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130  structures 1480  species 0  interactions 106776  sequences 728  architectures

Family: LIM (PF00412)

Summary: LIM domain

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

LIM domains are protein structural domains, composed of two contiguous zinc fingers, separated by a two-amino acid residue hydrophobic linker.[1] The domain name is an acronym of the three genes in which it was first identified (LIN-11, Isl-1 and MEC-3).[2] LIM is a protein interaction domain that is involved in binding to many structurally and functionally diverse partners.[1] The LIM domain appeared in eukaryotes sometime prior to the most recent common ancestor of plants, fungi, amoeba and animals.[3] In animal cells, LIM domain-containing proteins often shuttle between the cell nucleus where they can regulate gene expression, and the cytoplasm where they are usually associated with actin cytoskeletal structures involved in connecting cells together and to the surrounding matrix, such as stress fibers, focal adhesions and adherens junctions.[1]

LIM domain organization


LIM domains are named after their initial discovery in the three homeobox proteins that have the following functions:[4][2]

  • Lin-11 – asymmetric division of vulvar blast cells
  • Isl-1 – motor neuron development of neuroepithelial cells
  • Mec-3 – differentiation of touch receptor neurons[2]

Sequence and Structure

Humans contain 73 described genes encoding different LIM domain-containing proteins. These LIM domains have divergent amino acid sequences apart from certain key residues involved in zinc binding, which facilitate the formation of a stable protein core and tertiary fold. The sequence variation between different LIM domains may be due to the evolution of novel binding sites for diverse partners on top of the conserved stable core. Additionally, LIM domain proteins are functionally diverse; especially during the early evolution of animals, the LIM domain recombined with a variety of other domain types to create these diverse proteins with new functionality.[5][3]

The sequence signature of LIM domains is as follows:


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.


LIM-domain containing proteins have been shown to play roles in cytoskeletal organization, organ development, regulation of plant cell development, cell lineage specification, and regulation of gene transcription.[6] LIM proteins are also implicated in a variety of heart and muscle conditions, oncogenesis, neurological disorders and other diseases.[6] LIM-domains mediate a variety of protein–protein interactions in many different cellular processes. However a large subset of LIM proteins are recruited to actin cytoskeletal structures that are under a mechanical load. Direct force-activated F-actin binding by LIM recruits LIM domain proteins to stressed cytoskeletal networks[7] and is an example of a mechanosensing mechanism by which cytoskeletal tension governs mechanical homeostasis,[8] nuclear localization,[9] gene expression, and other cellular physiology.


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]

Asides lineage of animals, there are an entire class of plan LIM genes that were classified into four different classes: WLIM1, WLIM2, PLIM1, PLIM2, and FLIM (XLIM).[10] These are sorted into 4 different subfamilies: αLIM1, βLIM1, γLIM2, and δLIM2.[10] The αLIM1 subclades include PLIM1, WLIM1, and FLIM (XLIM).[10] βLIM1 is a new subfamily, so no current distinguishable subclades.[10] γLIM2 subclades contain WLIM2 and PLIM2.[10] The final subfamily δLIM2 contains WLIM2, and PLIM2.[10]

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 remarkably parallel to those of the prokaryotic versions of the B-box zinc finger and the AN1 zinc finger domains.[11]

LIM domain containing proteins serve many specific functions in cells such as adherens junction, cytoarchitecture, specification of cell polarity, nuclear-cytoplasmic shuttling, and protein trafficking.[4] These domains can be found in eukaryoes, plants, animal, fungi, and mycetozoa.[6] It was classified as A, B, C, and D.[6] These classifications are further sorted into three groups.

Group 1

This group contains LIM domain classes A and B.[6] They are typically fused to other functional domains such as kinases.[6] The subclasses for these domains are LIM-homeodomain transcription factors, LMO proteins, and LIM kinases.[6]

LIM-homeodomain transcription factors

They have multifunctionality primarily focusing on development of the nervous system, activation of transcription, and cell fate specification during development.[4][6] The nervous system relies on the LIM domain type for differentiation of neurotransmitter biosynthetic pathways.[4]

LMO proteins

These proteins focus on overall development of multiple cell types as well as oncogenesis and transcriptional regulation.[4] Oncogenesis was found to occur due to the expression of LMO 1 and LMO 2 in T-cell leukemia patients.[4][6]

LIM kinases

The purpose of these proteins is the establishment and regulation of the cytoskeleton.[6] The regulation of the cytoskeleton by these kinases is through phosphorylation of cofilin, which allows for the accumulation of actin filaments.[6] Notably, they have been found to be responsible for regulation of cell motility and morphogenesis.[4]

Group 2

This group contains LIM domain class C, which are localized typically in the cytoplasm.[4][6] These domains are internally duplicated with two copies per a protein.[6] Also, they are more similar to each than classes A and B.[6]

