PROSITE documentation PDOC50103

Zinc finger C3H1-type profile

The well conserved cysteine-histidine arrangement, C-x(8)-C-x(5)-C-x(3)-H, of the C3H1-type zinc finger is present in many eukaryotic proteins from yeast to mammals. In various proteins the C3H1-type zinc finger has been shown to interact with the 3'-untranslated region of mRNAs (see below). It is very often present in two copies [1,2].

The structure of the two C3H1-type zinc fingers of the protein TIS11d bound to its target mRNA has been solved (see <PDB:1RGO>) [3]. The two zinc fingers fold independently to form small, compact domains connected by the linker sequence. The polypeptide backbone adopts little regular secondary structure. In each zinc finger, there is a short α-helix immediately after the first cysteine ligand and a turn of 3/10 helix between the second and third cysteine ligands. All amino acid residues that exhibit intermolecular contacts with the RNA are positioned on a single surface of each zinc finger.

Some proteins known to contain a C3H1-type zinc finger are listed below:

• Mammalian tristetraprolin (TTP) proteins, prototype of the C3H1 zinc finger proteins, inhibit TNF α production from macrophages by destabilizing its messenger RNA [2]. TTP is a specific RNA-binding protein; the region encompassing the two C3H1-type zinc fingers recognizes nonameric UUAUUUAUU sequences present in the 3'-untranslated region (UTR) of TNF α [4,5].
• Eukaryotic TIS/CTH family. Regulatory protein involved in regulating the response to growth factors similar to TTP. The tandem zinc finger domain of the protein TIS11d binds to the class II AU-rich element (ARE) in the 3' untranslated region (3' UTR) of target mRNAs and promotes their deadenylation and degradation [6].
• Eukaryotic U2AG, U2R1, U2R2 proteins, small nuclear ribonucleoproteins (1 or 2 copies).
• Caenorhabditis Elegans PIE1 protein. It is required for specification of embryonic germ cells lineage and for the lack of mRNA transcription in these cells (2 copies).
• Caenorhabditis Elegans POS-1 protein. A cytoplasmic protein similar to TIS11, essential for germ line specification in C. elegans (2 copies).
• Eukaryotic cleavage and polyadenylation specificity factor subunit 4 (Cpsf4) protein. It plays a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. Cpsf4 binds RNA polymers with a preference for poly(U) (5 copies).
• Schizosaccharomyces pombe ZFS1 protein. It was isolated as a suppressor of the sterility caused by overexpression of a double-stranded RNase (2 copies).
• Human Z183 protein, contains one ring finger and one C3H1-type zinc finger.
• Mammalian Nucleoporin-like 2, required for the export of mRNAs containing poly(A) tails from the nucleus into the cytoplasm (1 copy).

The profile we developed covers the entire C3H1-type zinc finger.