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88  structures 437  species 2  interactions 16362  sequences 199  architectures

Family: LIM (PF00412)

Summary: LIM domain

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LIM domain Edit Wikipedia article

LIM domain
Lims.png
Structure of the 4th LIM domain of Pinch protein. Zinc atoms are shown in grey
Identifiers
Symbol LIM
Pfam PF00412
InterPro IPR001781
PROSITE PDOC50178
SCOP 1ctl
SUPERFAMILY 1ctl
CDD cd08368

LIM domains are protein structural domains, composed of two contiguous zinc finger domains, separated by a two-amino acid residue hydrophobic linker.[1] They are named after their initial discovery in the proteins Lin11, Isl-1 & Mec-3.[2] LIM-domain containing proteins have been shown to play roles in cytoskeletal organisation, organ development and oncogenesis. LIM-domains mediate protein:protein interactions that are critical to cellular processes.

LIM domains have highly divergent sequences, apart from certain key residues. The sequence divergence allow a great many different binding sites to be grafted onto the same basic domain. The conserved residues are those involved in zinc binding or the hydrophobic core of the protein. The sequence signature of LIM domains is as follows:

[C]-[X]2-4-[C]-[X]13-19-[W]-[H]-[X]2-4-[C]-[F]-[LVI]-[C]-[X]2-4-[C]-[X]13-20-C-[X]2-4-[C]

LIM domain organisation

LIM domains frequently occur in multiples, as seen in proteins such as TES, LMO4, and can also be attached to other domains in order to confer a binding or targeting function upon them, such as LIM-kinase.

The LIM superclass of genes have been classified into 14 classes: ABLIM, CRP, ENIGMA, EPLIN, LASP, LHX, LMO, LIMK, LMO7, MICAL, PXN, PINCH, TES, and ZYX. Six of these classes (i.e., ABLIM, MICAL, ENIGMA, ZYX, LHX, LM07) originated in the stem lineage of animals, and this expansion is thought to have made a major contribution to the origin of animal multicellularity. [3]

LIM domains are also found in various bacterial lineages where they are typically fused to a metallopeptidase domain. Some versions show fusions to an inactive P-loop NTPase at their N-terminus and a single transmembrane helix. These domain fusions suggest that the prokaryotic LIM domains are likely to regulate protein processing at the cell membrane. The domain architectural syntax is remarkable parallel to those of the prokaryotic versions of the B-box zinc finger and the AN1 zinc finger domains. [4]

References[edit]

  1. ^ Kadrmas JL, Beckerle MC (2004). "The LIM domain: from the cytoskeleton to the nucleus". Nat. Rev. Mol. Cell Biol. 5 (11): 920–31. doi:10.1038/nrm1499. PMID 15520811. 
  2. ^ Bach I (2000). "The LIM domain: regulation by association". Mech. Dev. 91 (1–2): 5–17. doi:10.1016/S0925-4773(99)00314-7. PMID 10704826. 
  3. ^ Koch BJ, Ryan JF, Baxevanis AD (March 2012). "The Diversification of the LIM Superclass at the Base of the Metazoa Increased Subcellular Complexity and Promoted Multicellular Specialization". PLoS ONE 7: e33261. doi:10.1371/journal.pone.0033261. PMID 22438907. 
  4. ^ Burroughs AM, Iyer LM, Aravind L (July 2011). "Functional diversification of the RING finger and other binuclear treble clef domains in prokaryotes and the early evolution of the ubiquitin system". Mol Biosyst. 7 (1): 2261–77. doi:10.1039/C1MB05061C. PMID 21547297. 


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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

LIM domain Provide feedback

This family represents two copies of the LIM structural domain.

Literature references

  1. Perez-Alvarado GC, Miles C, Michelsen JW, Louis HA, Winge DR, Beckerle MC, Summers MF; , Nat Struct Biol 1994;1:388-398.: Structure of the carboxy-terminal Lim domain from the cysteine rich protein Crp. PUBMED:7664053 EPMC:7664053


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001781

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates [PUBMED:10529348, PUBMED:15963892, PUBMED:15718139, PUBMED:17210253, PUBMED:12665246]. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few [PUBMED:11179890]. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

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 [PUBMED:1970421, PUBMED:1467648]. 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 INTERPRO).
  • 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 [PUBMED:8065929].
  • 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 [PUBMED:8506279]. LIM does not bind DNA, rather it seems to act as an interface for protein-protein interaction.

More information about these proteins can be found at Protein of the Month: Zinc Fingers [PUBMED:].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

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Alignments

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  Seed
(38)
Full
(16362)
Representative proteomes NCBI
(14824)
Meta
(48)
RP15
(2081)
RP35
(3129)
RP55
(5636)
RP75
(8615)
Alignment:
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  Seed
(38)
Full
(16362)
Representative proteomes NCBI
(14824)
Meta
(48)
RP15
(2081)
RP35
(3129)
RP55
(5636)
RP75
(8615)
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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Curation and family details

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Curation View help on the curation process

Seed source: Prosite
Previous IDs: none
Type: Domain
Author: Finn RD, Griffiths-Jones SR
Number in seed: 38
Number in full: 16362
Average length of the domain: 57.20 aa
Average identity of full alignment: 26 %
Average coverage of the sequence by the domain: 24.59 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.5 21.5
Trusted cut-off 21.5 21.5
Noise cut-off 21.4 21.4
Model length: 58
Family (HMM) version: 17
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Species distribution

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Interactions

There are 2 interactions for this family. More...

LIM SH3_1

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the LIM domain has been found. There are 88 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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