The 33-residue LIS1 homology (LisH) motif ( IPR006594 ) is found in eukaryotic intracellular proteins involved in microtubule dynamics, cell migration, nucleokinesis and chromosome segregation. The LisH motif is likely to possess a conserved protein-binding function and it has been proposed 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 LisH motif is found associated to other domains, such as WD-40 SPRY, Kelch, AAA ATPase, RasGEF, or HEAT [ (PUBMED:11734546) (PUBMED:12384287) (PUBMED:12559565) ].

The secondary structure of the LisH domain is predicted to be two alpha- helices [ (PUBMED:11734546) ].

Some proteins known to contain a LisH motif are listed below:

• Animal LIS1. It regulates cytoplasmic dynein function. In Homo sapiens (human) children with defects in LIS1 suffer from Miller-Dieker lissencephaly, a brain malformation that results in severe retardation, epilepsy and an early death.
• Emericella nidulans (Aspergillus nidulans) nuclear migration protein nudF, the orthologue of LIS1.
• Eukaryotic RanBPM, a Ran binding protein involved in microtubule nucleation.
• Eukaryotic Nopp140, a nucleolar phosphoprotein.
• Mammalian treacle, a nucleolar protein. In human, defects in treacle are the cause of Treacher Collins syndrome (TCS), an autosomal dominant disorder of craniofacial development.
• Animal muskelin. It acts as a mediator of cell spreading and cytoskeletal responses to the extracellular matrix component thrombospondin 1.
• Animal transducin beta-like 1 protein (TBL1).
• Plant tonneau.
• Arabidopsis thaliana LEUNIG, a putative transcriptional corepressor that regulates AGAMOUS expression during flower development.
• Fungal aimless RasGEF.
• Leishmania major katanin-like protein.

The C-terminal to LisH (CTLH) motif is a predicted alpha-helical sequence of unknown function that is found adjacent to the LisH motif in a number of these proteins but is absent in other (e.g. LIS1) [ (PUBMED:11734546) (PUBMED:12384287) (PUBMED:12559565) ]. The CTLH domain can also be found in the absence of the LisH motif, like in:

• Arabidopsis thaliana (Mouse-ear cress) hypothetical protein MUD21.5.
• Saccharomyces cerevisiae yeast protein RMD5.