Cysteine-rich proteins

There are three different cysteine rich proteins.[6] The purpose of these proteins is their role in myogenesis and muscle structure.[6] Although, it was found that structural role is played in multiple types of cells.[6] Each of the CRP proteins are activated throughout myogenesis.[6] CRP 3 plays a role in development of myoblasts, while CRP 1 is active in fibro blast cells.[6] CRP 1 has more roles involved with actin filaments and z lines of myofibers.[4]

Group 3

This group contains only class D, which are typically localized in the cytoplasm.[6][4] These LIM proteins contain 1 to 5 domains.[6] These domains can have additional functional domains or motifs.[6] This group is limited to three different adaptor proteins: zyxin, paxillin, and PINCH.[6] They each respectively have different number of LIM domains with 3, 4, and 5.[6] These are considered adaptor proteins related to adhesion plaques that regulate cell shape and spreading through distinct LIM-mediated protein-protein interactions.[6]

Protein-protein interactions


These proteins are formed through interaction of LIM domain binding families that are bound by LIM1.[6] LIM-Ldb interacts to form different heterodimers of LIM-HD.[6] THis will typically form a LIM-LID region that interacts with LIM proteins.[6] LIM-HD is known to determine distinct identities for motor neurons during development.[6] It has been found to bind LMO1, LMO2, Lhx1, Isl1, and Mec3.[6] LMO2 is found to be localized in the nucleus, which is involved in erythroid development especially in the fetal liver.[4][2]


This protein is localized between the cytoplasm and nucleus through shuttling.[4] It focuses on moving between cell adhesion sites and nucleus.[4] The zinc fingers of the LIM domain will act independently.[6] Zyxin has a variety of bind partners such as CRP, α-actinin, proto-oncogene Vav, p130, and members of Ena/VASP family of proteins.[6] The known interactions of zyxin are between Ena/VASP and CRP1.[6] LIM1 is responsible for recognition of CRP1, but cooperate with LIM2 for binding to zyxin.[6] The Ena/VASP will bind profilin that is known to act as a actin-polymerizing protein.[6] The zyxin-VASP complex will initiate actin-polymerization for the cytoskeletal structure.[6][2]


This protein is localized in the cytoplasm at focal adhesion sites.[4] It functions as a central protein for fatty acids and development of cystoskeletal structure.[6][2] In fatty acids, they act as scaffolds for many binding partners.[6] The LIM domain at the c-terminal bind protein tyrosine phosphatase-PEST.[6] PTP-PEST binds at c-termini LIM 3 and 4 to disassemble fatty acids that will lead to the modulation of the fatty acid targeting regions.[6] The extent of binding will depend on LIM 2 and 4.[6] This will occur upon dephosphorylation of p130 and paxillin.[6]


This protein is localized in the cytoplasm, which serves in signaling and protein trafficking.[4][2] The structure of this protein contains three LIM domains at the c-terminal.[6] It will bind insulin receptor internalization motif (InsRF) at LIM domain 3.[6] LIM domain 2 binds Ret receptor tyrosine kinase.[6]


This protein is localized in the cytoplasm and nucleus.[4] It is responsible for effecting specific muscle adherens junctions and mechanosensory functions of touch receptor neurons.[4] The protein sequence in the LIM domains are linked with very short interdomain peptides and c-terminal extension with high amounts of positive charges.[6] The protein has multiple functions even presenting in senescent erythrocyte antigens.[6] It can bind to ankyrin repeat domains of integrin-linked kinase.[6] Also, LIM domain 4 of PINCH can bind to Nck2 protein to act as a adaptor.[6]


