Alternative titles; symbols
HGNC Approved Gene Symbol: ANGPT4
Cytogenetic location: 20p13 Genomic coordinates (GRCh38) : 20:869,900-916,334 (from NCBI)
Angiopoietins are members of the vascular endothelial growth factor family and the only known growth factors largely specific for vascular endothelium. The angiopoietins include a naturally occurring agonist, angiopoietin-1 (ANGPT1; 601667), as well as a naturally occurring antagonist, angiopoietin-2 (ANGPT2; 601922), both of which act by means of the TIE2 receptor (600221). Using homology-based cloning approaches, Valenzuela et al. (1999) identified 2 novel angiopoietins: angiopoietin-3 (Angpt3) in mouse, and angiopoietin-4 (ANGPT4) in human. They also identified several more distantly related sequences that did not seem to be true angiopoietins in that they did not bind to TIE receptors. Although angiopoietin-3 and angiopoietin-4 are more structurally diverged from each other than are the mouse and human versions of angiopoietin-1 and angiopoietin-2, they appear to represent the mouse and human counterparts of the same gene locus, as revealed in chromosomal localization studies of all the angiopoietins in mouse and human. The structural divergence of angiopoietin-3 and angiopoietin-4 appeared to underlie the diverging functions of these counterparts. Northern blot analysis showed that angiopoietin-3 was expressed as a major 2.5- and a minor 1.1-kb transcript in multiple mouse tissues, whereas angiopoietin-4 was expressed as a major 5- and a minor 4-kb transcript primarily in human lung.
Expression studies by Valenzuela et al. (1999) suggested that mouse angiopoietin-3 acts as an antagonist, whereas its human counterpart, angiopoietin-4, functions as an agonist.
Ward et al. (2001) determined that the ANGPT4 gene contains 9 exons and spans 20.0 kb. Exons 1 to 5 encode the N terminus, the coiled-coil domain, and part of the hinge region, and exons 5 to 9 encode the remainder of the hinge region, the fibrinogen (see 134820)-like domain, and the C terminus.
By FISH, Valenzuela et al. (1999) mapped the ANGPT4 gene to human chromosome 20p13. By interspecific backcross hybridization, they mapped Angpt3, the mouse homolog, to a region of syntenic homology on chromosome 2. Using radiation hybrid analysis and FISH, Grosios et al. (1999) also mapped the ANGPT4 gene to chromosome 20p13.
Grosios, K., Leek, J. P., Markham, A. F., Yancopoulos, G. D., Jones, P. F. Assignment of ANGPT4, ANGPT1, and ANGPT2 encoding Angiopoietins 4, 1 and 2 to human chromosome bands 20p13, 8q22.3-q23 and 8p23.1, respectively, by in situ hybridization and radiation hybrid mapping. Cytogenet. Cell Genet. 84: 118-120, 1999. [PubMed: 10343124] [Full Text: https://doi.org/10.1159/000015235]
Valenzuela, D. M., Griffiths, J. A., Rojas, J., Aldrich, T. H., Jones, P. F., Zhou, H., McClain, J., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Huang, T., Papadopoulos, N., Maisonpierre, P. C., Davis, S., Yancopoulos, G. D. Angiopoietins 3 and 4: diverging gene counterparts in mice and humans. Proc. Nat. Acad. Sci. 96: 1904-1909, 1999. [PubMed: 10051567] [Full Text: https://doi.org/10.1073/pnas.96.5.1904]
Ward, E. G., Grosios, K., Markham, A. F., Jones, P. F. Genomic structures of the human angiopoietins show polymorphism in angiopoietin-2. Cytogenet. Cell Genet. 94: 147-154, 2001. [PubMed: 11856872] [Full Text: https://doi.org/10.1159/000048807]