Affinage

AOC3

Amine oxidase [copper-containing] 3 · UniProt Q16853

Length
763 aa
Mass
84.6 kDa
Annotated
2026-04-28
100 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AOC3 (VAP-1) is a copper-containing, TPQ-dependent primary amine oxidase that functions both as an endothelial adhesion molecule mediating leukocyte extravasation and as a metabolic enzyme in adipocytes driving insulin-mimetic glucose transport. On endothelial cells, AOC3 localizes to lipid rafts as a homodimer and mediates sialic-acid-dependent lymphocyte rolling, firm adhesion, and transmigration; its catalytic activity is essential for these functions, as oxidase-null knock-in mice phenocopy full knockouts in peritonitis and arthritis models, and the reactive products of amine oxidation induce endothelial E- and P-selectin expression to amplify leukocyte recruitment (PMID:15664163, PMID:23885334, PMID:17548577, PMID:14726375). In adipocytes, AOC3-catalyzed oxidation of substrates such as benzylamine stimulates glucose uptake independently of the insulin receptor, and loss of this activity leads to increased adiposity and altered adipose inflammatory tone (PMID:17406965, PMID:32712883). A soluble form generated by metalloprotease-dependent ectodomain shedding circulates in plasma and retains modulatory activity on lymphocyte adhesion (PMID:9686623, PMID:14968297).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1996 High

    Establishing VAP-1 as a novel endothelial adhesion molecule resolved how lymphocytes bind vascular endothelium independently of known selectins and integrins, revealing a sialic-acid-dependent adhesion pathway.

    Evidence Glycosidase digestion and flow-based adhesion assays with anti-VAP-1 blocking antibodies on endothelial cells

    PMID:8627168

    Open questions at the time
    • Identity of the lymphocyte counterreceptor for VAP-1 was unknown
    • Whether enzymatic activity was required for adhesion was untested
  2. 1997 High

    Demonstrating that VAP-1 mediates subtype-specific leukocyte rolling under shear in vivo established it as a physiologically relevant adhesion molecule distinct from L-selectin, PSGL-1, and α4-integrin pathways.

    Evidence Intravital microscopy with multiple blocking antibodies in peripheral lymph nodes and flow-based assays

    PMID:9254657

    Open questions at the time
    • Mechanism of lymphocyte subset selectivity not defined
    • Downstream signaling on engagement not characterized
  3. 1998 Medium

    Discovery of a circulating soluble form (sVAP-1) raised the question of whether AOC3 functions extend beyond cell-surface adhesion to systemic immunomodulation.

    Evidence Sandwich ELISA, immunoblotting, and lymphocyte adhesion assay on plasma-derived sVAP-1

    PMID:9686623

    Open questions at the time
    • Mechanism of shedding was unknown
    • Physiological relevance of soluble form in vivo not established
  4. 2000 High

    Reconstitution of VAP-1-dependent adhesion in a transfected endothelial cell line, combined with mutagenesis showing dispensability of the RGD motif and enzymatic activity individually, and identification of CD44 as a counterreceptor activation pathway, began to dissect the structural requirements for adhesion.

    Evidence cDNA transfection, site-directed mutagenesis, rotatory and flow-chamber adhesion assays, antibody blocking

    PMID:10864915

    Open questions at the time
    • Direct lymphocyte ligand for VAP-1 still unidentified
    • Relative contribution of enzymatic vs. structural adhesion not resolved
  5. 2001 High

    In vivo intravital imaging showed VAP-1 acts as a molecular brake during granulocyte rolling and is required for ~70% of extravasation, quantifying its contribution to the multi-step adhesion cascade.

    Evidence Intravital microscopy with anti-VAP-1 antibody blockade in rabbit peritoneal inflammation model

    PMID:11156953

    Open questions at the time
    • Whether the antibody blocks enzymatic activity, adhesion, or both was unclear
    • Species generalizability not confirmed
  6. 2004 High

    Definitive proof that the TPQ-dependent oxidase activity is required for leukocyte transmigration resolved the long-standing question of whether AOC3 functions purely as an adhesion scaffold or requires catalysis; an enzymatically inactive point mutant abolished transmigration.

    Evidence Enzymatically inactive VAP-1 point mutant, specific amine oxidase inhibitors, flow-based in vitro assays and in vivo inflammation model

    PMID:14726375

    Open questions at the time
    • Identity of endogenous substrate(s) driving transmigration unknown
    • Reactive products mediating downstream signaling not characterized
  7. 2004 Medium

    Identification of metalloprotease-dependent shedding as the mechanism generating soluble VAP-1 from adipocytes explained the origin of circulating sVAP-1 and linked it to TNFα-driven inflammation.

    Evidence Metalloprotease inhibitor (batimastat) blockade of sVAP-1 release from 3T3-L1 and human adipocyte explants stimulated with TNFα

    PMID:14968297

    Open questions at the time
    • Specific metalloprotease identity not determined
    • Whether endothelial shedding follows the same mechanism was untested
  8. 2005 High

    AOC3 knockout mice established the gene as genetically required for slow rolling, firm adhesion, transmigration, and lymphocyte homing in vivo, providing the definitive loss-of-function genetic evidence for its role in the leukocyte extravasation cascade.

    Evidence AOC3 KO mice with intravital imaging, peritonitis model, and lymphocyte homing assays

    PMID:15664163

    Open questions at the time
    • Could not distinguish whether loss of adhesion vs. loss of enzymatic activity caused the phenotype
    • Compensatory mechanisms in chronic KO not assessed
  9. 2006 High

    Discovery that VAP-1 oxidase activity induces E- and P-selectin transcription/translation on endothelial cells identified a feed-forward mechanism whereby amine oxidation products amplify the leukocyte adhesion cascade beyond VAP-1's own adhesive function.

