{PDOC50103} {PS50103; ZF_C3H1} {BEGIN} ********************************* * 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 ) [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 alpha-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 alpha 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 alpha [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. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: June 2008 / First entry. [ 1] Hall T.M. "Multiple modes of RNA recognition by zinc finger proteins." Curr. Opin. Struct. Biol. 15:367-373(2005). PubMed=15963892; DOI=10.1016/j.sbi.2005.04.004 [ 2] Brown R.S. "Zinc finger proteins: getting a grip on RNA." Curr. Opin. Struct. Biol. 15:94-98(2005). PubMed=15718139; DOI=10.1016/j.sbi.2005.01.006 [ 3] Hudson B.P., Martinez-Yamout M.A., Dyson H.J., Wright P.E. "Recognition of the mRNA AU-rich element by the zinc finger domain of TIS11d." Nat. Struct. Mol. Biol. 11:257-264(2004). PubMed=14981510; DOI=10.1038/nsmb738 [ 4] Lai W.S., Carballo E., Strum J.R., Kennington E.A., Phillips R.S., Blackshear P.J. "Evidence that tristetraprolin binds to AU-rich elements and promotes the deadenylation and destabilization of tumor necrosis factor alpha mRNA." Mol. Cell. Biol. 19:4311-4323(1999). PubMed=10330172 [ 5] Lai W.S., Parker J.S., Grissom S.F., Stumpo D.J., Blackshear P.J. "Novel mRNA targets for tristetraprolin (TTP) identified by global analysis of stabilized transcripts in TTP-deficient fibroblasts." Mol. Cell. Biol. 26:9196-9208(2006). PubMed=17030620; DOI=10.1128/MCB.00945-06 [ 6] Hudson B.P., Martinez-Yamout M.A., Dyson H.J., Wright P.E. "Recognition of the mRNA AU-rich element by the zinc finger domain of TIS11d." Nat. Struct. Mol. Biol. 11:257-264(2004). PubMed=14981510; DOI=10.1038/nsmb738 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}