TSPAN33
Description
The TSPAN33 (tetraspanin 33) is a protein-coding gene located on chromosome 7.
TSPAN33, also known as Penumbra or Proerythroblast new membrane, is a tetraspanin protein that belongs to the TspanC8 subgroup. This subgroup comprises six members that interact with the transmembrane metalloprotease ADAM10, which is required for ADAM10's exit from the endoplasmic reticulum, its enzymatic maturation and trafficking to the cell surface, and its substrate specificity. Different TspanC8/ADAM10 complexes have distinct substrates. TSPAN33 plays a significant role in normal erythropoiesis and the differentiation of erythroid progenitors. It negatively regulates ligand-induced Notch activity by regulating ADAM10 activity. TSPAN33 mediates the docking of ADAM10 to zonula adherens by interacting with ADAM10 and, in a PDZD11-dependent manner, with the zonula adherens protein PLEKHA7. It forms homodimers that are linked by disulfide bonds. TSPAN33 interacts with ADAM10 via its extracellular domain, and with PLEKHA7 via its cytoplasmic domain. This interaction with PLEKHA7 is dependent on PDZD11 being bound to PLEKHA7 and facilitates the docking of ADAM10 to zonula adherens.
TSPAN33 is a member of the TspanC8 subgroup, which consists of six proteins that interact with the transmembrane metalloprotease ADAM10. This interaction is essential for ADAM10's exit from the endoplasmic reticulum, its enzymatic maturation and trafficking to the cell surface, and its substrate specificity. Different TspanC8/ADAM10 complexes are known to have distinct substrates. TSPAN33 plays a crucial role in normal erythropoiesis and the differentiation of erythroid progenitors. It negatively regulates ligand-induced Notch activity, potentially by controlling ADAM10 activity. TSPAN33 facilitates the docking of ADAM10 to zonula adherens by interacting with both ADAM10 and the zonula adherens protein PLEKHA7 in a PDZD11-dependent manner.
TSPAN33 is also known as PEN, PEN., TSPAN-33.
Associated Diseases
- systemic lupus erythematosus
- beta-thalassemia-X-linked thrombocytopenia syndrome
- X-linked sideroblastic anemia 1
- hereditary persistence of fetal hemoglobin-sickle cell disease syndrome
- alpha-thalassemia-myelodysplastic syndrome
- dehydrated hereditary stomatocytosis
- primary familial polycythemia due to EPO receptor mutation
- hereditary elliptocytosis
- erythroleukemia, familial, susceptibility to
- dominant beta-thalassemia
