CLEC1B


C-type lectin domain family 1 member B is a cell surface receptor protein. It binds certain biomolecules that act as ligands that when bound to the CLEC-1b expressed by cells stimulates certain functions in these cells. The human CLEC-1b receptor is encoded by the CLEC1B gene which is located on the short -arm of chromosome 12 at region 1, band 3, sub-band 1 to sub-band 2. Most of the recent literature terms the C-type lectin domain family 1 member B as CLEC-2. Since current reports commonly use CLEC-2 rather than CLEC-1b, CLEC-2 will be used here in place of CLEC1b in further describing this protein.
CLEC-2 is a member of the broad family of pattern recognition receptors toll-like receptors, b) NOD-like receptors, c) RIG-I-like receptors, d) AIM2 C-type lectin receptors. CLRs are a superfamily of more than 1,000 proteins. They are subdivided into 17 subgroups. All members of this family possess one or more C-type lectin-like domains, i.e., protein domains that have a characteristic loop-in-a-loop structure formed by their amino acid sequences which form a large loop that encloses a smaller, internal loop or some other type of secondary structure. These internal loops or other structures are formed by two disulfide bridges located at the bases of these loops. CLEC-2 is a C-type lectin receptor.

Agents activating CLEC-2

While podoplanin is the most studied activator of CLEC-2, CLEC-2 is also activated by: rhodocytin ; hemin ; galectin-9; the human immunodeficiency virus ; dextran sulfate; sulfated polysaccharides; fucoidan ; katacine ; S100A13 ; humsn CLEC7A ; and the soot, carbon, and other particles in the exhaust gas of diesel engines.

Cells expressing CLEC-2

CLEC-2 is highly expressed on mouse and human platelets as well as megakaryocytes, i.e., platelet-forming cells. It is also expressed on the surface membranes of myeloid cells, epithelial cells in lymphatic vessels, and cancer-associated fibroblasts.

Functions of activated CLEC-2

Podoplanin activation of CLEC-2

Based primarily on preclinical studies done in rodents, podoplanin-induced activation of CLEC-2 on megakaryocytes promotes their production of platelets; b) ischemia/reperfusion tissue damage, cancer-associated venous thromboembolisms, atherosclerosis, and regeneration of the liver after 70% of it is removed experimentally; and c) on the platelets of fetuses in order for them to develop normal normal blood vessels, lymphatic vessels, the heart, and lung.

S100A13 activation of CLEC-2

Studies in isolated human and mouse aortas and mice strongly suggest that the S100A13 expressed on the surface of smooth muscle cells is responsible for activating platelets and causing thrombus formation during the early stages of thrombus formation before podoplanin is expressed.

C-type lectin domain family 7 member A activation of CLEC-2

Studies in various cultured cell systems indicate that the CLEC7A from humans as well as the dectin-1 proteins isolated from the cells of higher primates activate human as well as mouse CLEC-2. However, the CLEC7A protein isolated from mouse cells does not activate human or mouse CLEC-2. A structurally similar protein, CLEC6A has a very different set of actions and does not activate CLEC-2. CLEC7A in humans is expressed on the surface membranes of vascular endothelial cells, tissue dendritic cells, tissue macrophages, and circulating white blood cells such as neutrophils, monocytes, and circulating dendritic cells. CLEC7A identifies and interacts with various fungi which may control physiological processes through platelets thrombosis-independent mechanisms. Further studies may show that CLEC-2 is useful for inhibiting bleeding without causing thrombosis.