Affinage

NOM1

Nucleolar MIF4G domain-containing protein 1 · UniProt Q5C9Z4

Length
860 aa
Mass
96.3 kDa
Annotated
2026-06-10
40 papers in source corpus 10 papers cited in narrative 10 extracted findings
Cross-family judge faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NOM1 is an evolutionarily conserved nucleolar protein that functions as an eIF4G-like cofactor for the DEAD-box RNA helicase eIF4AIII, coupling helicase activity to ribosome biogenesis (PMID:15715967, PMID:21576267). Through its MIF4G domain it binds eIF4AIII directly (and the yeast Sgd1p–Fal1p pair is conserved), and the resulting complex drives pre-rRNA processing for 18S rRNA biogenesis at cleavage sites A0/A1/A2 — a role distinct from the EJC function of eIF4AIII (PMID:21576267, PMID:31994962). Work on the yeast ortholog established the molecular basis: the MIF4G domain stimulates the ATPase/helicase activity of Fal1, the protein co-purifies early SSU processome factors, and its C-terminal region crosslinks to helix H12 of 18S rRNA, which is required for ribosome biogenesis (PMID:31994962). Independently, NOM1 acts as the first identified nucleolar targeting subunit for protein phosphatase 1 (PP1), recruiting PP1 to the nucleolus via an RVXF motif together with its nucleolar localization sequence (PMID:17965019); this PP1-targeting activity is functionally required for proliferation of ptf1a-expressing pancreatic progenitor cells in zebrafish, where loss of nom1 disrupts ribosome biogenesis in a p53-independent manner (PMID:24967912). NOM1 expression supports stem and progenitor cell maintenance, being regulated by KDM4-mediated H3K9 demethylation at its promoter in hematopoietic stem cells (PMID:31434704).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2000 Medium

    Established the yeast ortholog Sgd1p as an essential nuclear protein and first linked it to osmoregulatory signaling, raising the question of what essential nuclear function it serves.

    Evidence Gene deletion lethality, multicopy suppression of HOG-pathway mutants, and GFP localization in yeast

    PMID:11042259

    Open questions at the time
    • Essential molecular activity not identified
    • Connection between nuclear localization and HOG suppression unexplained
    • No biochemical partners defined
  2. 2002 Medium

    Placed Sgd1p at a convergence of Plc1p- and Hog1p-dependent osmoregulatory pathways through physical and genetic interactions, though its biochemical role remained undefined.

    Evidence Two-hybrid screen, affinity chromatography, and double/triple-mutant epistasis in yeast

    PMID:12073033

    Open questions at the time
    • Direct enzymatic or RNA-related function still unknown
    • Mechanism connecting Plc1p binding to GPD1 control unresolved
  3. 2005 Medium

    Defined human NOM1 domain architecture (MIF4G and MA3) and its eIF4A-family binding and nucleolar localization, framing it as a translation-factor-like nucleolar protein.

    Evidence Domain analysis, binding assays with eIF4A family members, and subcellular imaging in human cells

    PMID:15715967

    Open questions at the time
    • Which eIF4A paralog is the functional partner not resolved
    • No functional readout for the interaction
    • Nucleolar role not yet defined
  4. 2007 High

    Revealed a second, distinct function: NOM1 is the first nucleolar targeting subunit for PP1, answering how PP1 is recruited to the nucleolus.

    Evidence Reciprocal Co-IP, RVXF motif mutagenesis, and localization/targeting assays in human cells

    PMID:17965019

    Open questions at the time
    • Nucleolar PP1 substrates not identified
    • Relationship between PP1-targeting and rRNA processing roles unclear
  5. 2011 High

    Identified NOM1 as the eIF4G-like partner of eIF4AIII in pre-rRNA processing, establishing a ribosome biogenesis role separate from eIF4AIII's EJC function.

