Affinage

MOXD1

DBH-like monooxygenase protein 1 · UniProt Q6UVY6

Length
613 aa
Mass
69.7 kDa
Annotated
2026-06-10
52 papers in source corpus 6 papers cited in narrative 6 extracted findings
Cross-family judge faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MOXD1 (monooxygenase DBH-like 1) is a regulator of hepatic lipid homeostasis that also shapes cell-fate and proliferative programs in neural and tumor lineages (PMID:42167911, PMID:38905335). In hepatocytes, MOXD1 directly interacts with the ACOX1-PEX5 translocation complex through four defined residues, promoting ACOX1 trafficking into peroxisomes and thereby blocking lipolysis and lipophagy; this activity drives metabolic dysfunction-associated steatohepatitis, and a small molecule (rM15) that binds MOXD1 and disrupts the ACOX1 interaction protects against hepatocyte lipid accumulation and diet-induced disease in vivo (PMID:42167911). MOXD1 mRNA is a target of the m6A demethylase FTO, which promotes its expression (PMID:38200441). In neuroblastoma, MOXD1 acts as a lineage-restricted tumor suppressor whose expression is confined to mesenchymal neuroblastoma cells and Schwann cell precursors, with loss associating with advanced disease across zebrafish, chick, and mouse models (PMID:38905335). In glioblastoma, MOXD1 binds β3GnT2 to influence protein glycosylation, and its loss induces ER stress and ER-mitochondrial apoptosis (PMID:35393406). In the brain, Moxd1 marks specific sexually dimorphic nuclei, and its dimorphic expression is organized perinatally by androgen exposure (PMID:28396628).

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 2017 Medium

    Established that Moxd1 marks specific sexually dimorphic brain nuclei and that this dimorphism is set during a perinatal hormonal window rather than maintained by circulating adult hormones.

    Evidence In situ hybridization and immunohistochemistry with neonatal castration versus adult gonadectomy in mice

    PMID:28396628

    Open questions at the time
    • No molecular function for Moxd1 within these neurons identified
    • Mechanism linking androgen exposure to Moxd1 cell number not resolved
  2. 2022 Medium

    Identified a physical partner and cellular consequence for MOXD1 in tumor cells, linking it to glycosylation and ER-stress-driven apoptosis.

    Evidence siRNA/shRNA knockdown and Co-IP (β3GnT2 binding) with viability, migration, ER-stress, and apoptosis readouts plus in vivo tumorigenesis in glioblastoma cells

    PMID:35393406

    Open questions at the time
    • Glycosylation substrates affected by the MOXD1–β3GnT2 interaction not defined
    • Direct enzymatic role of MOXD1 in glycosylation unclear
    • Single lab, glioblastoma-specific
  3. 2024 Medium

    Defined MOXD1 as a lineage-restricted tumor suppressor in neuroblastoma, reframing it from a pro-tumor factor (as seen in glioblastoma) to a context-dependent determinant of tumor development.

    Evidence Single-cell and bulk RNA-seq of human samples plus loss-of-function in zebrafish, chick, and mouse

    PMID:38905335

    Open questions at the time
    • Molecular mechanism of tumor suppression not established
    • Reconciliation with pro-malignant roles in other cancers unresolved
  4. 2024 Medium

    Placed MOXD1 downstream of m6A regulation, showing its mRNA is an FTO target and its silencing alters cancer-related signaling.

    Evidence RIP-qPCR, RT-qPCR, shRNA knockdown, and RNA-seq pathway analysis in gastric cancer cells

    PMID:38200441

    Open questions at the time
    • Direct effector mechanism downstream of MOXD1 not identified
    • How m6A status changes MOXD1 stability/translation not detailed
  5. 2026 High

    Resolved a direct molecular mechanism for MOXD1 in metabolism: it binds the ACOX1-PEX5 complex via defined residues to control ACOX1 peroxisomal trafficking, blocking lipolysis/lipophagy and driving MASH, and is pharmacologically targetable.

