Affinage

RNF112

RING finger protein 112 · UniProt Q9ULX5

Length
631 aa
Mass
68.3 kDa
Annotated
2026-06-10
41 papers in source corpus 14 papers cited in narrative 14 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

RNF112 (ZNF179/BFP) is a brain-enriched RING-domain E3 ubiquitin ligase that drives neuronal differentiation and acts as a tumor suppressor by directing substrates to proteasomal degradation (PMID:30404641, PMID:37288663, PMID:40178292). Crystallographic analysis defines RNF112 as a dynamin-like large GTPase whose GTPase domain (GD) and three-helical middle domain (MD) adopt a self-restrained monomeric conformation in the apo state; at the GTP hydrolysis transition state the MD is released to form an intertwined homodimer, and ER-targeted chimeras reveal latent membrane-remodeling capacity (PMID:40198702). As an E3 ligase, RNF112 autoubiquitinates and uses its catalytic RING cysteine (C97) to assemble K48-linked polyubiquitin chains on its targets: it polyubiquitinates TDP-43 to accelerate turnover and prevent insoluble cytosolic inclusions in brain (PMID:30404641), and degrades the oncogenic transcription factors FOXM1 and c-Myc as well as NAA40, thereby suppressing proliferation, invasion, and lipid synthesis across gastric, bladder, cervical, and colorectal cancers (PMID:37288663, PMID:40178292, PMID:39757327, PMID:42180965). In neural development, RNF112 promotes cell-cycle exit required for differentiation, acting through p35/p27 in embryonal carcinoma and cerebellar granule cells and through p53/p21/p27 in glioblastoma cells (PMID:21566658, PMID:28684796). RNF112 expression is transcriptionally induced by Purα and KLF4 (PMID:33333713, PMID:39757327), and its activity is tuned post-translationally by oxidative-stress-induced dissociation from an HDAC1/HDAC6 complex, leading to hyperacetylation and Sp1-dependent antioxidant gene expression (PMID:30121389).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1997 Low

    Established RNF112 as a brain-predominant RING finger protein whose expression is induced during neural differentiation, framing it as a candidate regulator of neural cell fate.

    Evidence Northern/Western blot tissue profiling and retinoic acid-induced P19 differentiation

    PMID:9367872

    Open questions at the time
    • Expression correlation only, no direct functional mechanism established
    • Did not test E3 ligase activity
    • No substrate identified
  2. 1998 Low

    Determined RNF112 subcellular distribution as predominantly nuclear with cytoplasmic presence in brain, providing baseline localization for later functional work.

    Evidence Immunohistochemistry and in situ hybridization in mouse brain and primary neonatal cultures

    PMID:9806830

    Open questions at the time
    • Static localization without functional consequence
    • Did not resolve what governs nuclear vs cytoplasmic partitioning
  3. 2011 Medium

    Showed RNF112 is required for neuronal differentiation by enforcing G0/G1 cell-cycle exit, mechanistically linking it to the p35/p27 axis.

    Evidence RNAi knockdown with cell-cycle/BrdU analysis and p35/p27 Western blot in P19 and cerebellar granule cells

    PMID:21566658

    Open questions at the time
    • Did not establish whether RNF112 acts on p35/p27 enzymatically or transcriptionally
    • Single lab
  4. 2013 Medium

    Identified PLZF as an RNF112 partner that drives its cytoplasm-to-nucleus relocalization, beginning to define RNF112's protein-interaction landscape.

    Evidence Yeast two-hybrid, Co-IP, domain mapping, and fluorescence localization

    PMID:24359566

    Open questions at the time
    • Did not test whether PLZF is a ubiquitination substrate
    • Functional consequence of relocalization unresolved
  5. 2017 Medium

    Extended the differentiation/cell-cycle-exit role to glioblastoma via a distinct p53/p21/p27 readout, suggesting tumor-suppressive differentiation activity.

