Affinage

NOMO1

BOS complex subunit NOMO1 · UniProt Q15155

Length
1222 aa
Mass
134.3 kDa
Annotated
2026-06-10
51 papers in source corpus 7 papers cited in narrative 7 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NOMO1 is a type I transmembrane protein that functions as an endoplasmic reticulum-shaping factor, maintaining ER sheet morphology and setting intermembrane distance within a functional network that includes the ER-shaping proteins Atlastin2 and Climp63 (PMID:34224731). Its extracellular region forms a 'beads on a string' array of consecutive immunoglobulin-like domains, and the number of Ig folds directly scales the ER intermembrane spacing; loss of NOMO1 collapses ER morphology, produces LAMP1-positive membrane holes, and elevates autophagy markers LC3 and p62/SQSTM1 (PMID:34224731). Beyond ER architecture, NOMO1 supports Nodal/Smad2 signaling: its depletion lowers Smad2 phosphorylation and blocks Nodal-dependent cardiomyocyte differentiation in P19 cells, downregulating Nodal, Cripto, and cardiac markers including Nkx2.5, Gata4, and Tbx5 (PMID:25576386). NOMO1 protein levels are set post-transcriptionally through direct targeting of its 3'-UTR by miR-675 (within the DLX3/H19/miR-675 axis) and by miR-33a-5p, both of which restrain proliferation and differentiation in trophoblast, mesenchymal stem cell, and cardiac progenitor contexts (PMID:22832245, PMID:33054489, PMID:28963438). In colorectal cancer cells, NOMO1 loss instead acts independently of Nodal signaling, deregulating epithelial-mesenchymal transition and increasing cell migration (PMID:36011023).

Mechanistic history

Synthesis pass · year-by-year structured walk · 7 steps
  1. 2012 Medium

    Established the first regulatory and functional context for NOMO1, placing it downstream of the H19/miR-675 axis as an effector controlling Smad2-dependent proliferation.

    Evidence Luciferase 3'-UTR reporter, NOMO1 overexpression rescue, and Smad2 phospho-Western in JEG-3 trophoblast cells

    PMID:22832245

    Open questions at the time
    • Did not define how NOMO1 mechanistically supports Smad2 phosphorylation
    • Single cell type; generality of the miR-675–NOMO1 link untested
  2. 2015 Medium

    Connected NOMO1 to a developmental program by showing it is required for Nodal-driven cardiomyocyte differentiation.

    Evidence RNAi knockdown in P19 cells with Western/qPCR for Nodal mediators and cardiac differentiation markers

    PMID:25576386

    Open questions at the time
    • Mechanism by which NOMO1 sustains Nodal/Cripto/Smad2 signaling unresolved
    • No in vivo cardiogenesis validation in this study
  3. 2017 Medium

    Extended the regulatory logic upstream, showing NOMO1 is the proliferative effector of a DLX3/H19/miR-675 axis where a disease mutation derepresses NOMO1.

    Evidence DLX3 Q178R mutation analysis, H19 restoration rescue, clonogenic/CCK-8 assays in bone marrow mesenchymal stem cells

    PMID:28963438

    Open questions at the time
    • Direct molecular consequence of elevated NOMO1 on proliferation machinery not defined
    • Does not address whether ER-shaping function underlies the proliferative effect
  4. 2020 Medium

    Demonstrated a second microRNA controls NOMO1, broadening its post-transcriptional regulation in cardiac progenitor biology.

    Evidence Dual-luciferase 3'-UTR reporter, miR-33a-5p mimic/inhibitor, NOMO1 overexpression rescue, proliferation/cell-cycle/apoptosis assays in hCMPCs

    PMID:33054489

    Open questions at the time
    • Whether miR-33a-5p and miR-675 co-regulate NOMO1 in the same cells unknown
    • Downstream effectors of NOMO1 in progenitor proliferation not mapped
  5. 2021 High

    Defined the core molecular function of NOMO1 as an ER-shaping protein whose Ig-domain array sets ER intermembrane distance, the first structural-mechanistic account.

    Evidence Proteomic screen, overexpression/depletion morphology phenotypes, in vitro reconstitution, Ig-fold insertion mutagenesis, genetic epistasis with Atlastin2 and Climp63

    PMID:34224731

    Open questions at the time
    • How ER-shaping activity relates to its Nodal/Smad2 signaling roles is unintegrated
    • Direct binding partners within the ER-shaping network not biochemically resolved
  6. 2022 Medium

    Revealed context-dependent NOMO1 function: in colorectal cancer its loss acts independently of Nodal signaling to deregulate EMT and enhance migration.

