InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: TSPAN12

Summary

InnateDB Protein

IDBP-385786.4

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

TSPAN12

Protein Name

tetraspanin 12

Synonyms

EVR5; NET-2; NET2; TM4SF12;

Species

Homo sapiens

Ensembl Protein

ENSP00000397699

InnateDB Gene

IDBG-38100 (TSPAN12)

Protein Structure

UniProt Annotation

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. {ECO:0000250, ECO:0000269PubMed:19211836, ECO:0000269PubMed:19587294}.

Subcellular Localization

Cell membrane {ECO:0000250}; Multi-pass membrane protein {ECO:0000250}.

Disease Associations

Vitreoretinopathy, exudative 5 (EVR5) [MIM:613310]: 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. {ECO:0000269PubMed:20159111, ECO:0000269PubMed:20159112, ECO:0000269PubMed:22427576}. Note=The disease is caused by mutations affecting the gene represented in this entry. TSPAN12 dominant and recessive mutations have been identified in patients with exudative vitreoretinopathy. Patients with mutations in both alleles of TSPAN12 have severe exudative vitreoretinopathy or retinal dysplasia. These mutations appear to result in a milder phenotype in heterozygous mutation carriers (PubMed:22427576). {ECO:0000269PubMed:22427576}.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 2 experimentally validated interaction(s) in this database.