    Evidence RNF112 overexpression in primary GBM cells with cell-cycle and p53/p21/p27/GFAP analysis

    PMID:28684796

    Open questions at the time
    • Did not connect cell-cycle effects to direct ubiquitination targets
    • Overexpression only
  6. 2018 High

    Defined RNF112 as a bona fide E3 ligase that ubiquitinates TDP-43 to suppress aggregation in vivo, establishing its mechanistic role in proteostasis and neurodegeneration.

    Evidence In vitro/in vivo ubiquitination assays, Co-IP/MS substrate identification, and Znf179 knockout mouse with biochemical fractionation

    PMID:30404641

    Open questions at the time
    • Did not map the ubiquitinated lysines on TDP-43
    • Relationship between proteasome modulation and direct substrate ubiquitination not fully resolved
  7. 2018 Medium

    Revealed post-translational control of RNF112 by oxidative-stress-regulated acetylation, coupling redox state to an antioxidant transcriptional response via Sp1.

    Evidence Acetyl-lysine IP, reciprocal Co-IP with HDAC1/HDAC6, SAHA treatment, and antioxidant reporter assays

    PMID:30121389

    Open questions at the time
    • Did not link acetylation state to E3 ligase activity
    • Single lab
  8. 2018 Medium

    Showed RNF112 suppresses TLR-4/NF-κB inflammatory signaling in brain injury, broadening its protective role beyond proteostasis.

    Evidence Rnf112 knockout mouse intracerebral hemorrhage model with NF-κB pathway Western blots and overexpression rescue

    PMID:30454900

    Open questions at the time
    • Mechanistic link between RNF112 and TLR-4/NF-κB components not defined (no direct substrate)
    • Single lab
  9. 2020 Medium

    Identified Purα as a direct transcriptional activator of RNF112 during neuronal differentiation, defining an upstream input to its expression.

    Evidence DNA affinity precipitation assay for promoter binding and Purα overexpression in differentiating P19 cells

    PMID:33333713

    Open questions at the time
    • Did not establish chromatin occupancy in vivo
    • Single lab
  10. 2023 High

    Demonstrated RNF112 directly ubiquitinates FOXM1 to inhibit gastric cancer proliferation/invasion, establishing it as a druggable tumor suppressor (via RCM-1).

    Evidence siRNA E3 ligase screen, Co-IP, in vitro/in vivo ubiquitination, and xenograft model

    PMID:37288663

    Open questions at the time
    • Did not map ubiquitinated FOXM1 lysines or linkage type
    • RCM-1 mechanism of interaction enhancement not structurally resolved
  11. 2025 High

    Provided high-resolution mechanism for c-Myc degradation, mapping the N-terminal zinc finger interaction with MB II, catalytic C97, and K48-linked ubiquitination of K389.

    Evidence Co-IP, domain/active-site (C97) and substrate-lysine (K389) mutagenesis, linkage analysis, and xenograft rescue in bladder cancer

    PMID:40178292

    Open questions at the time
    • Did not address whether the same residues mediate other substrate interactions
    • Did not connect to the GTPase activity
  12. 2025 High

    Resolved the structural basis of RNF112 as a self-restrained dynamin-like GTPase that dimerizes upon hydrolysis and has latent membrane-remodeling capacity.

    Evidence Crystal structures at multiple nucleotide states plus ER-targeted chimera membrane-remodeling assays

    PMID:40198702

    Open questions at the time
    • Native membrane substrate/physiological membrane target unknown
    • Relationship between GTPase cycle and E3 ligase activity unresolved
  13. 2025 Medium

    Placed RNF112 in a KLF4→RNF112⊣NAA40 axis in colorectal cancer, identifying both an upstream activator and a new degradation substrate.

    Evidence Co-IP, ubiquitination assay, KLF4 promoter-binding assay, and NAA40 rescue in CRC cells and xenografts

    PMID:39757327

    Open questions at the time
    • NAA40 ubiquitination lysines and linkage not mapped
    • Single lab
  14. 2026 Medium

    Extended FOXM1 degradation to cervical cancer with an immunological consequence, linking RNF112 to protection of T lymphocytes from ferroptosis in the tumor microenvironment.

