Recombinant Human ZAG Protein, CF

ZAG (zinc‑ alpha ₂‑glycoprotein; also called AZGP1) is a 40 ‑ 43 kDa secreted member of the MHC class I family of proteins (1 ‑ 5). It was previously called LMF in humans to reflect its activity as a lipid mobilizing factor that is upregulated in plasma and urine of cancer patients with cachexia (4, 6). Human ZAG cDNA encodes a 20 amino acid (aa) signal sequence and a 278 aa mature protein that contains one MHC class I antigen region and a C1‑type Ig‑like domain. The region equivalent to the MHC peptide groove is hydrophobic and likely binds lipid molecules rather than peptides (1, 3). An RGD sequence (aa 251 ‑ 253) that occurs in human but not mouse mediates integrin adhesion (1). ZAG is reported to associate with PIP (prolactin‑inducible protein) but not the MHC light chain, beta 2‑microglobulin (3, 7). Mature human ZAG shares 57 ‑ 66% aa sequence identity with mouse, rat, canine and equine ZAG. Human ZAG is active in mice (6, 8).  It is produced by secretory epithelia and is present in most body fluids (9). It is abundantly produced by adipocytes and is classed as an adipokine that stimulates adiponectin secretion (4, 10, 11). Its expression is downregulated by macrophage‑associated inflammation in adipose tissue, and it is underexpressed in obesity and diabetes (8, 10 ‑ 12). Serum ZAG is produced by liver epithelia, while prostate epithelia produce seminal fluid ZAG that can bind sperm and initiate motility (1, 12). ZAG stimulates lipid breakdown, at least in part by inducing expression of the uncoupling proteins UCP1 and UCP3 (1, 6, 8, 10, 12). It is considered a tumor suppressor, interfering with TGF‑ beta ‑mediated tumor cell invasion and epithelial/mesenchymal transition (5). ZAG can bind beta 3-AR (beta‑3 adrenergic receptor) and can alter beta 3‑AR signaling pathways (8, 10, 13).