Affinage

BMPER

BMP-binding endothelial regulator protein · UniProt Q8N8U9

Length
685 aa
Mass
76.0 kDa
Annotated
2026-04-28
82 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BMPER is a secreted extracellular glycoprotein that functions as a concentration-dependent modulator of BMP signaling: at low molar ratios relative to BMPs it acts as a co-activator facilitating Smad1/5 phosphorylation and Erk activation, while at high ratios it switches to an inhibitor that routes BMP ligands to lysosomal degradation via an endocytic trap-and-sink mechanism (PMID:12897139, PMID:18787191, PMID:19221194). BMPER directly binds BMP2, BMP4, and BMP6, cooperates with Twisted gastrulation (Tsg) in modulating BMP output, is tethered to the cell surface through C-terminal heparan sulfate proteoglycan interactions, and undergoes intracellular cleavage to release a diffusible N-terminal fragment that potently inhibits BMP-4 signaling (PMID:19914233, PMID:30125619). Beyond canonical BMP–Smad modulation, BMPER signals through the receptor LRP1 to activate NFATc1, regulate Erk, and control YAP nuclear entry in smooth muscle cells, linking it to vascular inflammation, endothelial barrier integrity via VE-cadherin, arteriovenous specification through BMP–Notch crosstalk, and pulmonary arterial hypertension (PMID:28596374, PMID:27995357, PMID:29473997, PMID:40964716). BMPER is essential for vascular development, hematopoietic stem cell maturation, coronary plexus remodeling, cardiac cushion EMT, hepcidin regulation, and smooth muscle contractile phenotype maintenance, and its expression is transcriptionally activated by KLF15 and KLF2 and post-transcriptionally stabilized through the RhoA/ROCK pathway and m5C methylation (PMID:19767294, PMID:39196179, PMID:20042706, PMID:40589169).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2003 High

    Identification of BMPER as a secreted BMP-binding protein that antagonizes BMP4-dependent Smad5 activation established the gene as a new extracellular BMP modulator distinct from known antagonists like Noggin and Chordin.

    Evidence Direct binding assays, Smad5 activation assays, Xenopus axis duplication, and embryoid body differentiation

    PMID:12897139

    Open questions at the time
    • Whether BMPER could also function as a BMP activator was not tested
    • The receptor through which BMPER signals was unknown
    • In vivo mammalian loss-of-function data were lacking
  2. 2007 High

    Zebrafish loss-of-function revealed that BMPER is required in vivo for vascular patterning and hematopoietic precursor specification, extending its role from a biochemical antagonist to a developmental regulator of vasculogenesis and hematopoiesis.

    Evidence Morpholino knockdown in zebrafish with vascular and hematopoietic marker analysis

    PMID:17618647

    Open questions at the time
    • Whether BMPER has a pro-BMP or anti-BMP net effect in vivo was unresolved
    • Mammalian genetic confirmation was pending
  3. 2008 High

    The paradoxical discovery that BMPER is required for BMP4-induced Smad1/5 phosphorylation and promotes endothelial sprouting overturned the simple antagonist model and established BMPER as a bipotential modulator of BMP signaling.

    Evidence siRNA knockdown in endothelial cells with Smad1/5 phosphorylation, Erk1/2 activation, sprouting/migration assays, and zebrafish validation

    PMID:18787191

    Open questions at the time
    • The mechanism underlying the switch from activator to inhibitor was unknown
    • Whether dose was the determining variable was untested
  4. 2009 High

    Three concurrent advances resolved the activator/inhibitor paradox, defined transcriptional control, and uncovered post-transcriptional regulation: BMPER switches from activator to inhibitor at high molar ratios via endocytic routing of BMP4 to lysosomes; KLF15 directly activates BMPER transcription while endothelin-1 suppresses it; and statins stabilize BMPER mRNA through RhoA/ROCK inhibition.

    Evidence Dose-response signaling with lysosomal inhibition (trap-and-sink); EMSA/promoter reporter for KLF15 binding; actinomycin-D chase with RhoA pathway pharmacology

    PMID:19221194 PMID:19767294 PMID:20042706

    Open questions at the time
    • The endocytic receptor mediating BMPER–BMP internalization was unidentified
    • Whether the cleavage products of BMPER have distinct activities was unknown
    • Genetic epistasis with known BMP modulators in mammals was lacking
  5. 2009 High

    Genetic epistasis in Cv2 (BMPER) and Tsg double-knockout mice demonstrated that BMPER acts as a pro-BMP factor upstream of Tsg during nephrogenesis, providing the first mammalian genetic evidence for tissue-specific BMP co-activation.

    Evidence Cv2-null and Cv2/Tsg double-null mouse kidney phenotyping with pSmad1 immunostaining

    PMID:19914233

    Open questions at the time
    • Whether the Cv2–Tsg epistasis applies to vascular contexts was untested
    • The biochemical mechanism of BMPER–Tsg cooperation remained unclear
  6. 2011 High

    BMPER was linked to vascular inflammation and iron homeostasis: loss of BMPER de-represses TNFα-NF-κB signaling and adhesion molecule expression in endothelium, while soluble BMPER inhibits BMP-dependent hepcidin expression and raises serum iron in vivo.

