RNF111 Antibody

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Description

Introduction to RNF111 Antibody

The RNF111 antibody is an affinity-purified polyclonal antibody generated in rabbits, targeting the human RNF111 protein. It is widely used in techniques like immunohistochemistry (IHC) and immunofluorescence (IF) to visualize RNF111's expression and localization in tissues and cells . RNF111 itself is an E3 ubiquitin-protein ligase involved in critical pathways, including transforming growth factor-beta (TGF-β) signaling and antiviral responses .

DNA Repair and Ubiquitination

RNF111 facilitates nucleotide excision repair (NER) by promoting ubiquitination of SUMOylated substrates, such as XPC, a DNA damage recognition factor. Depletion of RNF111 impairs UV-induced XPC ubiquitylation, highlighting its role in DNA damage response .

Antiviral Immune Response

RNF111 enhances the cGAS-STING (cyclic GMP-AMP synthase–stimulator of interferon genes) pathway by mediating neddylation of cGAS. This modification strengthens cGAS dimerization and DNA-binding capacity, critical for antiviral defense. Studies in Rnf111-deficient mice showed reduced interferon production and increased susceptibility to herpes simplex virus 1 (HSV-1) .

TGF-β Signaling Modulation

RNF111 interacts with SMAD proteins (e.g., SMAD3 and SMAD7) to regulate TGF-β signaling, influencing processes like embryonic development and cancer progression .

Technical Data and Validation

  • Specificity: Recognizes unmodified RNF111 protein in human tissues .

  • Immunohistochemistry: Staining patterns consistent with nuclear localization in multiple tissue types (per Human Protein Atlas) .

  • Protein Array Testing: Validated against 364 human recombinant protein fragments to ensure minimal cross-reactivity .

Product Specs

Buffer
Liquid in PBS containing 50% glycerol, 0.5% BSA, and 0.02% sodium azide.
Form
Liquid
Lead Time
We typically dispatch orders within 1-3 business days of receipt. Delivery time may vary depending on the shipping method and destination. Please consult your local distributor for specific delivery details.
Synonyms
RNF111 antibody; E3 ubiquitin-protein ligase Arkadia antibody; EC 2.3.2.27 antibody; RING finger protein 111 antibody; hRNF111 antibody; RING-type E3 ubiquitin transferase Arkadia antibody
Target Names
RNF111
Uniprot No.