    Evidence WT vs. enzymatically inactive VAP-1 transfectants and VAP-1-deficient mice carrying human VAP-1 transgene with gene/protein expression assays

    PMID:17548577

    Open questions at the time
    • Specific oxidation product(s) responsible for selectin induction not identified
    • Signaling pathway from oxidation products to selectin gene transcription not mapped
  10. 2007 High

    Two key advances established AOC3's metabolic and immune tissue roles: AOC3 KO adipocytes lost benzylamine/methylamine-stimulated glucose transport while retaining insulin responses, proving the SSAO activity drives insulin-mimetic metabolic effects; separately, AOC3 KO mice showed defective mucosal immunity with reduced Peyer's patch lymphocytes and impaired antimicrobial responses.

    Evidence AOC3 KO adipocyte hexose transport assays; AOC3 KO mice with immunization, microbial challenge, flow cytometry

    PMID:17406965 PMID:17947691

    Open questions at the time
    • Endogenous amine substrates driving glucose transport in vivo unidentified
    • Whether mucosal immune defect is purely homing-dependent or involves local signaling unclear
  11. 2011 High

    Crystal structures of AOC3 revealed the TPQ cofactor in on-copper and off-copper conformations with imidazole, and mutagenesis of active-site residues (Met211, Leu469) defined determinants of substrate specificity; concurrent kinetic isotope effect studies established C–H bond breakage as rate-limiting for TPQ reduction, providing a detailed enzymological framework.

    Evidence X-ray crystallography at 2.6–2.95 Å, site-directed mutagenesis, steady-state kinetics with KIE and pH-dependence analysis

    PMID:21585208 PMID:21737458

    Open questions at the time
    • No structure of AOC3 with a physiological substrate bound
    • Mechanism of substrate channeling in the homodimer not addressed
  12. 2011 Medium

    Localization of AOC3 to lipid rafts specifically in endothelial cells (not smooth muscle cells) explained cell-type-specific leukocyte adhesion function, separating the adhesion role from the broader tissue expression pattern.

    Evidence Lipid raft fractionation and leukocyte adhesion assays comparing stably transfected endothelial vs. smooth muscle cells

    PMID:21819380

    Open questions at the time
    • Lipid raft targeting signal within AOC3 not mapped
    • Whether raft localization is required for enzymatic activity not tested
  13. 2012 High

    Systematic substrate profiling of purified human AOC3 defined its catalytic efficiency across primary amines and showed Km(O2) approximates interstitial oxygen tension, suggesting the enzyme is tuned to physiological oxygen availability.

    Evidence Recombinant enzyme from insect cells, in vitro kinetics with multiple substrates, whole-cell kinetics on 3T3-L1 adipocytes

    PMID:22238597

    Open questions at the time
    • In vivo substrate concentrations and identity of primary endogenous substrate(s) remain uncertain
    • Oxygen-sensing implications not tested in intact organisms
  14. 2013 High

    Oxidase-null knock-in mice phenocopied full AOC3 knockouts in peritonitis and arthritis, definitively separating the catalytic function from any structural/adhesion role and establishing that the enzymatic activity alone accounts for the pro-inflammatory phenotype.

    Evidence Oxidase-null knock-in mouse compared to KO in sterile peritonitis and antibody-induced arthritis models

    PMID:23885334

    Open questions at the time
    • Whether adhesion-only function exists in other inflammatory contexts not excluded
    • Nature of endogenous substrates at inflamed sites not identified
  15. 2013 High

    Crystal structures of AOC3 with pyridazinone inhibitors revealed a reversible binding site in the active-site channel and identified species-specific residues affecting inhibitor affinity, advancing structure-based drug design.

    Evidence X-ray crystallography of inhibitor–VAP-1 complexes, enzyme inhibition assays, homology modeling for species comparison

    PMID:24304424

    Open questions at the time
    • In vivo efficacy of pyridazinone-class inhibitors not reported
    • Selectivity over other copper amine oxidases not fully characterized
  16. 2020 High

    Parallel comparison of AOC3 KO and oxidase-null knock-in mice established that loss of catalytic activity causes increased adiposity and loss of benzylamine-stimulated glucose transport, with downregulated adipose inflammatory markers — unifying the metabolic and anti-inflammatory consequences of AOC3 enzymatic function.

    Evidence Body composition analysis, adipocyte glucose transport assay, inflammatory marker expression in KO vs. oxidase-null knock-in mice

    PMID:32712883

    Open questions at the time
    • Mechanism linking amine oxidation to glucose transporter translocation not resolved
    • Whether increased adiposity reflects developmental compensation or acute metabolic role unclear
  17. 2021 Medium

    Identification of the MRTF–SRF pathway as a transcriptional regulator of AOC3 in smooth muscle cells, with KDM3A-dependent chromatin remodeling, provided the first defined transcriptional control mechanism for AOC3 expression.

    Evidence MRTF overexpression, SRF siRNA knockdown, promoter reporter assay, ChIP for SRF binding in human SMCs

    PMID:33727640

    Open questions at the time
    • Whether MRTF–SRF controls AOC3 in endothelial cells or adipocytes not tested
    • Upstream signals regulating MRTF activity toward AOC3 not identified
  18. 2024 Medium

    A non-canonical role for AOC3 was identified in GIST cells where its loss stabilizes HK2 by reducing ubiquitin-mediated degradation, enhancing glycolysis and H3K18 lactylation at the Myc promoter to drive Myc-dependent imatinib resistance.