    Evidence In vitro binding, reciprocal Co-IP, yeast complementation of fal1Δ by human eIF4AIII, and siRNA knockdown with rRNA processing readout

    PMID:21576267

    Open questions at the time
    • Mechanism of helicase stimulation not shown in human system
    • Precise rRNA contact sites undefined at this stage
  6. 2014 High

    Showed in vivo that NOM1-dependent nucleolar PP1 targeting and ribosome biogenesis are required for pancreatic progenitor proliferation, linking both molecular activities to development.

    Evidence Zebrafish forward genetic screen, positional cloning, RNA-seq, rescue with PP1α plus nucleolar localization signal, and p53 epistasis

    PMID:24967912

    Open questions at the time
    • How impaired ribosome biogenesis specifically limits progenitor proliferation unresolved
    • PP1 nucleolar substrates in this context unknown
  7. 2019 Medium

    Extended the interaction network to nuclear IGF1R, suggesting a bidirectional regulatory relationship, and to KDM4-controlled transcriptional regulation in hematopoietic stem cells.

    Evidence Nuclear proteomics with Co-IP and silencing (IGF1R study); Kdm4a/b/c triple-KO mice with ChIP-seq, RNA-seq and Nom1 knockdown (HSC study)

    PMID:30639046 PMID:31434704

    Open questions at the time
    • Functional significance of the NOM1–IGF1R complex unclear
    • Whether HSC maintenance reflects ribosome biogenesis or another role not determined
  8. 2020 High

    Provided the mechanistic basis for the rRNA processing role: the MIF4G domain stimulates helicase catalysis and the C-terminus engages 18S rRNA helix H12 within the SSU processome.

    Evidence In vitro ATPase/helicase stimulation assay, co-purification of SSU processome factors, in vivo CRAC crosslinking, and domain truncation in yeast

    PMID:31994962

    Open questions at the time
    • Structural model of the Sgd1/NOM1–Fal1/eIF4AIII complex on rRNA lacking
    • Coordination between PP1-targeting and helicase-cofactor roles unaddressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NOM1's two activities — eIF4AIII helicase cofactor for 18S biogenesis and PP1 nucleolar targeting — are integrated within a single protein, and whether they are mechanistically coupled, remains unresolved.
  • No structure of full-length NOM1
  • Nucleolar PP1 dephosphorylation substrates unidentified
  • Whether PP1-targeting and helicase-cofactor functions act on the same biogenesis steps unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 2 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005730 nucleolus 2 GO:0005634 nucleus 1
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-8953854 Metabolism of RNA 2
Partners
EIF4A3FAL1IGF1RPLC1PPP1CA
Complex memberships
SSU processome

Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 NOM1 (nucleolar protein with MIF4G domain 1) was identified as containing one MIF4G domain and one MA3 domain, and was shown to interact with members of the eIF4A family of ATP-dependent DEAD-box RNA helicases. NOM1 localizes predominantly to the nucleolus, consistent with its yeast homolog Sgd1p. Protein domain analysis, co-immunoprecipitation/binding assay with eIF4A family members, subcellular localization imaging Gene Medium 15715967
2007 NOM1 was identified as a PP1-interacting protein via an RVXF motif required for PP1 binding. NOM1 targets PP1 (protein phosphatase I) to the nucleolus, acting as the first identified nucleolar targeting subunit for PP1 in eukaryotic cells. Both the RVXF motif and the NOM1 nucleolar localization sequence are required for this targeting activity. Co-immunoprecipitation, RVXF motif mutagenesis, subcellular localization (fluorescence microscopy), functional targeting assays The Journal of biological chemistry High 17965019
2011 Human NOM1 is the eIF4G-like interacting partner of eIF4AIII. Direct physical interaction between NOM1 and eIF4AIII was demonstrated in vitro and in vivo. This interaction is evolutionarily conserved (yeast Sgd1p–Fal1p). Knockdown of eIF4AIII and NOM1 in human cells revealed that this complex acts in pre-rRNA processing (18S rRNA biogenesis), distinct from the EJC role of eIF4AIII. Yeast genetic complementation (fal1Δ rescued by human eIF4AIII), in vitro binding assay, co-immunoprecipitation in human cells, siRNA knockdown with rRNA processing readout, structural comparison to eIF4A/eIF4G crystal structure Genes & development High 21576267
2014 In zebrafish, nom1 mutants exhibit defects in exocrine pancreas development due to impaired proliferation of ptf1a-expressing pancreatic progenitor cells. Loss of nom1 disrupts pre-rRNA processing and ribosome biogenesis in a p53-independent manner. Targeting PP1α into the nucleolus (by adding a nucleolar localization signal) partially rescued the pancreatic defect in nom1 morphants, demonstrating that nucleolar targeting of PP1α by Nom1 is functionally important for pancreatic proliferation. Forward genetic screen, positional cloning, RNA-seq, morpholino knockdown, rescue with PP1α + nucleolar localization signal, p53 loss-of-function epistasis PloS one High 24967912
2019 NOM1 was identified as a nuclear IGF1R-interacting protein by mass spectrometry-based proteomics. Co-immunoprecipitation confirmed a complex between nuclear IGF1R and NOM1. Inhibition of nuclear IGF1R translocation reduced NOM1 levels in the nuclear fraction; IGF1R overexpression enhanced NOM1 nuclear levels. NOM1 silencing led to increased IGF1R biosynthesis, indicating a bi-directional interplay. Mass spectrometry-based nuclear proteomics, co-immunoprecipitation, siRNA silencing, pharmacological inhibition of IGF1R nuclear translocation (dansylcadaverine), western blot quantification Molecular genetics and metabolism Medium 30639046
2019 Nom1 (mouse/yeast ortholog) is a downstream transcriptional target of KDM4 (H3K9/H3K36 demethylases). In Kdm4a/b/c triple-knockout hematopoietic stem cells, H3K9me3 accumulates at the Nom1 transcription start site, leading to downregulation of Nom1 expression. Nom1 was shown to be essential for maintenance of hematopoietic cells by knockdown experiments. Conditional triple-knockout mice (Kdm4a/b/c), ChIP-seq for H3K9me3, RNA-seq, knockdown of Nom1 with hematopoietic cell maintenance readout Blood Medium 31434704
2020 Yeast Sgd1 (ortholog of human NOM1) interacts directly with the RNA helicase Fal1 (ortholog of human eIF4AIII) via its MIF4G domain. The MIF4G domain of Sgd1 stimulates the ATPase/helicase catalytic activity of Fal1 in vitro. The Fal1–Sgd1 interaction is required for efficient pre-rRNA processing at sites A0, A1, and A2. Sgd1 co-purifies early SSU processome factors Lcp5 and Rok1. In vivo crosslinking (CRAC) showed Sgd1 binds helix H12 of 18S rRNA via its C-terminal region, which is essential for ribosome biogenesis function. In vitro ATPase/helicase stimulation assay, co-purification/pull-down, in vivo UV crosslinking (CRAC), domain mutagenesis/truncation, pre-rRNA processing analysis (Northern blot) RNA biology High 31994962
2000 Yeast Sgd1p (ortholog of human NOM1) is an essential nuclear protein. Overexpression of SGD1 partially suppresses osmosensitivity of pbs2Δ and hog1Δ mutants (HOG MAP kinase pathway), partially restoring GPD1 transcription and glycerol production. A GFP-tagged Sgd1p localizes to the cell nucleus. Gene deletion (lethality), multicopy suppressor assay, GFP localization, quantitative GPD1 expression analysis FEBS letters Medium 11042259
2002 Yeast Sgd1p (ortholog of human NOM1) physically interacts with phospholipase C (Plc1p), confirmed by two-hybrid screen and affinity chromatography. SGD1 shows genetic interactions with PLC1 and HOG1: overexpression of SGD1 suppresses plc1-4 temperature sensitivity; double mutant plc1Δ sgd1-1 shows enhanced sensitivity; triple mutant plc1Δ hog1Δ sgd1-1 is inviable. These data place Sgd1p at a convergence point of Plc1p- and Hog1p-dependent osmoregulatory pathways controlling GPD1 expression. Two-hybrid screen, affinity chromatography, genetic epistasis (double/triple mutants), growth assays under osmotic stress, GPD1 expression analysis Molecular genetics and genomics Medium 12073033
2016 NOM1 knockdown in mouse pancreatic beta cells (MIN6) increases cleaved caspase-3 levels, elevates Bax and reduces Bcl-2 expression, and inhibits cell proliferation. NOM1 silencing reduced insulin 2 mRNA expression. These data suggest NOM1 supports beta cell survival and insulin production, with apoptosis occurring via the Bax/Bcl-2/caspase-3 pathway. siRNA knockdown in MIN6 cells, western blot (caspase-3, Bcl-2, Bax), MTT proliferation assay, RT-qPCR (insulin 1/2 mRNA) Experimental and therapeutic medicine Low 27698723