    Evidence shRNA/overexpression, xenograft, cancer-T cell co-culture, ubiquitination assay, and Foxm1 inhibition rescue

    PMID:42180965

    Open questions at the time
    • Direct vs indirect effect on T-cell ferroptosis not fully separated
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the dynamin-like GTPase cycle and membrane-remodeling capacity integrate with the E3 ligase activity, and whether they operate in the same physiological pathway, remains unresolved.
  • No physiological membrane substrate identified
  • Coupling between nucleotide-dependent dimerization and substrate ubiquitination unknown
  • Unified model linking neuronal, tumor-suppressive, and membrane functions absent

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0016874 ligase activity 3 GO:0003924 GTPase activity 1
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-1643685 Disease 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-1266738 Developmental Biology 2
Partners
FOXM1HDAC1HDAC6MYCNAA40PLZFSP1TDP-43

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2025 RNF112 (ZNF179) is a dynamin-like large GTPase with a crystal structure revealing a GTPase domain (GD) and three-helical middle domain (MD). In the nucleotide-free (apo) state, monomeric RNF112 adopts a self-restraint conformation where the proximal end of the MD docks to a groove in the GD. At the GTP hydrolysis transition state, the MD is released and the protein forms an intertwined homodimer. Engineered RNF112 fused with C-terminal elements of ATL1 or yeast Sac1p transmembrane domains relocates to the endoplasmic reticulum and mediates membrane remodeling, demonstrating latent membrane-remodeling capacity. Crystal structure determination at different nucleotide-loading states; engineered chimeric constructs with ER-targeting domains; functional membrane remodeling assay Proceedings of the National Academy of Sciences of the United States of America High 40198702
2018 RNF112 (Znf179) functions as a RING-domain E3 ubiquitin ligase that autoubiquitinates, regulates 26S proteasome activity by modulating 19S/20S proteasome subunit protein levels, directly interacts with TDP-43, and mediates polyubiquitination of TDP-43 both in vitro and in vivo, accelerating TDP-43 turnover and reducing insoluble TDP-43 aggregates. Knockout of Znf179 in mouse brain results in accumulation of insoluble TDP-43 and cytosolic TDP-43 inclusions in cortex, hippocampus, and midbrain. In vitro and in vivo ubiquitination assay; co-immunoprecipitation followed by mass spectrometry to identify TDP-43 as substrate; Znf179 knockout mouse model with biochemical fractionation Journal of biomedical science High 30404641
2023 RNF112 directly ubiquitinates FOXM1 in gastric cancer cells, leading to decreased FOXM1 protein levels and suppressed FOXM1 transcriptional network, thereby inhibiting gastric cancer cell proliferation and invasion. The small-molecule compound RCM-1 enhances the RNF112–FOXM1 interaction and promotes FOXM1 ubiquitination. siRNA E3 ligase library screen; co-immunoprecipitation; in vitro/in vivo ubiquitination assay; RNF112 knockdown/overexpression with proliferation and invasion readouts; xenograft mouse model JCI insight High 37288663
2025 RNF112 directly interacts with the MB II domain of c-Myc through its N-terminal zinc finger motif, and its catalytic site C97 facilitates K48-linked polyubiquitination of K389 on c-Myc, targeting c-Myc for proteasomal degradation and thereby suppressing proliferation, migration, and lipid synthesis (via ACLY) in bladder cancer cells. Co-immunoprecipitation; domain-mapping experiments; ubiquitination assay with catalytic-site (C97) mutant; K389 mutation on c-Myc; rescue with c-Myc or ACLY re-expression; in vivo xenograft model Advanced science (Weinheim, Baden-Wurttemberg, Germany) High 40178292
2025 RNF112 promotes ubiquitination and degradation of NAA40 through its E3 ubiquitin ligase activity in colorectal cancer. KLF4 acts as an upstream transcriptional regulator of RNF112 by binding its promoter. Overexpression of NAA40 reverses the anti-tumor effects of RNF112 overexpression, placing RNF112 upstream of NAA40 in CRC. RNF112 overexpression/knockdown in CRC cells and xenograft; co-immunoprecipitation; ubiquitination assay; chromatin-based KLF4 promoter binding assay; NAA40 rescue experiment Cell biology and toxicology Medium 39757327
