PROSITE documentation PDOC00382

LIM zinc-binding domain signature and profile

Recently [1,2] a number of proteins have been found to contain a conserved cysteine-rich domain of about 60 amino-acid residues. These proteins are:

• Caenorhabditis elegans mec-3; a protein required for the differentiation of the set of six touch receptor neurons in this nematode.
• Caenorhabditis elegans lin-11; a protein required for the asymmetric division of vulval blast cells.
• Vertebrate insulin gene enhancer binding protein isl-1. Isl-1 binds to one of the two cis-acting protein-binding domains of the insulin gene.
• Vertebrate homeobox proteins lim-1, lim-2 (lim-5) and lim3.
• Vertebrate lmx-1, which acts as a transcriptional activator by binding to the FLAT element; a β-cell-specific transcriptional enhancer found in the insulin gene.
• Mammalian LH-2, a transcriptional regulatory protein involved in the control of cell differentiation in developing lymphoid and neural cell types.
• Drosophila protein apterous, required for the normal development of the wing and halter imaginal discs.
• Vertebrate protein kinases LIMK-1 and LIMK-2.
• Mammalian rhombotins. Rhombotin 1 (RBTN1 or TTG-1) and rhombotin-2 (RBTN2 or TTG-2) are proteins of about 160 amino acids whose genes are disrupted by chromosomal translocations in T-cell leukemia.
• Mammalian and avian cysteine-rich protein (CRP), a 192 amino-acid protein of unknown function. Seems to interact with zyxin.
• Mammalian cysteine-rich intestinal protein (CRIP), a small protein which seems to have a role in zinc absorption and may function as an intracellular zinc transport protein.
• Vertebrate paxillin, a cytoskeletal focal adhesion protein.
• Mouse testin. Mouse testin should not be confused with rat testin which is a thiol protease homolog (see <PDOC00126>).
• Sunflower pollen specific protein SF3.
• Chicken zyxin. Zyxin is a low-abundance adhesion plaque protein which has been shown to interact with CRP.
• Yeast protein LRG1 which is involved in sporulation [4].
• Yeast rho-type GTPase activating protein RGA1/DBM1.
• Caenorhabditis elegans homeobox protein ceh-14.
• Caenorhabditis elegans homeobox protein unc-97.
• Yeast hypothetical protein YKR090w.
• Caenorhabditis elegans hypothetical proteins C28H8.6.

These proteins generally have two tandem copies of a domain, called LIM (for Lin-11 Isl-1 Mec-3) in their N-terminal section. Zyxin and paxillin are exceptions in that they contains respectively three and four LIM domains at their C-terminal extremity. In apterous, isl-1, LH-2, lin-11, lim-1 to lim-3, lmx-1 and ceh-14 and mec-3 there is a homeobox domain some 50 to 95 amino acids after the LIM domains.

In the LIM domain, there are seven conserved cysteine residues and a histidine. The arrangement followed by these conserved residues is C-x(2)-C-x(16,23)-H-x(2)-[CH]-x(2)-C-x(2)-C-x(16,21)-C-x(2,3)-[CHD]. The LIM domain binds two zinc ions [5]. LIM does not bind DNA, rather it seems to act as interface for protein-protein interaction. We developed a pattern that spans the first half of the LIM domain.