Summary: LIM domain

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LIM domain Edit Wikipedia article

LIM domain

Structure of the 4th LIM domain of Pinch protein. Zinc atoms are shown in grey

Identifiers

Symbol

LIM

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

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

^ 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.
^ 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.
^ 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 (3): e33261. doi:10.1371/journal.pone.0033261. PMC 3305314 . PMID 22438907.
^ 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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LIM domain Provide feedback

This family represents two copies of the LIM structural domain.

Literature references

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

Internal database links

SCOOP:

zf-dskA_traR

External database links

HOMSTRAD:	LIM
PROSITE:	PDOC00382
SCOP:	1ctl

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.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

Pfam Clan

This family is a member of clan Zn_Beta_Ribbon (CL0167), which has the following description:

A clan of zinc-binding ribbon domains.

The clan contains the following 85 members:

A2L_zn_ribbon Auto_anti-p27 Baculo_LEF5_C CpXC DNA_RNApol_7kD DUF1451 DUF1610 DUF1936 DUF2072 DUF2116 DUF2180 DUF2387 DUF2614 DUF35_N DUF4379 DZR Elf1 GATA Lar_restr_allev LIM Mu-like_Com NinF NOB1_Zn_bind Nudix_N_2 Ogr_Delta OrfB_Zn_ribbon PhnA_Zn_Ribbon PriA_CRR Prim_Zn_Ribbon RecO_C Ribosomal_L32p Ribosomal_L33 Ribosomal_L37ae Ribosomal_L37e Ribosomal_L40e Ribosomal_L44 Ribosomal_S27 Ribosomal_S27e RNA_POL_M_15KD Rubredoxin_2 Spt4 Stc1 TF_Zn_Ribbon TFIIS_C Tnp_zf-ribbon_2 Topo_Zn_Ribbon Toprim_Crpt Trm112p UPF0547 zf-C4 zf-C4_ClpX zf-C4_Topoisom zf-CHC2 zf-CSL zf-dskA_traR zf-FPG_IleRS zf-GRF zf-ISL3 zf-NADH-PPase zf-PARP zf-RanBP zf-ribbon_3 zf-RING_7 zf-RRN7 zf-TFIIB zf-trcl zf-ZPR1 zf_PR_Knuckle zf_Rg zinc-ribbon_6 zinc-ribbons_6 zinc_ribbon_10 zinc_ribbon_11 zinc_ribbon_12 zinc_ribbon_13 zinc_ribbon_15 zinc_ribbon_2 zinc_ribbon_4 zinc_ribbon_5 zinc_ribbon_9 Zn-ribbon_8 Zn_ribbon_recom Zn_ribbon_SprT Zn_Tnp_IS1 Zn_Tnp_IS1595

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.

Alignment types

We make a range of alignments for each Pfam-A family:

seed: the curated alignment from which the HMM for the family is built
full: the alignment generated by searching the sequence database using the HMM
RP15/RP35/RP55/RP75: Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
UniProt: alignment generated by searching the UniProtKB sequence database using the family HMM
NCBI: alignment generated by searching the NCBI sequence database using the family HMM
meta: alignment generated by searching the metagenomics sequence database using the family HMM

Viewing

You can see the alignments as HTML or in three different sequence viewers:

jalview: a Java applet developed at the University of Dundee. You will need Java installed before running jalview
HTML: an HTML page showing the whole alignment.Please note: full Pfam alignments can be very large. These HTML views are extremely large and often cause problems for browsers. Please use either jalview or the Pfam viewer if you have trouble viewing the HTML version
PP/Heatmap: an HTML-based representation of the alignment, coloured according to the posterior-probability (PP) values from the HMM. As for the standard HTML view, heatmap alignments can also be very large and slow to render.

Reformatting

You can download (or view in your browser) a text representation of a Pfam alignment in various formats:

Selex
Stockholm
FASTA
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You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.

Downloading

You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

	Seed (34)	Full (44875)	Representative proteomes				UniProt (69528)	NCBI (139984)	Meta (44)
	Seed (34)	Full (44875)	RP15 (9213)	RP35 (19042)	RP55 (31393)	RP75 (37485)	UniProt (69528)	NCBI (139984)	Meta (44)
Jalview	View	View	View	View	View	View	View	View	View
HTML	View
PP/heatmap	₁

¹Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: available, not generated, — not available.

Format an alignment

	Seed (34)	Full (44875)	Representative proteomes				UniProt (69528)	NCBI (139984)	Meta (44)
	Seed (34)	Full (44875)	RP15 (9213)	RP35 (19042)	RP55 (31393)	RP75 (37485)	UniProt (69528)	NCBI (139984)	Meta (44)
Alignment:
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

	Seed (34)	Full (44875)	Representative proteomes				UniProt (69528)	NCBI (139984)	Meta (44)
	Seed (34)	Full (44875)	RP15 (9213)	RP35 (19042)	RP55 (31393)	RP75 (37485)	UniProt (69528)	NCBI (139984)	Meta (44)
Raw Stockholm	Download	Download	Download	Download	Download	Download	Download	Download	Download
Gzipped	Download	Download	Download	Download	Download	Download	Download	Download	Download

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation

Seed source:

Prosite

Previous IDs:

none

Type:

Domain

Sequence Ontology:

SO:0000417

Author:

Finn RD

, Griffiths-Jones SR

Number in seed:

34

Number in full:

44875

Average length of the domain:

57.20 aa

Average identity of full alignment:

26 %

Average coverage of the sequence by the domain:

22.23 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	22.9	22.9
Trusted cut-off	22.9	22.9
Noise cut-off	22.8	22.8

Model length:

58

Family (HMM) version:

22

Download:

download the raw HMM for this family

Species distribution

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Colour assignments

Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Selections

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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.

How the sunburst is generated

The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.

In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:

superkingdom
kingdom
phylum
class
order
family
genus
species

Colouring and labels

Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.

As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.

Anomalies in the taxonomy tree

There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.

Missing taxonomic levels

Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.

Unmapped species names

The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.

So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".

Sub-species

Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.

Too many species/sequences

For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.

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Tree controls

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The tree shows the occurrence of this domain across different species. More...

Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

You can use the tree controls to manipulate how the interactive tree is displayed:

show/hide the summary boxes
highlight species that are represented in the seed alignment
expand/collapse the tree or expand it to a given depth
select a sub-tree or a set of species within the tree and view them graphically or as an alignment
save a plain text representation of the tree

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Interactions

There are 8 interactions for this family. More...

Ank_2 Ank_4 WH1 SH3_1 LIM Ank HLH GATA

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 108 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 sequence.

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Family: LIM (PF00412)

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