TSPAN12

TSPAN12 is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. It mediate signal transduction events that function in the regulation of cell development, activation, growth and motility.

Full Name

Tetraspanin 12

Function

Regulator of cell surface receptor signal transduction. Plays a central role in retinal vascularization by regulating norrin (NDP) signal transduction. Acts in concert with norrin (NDP) to promote FZD4 multimerization and subsequent activation of FZD4, leading to promote accumulation of beta-catenin (CTNNB1) and stimulate LEF/TCF-mediated transcriptional programs. Suprisingly, it only activate the norrin (NDP)-dependent activation of FZD4, while it does not activate the Wnt-dependent activation of FZD4, suggesting the existence of a Wnt-independent signaling that also promote accumulation the beta-catenin (CTNNB1) (By similarity).
Acts as a regulator of membrane proteinases such as ADAM10 and MMP14/MT1-MMP. Activates ADAM10-dependent cleavage activity of amyloid precursor protein (APP). Activates MMP14/MT1-MMP-dependent cleavage activity.

Biological Process

Biological Process angiogenesis Source:UniProtKB-KW
Biological Process cell surface receptor signaling pathway Source:UniProtKB
Biological Process regulation of angiogenesis Source:UniProtKB
Biological Process regulation of vascular endothelial growth factor signaling pathway Source:GO_Central1 Publication
Biological Process retina layer formation Source:UniProtKB

Cellular Location

Cell membrane

Involvement in disease

Vitreoretinopathy, exudative 5 (EVR5):
A disorder of the retinal vasculature characterized by an abrupt cessation of growth of peripheral capillaries, leading to an avascular peripheral retina. This may lead to compensatory retinal neovascularization, which is thought to be induced by hypoxia from the initial avascular insult. New vessels are prone to leakage and rupture causing exudates and bleeding, followed by scarring, retinal detachment and blindness. Clinical features can be highly variable, even within the same family. Patients with mild forms of the disease are asymptomatic, and their only disease related abnormality is an arc of avascular retina in the extreme temporal periphery.

Topology

Cytoplasmic: 1-12
Helical: 13-33
Extracellular: 34-59
Helical: 60-80
Cytoplasmic: 81-89
Helical: 90-110
Extracellular: 111-224
Helical: 225-245
Cytoplasmic: 246-305

PTM

Palmitoylated; required for interaction with ADAM10. The precise position of palmitoylated residues is unclear and occurs either on Cys-9, Cys-12 and/or Cys-83.