Angiomotin

15479627494ENSG00000126016ENSMUSG00000041688Q4VCS5Q8VHG2NM_001113490NM_133265NM_001290274NM_153319NP_001106962NP_573572NP_001277203NP_695231Angiomotin (AMOT) is a protein that in humans is encoded by the AMOT gene. It belongs to the motin family of angiostatin binding proteins, which includes angiomotin, angiomotin-like 1 (AMOTL1) and angiomotin-like 2 (AMOTL2) characterized by coiled-coil domains at N-terminus and consensus PDZ-binding domain at the C-terminus. Angiomotin is expressed predominantly in endothelial cells of capillaries as well as angiogenic tissues such as placenta and solid tumor. Angiomotin (AMOT) is a protein that in humans is encoded by the AMOT gene. It belongs to the motin family of angiostatin binding proteins, which includes angiomotin, angiomotin-like 1 (AMOTL1) and angiomotin-like 2 (AMOTL2) characterized by coiled-coil domains at N-terminus and consensus PDZ-binding domain at the C-terminus. Angiomotin is expressed predominantly in endothelial cells of capillaries as well as angiogenic tissues such as placenta and solid tumor. Angiomotin was discovered in 2001 by screening a placenta yeast two-hybrid cDNA library for angiostatin-binding peptides, using a construct encoding the kringle domains 1-4 of angiostatin. AMOT gene is located on human chromosome X:112,021,794-112,066,354, containing 3252 nucleotides in coding sequence as 11 exons. Two splice isoforms are known for angiomotin: p80 and p130. The alternative splicing is somewhat tissue specific. Cells expressing p130 contained more actin than those expressing p80. p80 is not the product of cleavage of p130, as p130 contains no potential proteolytic cleavage site for such conversion. Angiomotin p80 is a 72.54 kD protein of 675 residues, characterized by conserved N-terminal coiled coil domains and C-terminal PDZ binding motifs, with angiostatin binding domain (ABD) located in the central region. It is hypothesized that the ABD is extracellular, while the coiled-coil and the PDZ binding domain are intracellular. The PDZ-binding motif of angiomotin serves as a protein recognition site and deletion of as few as three amino acids from the C-terminal results in complete loss of pro-migratory activity, and endothelial cells expressing such mutant angiomotin failed to migrate or form tubes. Angiomotin p130 differs from p80 by having an N-ternimal cytoplasmic extension of 409 amino acids rich in glutamine, which mediates the binding of p130 to F-actin and tight cell-cell junctions. This binding remains after destabilizing actin with cytochalasin B. Like other surface-associated proteins that can bind plasminogen and its derivatives, angiomotin does not appear to have a signal sequence, thus its association with the cell surface may be via protein–protein interaction usually referred to as non-classic secretion. Expression of angiomotin p80 in endothelial cells increases the random migration of endothelial cells, as well as the migration of endothelial cells toward growth factors, e.g. bFGF, VEGF and LPA etc. Angiomotin also mediates tube formation of endothelial cells. Angiomotin promotes angiogenesis by both stimulating cell spreading and stabilizing established tubes, e.g. in mouse aortic endothelial (MAE) cells the tubes remained stable for over 30 days, while control tubes started to regress after 3 days. In the presence of angiostatin, endothelial cells expressing angiomotin p80 exhibit reduction in migration as well as reduction in tubules formation in vitro. These observations are consistent with the localization of angiomotin in the leading edge of migrating cells. Angiostatin therefore, is an inhibitor of angiomotin. Angiomotin p80 locates and binds angiostatin on the cell surface. In primary endothelial of Chinese hamster ovary, it localizes to cell-cell junction, recruits ZO-1 and interacts with MAGI-1. It may play a role in the assembly of endothelial cell-cell junctions, as well.