    Evidence CRISPR/Cas9 knockout in HCT-116, expression microarrays, RNA-seq, LC-IMS/MS proteomics, migration assays, gut-specific conditional KO mouse

    PMID:36011023

    Open questions at the time
    • Molecular link between NOMO1 loss and EMT pathway activation not identified
    • Reconciliation with Nodal-dependence seen in developmental contexts unexplained
  7. 2025 Low

    Implicated NOMO in cancer treatment resistance via checkpoint kinase signaling.

    Evidence siRNA knockdown in lung cancer cells, viability/apoptosis assays, antibody array showing increased Chk1/Chk2 phosphorylation

    PMID:41151896

    Open questions at the time
    • Pathway placement rests on a single antibody array without mechanistic reconstitution
    • Whether NOMO acts directly on Chk2 or via ER stress/apoptosis is undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NOMO1's ER-shaping activity mechanistically connects to its roles in Nodal/Smad2 signaling, EMT/migration, and checkpoint-kinase-dependent treatment resistance remains unresolved.
  • No unifying mechanism linking ER architecture to signaling phenotypes
  • Direct molecular partners of NOMO1 beyond epistatic network not biochemically established
  • Tissue-specific determinants of Nodal-dependent versus Nodal-independent behavior unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 1
Localization
GO:0005783 endoplasmic reticulum 1
Partners
ATL2CKAP4

Evidence

Reading pass · 7 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2021 NOMO1 is a type I transmembrane protein required to sustain ER morphology: overexpression imposes a sheet morphology on the ER, while depletion of NOMO1 and its orthologs causes collapse of ER morphology with formation of membrane-delineated holes positive for lysosomal marker LAMP1, and increases levels of autophagy markers LC3 and p62/SQSTM1. In vitro reconstitution revealed a 'beads on a string' structure consistent with consecutive immunoglobulin-like domains, and insertion of additional Ig folds correlatively increases the ER intermembrane distance. Genetic epistasis with known ER-shaping proteins Atlastin2 and Climp63 places NOMO1 in the functional network of ER-shaping proteins. Proteomic screen, overexpression/depletion in cells, in vitro reconstitution, domain insertion mutagenesis, genetic epistasis with Atlastin2 and Climp63 The Journal of biological chemistry High 34224731
2012 miR-675 (encoded by H19) directly downregulates NOMO1 protein expression by binding to the 3'-UTR of NOMO1, as validated by luciferase reporter assay. Overexpression of NOMO1 rescues miR-675-suppressed cell proliferation and phosphorylation of Smad2 in JEG-3 trophoblast cells, placing NOMO1 downstream of miR-675 in the Nodal/Smad2 signaling axis controlling trophoblast proliferation. Luciferase 3'-UTR reporter assay, NOMO1 overexpression rescue experiment, Western blot for Smad2 phosphorylation, H19/miR-675 knockdown RNA biology Medium 22832245
2015 NOMO1 gene silencing by RNAi in P19 cells inhibits their differentiation into cardiomyocytes, with downregulation of Nodal signaling mediators (Nodal, Cripto, Smad2) and cardiomyocyte-specific markers (cardiac troponin T, Nkx2.5, Gata4, Tbx5), indicating NOMO1 supports Nodal pathway activity required for early cardiogenesis. RNAi knockdown in P19 cells, Western blot/qPCR for Nodal pathway components and cardiomyocyte differentiation markers Experimental cell research Medium 25576386
2020 miR-33a-5p targets NOMO1 via its 3'-UTR (validated by dual-luciferase reporter assay), and upregulation of miR-33a-5p inhibits human cardiomyocyte progenitor cell (hCMPC) proliferation, G0/S transition, and differentiation into cardiomyocytes while promoting apoptosis; these effects are partially rescued by NOMO1 overexpression, establishing NOMO1 as a functional target of miR-33a-5p in cardiac progenitor biology. Dual-luciferase reporter assay, miR-33a-5p mimic/inhibitor transfection, NOMO1 overexpression rescue, CCK-8 proliferation assay, flow cytometry (apoptosis/cell cycle), Western blot Journal of receptor and signal transduction research Medium 33054489
2022 NOMO1 knockout in HCT-116 colorectal cancer cells (by CRISPR/Cas9) does not perturb Nodal pathway signaling or cell proliferation, but deregulates epithelial-mesenchymal transition and cell migration pathways, significantly increasing migration capacity. Expression microarrays, RNA-seq, and LC-IMS/MS proteomics revealed these Nodal-independent pathway changes. CRISPR/Cas9 knockout, expression microarrays, RNA-seq, LC-IMS/MS proteomics, cell migration assays, gut-specific conditional KO mouse model Cancers Medium 36011023
2025 NOMO silencing by siRNA in lung cancer cells counters chemo- and radioresistance through caspase-dependent apoptosis, and antibody array analysis reveals that NOMO inhibition leads to increased phosphorylation of checkpoint kinases Chk1 and Chk2, indicating NOMO modulates chemo- and radioresistance via the Chk2 pathway. siRNA knockdown, cell viability/apoptosis assays, antibody array for phospho-kinase profiling Anticancer research Low 41151896
2017 NOMO1 protein expression is regulated through the DLX3/H19/miR-675 axis in bone marrow mesenchymal stem cells: DLX3 mutation (Q178R) reduces H19 and miR-675 expression, leading to increased NOMO1 levels and enhanced cell proliferation; restoration of H19 suppresses the elevated NOMO1 expression and proliferation, confirming NOMO1 as a downstream effector of this axis. Lentiviral overexpression/knockdown, clonogenic and CCK-8 proliferation assays, H19 restoration rescue experiment, Western blot/qPCR for NOMO1 Clinical science Medium 28963438

