{PDOC51999}
{PS51999; ZF_GRF}
{BEGIN}
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* Zinc finger GRF-type profile *
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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 beta-sheet (beta1-beta3)
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., Top3alpha (Topoisomerase
3alpha)] substitute   the  His  of  this  motif  with  a  Cys  residue  (CCCC-
coordination). The  first  two  Zn(2+)  ligands  are found in a loop preceding
beta1, whereas the second half of the motif maps to the beta2-beta3 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 3alpha (TOP3alpha).
 - 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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: May 2022 / First entry.

[ 1] Wallace 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.
     "APE2 Zf-GRF facilitates 3'-5' resection of DNA damage following
     oxidative stress."
     Proc. Natl. Acad. Sci. U. S. A. 114:304-309(2017).
     PubMed=28028224; DOI=10.1073/pnas.1610011114
[ 2] Lin Y., McMahon A., Driscoll G., Bullock S., Zhao J., Yan S.
     "Function and molecular mechanisms of APE2 in genome and epigenome
     integrity."
     Mutat. Res. Rev. Mutat. Res. 787:108347-108347(2021).
     PubMed=34083046; DOI=10.1016/j.mrrev.2020.108347
[ 3] Rodriguez A.A., Wojtaszek J.L., Greer B.H., Haldar T., Gates K.S.,
     Williams R.S., Eichman B.F.
     "An autoinhibitory role for the GRF zinc finger domain of DNA
     glycosylase NEIL3."
     J. Biol. Chem. 295:15566-15575(2020).
     PubMed=32878989; DOI=10.1074/jbc.RA120.015541
[ 4] Ren W., Lu J., Huang M., Gao L., Li D., Wang G.G., Song J.
     "Structure and regulation of ZCCHC4 in m(6)A-methylation of 28S
     rRNA."
     Nat. Commun. 10:5042-5042(2019).
     PubMed=31695039; DOI=10.1038/s41467-019-12923-x

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