    Evidence AOC3 knockdown in GIST cell lines, HK2 ubiquitination assay, ChIP for H3K18la, HK2 overexpression rescue, xenograft model

    PMID:41570175

    Open questions at the time
    • Whether AOC3 enzymatic activity or protein scaffolding drives HK2 destabilization not resolved
    • Not independently replicated; relevance to non-GIST cancers unknown
    • Mechanism of AOC3-dependent HK2 ubiquitination (E3 ligase identity) not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • The identity of the endogenous leukocyte counterreceptor for AOC3 and the specific endogenous amine substrates oxidized at sites of inflammation to drive the extravasation cascade remain unresolved; the mechanism linking amine oxidation products to glucose transporter translocation in adipocytes is also undefined.
  • Leukocyte counterreceptor identity unknown
  • Endogenous substrate(s) at inflammatory sites not identified
  • Signaling from oxidation products to GLUT4 translocation not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 5 GO:0098631 cell adhesion mediator activity 5
Localization
GO:0005886 plasma membrane 3 GO:0005576 extracellular region 2
Pathway
R-HSA-168256 Immune System 7 R-HSA-1430728 Metabolism 4 R-HSA-1500931 Cell-Cell communication 4
Partners
HK2KDM3AMKL1NKX2-3SRF

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 VAP-1 (AOC3) mediates lymphocyte binding to endothelial cells in a sialic acid-dependent, L-selectin-independent manner; desialylation of VAP-1 abolishes its adhesive function, and it naturally exists as a 170-kDa sialoglycoprotein on the luminal surface of vessels. Glycosidase digestion, flow-based adhesion assays, anti-VAP-1 monoclonal antibody blocking The Journal of experimental medicine High 8627168
1997 VAP-1 mediates subtype-specific (CD8+ T cells and NK cells) rolling adhesion to peripheral lymph node HEVs under shear stress, independently of L-selectin, PSGL-1, and α4 integrins; intravital microscopy confirmed VAP-1 involvement in initial leukocyte–endothelial contacts in vivo. Flow-based adhesion assays with blocking antibodies, intravital microscopy The Journal of experimental medicine High 9254657
1998 A soluble circulating form of VAP-1 (sVAP-1) exists in plasma with slightly higher apparent molecular mass than transmembrane VAP-1 under non-reducing conditions but identical mobility after reduction; sVAP-1 retains the ability to modulate lymphocyte binding to endothelial cells. Sandwich ELISA, immunoblotting, lymphocyte adhesion assay Journal of immunology Medium 9686623
2000 Recombinant VAP-1 transfected into an endothelial cell line reconstitutes shear-dependent lymphocyte adhesion; the RGD integrin-binding motif and the enzymatic (monoamine oxidase) activity are not individually indispensable for adhesion, but CD44 ligation on lymphocytes markedly upregulates VAP-1-dependent adhesion, identifying a counterreceptor activation pathway. cDNA transfection into endothelial cell line, rotatory and flow-chamber adhesion assays, site-directed mutagenesis, antibody blocking Circulation research High 10864915
2001 VAP-1 functions as a molecular brake during granulocyte rolling, increasing rolling velocity and jerky skipping when blocked; anti-VAP-1 antibodies reduced granulocyte extravasation by ~70% and firm adhesion by 44% in vivo. Intravital microscopy with anti-VAP-1 monoclonal antibody blockade in rabbit inflammation model FASEB journal High 11156953
2004 The oxidase (amine oxidase) enzymatic activity of VAP-1 is required for PMN transmigration through the endothelium; an enzymatically inactive point mutant abolished VAP-1-mediated transmigration, and amine oxidase inhibitors blocked PMN rolling and transmigration under laminar shear stress in vitro and PMN extravasation in vivo. Enzymatically inactive VAP-1 point mutant, specific amine oxidase inhibitors, flow-based in vitro assays, in vivo inflammation model Blood High 14726375
2004 Adipocytes (3T3-L1 and human adipose tissue explants) release a soluble form of VAP-1/SSAO by metalloprotease-dependent shedding of the membrane form; this release is stimulated by TNF-α and blocked by the metalloprotease inhibitor batimastat. Culture medium collection, VAP-1 immunoprecipitation/Western blot, metalloprotease inhibitor (batimastat), TNF-α stimulation of adipocytes Diabetologia Medium 14968297
2005 AOC3-deficient mice show impaired slow rolling, firm adhesion, and transmigration of leukocytes at inflammatory sites and lymphoid tissues; AOC3 knockout results in reduced lymphocyte homing to lymphoid organs and attenuated peritonitis, establishing the endothelial amine oxidase as a required mediator of the leukocyte extravasation cascade in vivo. Gene knockout mouse model, real-time intravital imaging, peritonitis model, lymphocyte homing assay Immunity High 15664163
2006 The oxidase activity of VAP-1 induces transcription and translation of endothelial E- and P-selectins; using WT vs. enzymatically inactive VAP-1 point mutant transfectants and VAP-1-deficient mice carrying human VAP-1 transgene, P-selectin induction was shown to be enzyme-activity-dependent in vivo, leading to enhanced lymphocyte binding. Endothelial cell transfection with WT and enzymatically inactive VAP-1 mutant, VAP-1-deficient + humanized transgenic mice, gene/protein expression assays Blood High 17548577
