Affinage

NOMO1

BOS complex subunit NOMO1 · UniProt Q15155

Round 2 corrected
Length
1222 aa
Mass
134.3 kDa
Annotated
2026-04-29
46 papers in source corpus 8 papers cited in narrative 8 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NOMO1 is an endoplasmic reticulum-resident protein that functions as a subunit of the Nicalin–TMEM147–NOMO (BOS) complex, an accessory module of the Sec61 translocon required for multi-pass membrane protein biogenesis; cryo-EM resolves this complex at the ribosome exit tunnel, and loss of NOMO1 reduces levels of multi-pass clients such as the glutamate transporter EAAT1 (PMID:32820719). NOMO1 also participates in Nodal–TGF-β signaling, acting upstream of Smad2 phosphorylation to promote trophoblast proliferation and cardiomyocyte progenitor cell differentiation (PMID:22832245, PMID:33054489). In colorectal cancer cells, CRISPR knockout of NOMO1 increases cell migration through deregulation of epithelial–mesenchymal transition pathways independently of canonical Nodal signaling (PMID:36011023).

Mechanistic history

Synthesis pass · year-by-year structured walk · 7 steps
  1. 2004 Medium

    NOMO1 was first placed within the Nodal/TGF-β–Smad signaling network, answering whether this uncharacterized protein had a role in a defined signaling pathway.

    Evidence Yeast two-hybrid screen coupled with siRNA knockdown and Smad reporter assays in mammalian cells

    PMID:15231748

    Open questions at the time
    • Mechanism by which NOMO1 promotes Smad signaling was not defined
    • No independent replication of the NOMO1-specific phenotype in this study
  2. 2012 Medium

    The functional position of NOMO1 upstream of Smad2 phosphorylation was established, resolving whether NOMO1 acts as a positive or negative regulator of Nodal signaling and linking it to trophoblast proliferation.

    Evidence Luciferase 3′-UTR reporter assay confirmed miR-675 targeting of NOMO1; NOMO1 overexpression rescued phospho-Smad2 levels and proliferation in JEG-3 trophoblast cells

    PMID:22832245

    Open questions at the time
    • Direct binding partners mediating Smad2 activation were not identified
    • In vivo relevance in trophoblast biology not tested
  3. 2019 Medium

    Generation of a conditional Nomo1 knockout mouse provided the genetic tool needed to dissect in vivo functions, establishing that exon 3 is essential for full-length protein production.

    Evidence CRISPR/Cas9-generated floxed allele; Cre recombination in MEFs and Msi1+ intestinal stem cells abolished NOMO1 protein by western blot

    PMID:31833031

    Open questions at the time
    • In vivo phenotypic consequences of Nomo1 loss were not fully characterized
    • Tissue-specific roles (e.g. intestinal stem cell homeostasis) remain unexplored
  4. 2020 High

    Cryo-EM and functional studies resolved NOMO1's primary molecular role as a structural subunit of the Nicalin–TMEM147–NOMO translocon accessory complex required for multi-pass membrane protein biogenesis at the ER.

    Evidence Cryo-EM structure of the ribosome–Sec61 complex with accessory modules; AP-MS identification; loss-of-function assays showing reduced EAAT1 levels

    PMID:32820719

    Open questions at the time
    • Substrate selectivity of the NOMO-containing complex beyond EAAT1 is not defined
    • Whether NOMO1's translocon role is mechanistically linked to its Nodal signaling function remains unresolved
  5. 2020 Medium

    NOMO1 was established as a pro-proliferative and pro-differentiation factor in cardiomyocyte progenitors, extending its Smad-associated role to cardiac lineage commitment.

    Evidence miR-33a-5p targeting confirmed by dual-luciferase assay; NOMO1 overexpression rescued proliferation, cell cycle progression, apoptosis, and cardiomyocyte differentiation markers in hCMPCs

    PMID:33054489

    Open questions at the time
    • Whether rescue operates through Smad2 or an alternative downstream pathway was not dissected
    • Single-lab finding without independent confirmation
  6. 2022 Medium

    NOMO1 loss in colorectal cancer cells was shown to promote migration via EMT pathways independently of Nodal signaling, revealing a Nodal-independent tumor-suppressive function.

    Evidence CRISPR/Cas9 knockout in HCT-116 cells with migration assays, expression microarray, RNA-seq, and LC-IMS/MS proteomics; Nodal reporter unaffected

    PMID:36011023

    Open questions at the time
    • Molecular target(s) mediating the Nodal-independent EMT regulation not identified
    • Whether this function relates to the ER translocon role or is entirely distinct is unknown
  7. 2022 Medium

    Endogenous tagging confirmed NOMO1's ER localization in living cells, consistent with its translocon complex membership.

