellular fractionation, co-immunoprecipitation (FAM3A with F1-ATPS), FOXD3 KO/KD, CREB pathway inhibition, RNA sequencing, in vivo FAM3A-deficient mice with metabolic phenotyping Metabolism: clinical and experimental High 36470472
2022 FAM3A-induced ATP release activates P2 receptors, promoting CaM translocation from cytoplasm to nucleus, where CaM acts as a co-activator of FOXA2 to transcribe CPT2 (carnitine palmitoyltransferase 2), increasing fatty acid oxidation and reducing lipid deposition. Imipramine activates this FAM3A-ATP-CaM-FOXA2-CPT2 pathway; FAM3A deficiency abolishes imipramine's lipid-lowering effect. RNA sequencing, CaM nuclear translocation assay, FOXA2 ChIP on CPT2 promoter, FAM3A KO mice on HFD, imipramine administration Metabolism: clinical and experimental High 35995281
2023 FAM3A induces KLF4 ubiquitination and reduces its phosphorylation and nuclear localization in VSMCs, maintaining well-differentiated VSMC status and inhibiting VSMC transformation toward macrophage-, chondrocyte-, osteogenic-, mesenchymal-, and fibroblast-like phenotypes, thereby attenuating abdominal aortic aneurysm (AAA) formation. FAM3A overexpression/supplementation in murine AAA models, ubiquitination assays, KLF4 phosphorylation and nuclear localization assays, single-cell analyses, AAA histology Nature communications Medium 37660071
2024 FAM3A stimulates expression of the ATP-permeable channel PANX1 via HSF1 in hepatocytes; PANX1 mediates ATP release required for FAM3A's suppression of hepatic gluconeogenesis and lipogenesis. FAM3A overexpression fails to inhibit gluconeogenic/lipogenic genes in PANX1-deficient hepatocytes, establishing PANX1 as the conduit for FAM3A-driven ATP release. Co-immunoprecipitation with mass spectrometry, PANX1 global KO mice, hepatic PANX1 overexpression/knockdown via adenovirus/AAV, metabolic tolerance tests, OGTT/ITT/PTT, FAM3A overexpression in PANX1-KO hepatocytes Military Medical Research High 38937853
2024 In pancreatic α-cells, FAM3A deficiency increases Nr4a2 expression; Nr4a2 forms a complex with FOXA2 to facilitate FOXA2 nuclear localization, and FOXA2 negatively regulates PCSK1 (PC1/3) transcription at specific promoter binding sites. Loss of α-cell FAM3A therefore de-represses PC1/3, shifting proglucagon processing from glucagon toward GLP-1 production, improving glucose tolerance via paracrine insulin secretion. α cell-specific Fam3a KO mice, transcriptomic analysis, Nr4a2 siRNA/overexpression, FOXA2 nuclear translocation assay, dual-luciferase reporter (Pcsk1 promoter), Nr4a2-FOXA2 co-IP, scRNA-seq correlation analysis, Ex9 GLP-1R antagonist in vivo Metabolism: clinical and experimental High 39362520
2024 FAM3A promotes PI3K/AKT/NRF2 signaling to block mitochondrial ROS accumulation; excess mt-ROS activates the NLRP3 inflammasome and Caspase-1, which cleaves GSDMD, pro-IL-1β, and pro-IL-18 to mediate pyroptosis in renal tubular cells. FAM3A KO worsens AKI and tubular pyroptosis, while FAM3A overexpression or NRF2 activator alleviates it; NRF2 deletion blocks FAM3A's anti-pyroptotic function. FAM3A KO and overexpression in renal ischemia/reperfusion model, NRF2 activator/inhibitor, Caspase-1/GSDMD cleavage assays, NLRP3 inflammasome activation assays, mt-ROS measurement Redox biology Medium 38875957
2015 FAM3A is subcellularly located in mitochondria of neuronal HT22 cells. FAM3A overexpression protects against H2O2-induced injury by reducing ROS and preserving ATP production; PI3K/Akt (but not MEK/ERK) pathway inhibition partially abolishes FAM3A-induced neuroprotection. Fluorescence subcellular localization, lentiviral overexpression, selective kinase inhibitors (PI3K/Akt vs MEK/ERK), cell viability, flow cytometry apoptosis, cytochrome c release, caspase-3 activation Cellular physiology and biochemistry Medium 26492522