    Evidence Co-IP/MS, structural modelling, residue mutagenesis, hepatocyte-specific transgenic/KO and AAV8 knockdown mice, and AI-based small molecule (rM15) validation in vivo

    PMID:42167911

    Open questions at the time
    • Whether copper-dependent monooxygenase activity is required for ACOX1 binding not shown
    • Connection between hepatic metabolic role and tumor/neural roles unexplored
    • Experimental structure of the complex not solved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MOXD1's distinct activities—ACOX1 trafficking, β3GnT2-linked glycosylation, and tumor-lineage restriction—derive from a single biochemical function remains unresolved.
  • No catalytic substrate of MOXD1 directly demonstrated
  • Unifying enzymatic mechanism across tissues unknown
  • No experimentally determined protein structure

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 1
Localization
GO:0005777 peroxisome 1
Pathway
R-HSA-1643685 Disease 2 R-HSA-1430728 Metabolism 1
Partners
ACOX1B3GNT2FTOPEX5

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2022 MOXD1 knockdown in glioblastoma cells inhibits cell viability, proliferation, migration, invasion, and tumorigenesis, and was shown for the first time to bind β3GnT2, affecting glycosylation modification of certain proteins. Additionally, MOXD1 knockdown induces endoplasmic reticulum stress and triggers the ER-mitochondrial apoptosis pathway. siRNA/shRNA knockdown, co-immunoprecipitation (binding to β3GnT2), cell viability/proliferation/migration/invasion assays, in vivo tumorigenesis assay, ER stress markers Cell death discovery Medium 35393406
2024 MOXD1 is a lineage-restricted tumor suppressor gene in neuroblastoma; its expression is highly conserved and restricted to mesenchymal neuroblastoma cells and Schwann cell precursors during healthy development, and loss of MOXD1 expression associates with advanced disease. In vivo models (zebrafish, chick, mouse) confirmed its role as a determinant of tumor development. Single-cell RNA sequencing, in vivo loss-of-function models (zebrafish, chick, mouse), RNA sequencing of human neuroblastoma samples Science advances Medium 38905335
2024 FTO (m6A demethylase) targets MOXD1 mRNA, promoting its expression via m6A methylation modification; MOXD1 silencing suppressed malignant phenotype of gastric cancer cells and activated cancer-related signaling pathways (MAPK, TGF-β, NOTCH, JAK/STAT). RIP-qPCR (RNA immunoprecipitation), RT-qPCR, shRNA knockdown, cell proliferation/migration/apoptosis assays, RNA-seq pathway analysis BMC gastroenterology Medium 38200441
2026 MOXD1 directly interacts with the ACOX1-PEX5 translocation complex, promoting ACOX1 trafficking to peroxisomes to block lipolysis and lipophagy in hepatocytes, thereby driving MASH (metabolic dysfunction-associated steatohepatitis) pathogenesis. Four key MOXD1 residues required for ACOX1 binding were identified. A small molecule inhibitor (rM15) that directly binds MOXD1 and blocks its interaction with ACOX1 was identified and shown to protect against hepatocyte lipid accumulation and suppress diet-induced MASH in vivo. Co-immunoprecipitation-mass spectrometry, structural modelling, colocalization analysis, hepatocyte-specific transgenic and knockout mice, AAV8-based knockdown, AI-based inhibitor screening, in vitro and in vivo functional assays Gut High 42167911
2023 Fenofibrate binds tightly to MOXD1 protein (demonstrated by molecular docking) and inhibits hepatic MOXD1 expression independently of PPARα signaling in NIAAA model mice with alcoholic liver disease, ameliorating lipid deposition, oxidative stress, and inflammatory responses. Molecular docking, gene silencing (Ppar-α siRNA), gene expression analysis, in vivo NIAAA mouse model Life sciences Low 38042280
2017 Moxd1 expression is restricted to specific sexually dimorphic nuclei (SDN-POA, BNSTpr, MePD) in the mouse brain; neonatal castration of male mice reduced Moxd1-positive cell numbers in the SDN-POA, whereas adult gonadectomy did not affect Moxd1 expression, indicating that its sexual dimorphic expression is organized perinatally by androgen exposure. In situ hybridization, immunohistochemistry, neonatal castration and adult gonadectomy experiments, Allen brain atlas screening Frontiers in neuroanatomy Medium 28396628

