angiomotin interacts with TEAD and actin cytoskeleton.
//////Angiomotin belongs to a novel protein family with conserved coiled-coil and PDZ binding domains. Bratt A et al. Angiomotin has previously been identified in a yeast two-hybrid screen by its ability to bind to angiostatin, an inhibitor of novel formation of blood vessels (angiogenesis). Angiomotin mediates the inhibitory effect of angiostatin on endothelial cell migration and tube formation in vitro. Here we report that two human protein sequences, of which one is novel and one has been cloned previously, are similar to angiomotin and are members of a novel protein family, which we propose to call motins. These two genes have been named angiomotin-like 1 (amotl1) and angiomotin-like 2 (amotl2). We have cloned mouse angiomotin and identified amotl1 and amotl2 homologs in mice. The alignment of the amino acid sequences encoded by these six sequences spans 455 residues of which 64% was conserved in all six proteins. Sequence analysis showed that these sequences all share putative coiled-coil domains and PDZ-binding motifs. Sequence information from GenBank indicate that motins can be found in several species including the frog Xenopus laevis, the pufferfish Fugu rubripes and the nematode Caenorhabditis elegans. Further phylogenetic analysis indicates that amotl2 is an evolutionary outgroup in relation to angiomotin and amotl1. Northern blot analysis shows distinct expression patterns for each motin in various mouse tissues.
NCBI Summary:
Angiomotin is a protein that binds angiostatin, a circulating inhibitor of the formation of new blood vessels (angiogenesis). Angiomotin mediates angiostatin inhibition of endothelial cell migration and tube formation in vitro. The protein encoded by this gene is related to angiomotin and is a member of the motins protein family. [provided by RefSeq, Jul 2008]
General function
Comment
Angiomotin family proteins are novel activators of the LATS2 kinase tumor suppressor. Paramasivam M et al. LATS2 kinase functions as part of the Hippo pathway to promote contact inhibition of growth and tumor suppression by phosphorylating and inhibiting the transcriptional coactivator YAP. LATS2 is activated by the MST2 kinase. How LATS2 is activated by MST2 in response to changes in cell density is unknown. Here we identify the angiomotin-family tight junction protein AMOTL2 as a novel activator of LATS2. Like AMOTL2, the other angiomotin-family proteins AMOT and AMOTL1 also activate LATS2 through a novel conserved domain that binds and activates LATS2. AMOTL2 binds MST2, LATS2, and YAP, suggesting that AMOTL2 might serve as a scaffold protein. We show that LATS2, AMOTL2, and YAP all localize to tight junctions, raising the possibility that clustering of Hippo pathway components at tight junctions might function to trigger LATS2 activation and growth inhibition in response to increased cell density.