2006 VAP-1 is expressed in smooth muscle cells as early as embryonic week 7 and is enzymatically active in fetal vessels; fetal VAP-1 is dimerized and functionally mediates cord blood lymphocyte rolling and firm adhesion under shear stress. Immunohistochemistry of human fetal tissues, enzymatic activity assay, adenoviral transfection of HUVEC, flow-based adhesion assay Blood Medium 16556889
2007 AOC3/VAP-1-deficient mice show age-dependent paucity of lymphocytes in Peyer's patches, lower serum IgA, defective oral immunization responses, and impaired antimicrobial immune responses against S. aureus and coxsackie B4 virus, demonstrating VAP-1 is required for normal mucosal immunity. AOC3 knockout mouse model, immunization, microbial challenge, flow cytometry, immunoglobulin quantification Journal of immunology High 17947691
2008 VAP-1 enzymatic activity mediates intestinal damage and acute lung injury after ischemia-reperfusion; VAP-1-deficient mice show attenuated injury, and separate inhibition with small molecule enzyme inhibitors or function-blocking antibody in WT mice confirms that the catalytic activity drives the pro-inflammatory response. VAP-1 KO mice, humanized VAP-1 transgenic mice, small molecule enzyme inhibitors, function-blocking antibody, ischemia-reperfusion injury model European journal of immunology High 18991279
2008 Membrane-bound SSAO/VAP-1 catalytic activity induces vascular cell death via p53 phosphorylation and PUMA-α induction, leading to mitochondrial Bcl-2 family protein alterations and effector caspase activation, upon methylamine substrate oxidation. Stable transfection of smooth muscle cell line with hSSAO/VAP-1, substrate (methylamine) treatment, Western blot for p53/PUMA/Bcl-2, caspase activity assays Biochimica et biophysica acta Medium 18348872
2011 Crystal structures of soluble AOC3 (sAOC3) reveal two imidazole binding sites: one where imidazole hydrogen-bonds to the TPQ cofactor in the inactive on-copper conformation, and another covalently bound to the active off-copper TPQ conformation; single-residue mutagenesis (Met211, Leu469) identifies these as key determinants of substrate specificity. X-ray crystallography (2.6 Å and 2.95 Å structures), site-directed mutagenesis of active-site residues, enzyme activity assays with multiple substrates, computational docking Biochemistry High 21585208
2011 VAP-1-mediated IL-1β-induced M2 macrophage infiltration underlies lymph- and angiogenesis; VAP-1 is expressed in blood but not lymphatic endothelium in vivo, and VAP-1 inhibition blocks IL-1β-induced but not VEGF-A-induced angiogenesis and lymphangiogenesis. Corneal micropocket assay, in vivo molecular imaging, VAP-1 inhibitor, immunohistochemistry The American journal of pathology Medium 21435467
2011 Engineered endothelial cells stably expressing human SSAO/VAP-1 show the protein is localized to lipid rafts of the plasma membrane as a dimer and mediates leukocyte adhesion to the endothelium; SSAO/VAP-1 in smooth muscle cells (expressing 3-fold higher protein) does not mediate leukocyte adhesion, indicating cell-type-specific function. Stable transfection, lipid raft fractionation, immunofluorescence, leukocyte adhesion assay Biology of the cell Medium 21819380
2011 VAP-1 reaction with primary amines is mechanistically characterized: a KIE of ~6–7.6 on kcat/Km with d2-benzylamine indicates an isotopically sensitive step in substrate binding/oxidation; large KIE on kcat with phenylethylamine (8.01) shows C-H bond breakage is rate-limiting for TPQ reduction; two macroscopic pKa values govern kcat as a function of pH. In vitro steady-state kinetics with soluble recombinant VAP-1, kinetic isotope effects (KIE), pH-dependence analysis, QSAR with para-substituted substrates The Journal of biological chemistry High 21737458
2012 Purified human AOC3 contains a TPQ cofactor (~6% titer) and oxidizes a broad range of primary amines (kcat/Km 10²–10⁴ M⁻¹s⁻¹); Km(O2) approximates interstitial oxygen partial pressure; dopamine and cysteamine are among the substrates with relatively high efficiency, implicating roles in insulin signaling and fatty acid metabolism; AOC3 is uniformly distributed on the adipocyte cell surface as confirmed by whole-cell kinetics matching purified enzyme. Recombinant enzyme expression in insect cells, in vitro enzyme kinetics, substrate profiling, cell-surface distribution imaging of 3T3-L1 adipocytes PloS one High 22238597
2013 AOC3/VAP-1 oxidase activity-null knock-in mice (expressing catalytically inactive VAP-1 protein) phenocopy AOC3 KO mice in sterile peritonitis and antibody-induced arthritis models, demonstrating that the oxidase catalytic activity is responsible for the inflammatory function of VAP-1 in vivo. Oxidase-null knock-in mouse generation, peritonitis model, antibody-induced arthritis model, comparison to KO mice American journal of clinical and experimental immunology High 23885334
2013 Crystal structures of VAP-1 complexed with novel pyridazinone inhibitors reveal a unique reversible binding site in the active site channel; species-specific binding is explained by specific amino acid differences between human and rodent VAP-1 identified by structural comparison. X-ray crystallography of inhibitor–VAP-1 complexes, homology modeling, enzyme inhibition assays Journal of medicinal chemistry High 24304424