    Evidence BMPER+/- mice with intravital leukocyte adhesion; BMPER peptide injection with hepatic hepcidin and iron measurement; siRNA in HUVECs and hepatocytes

    PMID:21900199 PMID:22144676

    Open questions at the time
    • The receptor for BMPER's anti-inflammatory effect was unidentified
    • Whether BMPER directly signals in hepatocytes or acts only as a BMP sink was unclear
  7. 2012 High

    BMPER was shown to promote osteoblast-like differentiation of coronary smooth muscle cells via NF-κB activation, and Bmper haploinsufficiency in ApoE-null mice increased atherosclerotic burden, linking BMPER to vascular calcification and disease.

    Evidence ApoE−/−/Bmper+/− atherosclerosis quantification; NF-κB decoy oligonucleotides blocking BMPER-induced SMC osteogenic differentiation

    PMID:22772758 PMID:22778264

    Open questions at the time
    • Whether BMPER's pro-osteogenic and anti-inflammatory roles represent cell-type-specific effects was untested
    • The surface receptor mediating BMPER effects on SMCs was unknown
  8. 2013 High

    BMPER-null embryos displayed atretic coronary arteries and dysregulated endocardial cushion EMT with excessive Sox9 expression, establishing BMPER as essential for coronary remodeling and cardiac valve morphogenesis through dose-dependent BMP2 antagonism.

    Evidence BMPER−/− mouse embryo coronary and cushion phenotyping, BMP2 binding and Smad activation dose-response assays

    PMID:23641068 PMID:24373957

    Open questions at the time
    • The relationship between the coronary and cushion phenotypes was unclear
    • Whether the embryonic lethality was primarily vascular or cardiac was not resolved
  9. 2015 High

    BMPER was found to promote angiogenesis by upregulating bFGF/FGFR-1 and downregulating thrombospondin-1, and to regulate cardiac cushion EMT through BMP2-Smad-Sox9, establishing cross-pathway effector mechanisms beyond BMP–Smad alone.

    Evidence Anti-bFGF neutralizing antibody blocking BMPER angiogenesis; BMPER−/− AV cushion Sox9 quantification; aortic ring assays in Bmper+/− mice

    PMID:25503991 PMID:26418455

    Open questions at the time
    • How BMPER activates bFGF transcription was not determined
    • Whether bFGF induction depends on BMP signaling or is a BMP-independent BMPER function was unclear
  10. 2017 High

    The discovery that BMPER signals through LRP1 to activate NFATc1 via ERK and calcineurin pathways, independently of canonical BMP receptors, identified the first BMP-independent receptor-mediated signaling axis for BMPER and linked it to sepsis-related vascular inflammation.

    Evidence BMPER+/− mouse LPS challenge, LRP1 interaction studies, NFATc1 reporter assays, calcineurin inhibition

    PMID:28596374

    Open questions at the time
    • The BMPER–LRP1 binding interface was uncharacterized
    • Whether LRP1 mediates the endocytic trap-and-sink mechanism was untested
  11. 2017 High

    BMPER was shown to maintain endothelial barrier integrity by sustaining VE-cadherin expression through inhibition of BMP4-Smad5-Id1 signaling, and to promote hematopoietic stem cell maturation in the AGM region, broadening its functional repertoire.

    Evidence BMPER+/− Evans blue permeability, siRNA VE-cadherin/Id1 assays; AGM reaggregate HSC maturation culture

    PMID:27995357 PMID:29093060

    Open questions at the time
    • Whether barrier function and HSC maturation share the same BMPER concentration threshold was unknown
    • In vivo HSC-specific BMPER deletion data were lacking
  12. 2018 High

    Structural and biochemical analysis revealed that BMPER's N-terminal fragment is generated by intracellular cleavage, binds both BMP-4 and Tsg, and is more potent than full-length BMPER, while the full-length protein is tethered at the cell surface via C-terminal heparan sulfate proteoglycan binding; additionally, BMPER and TWSG1 cooperate to activate Notch signaling for arteriovenous specification.

    Evidence SAXS/EM structural analysis, cleavage/binding assays, P370L disease mutant analysis; zebrafish morpholino with Notch target readouts, DMH1 BMP receptor antagonist

    PMID:29473997 PMID:30125619

    Open questions at the time
    • The protease responsible for BMPER cleavage was not identified
    • Whether the P370L mutation causes disease solely through cleavage deficiency was unresolved
    • Crystal structure of BMPER–BMP or BMPER–Tsg complex was lacking
  13. 2023 Medium

    BMPER was found to bind IGFBP4 and maintain the contractile phenotype of vascular smooth muscle cells, preventing neointima formation, and separately shown to be required for adipocyte differentiation, extending its roles to IGF signaling modulation and metabolic biology.

    Evidence IGFBP4 binding assay, Bmper+/− carotid ligation model; siRNA in 3T3-L1 and mouse adipose progenitor cells with scRNA-seq

    PMID:36902380 PMID:37311809

    Open questions at the time
    • The structural basis for BMPER–IGFBP4 interaction is unknown
    • Whether BMPER's adipogenic role is BMP-dependent or BMP-independent was not determined
    • Independent replication of the IGFBP4 interaction is needed
  14. 2024 High

    A mechanosensitive KLF2–BMPER–Smad1/5–Akt axis was identified as a checkpoint for outward vascular remodeling under high fluid shear stress, using endothelial-specific BMPER deletion, and separately BMPER was placed in the SUGP2/CIRBP/BMPER/SMAD/hepcidin iron regulatory pathway.

