Several extracellular heparin-binding proteins involved in regulation of growth and differentiation belong to a new family of growth factors. These growth factors are highly related proteins of about 140 amino acids that contain 10 conserved cysteines probably involved in disulphide bonds, and include pleiotrophin [<cite idref="PUB00015072"/>] (also known as heparin-binding growth-associated molecule HB-GAM, heparin-binding growth factor 8 HBGF-8, heparin-binding neutrophic factor HBNF and osteoblast specific protein OSF-1); midkine (MK) [<cite idref="PUB00015070"/>]; retinoic acid-induced heparin-binding protein (RIHB) [<cite idref="PUB00015071"/>]; and pleiotrophic factors alpha-1and -2 and beta-1 and -2 from <taxon tax_id="8355">Xenopus laevis</taxon>, the homologs of midkine and pleiotrophin respectively. Pleiotrophin is a heparin-binding protein that has neurotrophic activity and has mitogenic activity towards fibroblasts. It is highly expressed in brain and uterus tissues, but is also found in gut, muscle and skin. It is thought to possess an important brain-specific function. Midkine is a regulator of differentiation whose expression is regulated by retinoic acid, and, like pleiotrophin, is a heparin-binding growth/differentiation factor that acts on fibroblasts and nerve cells.<p>This entry represents two conserved sites found within Midkine heparin-binding growth factors; these conserved sites include the majority of the conserved cysteines.</p>