Worm Breeder's Gazette 11(1): 42

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lin-11 Contains Two Repeats of a Potential Metal-Binding Region Upstream of the Homeodomain

Gwen Freyd and Bob Horvitz

Figure 1

Mutations in the gene lin-11 cause certain vulval precursor cells (
the 2  cells) to divide symmetrically instead of asymmetrically.  
Hence, the gene appears to play a role in the ability of one cell to 
divide asymmetrically to produce daughter cells of two different types.
We previously reported the cloning and sequencing of a small region 
of a putative lin-11 cDNA (WBG 10:3, 33) and the finding that it 
encodes a homeodomain that is very similar to that of mec-3, a gene 
involved in the development of the touch neurons (Way and Chalfie, 
Cell 54, 5, 1988).  A 1.7 kb lin-11 cDNA has now been sequenced and 
the two genes appear to have extensive similarity upstream of the 
Interestingly, a large percentage of the conserved residues between 
the two proteins are histidines and cysteines.  A comparison of the 
conserved residues between lin-11 and mec-3 has revealed a repeated 
motif of the histidine and cysteine residues (see figure).  This motif 
is repeated twice in lin-11 and one and a half times in the published 
protein sequence of mec-3.  Analysis of the mec-3 DNA sequence, which 
was obtained from genomic clones, indicates that there are alternative 
splicing patterns possible that could encode two full repeats of the 
motif in mec-3.  A computer search of the National Biomedical Research 
Foundation Protein Sequence Database using the search program FASTP 
identified one copy of the motif in a cysteine-rich intestinal protein 
(CRIP) cloned from rat (Birkenmeier and Gordon, PNAS 83, 2516, 1986).  
We know of no other homeodomain-containing protein that contains a 
similar motif.
The motif is similar but not identical to the pattern of cysteine 
and histidine residues in known metal-binding regions, but there is 
large variation among different classes of metal-binding proteins.  
Jeff Way previously noted the possibility that mec-3 might be a metal-
binding protein because of the CxxC pattern of residues in the protein 
sequence (WBG 10:3, 32).  Metal-binding regions can be sites for 
protein/protein interactions (including dimerization) or, in some 
proteins such as the zinc-finger containing proteins, metal-binding 
regions provide sites of contact with DNA.  In either case, the region 
is of interest.  If the metal-binding region is the site of a 
protein/protein interaction, it could be a region important in 
interacting with other components of the transcriptional machinery or 
it may play a role in the ability of the lin-11 protein to be 
localized to the correct cell type.  If the potential metal-binding 
region is the site of nucleic acid contact, it could be binding to the 
same region of DNA as the homeodomain, to a separate region of the 
chromosome, or to RNA.  We hope to test the functional importance of 
this region of lin-11.[See Figure 1]

Figure 1