Alternative titles; symbolsANGIOPOIETIN 3, FORMERLY; ANGPT3, FORMERLY; ANG3, FORMERLYHGNC Approved Gene Symbol: ANGPTL1Cytogenetic location: 1q25.2 Genomic c...
Alternative titles; symbols
HGNC Approved Gene Symbol: ANGPTL1
Cytogenetic location: 1q25.2 Genomic coordinates (GRCh38): 1:178,849,534-178,871,076 (from NCBI)
ANGPTL1 encodes an angiopoietin-like protein (ANGPTL) and is a member of a family of secreted glycoproteins that support the activity of hematopoietic stem cells (summary by Zheng et al., 2012).
▼ Cloning and Expression
Angiopoietin-1 (ANGPT1; 601667), angiopoietin-2 (ANGPT2; 601922), and angiopoietin-4 (ANGPT4; 603705) are members of the vascular endothelial growth factor family and participate in the formation of blood vessels. Kim et al. (1999) used homology-based PCR to isolate an adult human heart cDNA encoding a novel member of the angiopoietin family, angiopoietin-like-1 (ANGPTL1), which they called angiopoietin-3 (ANGPT3). ANGPTL1 is widely expressed in human adult tissues as a major 3.0-kb transcript and a less abundant 4.0-kb transcript. Its mRNA levels are highest in highly vascularized tissues. The deduced 491-amino acid ANGPTL1 protein is 29% identical to ANGPT1 and 26% identical to ANGPT2. ANGPTL1 contains the N-terminal coiled-coil domain and C-terminal fibrinogen-like domain characteristic of angiopoietins, as well as several potential glycosylation sites. ANGPTL1 has a putative signal sequence at its N terminus, and the authors demonstrated that the protein is secreted. Like ANGPT1, ANGPTL1 is not an endothelial cell mitogen in vitro.
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 ANGPTL1. 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.