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.