    Evidence Endothelial-specific BMPER KO in high-FSS mouse model; SUGP2 CRISPR knock-in mice with BMPER mRNA stability and pSMAD1/5 analysis

    PMID:38800953 PMID:39196179

    Open questions at the time
    • Whether the KLF2–BMPER axis operates in human arteriogenesis is untested
    • The relative contribution of BMPER versus other BMP antagonists to hepcidin regulation in vivo is unclear
  15. 2025 High

    Endothelial BMPER was shown to promote pulmonary arterial hypertension by releasing YAP from LRP1-mediated sequestration at the smooth muscle cell membrane, establishing a paracrine BMPER–LRP1–YAP axis in pulmonary vascular remodeling.

    Evidence Endothelial-specific BMPER KO and overexpression in hypoxia-induced PH mice, LRP1 co-depletion epistasis, YAP activation assays

    PMID:40964716

    Open questions at the time
    • Whether pharmacological BMPER neutralization can reverse established PH is unknown
    • The BMPER–LRP1 binding stoichiometry and structural interface remain unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the protease that cleaves BMPER intracellularly, the atomic structure of BMPER alone and in complex with BMP ligands/Tsg/LRP1, the mechanisms governing tissue-specific activator-versus-inhibitor output, and whether BMPER–LRP1–YAP signaling operates in vascular beds beyond the pulmonary circulation.
  • No protease identified for BMPER cleavage
  • No crystal or cryo-EM structure available
  • Tissue-specific concentration thresholds for activator/inhibitor switch are not quantitatively defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 8 GO:0008289 lipid binding 1
Localization
GO:0005576 extracellular region 4 GO:0031012 extracellular matrix 2 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 10 R-HSA-1266738 Developmental Biology 5 R-HSA-168256 Immune System 3 R-HSA-1430728 Metabolism 2
Partners
BMP2BMP4BMP6IGFBP4LRP1TSG

