PROSITE documentation PDOC51803
Zinc finger C2HC RNF-type profile


Ubiquitination is a posttranslational modification that mediates the covalent attachment of ubiquitin (Ub), a small, highly conserved, cytoplasmic protein of 76 amino acid residues, to target proteins. This conjugation is catalyzed by the sequential action of three enzymes: Ub-activating (E1) enzyme, Ub-conjugating (E2) enzyme and Ub ligase (E3). A large number of RING finger (RNF) (see <PDOC00449>) proteins are present in eukaryotic cells and the majority of them are believed to act as E3 ubiquitin ligases. The closely related proteins RNF125/TRAC-1, RNF114 (also known as Zpf313), RNF138 (or NARF) and RNF166 contain, apart from the RING domain, a C2HC (Cys2-His-Cys)- and two C2H2 (Cys2-His2)-type zinc fingers, as well as an ubiquitin interacting motif (UIM) (see <PDOC50330>) [1,2,3,4].

Some proteins known to contain a C2HC RNF-type zinc finger are listed below:

  • Mammalian RNF125/T-cell RING protein in activation 1 (TRAC-1)/, a positive regulator of T-cell activation. It negatively regulates RIG-1 mediated antiviral activity via conjugating ubiquitin chains to RIG-1 and MDA5, leading to their degradation by the proteasome.
  • Vertebrate RNF114, acts as negative regulator of NF-kappaB-dependent transcription. It interacts with A20 in T cells and modulates A20 ubiquitylation.
  • Vertebrate RNF138, likely involved in regulating homologous recombination repair pathway.
  • Vertebrate RNF166, potentiates the RNA virus-induced production of IFN- β via enhancing the ubiquitination of TRAF3 and TRAF6.

The profile we developed covers the entire C2HC RNF-type zinc finger.

Last update:

June 2016 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

ZF_C2HC_RNF, PS51803; Zinc finger C2HC RNF-type profile  (MATRIX)


1AuthorsGiannini A.L. Gao Y. Bijlmakers M.-J.
TitleT-cell regulator RNF125/TRAC-1 belongs to a novel family of ubiquitin ligases with zinc fingers and a ubiquitin-binding domain.
SourceBiochem. J. 410:101-111(2008).
PubMed ID17990982

2AuthorsRodriguez M.S. Egana I. Lopitz-Otsoa F. Aillet F. Lopez-Mato M.P. Dorronsoro A. Lobato-Gil S. Sutherland J.D. Barrio R. Trigueros C. Lang V.
TitleThe RING ubiquitin E3 RNF114 interacts with A20 and modulates NF-kappaB activity and T-cell activation.
SourceCell Death Dis. 5:E1399-E1399(2014).
PubMed ID25165885

3AuthorsHan D. Liang J. Lu Y. Xu L. Miao S. Lu L.-Y. Song W. Wang L.
TitleUbiquitylation of Rad51d Mediated by E3 Ligase Rnf138 Promotes the Homologous Recombination Repair Pathway.
SourcePLoS ONE 11:E0155476-E0155476(2016).
PubMed ID27195665

4AuthorsChen H.W. Yang Y.K. Xu H. Yang W.W. Zhai Z.H. Chen D.Y.
TitleRing finger protein 166 potentiates RNA virus-induced interferon-beta production via enhancing the ubiquitination of TRAF3 and TRAF6.
SourceSci. Rep. 5:14770-14770(2015).
PubMed ID26456228

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