2026 RNF112 promotes ubiquitination and degradation of FOXM1 (Foxm1) in cervical cancer, reducing tumor proliferation and alleviating immunosuppression in the tumor microenvironment by protecting T lymphocytes from oxidative stress-induced mitochondrial dysfunction and ferroptosis. RNF112 knockdown (shRNA) and overexpression; xenograft mouse model; co-culture system of cancer cells with T lymphocytes; ubiquitination assay; Foxm1 inhibition rescue experiment Translational cancer research Medium 42180965
2018 Znf179 (RNF112) is acetylated on specific lysine residues; oxidative stress induces dissociation of a Znf179–HDAC1/HDAC6 complex, increasing Znf179 acetylation. Hyperacetylated Znf179 forms a transcriptional complex with Sp1 and promotes antioxidant gene expression. HDAC inhibition by SAHA further increases Znf179 acetylation and enhances this protective response. Immunoprecipitation with acetyl-lysine antibodies; co-immunoprecipitation of Znf179 with HDAC1/HDAC6; SAHA treatment; bioinformatics sequence alignment; reporter assays for antioxidant gene expression Redox biology Medium 30121389
2013 Znf179 (RNF112) interacts with PLZF (promyelocytic leukemia zinc finger protein); the first two zinc fingers of PLZF are critical for this interaction. Co-expression of PLZF causes Znf179 to relocalize from cytoplasm to nucleus. Znf179 also increases PLZF protein abundance. Yeast two-hybrid screen; co-immunoprecipitation; domain-deletion mapping; fluorescence microscopy for subcellular localization; Western blot for protein expression Journal of biomedical science Medium 24359566
2011 Znf179 (RNF112) is required for neuronal differentiation of P19 embryonal carcinoma cells and cerebellar granule cells. Znf179 knockdown reduces G0/G1 cell-cycle arrest, increases BrdU incorporation, and decreases levels of p35 (neuronal Cdk5 activator) and p27 (CDK inhibitor), linking Znf179 to cell cycle exit as a prerequisite for neuronal differentiation. RNA interference knockdown; flow cytometry for cell cycle analysis; BrdU incorporation assay; microarray gene expression profiling; Western blot for p35 and p27; primary cerebellar granule cell culture Cell death and differentiation Medium 21566658
2017 Znf179 (RNF112) overexpression induces differentiation of primary glioblastoma multiforme cells, accompanied by elevated GFAP expression and upregulation of p53, p21, and p27, causing G0/G1 cell-cycle arrest. Znf179 overexpression in primary GBM cells; flow cytometry for cell cycle; Western blot for p53, p21, p27, GFAP; immunostaining Scientific reports Medium 28684796
2018 Rnf112 knockout in mice exacerbates brain injury after intracerebral hemorrhage, associated with upregulation of TLR-4, MyD88, and phosphorylation of IKKα, IκBα, and NF-κB, indicating that Rnf112 suppresses the TLR-4/NF-κB inflammatory pathway. Conversely, Rnf112 overexpression attenuates ICH-induced brain injury by inhibiting this pathway. Rnf112 knockout mouse model with ICH induction; brain water content and neurological deficit scoring; Western blot for TLR-4/NF-κB pathway components; cytokine measurement; Rnf112 overexpression in LPS-stimulated glial cells Biochemical and biophysical research communications Medium 30454900
2020 Purα binds directly to the Znf179 (RNF112) promoter and is required for Znf179 transcriptional induction during neuronal differentiation. Overexpression of Purα increases Znf179 expression in neuronal-differentiated P19 cells, and concurrent expression of Purα and Znf179 occurs during neuronal differentiation. DAPA (DNA affinity precipitation assay) for direct Purα–Znf179 promoter binding; Purα overexpression with Znf179 expression readout; co-expression analysis during P19 differentiation Biochemical and biophysical research communications Medium 33333713
1997 BFP (brain finger protein, RNF112/ZNF179) is a novel RING finger protein predominantly expressed in the brain and induced during retinoic acid-mediated neural differentiation of P19 embryonal carcinoma cells, indicating a role in neural cell regulation. Northern blot for tissue expression; Western blot with anti-BFP antibody; retinoic acid-induced P19 differentiation model Biochemical and biophysical research communications Low 9367872
1998 Mouse Bfp (RNF112) protein is detected predominantly in the nucleus, with some cytoplasmic localization, in primary neonatal brain cultures containing both neurons and glial cells, as determined by immunohistochemistry. Immunohistochemistry and in situ hybridization in mouse brain sections and primary neonatal brain cultures Genomics Low 9806830

