LIM-homeodomain (LIM-HD) proteins are transcription factors that are critical in the development of many cell types and tissues. The activity of LIM-HD proteins is dependent on the essential cofactor LIM domain-binding protein 1 (Ldb1). This entry represents a 30-residue LIM interaction domain (LID) that binds to the LIM domains of all LIM-HD and closely related LIM-only (LMO) proteins. Isl1 (Insulin gene enhancer protein 1) and Isl2 each contain a LID-like sequence in their C-terminal regions, the Lhx3-binding domain (LBD), which binds the LIM domains Lhx3 and Lhx4 [].
In general, LIM domains coordinate one or more zinc atoms, and are named after the three proteins (LIN-11, Isl1 and MEC-3) in which they were first found. They consist of two zinc-binding motifs that resemble GATA-like Znf's, however the residues holding the zinc atom(s) are variable, involving Cys, His, Asp or Glu residues. LIM domain-containing proteins have diverse cellular roles such as regulators of gene expression, cyto-architecture, cell adhesion, cell motility, and signal transduction. LIM domain-containing proteins have been shown to be key molecules in a wide variety of human cancers [].LIMD2 binds directly to the kinase domain of integrin-linked kinase (ILK) near the active site and strongly activated ILK kinase activity. Its LIM-domain structure is highly related to LIM1 of PINCH1, a core component of the integrin-linked kinase-parvin-pinch complex [].
This entry includes the LIM-domain binding proteins and similar proteins, such as protein Chip from Drosophila, SEUSS from Arabidopsis and Adn1 from fission yeasts. The LIM-domain binding protein, binds to the LIM domain of LIM homeodomain proteins which are transcriptional regulators of development. Nuclear LIM interactor (NLI) / LIM domain-binding protein 1 (LDB1) is located in the nuclei of neuronal cells during development, it is co-expressed with Isl1 in early motor neuron differentiation and has a suggested role in the Isl1 dependent development of motor neurons []. It is suggested that these proteins act synergistically to enhance transcriptional efficiency by acting as co-factors for LIM homeodomain and Otx class transcription factors, both of which have essential roles in development [].The Drosophila protein Chip () is required for segmentation and activity of a remote wing margin enhancer []. Chip is a ubiquitous chromosomal factor required for normal expression of diverse genes at many stages of development. It is suggested that Chip cooperates with different LIM domain proteins and other factors to structurally support remote enhancer-promoter interactions [].SEUSS is a transcriptional corepressor from Arabidopsis thaliana []. SEUSS contains two glutamine-rich domains and a highly conserved domain that shares sequence identity with the dimerisation domain of the LIM-domain-binding transcription co-regulators in animals [].Several proteins in this entry are transcriptional regulators in fungi. In fission yeasts, adhesion defective protein 1 (Adn1) is a probable transcriptional regulator involved in cell adhesion []. In Aspergillus fumigatus, the transcriptional activator ptaB forms a complex with somA to control biofilm formation []. In Candida albicans, MFG1 (morphogenetic regulator of filamentous growth protein 1) has a role in all morphogenetically distinct forms of filamentous growth, including invasive growth and biofilm formation, probably by forming a complex with FLO8 and MSS1 which binds the promoter of the FLO11 gene [].
This entry represents LIM-type zinc finger (Znf) domains. LIM domains coordinate one or more zinc atoms, and are named after the three proteins (LIN-11, Isl1 and MEC-3) in which they were first found. They consist of two zinc-binding motifs that resemble GATA-like Znf's, however the residues holding the zinc atom(s) are variable, involving Cys, His, Asp or Glu residues. LIM domains are involved in proteins with differing functions, including gene expression, and cytoskeleton organisation and development [, ]. Protein containing LIM Znf domains include:Caenorhabditis elegans mec-3; a protein required for the differentiation of the set of six touch receptor neurons in this nematode.C. 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 beta-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 melanogaster (Fruit fly) 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.Mus musculus (Mouse) testin which should not be confused with rat testin which is a thiol protease homologue (see ).Helianthus annuus (Common 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 [].Saccharomyces cerevisiae (Baker's yeast) rho-type GTPase activating protein RGA1/DBM1.C. elegans homeobox protein ceh-14.C. elegans homeobox protein unc-97.S. cerevisiae hypothetical protein YKR090w.C. elegans hypothetical proteins C28H8.6.These proteins generally contain two tandem copies of the LIM domain in their N-terminal section. Zyxin and paxillin are exceptions in that they contain 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.LIM domains contain 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]LIM domains bind two zinc ions []. LIM does not bind DNA, rather it seems to act as an interface for protein-protein interaction.