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 BMPER is a secreted protein that directly interacts with BMP2, BMP4, and BMP6, and antagonizes BMP4-dependent Smad5 activation in endothelial cell precursors. It contains an amino-terminal signal peptide, five cysteine-rich domains, a von Willebrand D domain, and a trypsin inhibitor domain. Direct protein binding assays, Smad5 activation assays, Xenopus ventral injection axis duplication assay, embryoid body differentiation assay Molecular and cellular biology High 12897139
2008 BMPER is an extracellular matrix protein expressed by endothelial cells and acts as a downstream target of FoxO3a. It promotes endothelial cell sprouting and migration and is necessary for BMP4-induced Smad1/5 phosphorylation and Erk1/2 activation. BMP4 and BMPER are mutually required for their respective activities. Western blotting, immunocytochemistry, siRNA knockdown, in vitro sprouting/migration assays, in vivo zebrafish model, Smad1/5 phosphorylation assay Circulation research High 18787191
2009 At molar concentrations exceeding BMP4, BMPER switches from a BMP activator to an inhibitor via a novel endocytic trap-and-sink mechanism, leading to lysosomal degradation of both BMPER and BMP4, reducing the duration and magnitude of BMP4-dependent Smad signaling. Noggin and Gremlin, but not Chordin, trigger similar BMP endocytosis. Dose-response signaling assays, endocytosis tracking, lysosomal inhibition experiments, Smad reporter assays The Journal of cell biology High 19221194
2007 Zebrafish BMPER ortholog (zbmper) is expressed at sites of BMP activity including vascular precursor cells. Knockdown of zbmper results in a dorsalized phenotype, reduced hematopoietic precursors, and vascular patterning defects, establishing a conserved role in vascular and hematopoietic development. Morpholino knockdown in zebrafish, in situ hybridization, gata1 marker analysis Journal of molecular and cellular cardiology High 17618647
2009 Cv2 (mouse BMPER ortholog) acts as a pro-BMP factor in nephron precursor development through Twisted gastrulation (Tsg). Cv2-null mice show reduced cap condensates and lower pSmad1 levels. The renal defects of Cv2-/- are fully suppressed by Tsg null mutation, placing Cv2 upstream of Tsg in the BMP signaling hierarchy for nephrogenesis. Genetic epistasis (double knockout), immunostaining for pSmad1, embryonic kidney cell line assays Developmental biology High 19914233
2011 BMPER modulates vascular inflammation by suppressing TNFα-NFκB signaling. BMPER is downregulated by the TNFα-NFκB-KLF2 pathway. Loss of BMPER (siRNA or BMPER+/- mice) induces proinflammatory endothelial phenotype with reduced eNOS and enhanced adhesion molecule expression, increased leukocyte adhesion. The anti-inflammatory effects of BMPER are dependent on BMP signaling through NFκB. siRNA knockdown, BMPER+/- mouse model, intravital microscopy, ex vivo and in vivo leukocyte adhesion assays, eNOS/adhesion molecule expression Blood High 21900199
2011 BMPER is a negative regulator of hepcidin. Soluble BMPER peptide inhibits BMP2- and BMP6-dependent hepcidin promoter activity and reduces pSMAD1/5/8 levels in hepatocytes. Injection of BMPER peptide into mice reduces liver hepcidin and increases serum iron levels. Hepcidin promoter reporter assays in HepG2 and HuH7 cells, primary human hepatocyte treatment, in vivo BMPER peptide injection with iron and hepcidin measurement The Journal of biological chemistry High 22144676
2012 Bmper haploinsufficiency in ApoE-/- mice leads to increased atherosclerosis with elevated BMP activity in endothelial cells. siRNA knockdown of Bmper in HUVECs dramatically increases ICAM-1 and VCAM-1 expression at rest and under shear stress, identifying Bmper as a critical regulator of BMP-mediated vascular inflammation. ApoE-/-/Bmper+/- mouse model, siRNA knockdown, ICAM-1/VCAM-1 expression, atherosclerotic plaque quantification, shear stress experiments Arteriosclerosis, thrombosis, and vascular biology High 22772758
2012 BMPER promotes osteoblast-like differentiation of human coronary artery smooth muscle cells (HCASMCs) by antagonizing BMP-2-induced Smad1/5/8 phosphorylation and by increasing IκBα phosphorylation and NF-κB activity. NF-κB decoy oligonucleotides impair BMPER-induced osteoblast-like differentiation. RNA interference, recombinant BMPER treatment, Smad1/5/8 phosphorylation assay, NF-κB reporter, alkaline phosphatase and mineralization assays The Journal of biological chemistry High 22778264
2013 BMPER-regulated BMP signaling is critical for coronary plexus remodeling. BMPER-/- embryos show atretic coronary arteries or distal connections. BMPER directly binds BMP2 and blocks BMP2-induced Smad activation in a dose-dependent manner. BMPER inhibits BMP2-induced Sox9 increase during endocardial cushion EMT. BMPER-/- mouse embryo analysis, in vitro tubulogenesis, migration assay, pulldown/binding assay, Smad activation quantification, Sox9 immunostaining Developmental biology High 24373957
