AMOT (angiomotin)

2010-03-01   Roshan Mandrawalia , Ranjan Tamuli 

Department of Biotechnology, Indian Institute of Technology Guwahati, Guwahati-781 039, Assam, India

Identity

HGNC
LOCATION
Xq23
LOCUSID
ALIAS
KIAA1071
FUSION GENES

DNA/RNA

Atlas Image

Description

DNA size 66.31 kb, mRNA size 6888 bp, 12 exons.

Proteins

Atlas Image

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

Mutations

Note

Several polymorphisms have been found but none of them has shown any association with a disease. Furthermore, endothelial cells expressing mutated angiomotins have been reported failure in their function, including failure to migrate and inhibition of angiogenesis. Mutation with deletion of three amino acids from PDZ-binding motif results in inhibition of chemotaxis, embryos with this mutation may lead to death on embryonic day 9.5.

Implicated in

Entity name
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
Entity name
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.
Entity name
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.

Bibliography

Pubmed IDLast YearTitleAuthors
160434882005Angiomotin regulates endothelial cell-cell junctions and cell motility.Bratt A et al
124065772002Angiomotin belongs to a novel protein family with conserved coiled-coil and PDZ binding domains.Bratt A et al
188245982009The Amot/Patj/Syx signaling complex spatially controls RhoA GTPase activity in migrating endothelial cells.Ernkvist M et al
195656392009Human angiomotin-like 1 associates with an angiomotin protein complex through its coiled-coil domain and induces the remodeling of the actin cytoskeleton.Gagné V et al
167548572006A DNA vaccine targeting angiomotin inhibits angiogenesis and suppresses tumor growth.Holmgren L et al
164307772006Angiomotin and angiomotin like proteins, their expression and correlation with angiogenesis and clinical outcome in human breast cancer.Jiang WG et al
147303442004Angiomotin expression promotes hemangioendothelioma invasion.Levchenko T et al
112571242001Angiomotin: an angiostatin binding protein that regulates endothelial cell migration and tube formation.Troyanovsky B et al
166780972006A Rich1/Amot complex regulates the Cdc42 GTPase and apical-polarity proteins in epithelial cells.Wells CD et al
112571322001Hold that line. Angiomotin regulates endothelial cell motility.Zetter BR et al

Other Information

Locus ID:

NCBI: 154796
MIM: 300410
HGNC: 17810
Ensembl: ENSG00000126016

Variants:

dbSNP: 154796
ClinVar: 154796
TCGA: ENSG00000126016
COSMIC: AMOT

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000126016ENST00000304758Q4VCS5
ENSG00000126016ENST00000371958A6NP16
ENSG00000126016ENST00000371959Q4VCS5
ENSG00000126016ENST00000371962E7ERM3
ENSG00000126016ENST00000524145Q4VCS5

Expression (GTEx)

0
5
10
15
20

Pathways

PathwaySourceExternal ID
Tight junctionKEGGko04530
Tight junctionKEGGhsa04530
Hippo signaling pathwayKEGGhsa04390
Hippo signaling pathwayKEGGko04390
Signal TransductionREACTOMER-HSA-162582
Signaling by HippoREACTOMER-HSA-2028269

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
212243872011Hippo pathway-independent restriction of TAZ and YAP by angiomotin.161
214817932011A tight junction-associated Merlin-angiomotin complex mediates Merlin's regulation of mitogenic signaling and tumor suppressive functions.95
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
246484942014Angiomotins link F-actin architecture to Hippo pathway signaling.66
240032542013The p130 isoform of angiomotin is required for Yap-mediated hepatic epithelial cell proliferation and tumorigenesis.60
241062672013Phosphorylation of angiomotin by Lats1/2 kinases inhibits F-actin binding, cell migration, and angiogenesis.60
160434882005Angiomotin regulates endothelial cell-cell junctions and cell motility.58
188245982009The Amot/Patj/Syx signaling complex spatially controls RhoA GTPase activity in migrating endothelial cells.57
241015132013Serum deprivation inhibits the transcriptional co-activator YAP and cell growth via phosphorylation of the 130-kDa isoform of Angiomotin by the LATS1/2 protein kinases.57
195900462009Angiomotin-like protein 1 controls endothelial polarity and junction stability during sprouting angiogenesis.48

Citation

Roshan Mandrawalia ; Ranjan Tamuli

AMOT (angiomotin)

Atlas Genet Cytogenet Oncol Haematol. 2010-03-01

Online version: http://atlasgeneticsoncology.org/gene/632/amot