Source papers

Stage 0 corpus · 52 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1992 Mox-1 and Mox-2 define a novel homeobox gene subfamily and are differentially expressed during early mesodermal patterning in mouse embryos. Development (Cambridge, England) 263 1363541
2001 FeMo cofactor of nitrogenase: a density functional study of states M(N), M(OX), M(R), and M(I). Journal of the American Chemical Society 137 11734043
2001 H(mox-1) constitutes an adaptive response to effect antioxidant cardioprotection: A study with transgenic mice heterozygous for targeted disruption of the Heme oxygenase-1 gene. Circulation 130 11273999
2012 Evaluation of a DNA microarray for the rapid detection of extended-spectrum β-lactamases (TEM, SHV and CTX-M), plasmid-mediated cephalosporinases (CMY-2-like, DHA, FOX, ACC-1, ACT/MIR and CMY-1-like/MOX) and carbapenemases (KPC, OXA-48, VIM, IMP and NDM). The Journal of antimicrobial chemotherapy 114 22604450
2018 Sulforaphane Inhibits Lipopolysaccharide-Induced Inflammation, Cytotoxicity, Oxidative Stress, and miR-155 Expression and Switches to Mox Phenotype through Activating Extracellular Signal-Regulated Kinase 1/2-Nuclear Factor Erythroid 2-Related Factor 2/Antioxidant Response Element Pathway in Murine Microglial Cells. Frontiers in immunology 61 29410668
1997 The human homeobox genes MSX-1, MSX-2, and MOX-1 are differentially expressed in the dermis and epidermis in fetal and adult skin. Differentiation; research in biological diversity 54 9373945
2003 Genesis and evolution of the Evx and Mox genes and the extended Hox and ParaHox gene clusters. Genome biology 41 12620122
1996 Differential localization of Mox-1 and Mox-2 proteins indicates distinct roles during development. The International journal of developmental biology 40 9032023
2001 Development of expression systems for the production of recombinant human serum albumin using the MOX promoter in Hansenula polymorpha DL-1. Biotechnology and bioengineering 33 11505387
2017 Moxd1 Is a Marker for Sexual Dimorphism in the Medial Preoptic Area, Bed Nucleus of the Stria Terminalis and Medial Amygdala. Frontiers in neuroanatomy 32 28396628
2014 Perinatal hypoxia-ischemia reduces α 7 nicotinic receptor expression and selective α 7 nicotinic receptor stimulation suppresses inflammation and promotes microglial Mox phenotype. BioMed research international 27 24757672
2002 Mox homeobox expression in muscle lineage of the gastropod Haliotis asinina: evidence for a conserved role in bilaterian myogenesis. Development genes and evolution 27 11976952
2002 The single amphioxus Mox gene: insights into the functional evolution of Mox genes, somites, and the asymmetry of amphioxus somitogenesis. Developmental biology 26 12051829
2010 Emergence of CTX-M-3, TEM-1 and a new plasmid-mediated MOX-4 AmpC in a multiresistant Aeromonas caviae isolate from a patient with pneumonia. Journal of medical microbiology 24 20339022
1995 The expression pattern of Xenopus Mox-2 implies a role in initial mesodermal differentiation. Mechanisms of development 24 7577672
1995 Multiple overlapping positions of nucleosomes with single in vivo rotational setting in the Hansenula polymorpha RNA polymerase II MOX promoter. The Journal of biological chemistry 24 7744739
2016 Mesoderm patterning and morphogenesis in the polychaete Alitta virens (Spiralia, Annelida): Expression of mesodermal markers Twist, Mox, Evx and functional role for MAP kinase signaling. Mechanisms of development 22 27000638
1997 Temperate Myxococcus xanthus phage Mx8 encodes a DNA adenine methylase, Mox. Journal of bacteriology 22 9209041
2022 MOXD1 knockdown suppresses the proliferation and tumor growth of glioblastoma cells via ER stress-inducing apoptosis. Cell death discovery 19 35393406
1996 Conserved regulation of the Hansenula polymorpha MOX promoter in Saccharomyces cerevisiae reveals insights in the transcriptional activation by Adr1p. European journal of biochemistry 17 8665936
2012 Repression vs. activation of MOX, FMD, MPP1 and MAL1 promoters by sugars in Hansenula polymorpha: the outcome depends on cell's ability to phosphorylate sugar. FEMS yeast research 16 23164245
2003 A detailed kinetic study of Mox-1, a plasmid-encoded class C beta-lactamase. FEMS microbiology letters 13 12951239
2020 iHWG-MOX: A Hybrid Breath Analysis System via the Combination of Substrate-Integrated Hollow Waveguide Infrared Spectroscopy with Metal Oxide Gas Sensors. ACS sensors 12 32189494
2016 The MOX promoter in Hansenula polymorpha is ultrasensitive to glucose-mediated carbon catabolite repression. FEMS yeast research 12 27527102