2013 BMPER and Tsg cooperate in BMP pathway modulation to control endothelial cell angiogenesis. Both proteins show concentration-dependent proangiogenic activity via Akt, Erk, and Smad signaling. BMPER and Tsg interfere with each other to enhance proangiogenic events; in vivo, both are required for normal zebrafish vascular development. Matrigel assay, HUVEC sprouting/migration/proliferation, siRNA knockdown, Akt/Erk/Smad signaling assays, zebrafish morpholino knockdown Journal of cell science High 23641068
2014 BMPER promotes angiogenesis in endothelial cells by upregulating bFGF/FGF-2 expression and FGF receptor-1 expression and phosphorylation, and downregulating thrombospondin-1. The proangiogenic effect of BMPER is blocked by an anti-bFGF antibody. In Bmper+/- mice, aortic ring assays confirm a specific effect for bFGF but not VEGF. Angiogenesis antibody array, siRNA knockdown, anti-bFGF neutralizing antibody, Matrigel/spheroid/migration assays, in vivo Matrigel plug assay, aortic ring assay Arteriosclerosis, thrombosis, and vascular biology High 25503991
2009 KLF15 directly activates BMPER expression by binding to a KLF-binding element at -284 bp within the BMPER promoter. Sp1 antagonizes KLF15-induced BMPER promoter activation. Endothelin-1 downregulates BMPER expression via the ETB receptor by suppressing KLF15. BMPER promoter deletion analysis, gelshift/EMSA assays, KLF15 overexpression and siRNA knockdown, promoter reporter assays, ET-receptor antagonist (BQ788) Cardiovascular research High 19767294
2009 Statins upregulate BMPER expression in endothelial cells mainly through a posttranscriptional mechanism (prolonged RNA half-life) via the RhoA/ROCK/actin pathway. BMPER upregulation by mevastatin is prevented by RhoA activators and enhanced by RhoA/ROCK/actin inhibitors. Increasing BMPER concentrations downregulate ICAM-1 expression and have anti-inflammatory effects. Actinomycin D chase analysis, BMPER promoter reporter assays, RhoA pathway activators/inhibitors (C3-toxin, RhoAN19, fasudil, cytochalasin D), RT-PCR, Western blotting, ICAM-1 expression assay Arteriosclerosis, thrombosis, and vascular biology High 20042706
2017 BMPER is a novel positive regulator of HSC maturation in the AGM region. BMPER is associated with BMP signaling inhibition but is transcriptionally induced by BMP4, suggesting BMPER contributes to the precise control of BMP activity enabling HSC maturation in a BMP-negative environment. RNA sequencing of AGM spatiotemporal transitions, ex vivo reaggregate culture system, BMP4 stimulation, HSC maturation assay The Journal of experimental medicine Medium 29093060
2017 BMPER activates nuclear factor of activated T cells c1 (NFATc1) in endothelial cells through multiple BMP-independent signaling pathways: LRP1-ERK activation, calcineurin signaling, and LRP1β-mediated NF45 nuclear export. BMPER-induced NFATc1 activation is required for lipopolysaccharide-induced vascular inflammation. BMPER+/- mouse LPS challenge, survival assay, cytokine measurement, NFATc1 reporter assays, LRP1 interaction studies, calcineurin inhibition, NF45 nuclear export assay Arteriosclerosis, thrombosis, and vascular biology High 28596374
2017 BMPER regulates endothelial barrier function by maintaining VE-cadherin expression. BMPER knockdown reduces VE-cadherin and impairs endothelial barrier through enhanced BMP4-Smad-Id1 signaling. High levels of BMPER antagonize BMP4-Smad5-Id1 signaling and prevent VE-cadherin downregulation and endothelial leakage in vivo. BMPER+/- mouse Evans blue dye leakage, siRNA knockdown, FITC-dextran transwell permeability assay, VE-cadherin expression analysis, Smad-Id1 signaling assay Inflammation High 27995357
2015 BMPER promotes epithelial-mesenchymal transition (EMT) during cardiac cushion development by modulating BMP2-induced Smad and Sox9 activity. BMPER directly binds BMP2 and dose-dependently blocks BMP2-induced Smad activation. In BMPER-/- embryos, canonical BMP pathway is more active in AV cushions during EMT, resulting in increased Sox9-positive cells. BMPER-/- embryo histology, direct BMP2 binding assay, Smad activation quantification, Sox9 immunostaining, in vitro endothelial cell BMP2/BMPER co-treatment PloS one High 26418455
2018 BMPER and TWSG1 activate arteriovenous specification in zebrafish endothelial cells by stimulating Notch signaling targets (HEY1/2, EPHRINB2). Silencing of bmper and twsg1b in zebrafish results in enhanced venous marker expression and dysregulated arterial marker expression. BMP receptor antagonist DMH1 abolishes BMPER and BMP4-induced Notch signaling. Zebrafish morpholino knockdown, in situ hybridization for arteriovenous markers, qRT-PCR, Western blot for Notch targets, DMH1 BMP receptor antagonism The FEBS journal High 29473997
2018 BMPER binds Tsg through its N-terminal BMP-binding region; this N-terminal fragment alone inhibits BMP-4 signaling more potently than full-length BMPER. BMPER and Tsg cooperatively inhibit BMP-4 signaling. Full-length BMPER is targeted to the plasma membrane via C-terminal heparan sulphate proteoglycan binding, while an active cleavage fragment is diffusible. A disease-causing P370L mutation prevents intracellular cleavage. Pulldown/binding assay, BMP-4 signaling reporter assays, SAXS and electron microscopy structural analysis, heparan sulphate proteoglycan binding assay, P370L mutant analysis, intracellular cleavage assay Matrix biology High 30125619