2013 VAP-1 inhibition with a small molecule reduces myeloid cell recruitment to pulmonary metastatic sites and decreases tumor cell survival; simultaneous inhibition of VCAM-1 and VAP-1 does not produce additive effects, suggesting closely related downstream mechanisms. VAP-1 small molecule inhibitor, VCAM-1 blocking antibody, murine pulmonary metastasis model, myeloid cell quantification Blood Medium 23407548
2014 AOC3/VAP-1 expression in endothelial cells enhances susceptibility to oxygen-glucose deprivation (OGD); its enzymatic activity amplifies vascular cell damage through substrate oxidation (methylamine); OGD induces metalloprotease-2-dependent shedding of soluble SSAO/VAP-1; OGD induces SSAO/VAP-1-dependent leukocyte adhesion partly through enzymatic activity. Endothelial cells stably expressing hSSAO/VAP-1 subjected to OGD, metalloprotease inhibitors, Western blot for caspase-3/8, leukocyte adhesion assay Cerebrovascular diseases Medium 24503888
2014 AOC3/VAP-1 contributes transiently to antigen-specific CD4+ T-cell traffic to bronchial draining lymph nodes (89% reduction at day 3) in an OVA tracheal allergen model, but this difference was absent at day 6; dispersal of effector cells to lung and tracheal mucosa is AOC3-independent. AOC3 KO mice, OVA-specific CD4+ T-cell tracking kinetic model, flow cytometry European journal of immunology Medium 25116373
2007 AOC3 (VAP-1) in adipocytes is the enzyme encoded by the AOC3 gene responsible for SSAO-dependent insulin-like stimulation of glucose transport; adipocytes from AOC3 KO mice fail to respond to benzylamine, methylamine, and tyramine with increased glucose uptake while insulin responsiveness is preserved, proving the effect is oxidation-dependent rather than receptor-mediated. AOC3 knockout mouse adipocytes, hexose transport assay, SSAO activity measurement Journal of neural transmission High 17406965
2010 Histamine oxidation in mouse adipose tissue is predominantly controlled by AOC3-encoded SSAO; in AOC3 KO mice, benzylamine and histamine oxidation are abolished in adipose tissue but histamine oxidation persists in the intestine (controlled by AOC1/diamine oxidase); when protected from SSAO-mediated oxidation, histamine moderately stimulates lipolysis in adipocytes. AOC3 KO mice, enzyme activity assays in tissue homogenates, qRT-PCR, lipolysis (glycerol release) in isolated adipocytes Inflammation research Medium 20012150
2019 SSAO/VAP-1 expression in endothelial cells promotes BBB dysfunction associated with Alzheimer's disease by altering release of pro-inflammatory angioneurins (IL-6, IL-8, VEGF), decreasing tight-junction proteins (ZO-1, claudin-5), and increasing vascular Aβ deposition through both activity-dependent and -independent mechanisms. In vitro BBB model with SSAO/VAP-1-expressing endothelial cells, cytokine ELISA, Western blot for tight-junction proteins, permeability assay, leukocyte adhesion assay, Aβ deposition assay Biochimica et biophysica acta. Molecular basis of disease Medium 31047972
2020 Both AOC3 KO and AOC3 oxidase-null knock-in mice are heavier and fatter than controls with loss of benzylamine insulin-like action in adipocytes but preserved insulin lipogenic responsiveness; downregulated inflammatory markers in adipose tissue; the metabolic phenotype is reproduced by oxidase-null knock-in alone, demonstrating that the enzymatic activity is responsible for these metabolic functions. AOC3 KO and AOC3 knock-in (oxidase-null) mice compared, body composition analysis, adipocyte glucose transport assay, inflammatory marker expression Journal of physiology and biochemistry High 32712883
2021 AOC3 expression in smooth muscle cells is transcriptionally regulated by myocardin-related transcription factors (MRTFs: MYOCD, MRTF-A/MKL1, MRTF-B/MKL2) acting through serum response factor (SRF); the AOC3 gene locus contains SRF binding sites; SRF silencing reduces AOC3 transcripts; MRTF-A/MKL1 increases AOC3 promoter reporter activity via KDM3A chromatin remodeling. MRTF overexpression in human SMCs, SRF siRNA knockdown, promoter reporter assay, ChIP/SRF binding site analysis, KDM3A co-regulation Scientific reports Medium 33727640
2016 AOC3 is expressed on the surface of pericryptal myofibroblasts (identified as the target of mAb PR2D3) and its expression is sensitive to trypsin/collagenase digestion; TGFβ substantially downregulates AOC3 in myofibroblasts but not in skin fibroblasts; knockdown of NKX2-3 (co-expressed with AOC3 in myofibroblasts) decreases myofibroblast gene expression including AOC3 and increases fibroblast marker SHOX2. mAb target identification, immunofluorescence, FACS sorting, TGFβ treatment, whole-genome microarray, NKX2-3 knockdown PNAS Medium 27036009
2024 AOC3 loss in GIST cells stabilizes HK2 by attenuating ubiquitin-mediated degradation, leading to enhanced glycolysis and lactate production; elevated H3K18 lactylation at the Myc promoter drives Myc transcription; HK2 overexpression reverses AOC3-suppressive effects on glycolysis, lactylation, Myc expression, and imatinib resistance. AOC3 knockdown in GIST cell lines and patient samples, HK2 ubiquitination assay, ChIP for H3K18la at Myc promoter, HK2 overexpression rescue, in vivo xenograft model Molecular carcinogenesis Medium 41570175

