Alternative titles; symbols
HGNC Approved Gene Symbol: ANGPTL2
Cytogenetic location: 9q33.3 Genomic coordinates (GRCh38) : 9:127,087,348-127,122,635 (from NCBI)
Angiopoietin family members have characteristic protein structures that include an N-terminal coiled-coil domain and a C-terminal fibrinogen-like domain. By degenerate PCR using oligonucleotides based on ANGPT1 (601667) and ANGPT2 (601922), Kim et al. (1999) identified a human heart cDNA encoding ANGPTL2, which they called ARP2 for 'angiopoietin-related protein-2.' The predicted 493-amino acid ANGPTL2 protein contains the coiled-coil and fibrinogen-like domains that are conserved in angiopoietins. ANGPTL2 also has a putative N-terminal secretory signal sequence and 2 potential glycosylation sites. Human ANGPTL2 shares 95% amino acid sequence identity with mouse Angptl2, 59% identity with human ANGPTL1 (603874), 35% identity with mouse Angpt3 and human ANGPT4 (603705), and 34% identity with human ANGPT1 and ANGPT2. Recombinant ANGPTL2 expressed in mammalian cells was secreted and glycosylated. By Western blot analysis, recombinant ANGPTL2 had a molecular mass of approximately 64 kD. Northern blot analysis of human adult tissues detected abundant expression of a major 4.0- and a minor 2.6-kb ANGPTL2 transcript in heart, small intestine, spleen, and stomach. Both transcripts were expressed less abundantly in colon, ovary, adrenal gland, skeletal muscle, and prostate. In situ hybridization of rat embryo showed abundant expression of Angptl2 transcripts in the walls of the aortic trunk, pulmonary trunk, and descending aorta, and expression in the tongue, abdominal muscles, and back muscles.
Kim et al. (1999) found that recombinant ANGPTL2 protein induced sprouting in vascular endothelial cells but did not bind to the TIE1 (600222) or TIE2 (600221) receptors. They suggested that ANGPTL2 may exert a function on endothelial cells through autocrine or paracrine action.
By microarray analysis, Zhang et al. (2006) showed that mouse hematopoietic stem cell (HSC)-supportive fetal liver Cd3 (see 186830)-positive cells expressed Angptl2 and Angptl3 (604774). Long-term HSC expansion occurred when HSCs were cultured in the presence of Angptl2 and Angptl3 together with saturating levels of other growth factors. Several other angiopoietin-like proteins, though not all, also supported HSC growth. Zhang et al. (2006) concluded that angiopoietin-like proteins can be potent stimulators of ex vivo expansion of HSCs.
Zheng et al. (2012) showed that the human immune inhibitory receptor leukocyte immunoglobulin-like receptor B2 (LILRB2; 604815) and its mouse ortholog paired immunoglobulin-like receptor (PIRB) are receptors for several angiopoietin-like proteins, including ANGPTL2. LILRB2 and PIRB are expressed on human and mouse hematopoietic stem cells, respectively, and the binding of ANGPTLs to these receptors supported ex vivo expansion of hematopoietic stem cells. In mouse transplantation acute myeloid leukemia models, a deficiency in intracellular signaling of PIRB resulted in increased differentiation of leukemia cells, revealing that PIRB supports leukemia development. Zheng et al. (2012) concluded that their study indicated an unexpected functional significance of classical immune inhibitory receptors in maintenance of stemness of normal adult stem cells and in support of cancer development.
Kim, I., Moon, S.-O., Koh, K. N., Kim, H., Uhm, C.-S., Kwak, H. J., Kim, N.-G., Koh, G. Y. Molecular cloning, expression, and characterization of angiopoietin-related protein: angiopoietin-related protein induces endothelial cell sprouting. J. Biol. Chem. 274: 26523-26528, 1999. [PubMed: 10473614] [Full Text: https://doi.org/10.1074/jbc.274.37.26523]
Zhang, C. C., Kaba, M., Ge, G., Xie, K., Tong, W., Hug, C., Lodish, H. F. Angiopoietin-like proteins stimulate ex vivo expansion of hematopoietic stem cells. Nature Med. 12: 240-245, 2006. [PubMed: 16429146] [Full Text: https://doi.org/10.1038/nm1342]
Zheng, J., Umikawa, M., Cui, C., Li, J., Chen, X., Zhang, C., Huynh, H., Kang, X., Silvany, R., Wan, X., Ye, J., Canto, A. P., Chen, S.-H., Wang, H.-Y., Ward, E. S., Zhang, C. C. Inhibitory receptors bind ANGPTLs and support blood stem cells and leukaemia development. Nature 485: 656-660, 2012. Note: Erratum: Nature 488: 684 only, 2012. [PubMed: 22660330] [Full Text: https://doi.org/10.1038/nature11095]