2016 FAM3A overexpression attenuates ER stress-induced mitochondrial dysfunction in neuronal HT22 cells by inverting tunicamycin-induced decrease of Wnt signaling through the CHOP pathway; CHOP siRNA knockdown confirmed FAM3A's protection is mediated via CHOP-Wnt axis. Lentiviral overexpression, tunicamycin ER stress model, CHOP siRNA, mitochondrial membrane potential, cytochrome c release, mitochondrial swelling/Ca2+ buffering in isolated mitochondria Neurochemistry international Medium 26939760
2017 FAM3A overexpression in glutamate-injured PC12 neurons decreases surface expression of mGluR1/5, disrupts the STIM1-Orai1 interaction (confirmed by co-immunoprecipitation), and attenuates store-operated Ca2+ entry (SOCE) and IP3R-mediated ER Ca2+ release, thereby preserving intracellular Ca2+ homeostasis and reducing neuronal apoptosis. Co-immunoprecipitation (STIM1/Orai1), Ca2+ imaging, lentiviral overexpression, western blot for receptor surface expression, thapsigargin-induced SOCE assay Cellular physiology and biochemistry Medium 29241198
2016 C/EBPβ directly binds to the FAM3A promoter and acts as a transcriptional activator; mutation of C/EBPβ binding sites dramatically reduces FAM3A promoter activity. FAM3A overexpression inhibits preadipocyte-to-adipocyte differentiation. Dual luciferase reporter, electrophoretic mobility shift assay (EMSA), C/EBPβ binding site mutagenesis, FAM3A overexpression with Oil Red O staining Gene Medium 27688071
2021 Both intracellular and extracellular ATP contribute to FAM3A-induced PDX1 expression, insulin secretion, and β-cell proliferation. FAM3A-induced Ca2+ elevation, PDX1 expression, and insulin secretion are repressed by P2 receptor inhibitors, L-type Ca2+ channel inhibitors, or CaM inhibitor in pancreatic β cells. siRNA transfection in mouse islets, in vivo glucose tolerance test, P2 receptor inhibitor, L-type Ca2+ channel inhibitor, CaM inhibitor, intracellular/extracellular ATP measurement Experimental and clinical endocrinology & diabetes Medium 34592773
2023 FAM3A deficiency in cardiomyocytes reduces basal, ATP-linked respiration and respiratory reserve, and is associated with enlarged mitochondria, elevated mitochondrial Ca2+, higher mPTP opening, lower mitochondrial membrane potential, and elevated apoptosis. The mitochondrial dynamics protein Opa1 contributes to FAM3A's effects in cardiomyocytes. Fam3a-/- mice with MI model, Seahorse respirometry in isolated cardiomyocytes, transmission electron microscopy, mPTP opening assay, mitochondrial Ca2+ and membrane potential measurements, Opa1 analysis Journal of cardiovascular translational research Medium 37014466
2025 KLF4 directly binds to the FAM3A promoter (confirmed by CHIP and luciferase assays) and transcriptionally upregulates FAM3A expression in Ang II-stimulated VSMCs, with FAM3A mediating Ang II-induced proliferation and migration through PI3K/AKT pathway activation. Bioinformatics, luciferase reporter, chromatin immunoprecipitation (CHIP), KLF4 KD/OE, FAM3A siRNA, PI3K/AKT western blot, EdU proliferation, transwell/scratch migration Peptides Medium 40015605
2012 Hoxa13 binds to the FAM3A promoter and enhances its transcriptional activity in neuronal cells; the Snhg8/miR-384/Hoxa13/FAM3A axis regulates chronic cerebral ischemia-induced neuronal apoptosis. Promoter activity assay (Hoxa13 binding to FAM3A promoter), miRNA target site validation, Snhg8 and miR-384 overexpression/knockdown, in vivo ischemia mouse model Cell death & disease Medium 31165722