2011 BMPER promotes tumor growth and angiogenesis in lung carcinoma cells; its loss impairs proliferation, migration, invasion, and tumor cell-induced endothelial sprout formation. BMPER effects are transduced via regulation of Id1 (BMP target transcription factor) and MMP-9 and MMP-2. siRNA knockdown in A549 cells, proliferation/migration/invasion assays, in vivo Lewis lung carcinoma mouse model, Id1 and MMP expression analysis Oncogene Medium 22020334
2021 BMPER alleviates ischemic brain injury by activating the Smad3/Akt/Nrf2 pathway in neurons. BMPER administration reduces infarct size, brain edema, neuroinflammation, and cell death after MCAO. In OGD/R-challenged neurons, BMPER activates Smad3/Akt/Nrf2 signaling. MCAO mouse model, primary neuron OGD/R in vitro model, Western blotting for Smad3/Akt/Nrf2, immunohistochemistry, infarct measurement CNS neuroscience & therapeutics Medium 34904361
2021 BMPER inhibits TGF-β1-induced tubular dedifferentiation and fibroblast activation. Exogenous BMPER inhibits Id-1 upregulation, prevents E-cadherin loss, and suppresses fibroblast activation by inhibiting Erk1/2 phosphorylation. This Erk1/2 inhibition is abolished by LRP1 knockdown, identifying LRP1 as the BMPER receptor mediating this effect. siRNA knockdown, exogenous BMPER treatment, Erk1/2 phosphorylation assay, LRP1 knockdown, UUO mouse model with BMPER gene delivery Frontiers in cell and developmental biology Medium 33644047
2024 High fluid shear stress (FSS) suppresses Smad1/5 by elevating KLF2, which induces BMPER, thereby de-inhibiting Akt to facilitate outward vascular remodeling. Endothelial BMPER deletion impairs blood flow recovery and vascular remodeling in mice. This establishes the KLF2-BMPER-Smad1/5 axis as a mechanosensitive checkpoint. Surgical high FSS mouse model, endothelial-specific BMPER deletion, KLF2/BMPER/Smad1/5/Akt pathway analysis, diabetic mouse models with BMP9/10 blocking antibodies Nature cardiovascular research High 39196179
2023 BMPER is required for adipogenesis in 3T3-L1 preadipocytes and mouse adipose progenitor cells; BMPER expression and release peak at day 4 post-differentiation. BMPER is a conserved marker of adipose progenitor cells and adipocytes in visceral adipose tissue. siRNA knockdown in 3T3-L1 preadipocytes, mouse APC differentiation assays, lentiviral KD, single-cell/single-nucleus RNA-seq Communications biology Medium 37311809
2023 BMPER stimulation of vascular smooth muscle cells (vSMCs) promotes a contractile phenotype; BMPER silencing increases proliferation, migration, and reduces contractibility. BMPER binds IGFBP4, modulating IGF signaling. Perivascular BMPER application prevents neointima formation in a mouse carotid ligation model. siRNA knockdown and recombinant BMPER treatment of primary vSMCs, Bmper+/- mouse carotid ligation model, IGFBP4 binding assay, contractility/proliferation/migration assays International journal of molecular sciences Medium 36902380
2025 Endothelial BMPER promotes pulmonary arterial hypertension by activating YAP in pulmonary artery smooth muscle cells through releasing YAP from sequestration by LRP1 at the cell membrane. Endothelial-specific BMPER overexpression causes spontaneous PH; BMPER depletion attenuates pulmonary vascular remodeling via LRP1-YAP mechanism. Global and endothelial cell-specific BMPER knockout mice, AAV-assisted BMPER overexpression, hypoxia-induced PH model, LRP1 co-depletion epistasis, YAP activation assays, right ventricular pressure measurement Arteriosclerosis, thrombosis, and vascular biology High 40964716
2024 SUGP2 knockdown causes abnormal alternative splicing of CIRBP pre-mRNA, increasing CIRBP V1, which increases BMPER mRNA stability and translation. Elevated BMPER then downregulates pSMAD1/5 and hepcidin (HAMP), establishing a SUGP2/CIRBP/BMPER/SMAD/hepcidin axis in hemochromatosis. RNA-seq, RNA-protein pull-down, RNA immunoprecipitation, SUGP2 p.Arg622Gln CRISPR knock-in mice, Western blot for pSMAD1/5 and hepcidin, BMPER mRNA stability assay American journal of hematology Medium 38800953
2025 NSUN6 stabilizes BMPER expression in an m5C-dependent manner in hepatocellular carcinoma. BMPER knockdown reverses the tumor-suppressive effects of NSUN6 overexpression, establishing NSUN6 as an upstream regulator of BMPER through mRNA methylation-dependent stability. MeRIP-seq, actinomycin-D mRNA stability assay, luciferase reporter, NSUN6 overexpression in HCC cells and PDX mouse model, BMPER rescue experiment Biology of the cell Medium 40589169
2015 BMPER expression in lung fibroblasts is regulated by DNA methylation; demethylation with 5'-azacytidine decreases BMPER expression and attenuates fibroblast invasion/migration. siRNA-mediated BMPER reduction impairs fibroblast migration and invasion in IPF fibroblasts. 5'-azacytidine demethylation treatment, siRNA knockdown, invasion/migration assays, in vivo mouse fibrosis model Scientific reports Medium 26442443