2014 Crystal structure of Mox-1, a unique plasmid-mediated class C β-lactamase with hydrolytic activity towards moxalactam. Antimicrobial agents and chemotherapy 12 24777102
2000 Mutations affecting the expression of the MOX gene encoding peroxisomal methanol oxidase in Hansenula polymorpha. Current genetics 12 11126774
1997 A Mox homeobox gene in the gastropod mollusc Haliotis rufescens is differentially expressed during larval morphogenesis and metamorphosis. FEBS letters 12 9247155
2005 Identification of an upstream regulatory sequence that mediates the transcription of mox genes in Methylobacterium extorquens AM1. Microbiology (Reading, England) 11 16272393
2003 The Hansenula polymorpha MOX gene presents two alternative transcription start points differentially utilized and sensitive to respiratory activity. European journal of biochemistry 10 12755702
1988 RFLP and mapping of human MOX-1 gene on chromosome 3. Nucleic acids research 10 2902568
2024 Nanoparticles with intermediate hydrophobicity polarize macrophages to plaque-specific Mox phenotype via Nrf2 and HO-1 activation. Journal of hazardous materials 9 38280324
2023 Fenofibrate inhibits MOXD1 and PDZK1IP1 expression and improves lipid deposition and inflammation in mice with alcoholic fatty liver. Life sciences 9 38042280
2022 Tumour microenvironment landscape and immunotherapy response in bladder cancer decoded by stromal MOXD1 based on copper-related genes signature. Frontiers in oncology 7 36620542
2024 RNA N6-methyladenosine demethylase FTO targets MOXD1 promoting the malignant phenotype of gastric cancer. BMC gastroenterology 5 38200441
2022 Molecular and Kinetic Characterization of MOX-9, a Plasmid-Mediated Enzyme Representative of a Novel Sublineage of MOX-Type Class C β-Lactamases. Antimicrobial agents and chemotherapy 5 36040170
2024 MOXD1 is a lineage-specific gene and a tumor suppressor in neuroblastoma. Science advances 4 38905335
2024 Eicosapentaenoic acid induces macrophage Mox polarization to prevent diabetic cardiomyopathy. EMBO reports 4 39482491
2020 Safety and Efficacy of s-MOX Regimen in Patients with Colorectal Cancer Who Developed Cardiotoxicity Following Fluoropyrimidine Administration: A Case Series. Archives of medical case reports 4 32964213
2023 Promising M2CO2/MoX2 (M = Hf, Zr; X = S, Se, Te) Heterostructures for Multifunctional Solar Energy Applications. Molecules (Basel, Switzerland) 3 37110759
2023 Safety evaluation of the food enzyme peroxidase from the genetically modified Aspergillus niger strain MOX. EFSA journal. European Food Safety Authority 3 37405174
2022 Fabrication of High-Performance Solar Cells and X-ray Detectors Using MoX2@CNT Nanocomposite-Tuned Perovskite Layers. ACS applied materials & interfaces 3 35834414
2021 HES and Mox genes are expressed during early mesoderm formation in a mollusk with putative ancestral features. Scientific reports 3 34504115
2024 Safety evaluation of an extension of use of the food enzyme peroxidase from the genetically modified Aspergillus niger strain MOX. EFSA journal. European Food Safety Authority 2 38601871
2025 ZnO/MOx Nanofiber Heterostructures: MOx Receptor's Role in Gas Detection. Sensors (Basel, Switzerland) 1 39860746
2023 Dataset of observables for UOX and MOX spent fuel extracted from Serpent2 fuel depletion calculations for PWRs. Data in brief 1 37520646
2026 Blocking MOXD1-derived ACOX1 peroxisome trafficking suppresses metabolic dysfunction-associated steatohepatitis. Gut 0 42167911
2025 Neutronic and burnup analysis of OECD-NEA MOX fuel benchmark with Dragon5 lattice code. Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine 0 39764899
2025 Exploring the mechanistic link between the oxytocinergic system and mindfulness training in adults with heightened stress: study protocol for a double-blind, randomized, placebo-controlled trial (MOX-MIND). BMC psychiatry 0 40597247
2025 Low-Density Lipoproteins Induce a Pro-Inflammatory, Chemotactic Mox-like Phenotype in THP-1-Derived Human Macrophages. Cells 0 41511339
2024 The structural, stability, electronic, optical and thermodynamic properties of MoX2 (X= S, Se, and Te) under hydrostatic pressures: a plasmon approach and first-principle study. Journal of molecular modeling 0 38462593
2024 Effects of Strigolactones on NLRP3 Activation, Nitrosative Stress, and Antioxidant Mox Phenotype: In Vitro and In Silico Evidence. ACS bio & med chem Au 0 38911910
1995 Mox: a novel modifier of the tomato Xa locus. The Journal of heredity 0 7608511

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