    Evidence CRISPR-based endogenous fluorescent tagging with confocal live-cell imaging in human cells

    PMID:35271311

    Open questions at the time
    • Dynamic redistribution under stress or signaling conditions not examined

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown how NOMO1's structural role in the Sec61 translocon accessory complex relates to its signaling functions in the Nodal–Smad2 pathway and its Nodal-independent suppression of EMT, and whether these represent a single mechanism or distinct activities.
  • Full client repertoire of the Nicalin–TMEM147–NOMO complex is undefined
  • In vivo phenotype of Nomo1 conditional knockout has not been reported
  • No structural information on NOMO1 alone or its direct contacts within the complex beyond cryo-EM density

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 1
Localization
GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-392499 Metabolism of proteins 1
Partners
NCLNTMEM147
Complex memberships
Nicalin-TMEM147-NOMO (BOS) complex

Evidence

Reading pass · 8 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2020 NOMO1 is a component of a ~360 kDa ER-resident translocon complex for multi-pass membrane protein biogenesis. Cryo-EM reveals that NOMO forms the 'Nicalin-TMEM147-NOMO complex,' one of five accessory factors assembled around the core Sec61 channel at the ribosome exit tunnel. Loss of accessory components (including NOMO) reduces levels of multi-pass membrane protein clients such as the glutamate transporter EAAT1, establishing a functional role for NOMO1 in multi-pass membrane protein biogenesis at the ER. Cryo-electron microscopy, affinity purification–mass spectrometry, high-throughput mRNA sequencing, cell-based loss-of-function assays eLife High 32820719
2004 NOMO1 was identified as a component of the Nodal/TGF-β–Smad signaling pathway through large-scale two-hybrid and functional proteomics mapping. siRNA knockdown experiments placed NOMO1 among novel proteins functionally required for Smad signaling in mammalian cells. Yeast two-hybrid screen, siRNA knockdown with Smad reporter functional assay Genome research Medium 15231748
2012 miR-675 (encoded by H19) directly targets the 3′-UTR of NOMO1 mRNA to suppress NOMO1 protein expression, as validated by luciferase reporter assay. Overexpression of NOMO1 in JEG-3 trophoblast cells rescues miR-675-suppressed cell proliferation and restores phosphorylation of Smad2, placing NOMO1 upstream of Smad2 activation in the Nodal signaling pathway and establishing NOMO1 as a positive regulator of trophoblast proliferation via Nodal–Smad2. Luciferase 3′-UTR reporter assay, NOMO1 overexpression rescue experiment, western blot for phospho-Smad2, cell proliferation assay RNA biology Medium 22832245
2020 miR-33a-5p directly targets NOMO1 (confirmed by dual-luciferase reporter assay). Up-regulation of miR-33a-5p in human cardiomyocyte progenitor cells (hCMPCs) inhibits proliferation, blocks G0/S cell cycle transition, promotes apoptosis (increased Bax and cleaved caspase-3, decreased Bcl-2), and reduces cardiomyocyte differentiation markers (GATA4, cTnT, MEF2C). These effects are partially rescued by NOMO1 overexpression, establishing NOMO1 as a pro-proliferative and pro-differentiation factor in cardiomyocyte progenitors. Dual-luciferase reporter assay, CCK-8 proliferation assay, flow cytometry (cell cycle and apoptosis), western blot, qRT-PCR, NOMO1 overexpression rescue Journal of receptor and signal transduction research Medium 33054489
2022 CRISPR/Cas9-mediated knockout of NOMO1 in HCT-116 colorectal cancer cells does not perturb Nodal pathway signaling or cell proliferation, but significantly increases cell migration capacity. Expression microarray, RNA-seq, and LC-IMS/MS proteomics revealed that NOMO1 loss deregulates epithelial-mesenchymal transition (EMT) and cell migration pathways independently of the canonical Nodal pathway, demonstrating that NOMO1 suppresses CRC cell migration through non-Nodal mechanisms. CRISPR/Cas9 knockout, wound-healing and transwell migration assays, expression microarray, RNA-seq, LC-IMS/MS proteomics, Nodal pathway reporter assays Cancers Medium 36011023
2019 A conditional Nomo1 knockout mouse model was generated using CRISPR/Cas9 to flox exon 3. Cre-mediated recombination in mouse embryonic fibroblasts and in Msi1+ intestinal stem cells ablated exon 3 and eliminated full-length NOMO1 protein (confirmed by western blot), establishing that exon 3 is essential for production of functional NOMO1 protein. CRISPR/Cas9 conditional knockout, Cre-loxP recombination, western blot, genomic PCR Molecular biology reports Medium 31833031
2021 Large-scale affinity purification–mass spectrometry (BioPlex 3.0) in 293T and HCT116 cells identified NOMO1 as part of a protein interaction community, co-purifying with Nicalin (NCAN) and TMEM147, consistent with its membership in the ER translocon accessory complex. Affinity purification–mass spectrometry (AP-MS) at proteome scale Cell Low 33961781
2022 OpenCell endogenous tagging and live-cell imaging determined the subcellular localization of NOMO1 within human cells, placing it at the endoplasmic reticulum, consistent with its role in the ER translocon complex. CRISPR-based endogenous fluorescent tagging, confocal live-cell imaging, AP-MS Science Medium 35271311