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Crystal structures of VAP1 reveal ADAMs' MDC domain architecture and its unique C-shaped scaffold. The EMBO journal 150 16688218
2001 VAP-1: an adhesin and an enzyme. Trends in immunology 133 11274927
1998 Circulating form of human vascular adhesion protein-1 (VAP-1): increased serum levels in inflammatory liver diseases. Journal of immunology (Baltimore, Md. : 1950) 131 9686623
2005 Absence of the endothelial oxidase AOC3 leads to abnormal leukocyte traffic in vivo. Immunity 107 15664163
2004 Granulocyte transmigration through the endothelium is regulated by the oxidase activity of vascular adhesion protein-1 (VAP-1). Blood 107 14726375
2004 Adipocytes release a soluble form of VAP-1/SSAO by a metalloprotease-dependent process and in a regulated manner. Diabetologia 98 14968297
2007 VAP-1 and CD73, endothelial cell surface enzymes in leukocyte extravasation. Arteriosclerosis, thrombosis, and vascular biology 93 17962625
1996 Human vascular adhesion protein 1 (VAP-1) is a unique sialoglycoprotein that mediates carbohydrate-dependent binding of lymphocytes to endothelial cells. The Journal of experimental medicine 90 8627168
2007 The oxidase activity of vascular adhesion protein-1 (VAP-1) induces endothelial E- and P-selectins and leukocyte binding. Blood 87 17548577
1997 Vascular adhesion protein 1 (VAP-1) mediates lymphocyte subtype-specific, selectin-independent recognition of vascular endothelium in human lymph nodes. The Journal of experimental medicine 85 9254657
2016 Myofibroblasts are distinguished from activated skin fibroblasts by the expression of AOC3 and other associated markers. Proceedings of the National Academy of Sciences of the United States of America 81 27036009
2001 Vascular adhesion protein 1 (VAP-1) functions as a molecular brake during granulocyte rolling and mediates recruitment in vivo. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 72 11156953
2013 VCAM-1 and VAP-1 recruit myeloid cells that promote pulmonary metastasis in mice. Blood 71 23407548
1996 Lymphocyte binding to vascular endothelium in inflamed skin revisited: a central role for vascular adhesion protein-1 (VAP-1). European journal of immunology 59 8625974
2010 Plasma VAP-1/SSAO activity predicts intracranial hemorrhages and adverse neurological outcome after tissue plasminogen activator treatment in stroke. Stroke 58 20538694
2015 Effects of an anti-inflammatory VAP-1/SSAO inhibitor, PXS-4728A, on pulmonary neutrophil migration. Respiratory research 48 25889951
2013 PXS-4681A, a potent and selective mechanism-based inhibitor of SSAO/VAP-1 with anti-inflammatory effects in vivo. The Journal of pharmacology and experimental therapeutics 43 23943052
2011 VAP-1-mediated M2 macrophage infiltration underlies IL-1β- but not VEGF-A-induced lymph- and angiogenesis. The American journal of pathology 43 21435467
2000 Human vascular adhesion protein-1 (VAP-1) plays a critical role in lymphocyte-endothelial cell adhesion cascade under shear. Circulation research 38 10864915
2005 Properties of recombinant human N1-acetylpolyamine oxidase (hPAO): potential role in determining drug sensitivity. Cancer chemotherapy and pharmacology 37 15791459
2004 A peptide inhibitor of vascular adhesion protein-1 (VAP-1) blocks leukocyte-endothelium interactions under shear stress. European journal of immunology 37 15259025
2006 Elevated serum soluble vascular adhesion protein-1 (VAP-1) in patients with active relapsing remitting multiple sclerosis. Journal of neuroimmunology 35 16806498
1995 Different forms of human vascular adhesion protein-1 (VAP-1) in blood vessels in vivo and in cultured endothelial cells: implications for lymphocyte-endothelial cell adhesion models. European journal of immunology 35 7589075
2012 Implication for functions of the ectopic adipocyte copper amine oxidase (AOC3) from purified enzyme and cell-based kinetic studies. PloS one 34 22238597
2011 VAP-1/SSAO plasma activity and brain expression in human hemorrhagic stroke. Cerebrovascular diseases (Basel, Switzerland) 33 22133888
2015 VAP-1 blockade prevents subarachnoid hemorrhage-associated cerebrovascular dilating dysfunction via repression of a neutrophil recruitment-related mechanism. Brain research 32 25662771
2009 Circulating form of human vascular adhesion protein-1 (VAP-1): decreased serum levels in progression of colorectal cancer and predictive marker of lymphatic and hepatic metastasis. Journal of surgical oncology 30 19204971
2007 Vascular adhesion protein-1 (VAP-1) is overexpressed in psoriatic patients. Journal of the European Academy of Dermatology and Venereology : JEADV 30 17207171
2012 The discovery and development of selective 3-fluoro-4-aryloxyallylamine inhibitors of the amine oxidase activity of semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP-1). Bioorganic & medicinal chemistry letters 29 22595173
2008 Ischemia-reperfusion injury is attenuated in VAP-1-deficient mice and by VAP-1 inhibitors. European journal of immunology 29 18991279
2013 Novel pyridazinone inhibitors for vascular adhesion protein-1 (VAP-1): old target-new inhibition mode. Journal of medicinal chemistry 28 24304424
2011 Mini-PEG spacering of VAP-1-targeting 68Ga-DOTAVAP-P1 peptide improves PET imaging of inflammation. EJNMMI research 28 22214508
2007 VAP-1, Eotaxin3 and MIG as potential atherosclerotic triggers of severe calcified and stenotic human aortic valves: effects of statins. Experimental and molecular pathology 28 17490641
2019 Blood-brain barrier dysfunction underlying Alzheimer's disease is induced by an SSAO/VAP-1-dependent cerebrovascular activation with enhanced Aβ deposition. Biochimica et biophysica acta. Molecular basis of disease 26 31047972