Source papers

Stage 0 corpus · 41 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Enteropathogenic Escherichia coli (EPEC) adhesion to intestinal epithelial cells: role of bundle-forming pili (BFP), EspA filaments and intimin. Microbiology (Reading, England) 153 14993302
2000 Effects of bfp mutations on biogenesis of functional enteropathogenic Escherichia coli type IV pili. Journal of bacteriology 53 10762251
2018 Znf179 E3 ligase-mediated TDP-43 polyubiquitination is involved in TDP-43- ubiquitinated inclusions (UBI) (+)-related neurodegenerative pathology. Journal of biomedical science 42 30404641
2012 The novel phloroglucinol derivative BFP induces apoptosis of glioma cancer through reactive oxygen species and endoplasmic reticulum stress pathways. Phytomedicine : international journal of phytotherapy and phytopharmacology 39 22819448
2003 Identification of the DNA binding sites of PerA, the transcriptional activator of the bfp and per operons in enteropathogenic Escherichia coli. Journal of bacteriology 36 12700263
2011 A novel RING finger protein, Znf179, modulates cell cycle exit and neuronal differentiation of P19 embryonal carcinoma cells. Cell death and differentiation 30 21566658
2005 The ATPase activity of BfpD is greatly enhanced by zinc and allosteric interactions with other Bfp proteins. The Journal of biological chemistry 28 15866879
1999 Lack of expression of bundle-forming pili in some clinical isolates of enteropathogenic Escherichia coli (EPEC) is due to a conserved large deletion in the bfp operon. FEMS microbiology letters 25 10481102
2023 RNF112-mediated FOXM1 ubiquitination suppresses the proliferation and invasion of gastric cancer. JCI insight 24 37288663
2013 Analysis of the interaction between Zinc finger protein 179 (Znf179) and promyelocytic leukemia zinc finger (Plzf). Journal of biomedical science 24 24359566
2018 Rnf112 deletion protects brain against intracerebral hemorrhage (ICH) in mice by inhibiting TLR-4/NF-κB pathway. Biochemical and biophysical research communications 21 30454900
2018 Upregulation of Znf179 acetylation by SAHA protects cells against oxidative stress. Redox biology 19 30121389
2020 RNA editing of BFP, a point mutant of GFP, using artificial APOBEC1 deaminase to restore the genetic code. Scientific reports 18 33057101
2017 Aspirin enhances the osteogenic and anti-inflammatory effects of human mesenchymal stem cells on osteogenic BFP-1 peptide-decorated substrates. Journal of materials chemistry. B 15 32263906
1998 Molecular cloning, localization, and developmental expression of mouse brain finger protein (Bfp)/ZNF179: distribution of bfp mRNA partially coincides with the affected areas of Smith-Magenis syndrome. Genomics 15 9806830
2002 Limited utility of blue fluorescent protein (BFP) in monitoring plant virus movement. Biochimie 14 12504279
1998 Cloning, genomic structure, and expression of mouse ring finger protein gene Znf179. Genomics 14 9615224
1997 The brain finger protein gene (ZNF179), a member of the RING finger family, maps within the Smith-Magenis syndrome region at 17p11.2. American journal of medical genetics 12 9096764
1999 Dual detection of peptides in a fluorescence binding assay by employing genetically fused GFP and BFP mutants. Analytical chemistry 11 10517149
1997 A novel RING finger protein, BFP, predominantly expressed in the brain. Biochemical and biophysical research communications 11 9367872
1996 Chromosome mapping of human (ZNF179), mouse, and rat genes for brain finger protein (bfp), a member of the RING finger family. Genomics 11 8660987