Source papers

Stage 0 corpus · 82 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 BMPER, a novel endothelial cell precursor-derived protein, antagonizes bone morphogenetic protein signaling and endothelial cell differentiation. Molecular and cellular biology 191 12897139
2008 Onco-neural antibodies and tumour type determine survival and neurological symptoms in paraneoplastic neurological syndromes with Hu or CV2/CRMP5 antibodies. Journal of neurology, neurosurgery, and psychiatry 174 18931014
2008 BMPER is an endothelial cell regulator and controls bone morphogenetic protein-4-dependent angiogenesis. Circulation research 133 18787191
2001 Paraneoplastic anti-CV2 antibodies react with peripheral nerve and are associated with a mixed axonal and demyelinating peripheral neuropathy. Annals of neurology 102 11220741
2009 A concentration-dependent endocytic trap and sink mechanism converts Bmper from an activator to an inhibitor of Bmp signaling. The Journal of cell biology 97 19221194
2011 BMP activity controlled by BMPER regulates the proinflammatory phenotype of endothelium. Blood 59 21900199
1998 Paraneoplastic cerebellar syndrome and optic neuritis with anti-CV2 antibodies: clinical response to excision of the primary tumor. Archives of neurology 57 9520015
2017 A molecular roadmap of the AGM region reveals BMPER as a novel regulator of HSC maturation. The Journal of experimental medicine 52 29093060
2007 BMPER is a conserved regulator of hematopoietic and vascular development in zebrafish. Journal of molecular and cellular cardiology 44 17618647
2015 Methylation-mediated BMPER expression in fibroblast activation in vitro and lung fibrosis in mice in vivo. Scientific reports 41 26442443
2014 Fibroblast growth factor signaling pathway in endothelial cells is activated by BMPER to promote angiogenesis. Arteriosclerosis, thrombosis, and vascular biology 41 25503991
2012 Bmper inhibits endothelial expression of inflammatory adhesion molecules and protects against atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology 36 22772758
2009 Cv2, functioning as a pro-BMP factor via twisted gastrulation, is required for early development of nephron precursors. Developmental biology 35 19914233
2011 Bone morphogenetic protein modulator BMPER is highly expressed in malignant tumors and controls invasive cell behavior. Oncogene 34 22020334
2013 Antagonism and synergy between extracellular BMP modulators Tsg and BMPER balance blood vessel formation. Journal of cell science 31 23641068
2017 LRP1-Dependent BMPER Signaling Regulates Lipopolysaccharide-Induced Vascular Inflammation. Arteriosclerosis, thrombosis, and vascular biology 30 28596374
2011 BMPER protein is a negative regulator of hepcidin and is up-regulated in hypotransferrinemic mice. The Journal of biological chemistry 30 22144676
2017 Bone Morphogenetic Protein-Modulator BMPER Regulates Endothelial Barrier Function. Inflammation 28 27995357
2016 Extending the phenotype of BMPER-related skeletal dysplasias to ischiospinal dysostosis. Orphanet journal of rare diseases 27 26728142
2010 BMPER mutation in diaphanospondylodysostosis identified by ancestral autozygosity mapping and targeted high-throughput sequencing. American journal of human genetics 27 20869035
2018 BMPER Enhances Bone Formation by Promoting the Osteogenesis-Angiogenesis Coupling Process in Mesenchymal Stem Cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 26 29518774
2015 Pitfalls in the detection of CV2 (CRMP5) antibodies. Journal of neuroimmunology 26 26711575
2009 BMPER is upregulated by statins and modulates endothelial inflammation by intercellular adhesion molecule-1. Arteriosclerosis, thrombosis, and vascular biology 24 20042706
2013 BMPER-induced BMP signaling promotes coronary artery remodeling. Developmental biology 23 24373957
2009 Krüppel-like factor 15 regulates BMPER in endothelial cells. Cardiovascular research 22 19767294
2023 An overview on CV2/CRMP5 antibody-associated paraneoplastic neurological syndromes. Neural regeneration research 21 37282453
2023 BMPER is a marker of adipose progenitors and adipocytes and a positive modulator of adipogenesis. Communications biology 20 37311809
2012 Osteoblast-like differentiation of cultured human coronary artery smooth muscle cells by bone morphogenetic protein endothelial cell precursor-derived regulator (BMPER). The Journal of biological chemistry 20 22778264
2006 Expression of the onconeural CV2/CRMP5 antigen in thymus and thymoma. Journal of neuroimmunology 19 16519949
2018 CV2/CRMP5-antibody-related Paraneoplastic Optic Neuropathy Associated with Small-cell Lung Cancer. Internal medicine (Tokyo, Japan) 18 29321433
2018 Coexistence of Lambert-Eaton myasthenic syndrome and autoimmune encephalitis with anti-CRMP5/CV2 and anti-GABAB receptor antibodies in small cell lung cancer: A case report. Medicine 18 29742721
2015 Involvement of Rho-associated protein kinase (ROCK) and bone morphogenetic protein-binding endothelial cell precursor-derived regulator (BMPER) in high glucose-increased alkaline phosphatase expression and activity in human coronary artery smooth muscle cells. Cardiovascular diabetology 17 26264461
2015 BMPER Promotes Epithelial-Mesenchymal Transition in the Developing Cardiac Cushions. PloS one 17 26418455
2018 Extracellular bone morphogenetic protein modulator BMPER and twisted gastrulation homolog 1 preserve arterial-venous specification in zebrafish blood vessel development and regulate Notch signaling in endothelial cells. The FEBS journal 15 29473997
2015 BMPER variants associated with a novel, attenuated subtype of diaphanospondylodysostosis. Journal of human genetics 14 26467725
2018 Internal cleavage and synergy with twisted gastrulation enhance BMP inhibition by BMPER. Matrix biology : journal of the International Society for Matrix Biology 13 30125619
2020 Downregulation of Hsa_circ_0000735 Inhibits the Proliferation, Migration, Invasion, and Glycolysis in Non-small-cell Lung Cancer by Targeting miR-940/BMPER Axis. OncoTargets and therapy 12 32922033
2009 [Paraneoplastic chorea and behavioral disorders in a patient with anti-CV2/CRMP5 antibodies and two different tumors]. Revue neurologique 12 19497605
2024 A KLF2-BMPER-Smad1/5 checkpoint regulates high fluid shear stress-mediated artery remodeling. Nature cardiovascular research 11 39196179
2012 BMPER regulates cardiomyocyte size and vessel density in vivo. Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology 11 23200275
2011 A deleterious founder mutation in the BMPER gene causes diaphanospondylodysostosis (DSD). American journal of medical genetics. Part A 11 21990102