Source papers

Stage 0 corpus · 51 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 The imprinted H19 gene regulates human placental trophoblast cell proliferation via encoding miR-675 that targets Nodal Modulator 1 (NOMO1). RNA biology 134 22832245
2000 Calicheamicin-conjugated humanized anti-CD33 monoclonal antibody (gemtuzumab zogamicin, CMA-676) shows cytocidal effect on CD33-positive leukemia cell lines, but is inactive on P-glycoprotein-expressing sublines. Leukemia 117 10942240
2013 Aberrant Mer receptor tyrosine kinase expression contributes to leukemogenesis in acute myeloid leukemia. Oncogene 90 23474756
2007 Helicobacter pylori heat-shock protein 60 induces interleukin-8 via a Toll-like receptor (TLR)2 and mitogen-activated protein (MAP) kinase pathway in human monocytes. Journal of medical microbiology 79 17244794
2004 Expression of HOX genes in acute leukemia cell lines with and without MLL translocations. Leukemia & lymphoma 52 15160920
2017 Mechanisms of Pinometostat (EPZ-5676) Treatment-Emergent Resistance in MLL-Rearranged Leukemia. Molecular cancer therapeutics 51 28428443
1991 FDP D-dimer induces the secretion of interleukin-1, urokinase-type plasminogen activator, and plasminogen activator inhibitor-2 in a human promonocytic leukemia cell line. Blood 51 1845845
2001 5-Aminolaevulinic acid-mediated photodynamic therapy in multidrug resistant leukemia cells. Journal of photochemistry and photobiology. B, Biology 43 11470562
2002 Granulocyte colony-stimulating factor directly affects human monocytes and modulates cytokine secretion. Experimental hematology 38 12384141
2000 Increased sensitivity of multidrug-resistant myeloid leukemia cell lines to lovastatin. Leukemia 37 10942241
2021 Identification of Potent and Selective Inhibitors of Fat Mass Obesity-Associated Protein Using a Fragment-Merging Approach. Journal of medicinal chemistry 36 34727689
1990 Enhanced expression of DNA topoisomerase II by recombinant human granulocyte colony-stimulating factor in human leukemia cells. Cancer research 28 1699657
2020 Bortezomib enhances cytotoxicity of ex vivo-expanded gamma delta T cells against acute myeloid leukemia and T-cell acute lymphoblastic leukemia. Cytotherapy 23 33168453
1995 New flow cytometric method for detection of minimally expressed multidrug resistance P-glycoprotein on normal and acute leukemia cells using biotinylated MRK16 and streptavidin-RED670 conjugate. Japanese journal of cancer research : Gann 22 7622426
2024 Structure-Based Design of a Potent and Selective YTHDC1 Ligand. Journal of medicinal chemistry 19 38787793
2018 Dual FLT3/TOPK inhibitor with activity against FLT3-ITD secondary mutations potently inhibits acute myeloid leukemia cell lines. Future medicinal chemistry 19 29437468
2020 Kevetrin induces apoptosis in TP53 wild‑type and mutant acute myeloid leukemia cells. Oncology reports 17 32945487
2019 NKL homeobox gene activities in normal and malignant myeloid cells. PloS one 16 31825998
2017 DLX3 promotes bone marrow mesenchymal stem cell proliferation through H19/miR-675 axis. Clinical science (London, England : 1979) 16 28963438
2017 NOMO-1 gene is deleted in early-onset colorectal cancer. Oncotarget 15 28416736
1998 Modulation of homeobox B6 and B9 genes expression in human leukemia cell lines during myelomonocytic differentiation. Leukemia & lymphoma 15 9922051
2017 Cyclic Cystine-Bridged Peptides from the Marine Sponge Clathria basilana Induce Apoptosis in Tumor Cells and Depolarize the Bacterial Cytoplasmic Membrane. Journal of natural products 13 29094598
2014 Nodal pathway genes are down-regulated in facial asymmetry. The Journal of craniofacial surgery 12 25364968
2013 Rac1 signaling protects monocytic AML cells expressing the MLL-AF9 oncogene from caspase-mediated apoptotic death. Apoptosis : an international journal on programmed cell death 12 23624644