2021 The transcriptional activator of the bfp operon in EPEC (PerA) interacts with the RNA polymerase alpha subunit. Scientific reports 10 33879812
1999 cDNA cloning of a human brain finger protein, BFP/ZNF179, a member of the RING finger protein family. DNA research : an international journal for rapid publication of reports on genes and genomes 10 10574464
2017 Znf179 induces differentiation and growth arrest of human primary glioblastoma multiforme in a p53-dependent cell cycle pathway. Scientific reports 9 28684796
1996 A new adherent form of an attaching and effacing Escherichia coli (eaeA+, bfp-) to the intestinal epithelial cells of chicks. The Journal of veterinary medical science 9 8959668
2023 Biomembrane force probe (BFP): Design, advancements, and recent applications to live-cell mechanobiology. Exploration (Beijing, China) 7 37933233
2005 Recombination of the GFP gene to the BFP gene using a man-made site-selective DNA cutter. Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry 6 16341899
2025 RNF112 Facilitates Ubiquitin-Mediated Degradation of c-Myc, Suppressing Proliferation, Migration and Lipid Synthesis in Bladder Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 5 40178292
2025 RNF112, whose transcription is regulated by KLF4, inhibits colorectal cancer growth via promoting ubiquitin-dependent degradation of NAA40. Cell biology and toxicology 4 39757327
2021 Efficient generation of a single-copy eft-3p::TIR1::F2A:: BFP::AID*::NLS allele in the C. elegans ttTi5605 insertion site through recombination-mediated cassette exchange. microPublication biology 4 34355140
2020 Purα regulates the induction of Znf179 transcription during neuronal differentiation. Biochemical and biophysical research communications 3 33333713
1990 [The clinical usefulness of urinary basic fetoprotein (BFP) in patients with urological malignancies]. Nihon Hinyokika Gakkai zasshi. The japanese journal of urology 3 1698231
2025 Graphene Oxide Functionalized GelMA Platform Loaded With BFP-1 for Osteogenic Differentiation of BMSCs. Journal of biomedical materials research. Part A 1 39610336
2025 The novel CD16A/anti-CD3 bifunctional protein, eCD16A/anti-CD3-BFP, redirects T cell cytotoxicity toward antibody-bound target cells. Human vaccines & immunotherapeutics 1 39763374
2017 THE STRUCTURE OF THE INTESTINAL MICROBIOTA AND THE FREQUENCY OF DETECTION OF PATHOGENICITY GENES (STXI, STX2, BFP) IN ESCHERICHIA COLI WITH NORMAL ENZYMATIC ACTIVITY ISOLATED FROM CHILDREN DURING THE FIRST YEAR OF LIFE. Molekuliarnaia genetika, mikrobiologiia i virusologiia 1 30561943
1988 [Clinical evaluation on an enzyme immunoassay kit for basic fetoprotein (BFP). (1) Clinical usefulness of BFP]. Gan to kagaku ryoho. Cancer & chemotherapy 1 2456039
2026 RNF112 mediates immunosuppression to inhibit the proliferation of cervical cancer by Foxm1. Translational cancer research 0 42180965
2025 Structural and functional characterization of the brain-specific dynamin superfamily member RNF112. Proceedings of the National Academy of Sciences of the United States of America 0 40198702
2018 Author Correction: Znf179 induces differentiation and growth arrest of human primary glioblastoma multiforme in a p53-dependent cell cycle pathway. Scientific reports 0 30177766
1986 [Basic fetoprotein (BFP)]. Gan to kagaku ryoho. Cancer & chemotherapy 0 2425742
1985 [Clinical investigation of basic fetoprotein (BFP) and carcinoembryonic antigen (CEA) in stomach cancer and lung cancer]. Gan no rinsho. Japan journal of cancer clinics 0 2411961

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