2013 Novel 1H-imidazol-2-amine derivatives as potent and orally active vascular adhesion protein-1 (VAP-1) inhibitors for diabetic macular edema treatment. Bioorganic & medicinal chemistry 26 23664164
2013 The oxidase activity of vascular adhesion protein-1 (VAP-1) is essential for function. American journal of clinical and experimental immunology 26 23885334
2011 Identification of two imidazole binding sites and key residues for substrate specificity in human primary amine oxidase AOC3. Biochemistry 25 21585208
2008 p53 phosphorylation is involved in vascular cell death induced by the catalytic activity of membrane-bound SSAO/VAP-1. Biochimica et biophysica acta 25 18348872
2021 SSAO/VAP-1 in Cerebrovascular Disorders: A Potential Therapeutic Target for Stroke and Alzheimer's Disease. International journal of molecular sciences 24 33805974
2009 Localization of vascular adhesion protein-1 (VAP-1) in the human eye. Experimental eye research 24 19761765
2006 Developmental regulation of the adhesive and enzymatic activity of vascular adhesion protein-1 (VAP-1) in humans. Blood 24 16556889
2007 VAP-1-deficient mice display defects in mucosal immunity and antimicrobial responses: implications for antiadhesive applications. Journal of immunology (Baltimore, Md. : 1950) 23 17947691
2006 New efficient substrates for semicarbazide-sensitive amine oxidase/VAP-1 enzyme: analysis by SARs and computational docking. Journal of medicinal chemistry 23 17034126
2001 Vascular adhesion protein-1 (VAP-1) mediates lymphocyte-endothelial interactions in chronic kidney rejection. European journal of immunology 23 11592062
2021 Vascular Adhesion Protein-1 (VAP-1)/Semicarbazide-Sensitive Amine Oxidase (SSAO): A Potential Therapeutic Target for Atherosclerotic Cardiovascular Diseases. Frontiers in pharmacology 22 34322017
2016 Evaluation of serum and tissue levels of VAP-1 in colorectal cancer. BMC cancer 21 26912327
2011 Homing-associated molecules CD73 and VAP-1 as targets to prevent harmful inflammations and cancer spread. FEBS letters 21 21515268
2010 A structure-activity study to identify novel and efficient substrates of the human semicarbazide-sensitive amine oxidase/VAP-1 enzyme. Biochimie 21 20298739
2011 Vascular cell lines expressing SSAO/VAP-1: a new experimental tool to study its involvement in vascular diseases. Biology of the cell 20 21819380
2022 Vascular adhesion protein-1 (VAP-1) in vascular inflammatory diseases. VASA. Zeitschrift fur Gefasskrankheiten 19 36200383
2014 Cross-talk between Aβ and endothelial SSAO/VAP-1 accelerates vascular damage and Aβ aggregation related to CAA-AD. Neurobiology of aging 19 25457560
2020 Obesity of mice lacking VAP-1/SSAO by Aoc3 gene deletion is reproduced in mice expressing a mutated vascular adhesion protein-1 (VAP-1) devoid of amine oxidase activity. Journal of physiology and biochemistry 18 32712883
2014 Involvement of SSAO/VAP-1 in oxygen-glucose deprivation-mediated damage using the endothelial hSSAO/VAP-1-expressing cells as experimental model of cerebral ischemia. Cerebrovascular diseases (Basel, Switzerland) 18 24503888
2012 VAP-1, a novel molecule linked to endothelial damage and kidney function in kidney allograft recipients. Kidney & blood pressure research 18 23154672
2014 Endothelial amine oxidase AOC3 transiently contributes to adaptive immune responses in the airways. European journal of immunology 16 25116373
2013 Therapeutic advantage of anti-VAP-1 over anti-α4 integrin antibody in concanavalin a-induced hepatitis. Hepatology (Baltimore, Md.) 16 23686782
2021 Amine oxidase copper-containing 3 (AOC3) inhibition: a potential novel target for the management of diabetic retinopathy. International journal of retina and vitreous 15 33845913
2017 Simvastatin blocks soluble SSAO/VAP-1 release in experimental models of cerebral ischemia: Possible benefits for stroke-induced inflammation control. Biochimica et biophysica acta. Molecular basis of disease 15 29175057
2010 Human vascular adhesion proteın-1 (VAP-1): serum levels for hepatocellular carcinoma in non-alcoholic and alcoholic fatty liver disease. World journal of surgical oncology 15 20849600
2007 Semicarbazide-sensitive amine oxidase substrates fail to induce insulin-like effects in fat cells from AOC3 knockout mice. Journal of neural transmission (Vienna, Austria : 1996) 15 17406965
2005 The release of soluble VAP-1/SSAO by 3T3-L1 adipocytes is stimulated by isoproterenol and low concentrations of TNFalpha. Journal of physiology and biochemistry 15 16180338
2019 Vascular Adhesion Protein-1 (VAP-1) as Predictor of Radiographic Severity in Symptomatic Knee Osteoarthritis in the New York University Cohort. International journal of molecular sciences 14 31146362
2015 Protective effect of the multitarget compound DPH-4 on human SSAO/VAP-1-expressing hCMEC/D3 cells under oxygen-glucose deprivation conditions: an in vitro experimental model of cerebral ischaemia. British journal of pharmacology 14 26362823
2014 Novel inflammatory markers in psoriasis vulgaris: vaspin, vascular adhesion protein-1 (VAP-1), and YKL-40. Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia 14 25279492
2012 Synthesis and SAR study of new thiazole derivatives as vascular adhesion protein-1 (VAP-1) inhibitors for the treatment of diabetic macular edema. Bioorganic & medicinal chemistry 14 23337801
2019 Assessment of relationship between serum vascular adhesion protein-1 (VAP-1) and gestational diabetes mellitus. Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals 13 31638437
2013 Synthesis and SAR study of new thiazole derivatives as vascular adhesion protein-1 (VAP-1) inhibitors for the treatment of diabetic macular edema: part 2. Bioorganic & medicinal chemistry 13 23540955