Target Background

Function
RNF111 is an E3 ubiquitin-protein ligase essential for mesoderm patterning during embryonic development. It serves as an enhancer of the transcriptional responses of SMAD2/SMAD3 effectors, activated downstream of BMP. RNF111 mediates ubiquitination and degradation of SMAD inhibitors like SMAD7, promoting their proteasomal degradation and enhancing the transcriptional activity of TGF-beta and BMP. Beyond enhancing the transcription of SMAD2/SMAD3 effectors, RNF111 also regulates their turnover by mediating ubiquitination and subsequent degradation, coupling their activation with degradation to ensure only active effectors are degraded. It activates SMAD3/SMAD4-dependent transcription by triggering signal-induced degradation of the SNON isoform of SKIL. RNF111 associates with UBE2D2 as an E2 enzyme. It specifically binds polysumoylated chains via SUMO interaction motifs (SIMs) and mediates ubiquitination of sumoylated substrates. RNF111 catalyzes 'Lys-63'-linked ubiquitination of sumoylated XPC in response to UV irradiation, promoting nucleotide excision repair. It mediates ubiquitination and degradation of sumoylated PML. Notably, the regulation of BMP-SMAD signaling is independent of sumoylation and does not rely on SUMO interaction motifs (SIMs).
Gene References Into Functions
  1. RNF111 may play a role in regulating the pathogenesis and progression of hepatic fibrosis. PMID: 29286088
  2. Arkadia/RNF111 can lys-48 ubiquitinate Nrf2, protecting it from degradation and enabling Nrf2-dependent gene transcription. PMID: 29597191
  3. Research indicates a tumor-suppressive role of the ring finger protein 111 (Arkadia)-epithelial splicing regulatory protein 2 (ESRP2) axis in clear-cell renal cell carcinoma (ccRCC). PMID: 26522722
  4. These data show that the position occupied by W972 within wild-type Arkadia is critical for the function of its RING domain and is dependent on the nature of the residue at this position. PMID: 28647409
  5. Results suggest that -459CpG methylation in the Sp1-binding site of the RNF111 promoter transcriptionally decreases RNF111 expression, which inhibits TGF-beta/Smad signaling associated invasion in NSCLC cells. PMID: 26238425
  6. A study reports that the monomeric RING domains from the human E3 ligases Arkadia and Ark2C bind directly to free ubiquitin with an affinity comparable to that of other dedicated ubiquitin-binding domains. PMID: 26656854
  7. These data suggest that RNF111, together with the CRL4(DDB2) ubiquitin ligase complex, is responsible for sequential XPC ubiquitylation, which regulates the recruitment and release of XPC and is crucial for efficient progression of the NER reaction. PMID: 26151477
  8. Arkadia can both promote and inhibit gene expression, indicating that its activity in transcriptional control may depend on the epigenetic context, defined by Polycomb repressive complexes and DNA methylation. PMID: 24912682
  9. Our findings establish RNF111 as a new STUbL that directly links nonproteolytic ubiquitylation and SUMOylation in the DNA damage response. PMID: 23751493
  10. Findings indicate that Arkadia is not critical for regulating tumor growth per se, but is required for the early stages of cancer cell colonization at the sites of metastasis PMID: 23467611
  11. Arkadia is involved in arsenic-induced degradation of polysumoylated PML protein. PMID: 23530056
  12. RNF111-dependent neddylation activates DNA damage-induced ubiquitination PMID: 23394999
  13. FHL2 increases the stability of the TGF-beta pathway positive regulator Arkadia by inhibiting its ubiquitination and cooperates with Arkadia to activate TGF-beta signaling. PMID: 23212909
  14. We established that ARX polyA alterations damage the regulation of KDM5C expression. PMID: 23246292
  15. Determined the nuclear magnetic resonance solution structure of Arkadia's RING-H2 domain and revealed a (beta)betabetaalpha fold, fully consistent with the expected "cross-brace" mode of Zn(II)-ligation. PMID: 22411132
  16. Arkadia enhances transforming growth factor-beta signaling responses and supports its tumor-suppressing properties in colorectal cancer. PMID: 21998011
  17. RB1CC1 thus appears to play a unique role as a modulator of TGF-beta signaling by restricting substrate specificity of Arkadia. PMID: 21795712
  18. Arkadia complexes with clathrin adaptor AP2 and regulates EGF signalling. PMID: 20965945
  19. Findings show that Arkadia regulates the levels of expression of c-Ski protein in cell-type-dependent fashion, and exhibits a tumor suppressor function by inhibiting tumor cell growth PMID: 19959502
  20. Arkadia protein intensifies TGF-beta-induced effects by marking c-Ski and inhibitory Smad7 for destruction--REVIEW PMID: 19898560
  21. Silencing of the Arkadia gene resulted in repression of transcriptional activities induced by TGF-beta and BMP, and accumulation of the Smad7 protein. PMID: 14657019
  22. Arkadia induces degradation of SnoN and c-Ski in addition to Smad7. PMID: 17510063
  23. Results show that Arkadia specifically activates transcription via Smad3/Smad4 binding sites by inducing degradation of the transcriptional repressor SnoN. PMID: 17591695
  24. Arkadia stimulates renal tubular epithelial to mesenchymal cell transition through degradation of Smad7. PMID: 18059455
  25. Functional analysis of the mouse counterpart PMID: 11298452

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Database Links

HGNC: 17384

OMIM: 605840

KEGG: hsa:54778

STRING: 9606.ENSP00000288199

UniGene: Hs.404423

Protein Families
Arkadia family
Subcellular Location
Nucleus. Cytoplasm. Nucleus, PML body.
Tissue Specificity
Broadly expressed.

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