  1. ^ a b c Kadrmas JL, Beckerle MC (November 2004). "The LIM domain: from the cytoskeleton to the nucleus". Nature Reviews. Molecular Cell Biology. 5 (11): 920–31. doi:10.1038/nrm1499. PMID 15520811. S2CID 6030950.
  2. ^ a b c d e f g Gill GN (December 1995). "The enigma of LIM domains". Structure. 3 (12): 1285–9. doi:10.1016/S0969-2126(01)00265-9. PMID 8747454.
  3. ^ a b c 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. Bibcode:2012PLoSO...733261K. doi:10.1371/journal.pone.0033261. PMC 3305314. PMID 22438907.
  4. ^ a b c d e f g h i j k l m n o p q Bach I (March 2000). "The LIM domain: regulation by association". Mechanisms of Development. 91 (1–2): 5–17. doi:10.1016/S0925-4773(99)00314-7. PMID 10704826. S2CID 16093470.
  5. ^ Malay Kumar Basu, Liran Carmel, Igor B. Rogozin, and Eugene V. Koonin (2008). "Malay Kumar Basu, Liran Carmel, Igor B. Rogozin, and Eugene V. Koonin". Genome Res. 18 (3): 449–461. doi:10.1101/gr.6943508. PMC 2259109. PMID 18230802.CS1 maint: multiple names: authors list (link)
  6. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an ao ap aq ar as at au av aw Iuchi S, Kuldell N (6 March 2007). Zinc Finger Proteins: From Atomic Contact to Cellular Function. Springer Science & Business Media. ISBN 978-0-387-27421-8.
  7. ^ Winkelman JD, Anderson CA, Suarez C, Kovar DR, Gardel ML (October 2020). "Evolutionarily diverse LIM domain-containing proteins bind stressed actin filaments through a conserved mechanism". Proceedings of the National Academy of Sciences of the United States of America. 117 (41): 25532–25542. doi:10.1073/pnas.2004656117. PMC 7568268. PMID 32989126.
  8. ^ Smith MA, Hoffman LM, Beckerle MC (October 2014). "LIM proteins in actin cytoskeleton mechanoresponse". Trends in Cell Biology. 24 (10): 575–83. doi:10.1016/j.tcb.2014.04.009. PMC 4177944. PMID 24933506.
  9. ^ Sun X, Phua DY, Axiotakis L, Smith MA, Blankman E, Gong R, Cail RC, Espinosa de Los Reyes S, Beckerle MC, Waterman CM, Alushin GM (November 2020). "Mechanosensing through Direct Binding of Tensed F-Actin by LIM Domains". Developmental Cell. 55 (4): 468–482.e7. doi:10.1016/j.devcel.2020.09.022. PMC 7686152. PMID 33058779.
  10. ^ a b c d e f Cheng X, Li G, Muhammad A, Zhang J, Jiang T, Jin Q, et al. (February 2019). "Molecular identification, phylogenomic characterization and expression patterns analysis of the LIM (LIN-11, Isl1 and MEC-3 domains) gene family in pear (Pyrus bretschneideri) reveal its potential role in lignin metabolism". Gene. 686: 237–249. doi:10.1016/j.gene.2018.11.064. PMID 30468911. S2CID 53719270.
  11. ^ 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". Molecular BioSystems. 7 (7): 2261–77. doi:10.1039/C1MB05061C. PMC 5938088. 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

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001781

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:


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...

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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 and the UniProtKB sequence database. More...

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

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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...


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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 View help on the curation process

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: 106776
Average length of the domain: 57.10 aa
Average identity of full alignment: 27 %
Average coverage of the sequence by the domain: 21.18 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -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: 25
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
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Viroids Viroids Unclassified sequence Unclassified sequence


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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 130 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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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A061AD47 View 3D Structure Click here
A0A0G2JYM0 View 3D Structure Click here
A0A0G2K688 View 3D Structure Click here
A0A0G2K8R3 View 3D Structure Click here
A0A0G2K919 View 3D Structure Click here
A0A0G2K995 View 3D Structure Click here
A0A0G2KAE1 View 3D Structure Click here
A0A0G2KJM7 View 3D Structure Click here
A0A0G2QC60 View 3D Structure Click here
A0A0K3AQM0 View 3D Structure Click here
A0A0P0VM79 View 3D Structure Click here
A0A0R0GAE0 View 3D Structure Click here
A0A0R0H662 View 3D Structure Click here
A0A0R0I6V2 View 3D Structure Click here
A0A0R0K9J7 View 3D Structure Click here
A0A0R0LB42 View 3D Structure Click here
A0A0R4ICT4 View 3D Structure Click here
A0A0R4IJJ4 View 3D Structure Click here
A0A0R4IJP7 View 3D Structure Click here
A0A0R4IN44 View 3D Structure Click here
A0A0R4INF7 View 3D Structure Click here
A0A0R4IVV2 View 3D Structure Click here
A0A0R4IWT9 View 3D Structure Click here
A0A0R4IXJ5 View 3D Structure Click here
A0A1D5NSS7 View 3D Structure Click here
A0A1D6E4S2 View 3D Structure Click here
A0A1D6HEG9 View 3D Structure Click here
A0A1D6JXK9 View 3D Structure Click here
A0A1D6KF85 View 3D Structure Click here
A0A1D6KXJ5 View 3D Structure Click here
A0A1D6LVZ7 View 3D Structure Click here
A0A1D6PDX4 View 3D Structure Click here
A0A1D8PPS6 View 3D Structure Click here
A0A1D8PRQ6 View 3D Structure Click here
A0A1L8F1M4 View 3D Structure Click here
A0A2R8PVS7 View 3D Structure Click here
A0A2R8Q2U1 View 3D Structure Click here
A0A2R8Q4Q0 View 3D Structure Click here
A0A2R8Q887 View 3D Structure Click here
A0A2R8QEF4 View 3D Structure Click here