2011 Reaction of vascular adhesion protein-1 (VAP-1) with primary amines: mechanistic insights from isotope effects and quantitative structure-activity relationships. The Journal of biological chemistry 13 21737458
2009 Structure-activity relationships of SSAO/VAP-1 arylalkylamine-based substrates. ChemMedChem 13 19266512
2021 NG2/CSPG4, CD146/MCAM and VAP1/AOC3 are regulated by myocardin-related transcription factors in smooth muscle cells. Scientific reports 12 33727640
2019 Increased Circulating VAP-1 Levels Are Associated with Liver Fibrosis in Chronic Hepatitis C Infection. Journal of clinical medicine 12 30658395
2012 Benzylamine antihyperglycemic effect is abolished by AOC3 gene invalidation in mice but not rescued by semicarbazide-sensitive amine oxidase expression under the control of aP2 promoter. Journal of physiology and biochemistry 12 22547093
2022 Downregulation of VAP-1 in OSCC suppresses tumor growth and metastasis via NF-κB/IL-8 signaling and reduces neutrophil infiltration. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 11 35174543
2007 Characterization of A7r5 cell line transfected in a stable form by hSSAO/VAP-1 gene (A7r5 hSSAO/VAP-1 cell line). Journal of neural transmission (Vienna, Austria : 1996) 11 17393062
2005 Severe cell fragmentation in the endothelial cell apoptosis induced by snake apoptosis toxin VAP1 is an apoptotic characteristic controlled by caspases. Toxicon : official journal of the International Society on Toxinology 10 15922392
2008 Expression of mRNAs coding for VAP1/crotastatin-like metalloproteases in the venom glands of three South American pit vipers assessed by quantitative real-time PCR. Toxicon : official journal of the International Society on Toxinology 9 18926840
2007 L-lysine as a recognition molecule for the VAP-1 function of SSAO. Journal of neural transmission (Vienna, Austria : 1996) 9 17393063
2005 VAP1, with cystatin C motif, an oocyte protein encoded by a novel ovarian-specific gene during oogenesis in the common brushtail possum (Trichosurus vulpecula). Molecular reproduction and development 8 15736124
2015 Assessment of the Relationship Between Serum Vascular Adhesion Protein-1 (VAP-1) and Severity of Calcific Aortic Valve Stenosis. The Journal of heart valve disease 7 27997774
2024 AOC3 accelerates lung metastasis of osteosarcoma by recruiting tumor-associated neutrophils, neutrophil extracellular trap formation and tumor vascularization. Heliyon 6 39296147
2020 Circulating vascular adhesion protein-1(VAP-1): a possible biomarker for liver fibrosis associated with chronic hepatitis B and C. Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] 6 32959205
2018 Effector gene vap1 based DGGE fingerprinting to assess variation within and among Heterodera schachtii populations. Journal of nematology 5 31094153
2010 Histamine oxidation in mouse adipose tissue is controlled by the AOC3 gene-encoded amine oxidase. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 5 20012150
2024 Association Between Vascular Adhesion Protein-1 (VAP-1) and MACE in Patients with Coronary Heart Disease: A Cohort Study. Journal of inflammation research 4 38855169
2023 Identification of AOC3 and LRRC17 as Colonic Fibroblast Activation Markers and Their Potential Roles in Colorectal Cancer Progression. Asian Pacific journal of cancer prevention : APJCP 4 37774061
2022 Increased atherosclerotic plaque in AOC3 knock-out in ApoE-/- mice and characterization of AOC3 in atherosclerotic human coronary arteries. Frontiers in cardiovascular medicine 4 36176983
2015 Glitazones inhibit human monoamine oxidase but their anti-inflammatory actions are not mediated by VAP-1/semicarbazide-sensitive amine oxidase inhibition. Journal of physiology and biochemistry 4 25572340
2013 Lack of association between VAP-1/SSAO activity and corneal neovascularization in a rabbit model. Journal of neural transmission (Vienna, Austria : 1996) 4 23397320
2025 Therapeutic Potential of Vascular Adhesion Protein-1 (VAP-1)/Semicarbazide-Sensitive Amine Oxidase (SSAO) Inhibitors: Current Medicinal Chemistry and Emerging Opportunities. Medicinal research reviews 3 40396328
2023 ω-(5-Phenyl-2H-tetrazol-2-yl)alkyl-substituted glycine amides and related compounds as inhibitors of the amine oxidase vascular adhesion protein-1 (VAP-1). Bioorganic & medicinal chemistry 3 38142562
2022 ω-(5-Phenyl-2H-tetrazol-2-yl)alkyl-substituted hydrazides and related compounds as inhibitors of amine oxidase copper containing 3 (AOC3). Archiv der Pharmazie 3 35507758
1992 A novel vesicle-associated protein (VAP-1) in sea urchin eggs containing multiple RNA-binding consensus sequences. Journal of cell science 3 1478972
2025 The role of VAP-1 in cardiovascular disease: a review. Frontiers in cardiovascular medicine 2 40458597
2024 The first selective VAP-1 inhibitor in China, TT-01025-CL: safety, tolerability, pharmacokinetics, and pharmacodynamics of single- and multiple-ascending doses. Frontiers in pharmacology 2 38741586
2024 Amine Oxidase, Copper Containing 3 (Aoc3) Knockout Mice Are More Prone to DSS-induced Colitis and Colonic Tumorigenesis. In vivo (Athens, Greece) 1 39187313
2013 VAP-1 in peritoneally dialyzed patients. Postepy higieny i medycyny doswiadczalnej (Online) 1 24379274
2006 [Vascular adhesion protein-1 (VAP-1) in inflammatory process]. Przeglad lekarski 1 17083159
2026 AOC3 Loss Promotes Imatinib Resistance in GIST by Stabilizing HK2 and Enhancing H3K18la-Driven Myc Transcription. Molecular carcinogenesis 0 41570175
2025 Pan-cancer analysis reveals AOC3 as a potential therapeutic biomarker for colorectal cancer. Discover oncology 0 41021158
2025 Proof-of-concept PET imaging of pulmonary sarcoidosis using VAP-1-targeted radiotracer [68Ga]Ga-DOTA-Siglec-9. Respiratory research 0 41420234