THSD1: Proteins and Enzymes

Mouse THSD1 (Thrombospondin type-1 domain-containing protein 1), also known as Transmembrane molecule with thrombospondin module (Tmtsp), is a 95 kDa, type I transmembrane protein. It is synthesized as a precursor that is 851 amino acids (aa) in length, and has a 24 aa signal sequence, a 388 aa extracellular region, a 21 aa transmembrane region, and a 418 aa cytoplasmic region. The extracellular region contains six potential N-linked glycosylation sites and the thrombospondin type-1 (TSP1) domain, which is implicated in cell adhesion and migration. Also present in the molecule are 9 PKC-phosphorylation sites, 3 Ig-like domains, and a tyrosine-phosphorylation site by its C-terminus. Mouse THSD1 shares 78% aa sequence identity with human THSD1. THSD1 is highly expressed in hematopoietic stem cells (HSCs) and progenitor cells, including CD34^-/lowKit⁺Sca-1⁺Lin^- HSCs, CD34⁺Kit⁺Sca-1⁺Lin^- and Lin^- progenitor cells, and to a lesser degree in thymic CD4^-CD8^- cells. Expression gradually decreases during T cell differentiation. In addition, THSD1 is widely expressed on endothelial cells, with highest expression in the lung. THSD1's ligand and function are unknown, but it is postulated that THSD1 may be involved in the regulation of vasculogenesis and/or angiogenesis through its interaction with its specific ligand. THSD1 may function in primitive hematopoietic cells in the bone marrow niche, and through its TSP1 and Ig-like domains, it may play a role in HSC homing to the niche following cell-to-cell contact to maintain hematopoietic stem cell quiescence.