1997 Amount of mpl on bone marrow haemopoietic precursor cells from healthy volunteers and patients with refractory anaemia. British journal of haematology 12 9432017
2020 MiR-33a-5p targets NOMO1 to modulate human cardiomyocyte progenitor cells proliferation and differentiation and apoptosis. Journal of receptor and signal transduction research 11 33054489
2017 Genotype-based gene signature of glioma risk. Neuro-oncology 11 28339748
2021 Pharmacological Inhibition of WIP1 Sensitizes Acute Myeloid Leukemia Cells to the MDM2 Inhibitor Nutlin-3a. Biomedicines 10 33917342
2021 Nodal modulator (NOMO) is required to sustain endoplasmic reticulum morphology. The Journal of biological chemistry 10 34224731
2020 Functional Dependency Analysis Identifies Potential Druggable Targets in Acute Myeloid Leukemia. Cancers 10 33321907
2015 Silencing of nodal modulator 1 inhibits the differentiation of P19 cells into cardiomyocytes. Experimental cell research 8 25576386
2024 Spatial enrichment and genomic analyses reveal the link of NOMO1 with amyotrophic lateral sclerosis. Brain : a journal of neurology 7 38643019
2022 TH1 cytokines induce senescence in AML. Leukemia research 7 35490594
2014 Localized, non-random differences in chromatin accessibility between homologous metaphase chromosomes. Molecular cytogenetics 7 25520753
2019 Establishment of a conditional Nomo1 mouse model by CRISPR/Cas9 technology. Molecular biology reports 6 31833031
2022 Recurrent NOMO1 Gene Deletion Is a Potential Clinical Marker in Early-Onset Colorectal Cancer and Is Involved in the Regulation of Cell Migration. Cancers 5 36011023
2022 Genome-Wide Association Screening Determines Peripheral Players in Male Fertility Maintenance. International journal of molecular sciences 5 36613967
2016 [Chemical constituents from Phellinus igniarius and their anti-tumor activity in vitro]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 4 28920346
2024 De novo and inherited micro-CNV at 16p13.11 in 21 Chinese patients with defective cardiac left-right patterning. Frontiers in genetics 3 39315310
2022 Biological Role of Nodal Modulator: A Comprehensive Review of the Last Two Decades. DNA and cell biology 3 35133875
2019 Population-wide copy number variation calling using variant call format files from 6,898 individuals. Genetic epidemiology 3 31520489
2009 Detergent fractionation with subsequent subtractive suppression hybridization as a tool for identifying genes coding for plasma membrane proteins. Experimental dermatology 3 19175411
2025 Transcriptomic characterisation of acute myeloid leukemia cell lines bearing the same t(9;11) driver mutation reveals different molecular signatures. BMC genomics 2 40133836
2026 Mesothelin promotes acute myeloid leukemia progression through LYN-dependent signaling. The Journal of biological chemistry 0 41866035
2025 NOMO-1 cells expressing an NF-κB luciferase reporter gene facilitate a simple, rapid monocyte activation test that can detect a wide range of pyrogens. PloS one 0 40540471
2025 Effective imaging and treatment of Acute Myeloid Leukemia with radiotheranostics targeting the activated conformation of integrin-βeta2. bioRxiv : the preprint server for biology 0 40909732
2025 Enhancing Blast Detection in Leukopenic Patients by Identifying Apoptotic Regions in the Sysmex XN-Series WPC Scattergram. Clinical laboratory 0 40923732
2025 Nodal Modulator Regulates Chemo- and Radioresistance in Lung Cancer via the Chk2 Pathway. Anticancer research 0 41151896
2025 Effective imaging and treatment of Acute Myeloid Leukemia with radiotheranostics targeting the activated conformation of integrin-βeta2. Research square 0 41282197
2025 Structural and Functional Analysis of GGPPS Inhibition as a Therapeutic Mechanism for Acute Myeloid Leukemia (AML). Research square 0 41510247
2018 DEC205 mediates local and systemic immune responses to Helicobacter pylori infection in humans. Oncotarget 0 29662609

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