Source papers

Stage 0 corpus · 40 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Fibronectin activates matrix metalloproteinase-9 secretion via the MEK1-MAPK and the PI3K-Akt pathways in ovarian cancer cells. Clinical & experimental metastasis 115 11467775
1997 Effects of interleukin-6 on in vitro cell attachment, migration and invasion of human ovarian carcinoma. Anticancer research 91 9066674
2006 High incidence of t(7;12)(q36;p13) in infant AML but not in infant ALL, with a dismal outcome and ectopic expression of HLXB9. Genes, chromosomes & cancer 68 16646086
1997 Fibronectin secretion from human peritoneal tissue induces Mr 92,000 type IV collagenase expression and invasion in ovarian cancer cell lines. Cancer research 64 9393769
1999 A physical and transcriptional map of the preaxial polydactyly locus on chromosome 7q36. Genomics 63 10329000
2019 The KDM4/JMJD2 histone demethylases are required for hematopoietic stem cell maintenance. Blood 59 31434704
2010 A rice gid1 suppressor mutant reveals that gibberellin is not always required for interaction between its receptor, GID1, and DELLA proteins. The Plant cell 56 21098733
2013 Pharmacokinetic comparisons of two different combinations of Shaoyao-Gancao Decoction in rats: competing mechanisms between paeoniflorin and glycyrrhetinic acid. Journal of ethnopharmacology 55 23867078
2001 Fusion of the homeobox gene HLXB9 and the ETV6 gene in infant acute myeloid leukemias with the t(7;12)(q36;p13). Cancer research 53 11454678
2011 Human eIF4AIII interacts with an eIF4G-like partner, NOM1, revealing an evolutionarily conserved function outside the exon junction complex. Genes & development 52 21576267
2023 An E2-E3 pair contributes to seed size control in grain crops. Nature communications 42 37248257
1992 A new nylon oligomer degradation gene (nylC) on plasmid pOAD2 from a Flavobacterium sp. Journal of bacteriology 41 1459943
2014 NCI-60 whole exome sequencing and pharmacological CellMiner analyses. PloS one 38 25032700
2007 A single C to T transition in intron 5 of LMBR1 gene is associated with triphalangeal thumb-polysyndactyly syndrome in a Chinese family. Biochemical and biophysical research communications 31 17300748
2009 High expression of N-acetylglucosaminyltransferase V in mucinous tumors of the ovary. Oncology reports 27 19787216
1997 Increased matrix metalloproteinase-9 activity in human ovarian cancer cells cultured with conditioned medium from human peritoneal tissue. Clinical & experimental metastasis 21 9344045
2014 Identification of genes important for cutaneous function revealed by a large scale reverse genetic screen in the mouse. PLoS genetics 20 25340873
2007 NOM1 targets protein phosphatase I to the nucleolus. The Journal of biological chemistry 20 17965019
2017 An investigation of obesity susceptibility genes in Northern Han Chinese by targeted resequencing. Medicine 19 28207535
2014 Nom1 mediates pancreas development by regulating ribosome biogenesis in zebrafish. PloS one 19 24967912
2017 SGD1, a key enzyme in tocopherol biosynthesis, is essential for plant development and cold tolerance in rice. Plant science : an international journal of experimental plant biology 18 28554480
