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	PROSITE documentation PDOC51810 [for PROSITE entry PS51810]

Zinc finger CCHC FOG-type profile

Zinc fingers (ZnFs) are among the most common of all protein domains. They have traditionally been regarded as sequence-specific DNA-binding motifs. However it has also become apparent that many ZnFs mediate specific protein-protein interactions. Transcriptional cofactors of the Friend of GATA (FOG) family are diverse in sequence but their individual ZnF regions share considerable homology. They contain either eight or nine ZnFs that are related to the classical CCHH ZnFs (which have a conserved C-X(2,5)-C-X(12)-H-X(2,5)-H sequence). Several of the fingers in each FOG protein, however, have an altered consensus sequence in which the final zinc binding histidine is replaced with a cysteine. Interestingly, it is only these variant CCHC ZbFs that mediate interactions with GATA N-terminal zinc fingers (NFs) [1,2,3,4,5].

The FOG-type CCHC zinc finger comprises a short β hairpin followed by an α helix (see <PDB:1FU9>). It resembles classical CCHH fingers in structure. The only notable difference is a short extended portion of the polypeptide backbone before the fourth zinc ligand. Two of the residues implicated in GATA binding are located on the extended portion of the backbone, immediately preceding the final cysteine. Thus, the CCHC topology appears to play a key role in facilitating the interaction. The residues that are implicated in GATA binding are largely conserved across FOG family CCHC ZnFs, although three of the residues that affect the binding affinity show some variation [1,2].

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

• Vertebrate Friend of GATA-1 (FOG-1), a zinc finger protein that interacts physically with the erythroid DNA-binding protein GATA-1 and modulates its transcriptional activity.
• Mammalian FOG-2, associates with GATA-1 and other mammalian GATA factors.
• Drosophila melanogaster U-shaped (Ush), interacts with the GATA factors Pannier and Serpent to control development in the fly.

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

Last update:

September 2016 / First entry.

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

ZF_CCHC_FOG, PS51810; Zinc finger CCHC FOG-type profile  (MATRIX)

• Sequences in UniProtKB/Swiss-Prot known to belong to this class: 7
  • detected by PS51810: 7 (true positives)
  • undetected by PS51810: 0 (false negative or 'partial')
• Other sequence(s) in UniProtKB/Swiss-Prot detected by PS51810:
  NONE.
• Domain architecture view of Swiss-Prot proteins matching PS51810
  
• Retrieve an alignment of UniProtKB/Swiss-Prot true positive hits:
  Clustal format, color, condensed view  /  Clustal format, color  /  Clustal format, plain text  /  Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic distribution of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS51810
• Retrieve a list of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS51810
• Scan UniProtKB (Swiss-Prot and/or TrEMBL) entries against PS51810
• View ligand binding statistics of PS51810
• Matching PDB structures: 1FU9 1FV5 1JN7 1Y0J ... [ALL]

1	Authors	Liew C.K., Kowalski K., Fox A.H., Newton A., Sharpe B.K., Crossley M., Mackay J.P.
	Title	Solution structures of two CCHC zinc fingers from the FOG family protein U-shaped that mediate protein-protein interactions.
	Source	Structure 8:1157-1166(2000).
	PubMed ID	11080638

2	Authors	Kowalski K., Liew C.K., Matthews J.M., Gell D.A., Crossley M., Mackay J.P.
	Title	Characterization of the conserved interaction between GATA and FOG family proteins.
	Source	J. Biol. Chem. 277:35720-35729(2002).
	PubMed ID	12110675
	DOI	10.1074/jbc.M204663200

3	Authors	Tevosian S.G., Deconinck A.E., Cantor A.B., Rieff H.I., Fujiwara Y., Corfas G., Orkin S.H.
	Title	FOG-2: A novel GATA-family cofactor related to multitype zinc-finger proteins Friend of GATA-1 and U-shaped.
	Source	Proc. Natl. Acad. Sci. U.S.A. 96:950-955(1999).
	PubMed ID	9927674

4	Authors	Fox A.H., Liew C., Holmes M., Kowalski K., Mackay J., Crossley M.
	Title	Transcriptional cofactors of the FOG family interact with GATA proteins by means of multiple zinc fingers.
	Source	EMBO J. 18:2812-2822(1999).
	PubMed ID	10329627
	DOI	10.1093/emboj/18.10.2812

5	Authors	Liew C.K., Simpson R.J., Kwan A.H., Crofts L.A., Loughlin F.E., Matthews J.M., Crossley M., Mackay J.P.
	Title	Zinc fingers as protein recognition motifs: structural basis for the GATA-1/friend of GATA interaction.
	Source	Proc. Natl. Acad. Sci. U.S.A. 102:583-588(2005).
	PubMed ID	15644435
	DOI	10.1073/pnas.0407511102

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