Source papers

Stage 0 corpus · 36 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 FAM3A activates PI3K p110α/Akt signaling to ameliorate hepatic gluconeogenesis and lipogenesis. Hepatology (Baltimore, Md.) 101 24806753
2017 NFE2 Induces miR-423-5p to Promote Gluconeogenesis and Hyperglycemia by Repressing the Hepatic FAM3A-ATP-Akt Pathway. Diabetes 79 28411267
2019 The Stat3-Fam3a axis promotes muscle stem cell myogenic lineage progression by inducing mitochondrial respiration. Nature communications 55 30996264
2020 VSMC-Specific Deletion of FAM3A Attenuated Ang II-Promoted Hypertension and Cardiovascular Hypertrophy. Circulation research 43 32279581
2024 FAM3A plays a key role in protecting against tubular cell pyroptosis and acute kidney injury. Redox biology 40 38875957
2013 FAM3A is a target gene of peroxisome proliferator-activated receptor gamma. Biochimica et biophysica acta 35 23562554
2015 FAM3A Protects HT22 Cells Against Hydrogen Peroxide-Induced Oxidative Stress Through Activation of PI3K/Akt but not MEK/ERK Pathway. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 33 26492522
2014 FAM3A promotes vascular smooth muscle cell proliferation and migration and exacerbates neointima formation in rat artery after balloon injury. Journal of molecular and cellular cardiology 31 24857820
2017 FAM3A mediates PPARγ's protection in liver ischemia-reperfusion injury by activating Akt survival pathway and repressing inflammation and oxidative stress. Oncotarget 30 28562339
2023 FAM3A reshapes VSMC fate specification in abdominal aortic aneurysm by regulating KLF4 ubiquitination. Nature communications 27 37660071
2016 FAM3A attenuates ER stress-induced mitochondrial dysfunction and apoptosis via CHOP-Wnt pathway. Neurochemistry international 26 26939760
2019 Mechanism of Snhg8/miR-384/Hoxa13/FAM3A axis regulating neuronal apoptosis in ischemic mice model. Cell death & disease 24 31165722
2020 Repurposing Doxepin to Ameliorate Steatosis and Hyperglycemia by Activating FAM3A Signaling Pathway. Diabetes 23 32312868
2019 Endothelial FAM3A positively regulates post-ischaemic angiogenesis. EBioMedicine 20 31000420
2017 FAM3A enhances adipogenesis of 3T3-L1 preadipocytes via activation of ATP-P2 receptor-Akt signaling pathway. Oncotarget 19 28515350
2022 FAM3A maintains metabolic homeostasis by interacting with F1-ATP synthase to regulate the activity and assembly of ATP synthase. Metabolism: clinical and experimental 17 36470472
2020 FAM3A plays crucial roles in controlling PDX1 and insulin expressions in pancreatic beta cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 17 31944392
2022 Imipramine activates FAM3A-FOXA2-CPT2 pathway to ameliorate hepatic steatosis. Metabolism: clinical and experimental 16 35995281
2018 Exercise induced improvements in insulin sensitivity are concurrent with reduced NFE2/miR-432-5p and increased FAM3A. Life sciences 16 29802941
2017 FAM3A Protects Against Glutamate-Induced Toxicity by Preserving Calcium Homeostasis in Differentiated PC12 Cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 16 29241198
2019 FAM3A protects chondrocytes against interleukin-1β-induced apoptosis through regulating PI3K/Akt/mTOR pathway. Biochemical and biophysical research communications 14 31208715
2024 PANX1-mediated ATP release confers FAM3A's suppression effects on hepatic gluconeogenesis and lipogenesis. Military Medical Research 13 38937853
2022 Dulaglutide Ameliorates Palmitic Acid-Induced Hepatic Steatosis by Activating FAM3A Signaling Pathway. Endocrinology and metabolism (Seoul, Korea) 13 35144334
2024 Enhanced TROSY Effect in [2-19 F, 2-13 C] Adenosine and ATP Analogs Facilitates NMR Spectroscopy of Very Large Biological RNAs in Solution. Angewandte Chemie (International ed. in English) 11 38185473
2023 The circular RNA Rap1b promotes Hoxa5 transcription by recruiting Kat7 and leading to increased Fam3a expression, which inhibits neuronal apoptosis in acute ischemic stroke. Neural regeneration research 8 37056143
2016 Transcriptional regulation analysis of FAM3A gene and its effect on adipocyte differentiation. Gene 8 27688071
2025 KLF4 regulates FAM3A to promotes angiotensin II-induced proliferation and migration of vascular smooth muscle cells through the PI3K/AKT signaling pathway. Peptides 7 40015605
2024 Fam3a-mediated prohormone convertase switch in α-cells regulates pancreatic GLP-1 production in an Nr4a2-Foxa2-dependent manner. Metabolism: clinical and experimental 7 39362520
2021 FAM3A Ameliorates Brain Impairment Induced by Hypoxia-Ischemia in Neonatal Rat. Cellular and molecular neurobiology 7 34853925
2024 Circulating extracellular vesicle-derived miR-1299 disrupts hepatic glucose homeostasis by targeting the STAT3/FAM3A axis in gestational diabetes mellitus. Journal of nanobiotechnology 6 39182087
2021 Intracellular ATP Signaling Contributes to FAM3A-Induced PDX1 Upregulation in Pancreatic Beta Cells. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association 5 34592773
2023 FAM3A Deficiency - Induced Mitochondrial Dysfunction Underlies Post-Infarct Mortality and Heart Failure. Journal of cardiovascular translational research 3 37014466
2023 FAM3A mediates the phenotypic switch of human aortic smooth muscle cells stimulated with oxidised low-density lipoprotein by influencing the PI3K-AKT pathway. In vitro cellular & developmental biology. Animal 2 37474885
2025 FAM3A: a novel mitochondrial protein for the treatment of ischemic diseases. Cell cycle (Georgetown, Tex.) 1 40611502
2025 FAM3A drives uncoupling of muscle lipid accumulation and insulin resistance depending on insulin receptor. Cell death & disease 1 41353211
2021 Establishment of a human iPSC line XMDYYYi001-A from a patient with Becker muscular dystrophy harboring duplications of exons 2-19 in dystrophin gene. Stem cell research 0 33799273

Missed literature

Know a paper Affinage missed for FAM3A? Flag it for the maintainers and the community.

No submissions yet.