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.

Last update:

April 2005 / Profile revised.


Technical section

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

LIM_DOMAIN_2, PS50023; LIM domain profile  (MATRIX)

LIM_DOMAIN_1, PS00478; LIM zinc-binding domain signature  (PATTERN)


1AuthorsFreyd G. Kim S.K. Horvitz H.R.
TitleNovel cysteine-rich motif and homeodomain in the product of the Caenorhabditis elegans cell lineage gene lin-11.
SourceNature 344:876-879(1990).
PubMed ID1970421

2AuthorsBaltz R. Evrard J.-L. Domon C. Steinmetz A.
TitleA LIM motif is present in a pollen-specific protein.
SourcePlant Cell 4:1465-1466(1992).
PubMed ID1467648

3AuthorsSanchez-Garcia I. Rabbitts T.H.
SourceTrends Genet. 10:315-320(1994).

4AuthorsMueller A. Xu G. Wells R. Hollenberg C.P. Piepersberg W.
SourceNucleic Acids Res. 22:3151-3154(1994).

5AuthorsMichelsen J.W. Schmeichel K.L. Beckerle M.C. Winge D.R.
TitleThe LIM motif defines a specific zinc-binding protein domain.
SourceProc. Natl. Acad. Sci. U.S.A. 90:4404-4408(1993).
PubMed ID8506279

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 prosite_license.html.


View entry in original PROSITE document format
View entry in raw text format (no links)