2021 BMPER alleviates ischemic brain injury by protecting neurons and inhibiting neuroinflammation via Smad3-Akt-Nrf2 pathway. CNS neuroscience & therapeutics 10 34904361
2009 Anti-CV2 associated cerebellar degeneration after complete response to chemoradiation of head and neck carcinoma. Journal of neuro-oncology 9 19798470
2020 Effects of BMPER, CXCL10, and HOXA9 on Neovascularization During Early-Growth Stage of Primary High-Grade Glioma and Their Corresponding MRI Biomarkers. Frontiers in oncology 8 32432046
2022 IL-6/Stat3 suppresses osteogenic differentiation in ossification of the posterior longitudinal ligament via miR-135b-mediated BMPER reduction. Cell and tissue research 7 36305971
2021 Paraneoplastic Cerebellar Degeneration with Anti-CV2/CRMP5 Antibodies in Ovarian Cancer: Case Report and Review of the Literature. Case reports in oncology 7 35111012
2020 Anti-CV2/CRMP5 antibody-positive paraneoplastic neurological syndromes with chronic intestinal pseudo-obstruction in a small-cell lung cancer patient: a case report and literature review. The Journal of international medical research 7 33305627
2014 The effect of variants in the promoter of BMPER on the intramuscular fat deposition in longissimus dorsi muscle of pigs. Gene 7 24667095
2025 Anti-CV2/CRMP5 autoantibodies as drivers of sensory neuron excitability and pain in rats. Nature communications 6 40775229
2024 Mechanism, and treatment of anti-CV2/CRMP5 autoimmune pain. bioRxiv : the preprint server for biology 6 38766071
2012 [Neurologic paraneoplastic syndrome with anti-CV2/CRMP5 antibodies revealing a small cell lung cancer. Effectiveness of the lung cancer treatment]. Revue neurologique 6 22387203
2023 BMPER Improves Vascular Remodeling and the Contractile Vascular SMC Phenotype. International journal of molecular sciences 5 36902380
2021 Parkinsonism and dysautonomia with anti-CV2/CRMP5 associated paraneoplastic neurological syndromes mimicking multiple system atrophy: a case report. BMC neurology 5 34702214
2020 Overexpression of BMPER in Ovarian Cancer and the Mechanism by which It Promotes Malignant Biological Behavior in Tumor Cells. BioMed research international 5 32309430
2016 Paraneoplastic Choreoathetosis in a Patient with Small Cell Lung Carcinoma and Anti-CRMP5/CV2: A Case Report. Case reports in neurology 5 26889151
2021 BMPER Ameliorates Renal Fibrosis by Inhibiting Tubular Dedifferentiation and Fibroblast Activation. Frontiers in cell and developmental biology 4 33644047
2021 Expansion of the mutational spectrum of BMPER leading to diaphanospondylodysostosis and description of the associated disease process. Molecular genetics & genomic medicine 4 34288564
2020 BMPER is upregulated in obesity and seems to have a role in pericardial adipose stem cells. Journal of cellular physiology 4 32468615
2024 Predicting disability and mortality in CV2/CRMP5-IgG associated paraneoplastic neurologic disorders. Annals of clinical and translational neurology 3 38251800
2024 TMF suppresses chondrocyte hypertrophy in osteoarthritic cartilage by mediating the FOXO3a/BMPER pathway. Experimental and therapeutic medicine 3 38800044
2021 CV2/CRMP5-antibody-related Paraneoplastic Neurologic Syndrome Associated with Gastrointestinal Stromal Tumor. Internal medicine (Tokyo, Japan) 3 34670904
2020 [A case of paraneoplastic myelopathy associated with anti-CV2/CRMP5 antibodies with small-cell lung cancer]. Rinsho shinkeigaku = Clinical neurology 3 32641628
2018 Arteriovenous specification: BMPER and TWSG1 determine endothelial cell fate via activation of synergistic BMP and Notch signaling. The FEBS journal 3 29654706
2024 SUGP2 p.(Arg639Gln) variant is involved in the pathogenesis of hemochromatosis via the CIRBP/BMPER signaling pathway. American journal of hematology 2 38800953
2003 [Paraneoplastic ataxia associated to anti CV2 antibodies]. Revista de neurologia 2 12589599
2025 CircSARS-CV2-N1368 from SARS-CoV-2 impairs endothelial cell function through the upregulation of ATF7 to activate TLR4/NF-κB/ROS signaling. Acta pharmacologica Sinica 1 40069492
2025 Targeting BMPER as a therapeutic strategy for pulmonary arterial hypertension. Cellular signalling 1 40383173
2025 NSUN6 Maintains BMPER Stability in an m5C-Dependent Manner to Suppress Cell Proliferation and Migration in Hepatocellular Carcinoma. Biology of the cell 1 40589169
2024 Anti-Collapsin Response Mediator Protein 5(CV2/CRMP5) and Anti-Glutamic Acid Decarboxylase (GAD) Antibodies-Mediated Encephalopathy Mimicking Atypical Parkinsonism. Neurology international 1 39728758
2023 Anti-CV2/Collapsin Response Mediator Protein 5 (CRMP5) Paraneoplastic Encephalitis Induced by Small Cell Lung Cancer. Cureus 1 36865958
2022 Further evidence for attenuated phenotype with variants in the BMPER gene causing DSD: Case report and literature review. European journal of medical genetics 1 35240322
2022 Successfully Managed Respiratory Insufficiency in a Patient with a Novel Pathogenic Variant of the BMPER Gene: A Case Report. Diagnostics (Basel, Switzerland) 1 35328179
2020 Anti-CV2/CRMP5 antibody-associated hemorrhagic leukoencephalomyelitis treated with steroids, intravenous immunoglobulin, plasmapheresis, and cyclophosphamide. Multiple sclerosis and related disorders 1 32044694
2007 [Amyotrophic lateral sclerosis and anti-CV2 antibodies. Paraneoplastic association?]. Neurologia (Barcelona, Spain) 1 17610172
2026 BMPER induces the adipogenic differentiation of fibro/adipogenic progenitors and promotes intramuscular fat deposition in chickens. Journal of animal science and biotechnology 0 42001170
2025 Inhibition of BMPER Mitigates Pulmonary Hypertension by Modulating LRP1-YAP Interaction in Smooth Muscle Cells. Arteriosclerosis, thrombosis, and vascular biology 0 40964716
2025 Lambert-Eaton myasthenic syndrome presenting with occult mediastinal small cell carcinoma and positivity for anti-CV2/CRMP5 and anti-SOX1 antibodies: a case report. BMC neurology 0 41291493
2025 Severe Anti-CV2/CRMP5, Anti-Hu, and Anti-SOX1 Antibody-Positive Paraneoplastic Neurological Syndrome Associated With Tumor Recurrence During Atezolizumab Therapy. Cureus 0 41542009
2024 Selection on the vascular-remodeling BMPER gene is associated with altitudinal adaptation in an insular lizard. Evolution letters 0 39906579
2021 [Clinical characteristics of anti-CV2 antibody-associated neurological diseases]. Zhonghua yi xue za zhi 0 34275254
2021 Diaphanospondylodysostosis: Full Case Report with Novel Pathogenic BMPER Mutation. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 0 34877902
2020 Generalized and orofacial choreoathetosis: a case report of anti-CV2 paraneoplastic syndrome after cardiac arrest. Neurocase 0 33356843