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| Description | Angiomotin protein is 1084 amino acid residues in length. It contains two coiled coil domains 429-689 (261), 721-751 (31), a PDZ-binding motif 1081-1084 (4), a SMC_prok_B region 429-549 (121), and an angiomotin_C terminal 599-794 (196). Phosphorylations occur on S305, S312, S712, S714, T717, Y719, and T1061. Phosphorylated upon DNA damage, probably by ATM or ATR.
Isoforms:
- Isoform 1: p130 angiomotin
1084 amino acids, 118085 Da. This isoform has been chosen as the 'canonical' sequence.
- Isoform 2: p80 angiomotin
675 amino acids, 72540 Da. The isoform differs from the canonical sequence with N-terminal alternative splicing region 1-409 (409) missing, which mediates the binding of angiomotin to F-actin stress fibres. The SMC_prok_B region is also missing in this isoform. |
| Expression | Expressed in placenta and skeletal muscle. Predominantly expressed in endothelial cells of capillaries, larger vessels of the placenta. |
| Localisation | Cell junction, tight junction. Localized on the cell surface. May act as a transmembrane protein. |
| Function | Mediates inhibitory effect of angiostatin on tube formation and the migration of endothelial cells toward growth factors during the formation of new blood vessels in the larger vessels of the placenta. Isoform-1 is found to control cell shape by association with F-actin fibres through N-terminal part of protein. The isoform 2 (p80) promotes angiogenesis, in part, by conferring a hypermigratory phenotype to endothelial cells. |
| Homology | The percent identity below represents identity of AMOT over an aligned region in Unigene.
Mus musculus: 88.1 (percent identity)
Oryctolagus cuniculus: 79
Sus scrofa: 72
Danio rerio: 68.9
Fugu rubripes: 65
Xenopus laevis: 61.8
Caenorhabditis elegans: 46
Saccharomyces cerevisiae: 47
Drosophila melanogaster: 36 |
| Note | |
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| Entity | Breast cancer |
| Note | Angiomotin is linked to angiogenesis and aggressive nature of breast tumours. Angiomotin shows high level of expression in mammary tissues during tumour stages as compared to normal expression level (33.1 ± 11 in normal versus 86.5 ± 13.7 in tumour tissues, p=0.0003). Significant high expression was found in aggressive tumours (grade 2, grade 3 and with nodal involvement) compared with less aggressive grade 1 tumour (p<0.001 and p=0.05 respectively). Angiogenesis is the essential process in the development and spread of breast cancer, by providing blood supply to tumours and escape route for tumour cells to other part of the body. |
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| Entity | Hemangioendothelioma invasion |
| Disease | Angiomotin expression promotes hemangioendothelioma invasion. Expression of human angiomotin in mouse aortic endothelial (MAE) cells results in stabilization of tubes in the Matrigel assay. Cells from the established tubes invaded into the solidified matrigel, however, cells expressing a functional mutant lacking the PDZ protein interaction motif did not migrate and form tubes. Angiomotin may promote angiogenesis by both stimulating invasion as well as stabilizing established tubes. |
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| Entity | Endothelial cell migration and tube formation |
| Note | Upon expression of angiomotin in HeLa cells, angiomotin bound and internalized fluorescein-labeled angiostatin, a circulating inhibitor of angiogenesis. In endothelial cells, angiomotin protein is localized to the leading edge of migrating cells and results in increased cell migration. Angiomotin-transfected MAE cells bind and respond to angiostatin by inhibition of cell migration and tube formation, which suggest that angiomotin regulates endothelial cell migration and tube formation. |
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| Angiomotin regulates endothelial cell-cell junctions and cell motility. |
| Bratt A, Birot O, Sinha I, Veitonmaki N, Aase K, Ernkvist M, Holmgren L. |
| J Biol Chem. 2005 Oct 14;280(41):34859-69. Epub 2005 Jul 25. |
| PMID 16043488 |
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| Angiomotin belongs to a novel protein family with conserved coiled-coil and PDZ binding domains. |
| Bratt A, Wilson WJ, Troyanovsky B, Aase K, Kessler R, Van Meir EG, Holmgren L. |
| Gene. 2002 Sep 18;298(1):69-77. |
| PMID 12406577 |
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| The Amot/Patj/Syx signaling complex spatially controls RhoA GTPase activity in migrating endothelial cells. |
| Ernkvist M, Luna Persson N, Audebert S, Lecine P, Sinha I, Liu M, Schlueter M, Horowitz A, Aase K, Weide T, Borg JP, Majumdar A, Holmgren L. |
| Blood. 2009 Jan 1;113(1):244-53. Epub 2008 Sep 29. |
| PMID 18824598 |
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| Human angiomotin-like 1 associates with an angiomotin protein complex through its coiled-coil domain and induces the remodeling of the actin cytoskeleton. |
| Gagne V, Moreau J, Plourde M, Lapointe M, Lord M, Gagnon E, Fernandes MJ. |
| Cell Motil Cytoskeleton. 2009 Sep;66(9):754-68. |
| PMID 19565639 |
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| A DNA vaccine targeting angiomotin inhibits angiogenesis and suppresses tumor growth. |
| Holmgren L, Ambrosino E, Birot O, Tullus C, Veitonmaki N, Levchenko T, Carlson LM, Musiani P, Iezzi M, Curcio C, Forni G, Cavallo F, Kiessling R. |
| Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9208-13. Epub 2006 Jun 5. |
| PMID 16754857 |
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| Angiomotin and angiomotin like proteins, their expression and correlation with angiogenesis and clinical outcome in human breast cancer. |
| Jiang WG, Watkins G, Douglas-Jones A, Holmgren L, Mansel RE. |
| BMC Cancer. 2006 Jan 23;6:16. |
| PMID 16430777 |
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| Angiomotin expression promotes hemangioendothelioma invasion. |
| Levchenko T, Bratt A, Arbiser JL, Holmgren L. |
| Oncogene. 2004 Feb 19;23(7):1469-73. |
| PMID 14730344 |
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| Angiomotin: an angiostatin binding protein that regulates endothelial cell migration and tube formation. |
| Troyanovsky B, Levchenko T, Mansson G, Matvijenko O, Holmgren L. |
| J Cell Biol. 2001 Mar 19;152(6):1247-54. |
| PMID 11257124 |
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| A Rich1/Amot complex regulates the Cdc42 GTPase and apical-polarity proteins in epithelial cells. |
| Wells CD, Fawcett JP, Traweger A, Yamanaka Y, Goudreault M, Elder K, Kulkarni S, Gish G, Virag C, Lim C, Colwill K, Starostine A, Metalnikov P, Pawson T. |
| Cell. 2006 May 5;125(3):535-48. |
| PMID 16678097 |
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| Hold that line. Angiomotin regulates endothelial cell motility. |
| Zetter BR. |
| J Cell Biol. 2001 Mar 19;152(6):F35-6. |
| PMID 11257132 |
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