| SMART accession number: | SM00667
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| Description: |
Alpha-helical motif present in Lis1, treacle, Nopp140, some katanin p60 subunits, muskelin, tonneau, LEUNIG and numerous WD40 repeat-containing proteins. It is suggested that LisH motifs contribute to the regulation of microtubule dynamics, either by mediating dimerisation, or else by binding cytoplasmic dynein heavy chain or microtubules directly. |
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| Interpro abstract (IPR006594): |
The LisH motif is found in a large number of eukaryotic proteins, from metazoa, fungi and plants that have a wide range of functions. The recently solved structure of the LisH domain in the N-terminal region of LIS1 depicted it as a novel dimerization motif, and that other structural elements are likely to play an important role in dimerisation [(PUBMED:15274919), (PUBMED:16445939), (PUBMED:16258276)]. A sequence motif, LisH, has been identified in the products of genes mutated in Miller-Dieker lissencephaly, Treacher Collins, oral-facial-digital type 1 and contiguous syndrome ocular albinism with late onset sensorineural deafness syndromes. An additional homologous motif was detected in a gene product fused to the fibroblast growth factor receptor type 1 in patients with an atypical stem cell myeloproliferative disorder. In total, over 100 eukaryotic intracellular proteins are shown to possess a LIS1 homology (LisH) motif, including several katanin p60 subunits, muskelin, tonneau, LEUNIG, Nopp140, aimless and numerous WD repeat-containing beta-propeller proteins [(PUBMED:11734546)]. It is suggested that LisH motifs contribute to the regulation of microtubule dynamics, either by mediating dimerization, or else by binding cytoplasmic dynein heavy chain or microtubules directly. The predicted secondary structure of LisH motifs, and their occurrence in homologues of Gbeta beta-propeller subunits, suggests that they are analogues of Ggamma subunits, and might associate with the periphery of beta-propeller domains.
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| GO function: | protein binding (GO:0005515) |
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| Family alignment: |
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Click on the following links for more information.
- Evolution (species in which this domain is found)
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- Cellular role (predicted cellular role)
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Cellular role: signalling
Binding / catalysis: Unknown; possible microtubule and/or beta-propeller-binding motif
- Literature (relevant references for this domain)
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Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Morris R
- A rough guide to a smooth brain.
- Nat Cell Biol. 2000; 2: 2012-2012
- Reiner O
- LIS1. let's interact sometimes... (part 1).
- Neuron. 2000; 28: 633-6
- Smith DS et al.
- Regulation of cytoplasmic dynein behaviour and microtubule organization bymammalian Lis1.
- Nat Cell Biol. 2000; 2: 767-75
- Display abstract
Whereas total loss of Lis1 is lethal, disruption of one allele of the Lis1gene results in brain abnormalities, indicating that developing neuronsare particularly sensitive to a reduction in Lis1 dosage. Here we showthat Lis1 is enriched in neurons relative to levels in other cell types,and that Lis1 interacts with the microtubule motor cytoplasmic dynein.Production of more Lis1 in non-neuronal cells increases retrogrademovement of cytoplasmic dynein and leads to peripheral accumulation ofmicrotubules. These changes may reflect neuron-like dynein behavioursinduced by abundant Lis1. Lis1 deficiency produces the opposite phenotype.Our results indicate that abundance of Lis1 in neurons may stimulatespecific dynein functions that function in neuronal migration and axongrowth.
- Hirokawa N
- Kinesin and dynein superfamily proteins and the mechanism of organelle transport.
- Science. 1998; 279: 519-26
- Display abstract
Cells transport and sort proteins and lipids, after their synthesis, to various destinations at appropriate velocities in membranous organelles and protein complexes. Intracellular transport is thus fundamental to cellular morphogenesis and functioning. Microtubules serve as a rail on which motor proteins, such as kinesin and dynein superfamily proteins, convey their cargoes. This review focuses on the molecular mechanism of organelle transport in cells and describes kinesin and dynein superfamily proteins.
- Metabolism (metabolic pathways involving proteins which contain this domain)
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Click the image to view the interactive version of the map in iPath | | % proteins involved | KEGG pathway ID | Description |
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| 36.96 | map03022 | Basal transcription factors | | 30.43 | map04310 | Wnt signaling pathway | | 21.74 |  map00565 | Ether lipid metabolism | | 2.17 | map05211 | Renal cell carcinoma | | 2.17 | map03090 | Type II secretion system | | 2.17 | map04510 | Focal adhesion | | 2.17 | map04910 | Insulin signaling pathway | | 2.17 | map04330 | Notch signaling pathway |
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with LisH domain which could be assigned to a KEGG orthologous group, and not all proteins containing LisH domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%. |
- Structure (3D structures containing this domain)
3D Structures of LisH domains in PDB
| PDB code | Main view | Title | | 1uuj |  | N-terminal domain of lissencephaly-1 protein (lis-1) |
| 1vyh |  | Paf-ah holoenzyme: lis1/alfa2 |
| 2d68 |  | Structure of the n-terminal domain of fop (fgfr1op) protein |
| 2ikb |  | Crystal structure of a protein of unknown function nmb1012 from neisseria meningitidis |
| 2is5 |  | Crystal structure of 3 residues truncated version of protein nmb1012 from neisseria meningitides |
- Links (links to other resources describing this domain)
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to expand nodes. To display all proteins with a LisH domain in a specific node, click on it.