PROSITE documentation PDOC51999
Zinc finger GRF-type profile


Glycine-arginine-phenylalanine (GRF)-type zinc fingers (GRF-ZFs) are 45- to 50-residue domains with a conserved GRxF motif. GRF-ZFs are widely distributed throughout Eukarya in proteins that are involved in DNA damage response (DDR), transcriptional regulation, and RNA metabolism. GRF-ZFs are nucleic acid interaction modules and in several cases these motifs have been shown to enhance enzymatic activity [1,2,3,4].

The GRF-ZF comprises a three-stranded anti-parallel β-sheet (β1-β3) that folds into a crescent-shaped claw-like structure (see <PDB:5U6Z>). A single bound Zn(2+) ion plays a central structural role in this domain, and is coordinated with tetrahedral geometry by a "CHCC" sequence motif. The identity of these Zn(2+) ligands is conserved for the majority of GRF-ZF-containing proteins; however, a subset of GRF-ZF proteins [e.g., Top3α (Topoisomerase 3α)] substitute the His of this motif with a Cys residue (CCCC-coordination). The first two Zn(2+) ligands are found in a loop preceding β1, whereas the second half of the motif maps to the β2-β3 connecting loop [1,2,3,4].

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

  • Eukaryotic DNA-(apurinic or apyrimidinic site) endonuclease 2 (APE2, also termed APEX2, or Apn2 in yeast) [1,2].
  • Eukaryotic Topoisomerase 3α (TOP3α).
  • Animal Nei-like DNA glycosylase 3 (NEIL3) [3].
  • Vertebrate CCHC zinc finger-containing protein ZCCHC4, a 28S rRNA-specific N6-adenosine-methyltransferase [4].
  • Mammalian transcription termination factor 2 (TTF2).

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

Last update:

May 2022 / First entry.


Technical section

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

ZF_GRF, PS51999; Zinc finger GRF-type profile  (MATRIX)


1AuthorsWallace B.D. Berman Z. Mueller G.A. Lin Y. Chang T. Andres S.N. Wojtaszek J.L. DeRose E.F. Appel C.D. London R.E. Yan S. Williams R.S.
TitleAPE2 Zf-GRF facilitates 3'-5' resection of DNA damage following oxidative stress.
SourceProc. Natl. Acad. Sci. U. S. A. 114:304-309(2017).
PubMed ID28028224

2AuthorsLin Y. McMahon A. Driscoll G. Bullock S. Zhao J. Yan S.
TitleFunction and molecular mechanisms of APE2 in genome and epigenome integrity.
SourceMutat. Res. Rev. Mutat. Res. 787:108347-108347(2021).
PubMed ID34083046

3AuthorsRodriguez A.A. Wojtaszek J.L. Greer B.H. Haldar T. Gates K.S. Williams R.S. Eichman B.F.
TitleAn autoinhibitory role for the GRF zinc finger domain of DNA glycosylase NEIL3.
SourceJ. Biol. Chem. 295:15566-15575(2020).
PubMed ID32878989

4AuthorsRen W. Lu J. Huang M. Gao L. Li D. Wang G.G. Song J.
TitleStructure and regulation of ZCCHC4 in m(6)A-methylation of 28S rRNA.
SourceNat. Commun. 10:5042-5042(2019).
PubMed ID31695039

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