HGNC Approved Gene Symbol: ANGPTL5
Cytogenetic location: 11q22.1 Genomic coordinates (GRCh38) : 11:101,890,674-101,916,522 (from NCBI)
The angiopoietins are a family of growth factors specific for vascular endothelium. During large-scale DNA sequencing of a human fetal brain cDNA library, Zeng et al. (2003) cloned a novel human angiopoietin-like cDNA and termed it angiopoietin-like-5 (ANGPTL5). Like other members of the angiopoietin family, the deduced 388-amino acid ANGPTL5 protein has an N-terminal cleavable signal peptide, a predicted coiled-coil domain, and a fibrinogen-like domain. RT-PCR analysis detected expression of ANGPTL5 in all tissues tested, but mainly in adult human heart.
Romeo et al. (2009) examined levels of ANGPTL5 mRNA in 48 human tissues and found that expression was highest in adipose tissue, with bronchus, epididymis, and vena cava having the next highest levels of expression. The authors noted that although Zeng et al. (2003) reported highest expression of ANGPTL5 in the heart, they did not examine mRNA from adipose tissue; Romeo et al. (2009) detected ANGPTL5 mRNA in the heart at only 20% of the level found in adipose tissue. The transcript was also identified at very low levels in many other tissues.
Zeng et al. (2003) determined that the ANGPTL5 gene contains 8 exons and spans approximately 17.3 kb.
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 ANGPTL5. 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.
By genomic sequence analysis, Zeng et al. (2003) mapped the ANGPTL5 gene to chromosome 11q22.
Romeo, S., Yin, W., Kozlitina, J., Pennacchio, L. A., Boerwinkle, E., Hobbs, H. H., Cohen, J. C. Rare loss-of-function mutations in ANGPTL family members contribute to plasma triglyceride levels in humans. J. Clin. Invest. 119: 70-79, 2009. [PubMed: 19075393] [Full Text: https://doi.org/10.1172/JCI37118]
Zeng, L., Dai, J., Ying, K., Zhao, E., Jin, W., Ye, Y., Dai, J., Xu, J., Xie, Y., Mao, Y. Identification of a novel human angiopoietin-like gene expressed mainly in heart. J. Hum. Genet. 48: 159-162, 2003. [PubMed: 12624729] [Full Text: https://doi.org/10.1007/s100380300025]
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]