2005 Identification of NOM1, a nucleolar, eIF4A binding protein encoded within the chromosome 7q36 breakpoint region targeted in cases of pediatric acute myeloid leukemia. Gene 18 15715967
2002 Phospholipase C interacts with Sgd1p and is required for expression of GPD1 and osmoresistance in Saccharomyces cerevisiae. Molecular genetics and genomics : MGG 18 12073033
2000 SGD1 encodes an essential nuclear protein of Saccharomyces cerevisiae that affects expression of the GPD1 gene for glycerol 3-phosphate dehydrogenase. FEBS letters 18 11042259
2008 Mutation analysis of a large Chinese pedigree with congenital preaxial polydactyly. European journal of human genetics : EJHG 16 19066618
2022 Effective treatment of a BRAF V600E-mutant epithelioid glioblastoma patient by vemurafenib: a case report. Anti-cancer drugs 14 34232949
2019 Identification of nucleolar protein NOM1 as a novel nuclear IGF1R-interacting protein. Molecular genetics and metabolism 10 30639046
2016 A 1.35 Mb DNA fragment is inserted into the DHMN1 locus on chromosome 7q34-q36.2. Human genetics 10 27487800
2024 Detection of polymorphisms in six genes and their association analysis with litter size in sheep. Animal biotechnology 8 38294691
2021 From FISH to Hi-C: The Chromatin Architecture of the Chromosomal Region 7q36.3, Frequently Rearranged in Leukemic Cells, Is Evolutionary Conserved. International journal of molecular sciences 8 33652823
2020 Sgd1 is an MIF4G domain-containing cofactor of the RNA helicase Fal1 and associates with the 5' domain of the 18S rRNA sequence. RNA biology 8 31994962
1998 The different stimulatory effect of normal tissues on the secretion of matrix metalloproteinases and their inhibitors by human ovarian cancer cells. Anticancer research 7 9891486
1988 Salivary enzyme polymorphisms (Set, Sgd and AMY1) in the Galician population. Human heredity 7 2454216
2008 Fusion of Epstein-Barr virus nuclear antigen-1-derived glycine-alanine repeat to trans-dominant HIV-1 Gag increases inhibitory activities and survival of transduced cells in vivo. Human gene therapy 5 18533892
2024 Characterization of Pediatric Acute Myeloid Leukemia With t(7;12)(q36;p13). Genes, chromosomes & cancer 2 39508359
2016 Role of nucleolar protein NOM1 in pancreatic islet β cell apoptosis in diabetes. Experimental and therapeutic medicine 2 27698723
2010 Comparative genomic analysis of the false killer whale (Pseudorca crassidens) LMBR1 locus. Genome 2 20924415
2025 Genotype-phenotype correlations in specific granule deficiency: loss of DNA-binding ability and impaired nuclear localization cause severe manifestations due to the c.655_665del CEBPE variant. Clinical and experimental immunology 1 40581342
2024 Development and Validation of Diagnostic Models for Transcriptomic Signature Genes for Multiple Tissues in Osteoarthritis. Journal of inflammation research 1 39099665
2026 Reshaping the stress-growth balance in Saccharomyces cerevisiae through heavy ion beam irradiation and adaptive evolution to achieve high-efficiency osmotolerance: Phenotypic and mechanistic perspectives. Fungal biology 0 42191246

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