Source papers

Stage 0 corpus · 46 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2006 A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. Cell 610 16713569
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2011 The SARS-coronavirus-host interactome: identification of cyclophilins as target for pan-coronavirus inhibitors. PLoS pathogens 341 22046132
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2004 Functional proteomics mapping of a human signaling pathway. Genome research 247 15231748
2016 An organelle-specific protein landscape identifies novel diseases and molecular mechanisms. Nature communications 211 27173435
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
2011 Protein interactome reveals converging molecular pathways among autism disorders. Science translational medicine 180 21653829
2017 The E3 ubiquitin ligase and RNA-binding protein ZNF598 orchestrates ribosome quality control of premature polyadenylated mRNAs. Nature communications 176 28685749
2014 Global mapping of herpesvirus-host protein complexes reveals a transcription strategy for late genes. Molecular cell 173 25544563
2020 UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination. Nature cell biology 168 32807901
2007 Cooperative control of striated muscle mass and metabolism by MuRF1 and MuRF2. The EMBO journal 149 18157088
2012 The imprinted H19 gene regulates human placental trophoblast cell proliferation via encoding miR-675 that targets Nodal Modulator 1 (NOMO1). RNA biology 133 22832245
2004 The sequence and analysis of duplication-rich human chromosome 16. Nature 130 15616553
1999 Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q. Genomics 124 10493829
2004 A protein interaction framework for human mRNA degradation. Genome research 123 15231747
2021 Protein interaction landscapes revealed by advanced in vivo cross-linking-mass spectrometry. Proceedings of the National Academy of Sciences of the United States of America 113 34349018
2011 An important role for CDK2 in G1 to S checkpoint activation and DNA damage response in human embryonic stem cells. Stem cells (Dayton, Ohio) 113 21319273
2020 An ER translocon for multi-pass membrane protein biogenesis. eLife 108 32820719
2020 The Hsp70-Hsp90 co-chaperone Hop/Stip1 shifts the proteostatic balance from folding towards degradation. Nature communications 101 33239621
2018 Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei. Molecular & cellular proteomics : MCP 101 30021884
2012 Charting the landscape of tandem BRCT domain-mediated protein interactions. Science signaling 92 22990118
2021 SARS-CoV-2-host proteome interactions for antiviral drug discovery. Molecular systems biology 86 34709727
2017 Elucidation of the molecular responses of a cucumber segment substitution line carrying Pm5.1 and its recurrent parent triggered by powdery mildew by comparative transcriptome profiling. BMC genomics 31 28056792
2004 Semiempirical PM5 molecular orbital study on chlorophylls and bacteriochlorophylls: comparison of semiempirical, ab initio, and density functional results. Journal of computational chemistry 28 14635000
2019 Identification of a New Powdery Mildew Resistance Gene pmDHT at or Closely Linked to the Pm5 Locus in the Chinese Wheat Landrace Dahongtou. Plant disease 24 31453747
2001 Identification of novel polymorphisms in the pM5 and MRP1 (ABCC1) genes at locus 16p13.1 and exclusion of both genes as responsible for pseudoxanthoma elasticum. Human mutation 24 11139250
2017 NOMO-1 gene is deleted in early-onset colorectal cancer. Oncotarget 15 28416736
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
2023 Identification of a Wheat Powdery Mildew Dominant Resistance Gene in the Pm5 Locus for High-Throughput Marker-Assisted Selection. Plant disease 8 35815965
2024 Spatial enrichment and genomic analyses reveal the link of NOMO1 with amyotrophic lateral sclerosis. Brain : a journal of neurology 7 38643019
2019 Establishment of a conditional Nomo1 mouse model by CRISPR/Cas9 technology. Molecular biology reports 6 31833031
2011 Quantitative structure-cytotoxicity relationship of newly synthesised trihaloacetylazulenes determined by a semi-empirical molecular-orbital method (PM5). Anticancer research 6 21378332
2001 Peptide torsion angle measurements: effects of nondilute spin pairs on carbon-observed, deuterium-dephased PM5-REDOR. Journal of magnetic resonance (San Diego, Calif. : 1997) 6 11133282
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 4 36011023
2023 Bacillus subtilis PM5 from Camel Milk Boosts Chicken Immunity and Abrogates Salmonella entertitidis Infections. Microorganisms 3 37512891
2010 Estimation of relationship between the structure of trihaloacetylazulene derivatives determined by a semiempirical molecular-orbital method (PM5) and their cytotoxicity. Anticancer research 3 20393004
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