Sprouty-related, EVH1 domain-containing protein 2
Function
Negatively regulates Ras signaling pathways and downstream activation of MAP kinases (PubMed:15683364, PubMed:34626534). Recruits and translocates NF1 to the cell membrane, thereby enabling NF1-dependent hydrolysis of active GTP-bound Ras to inactive GDP-bound Ras (PubMed:34626534). Inhibits fibroblast growth factor (FGF)-induced retinal lens fiber differentiation, probably by inhibiting FGF-mediated phosphorylation of ERK1/2 (By similarity). Inhibits TGFB-induced epithelial-to-mesenchymal transition in lens epithelial cells (By similarity).
Involvement in disease
Noonan syndrome 14
NS14
A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. NS14 inheritance is autosomal recessive.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylated on serine and threonine residues (PubMed:15683364). Phosphorylated on tyrosine. Phosphorylation of Tyr-228 and Tyr-231 are required for ubiquitination (PubMed:17094949).
Ubiquitinated; leading to degradation by the proteasome.
Tissue Specificity
Expressed in liver, skin, small intestine, salivary gland and prostate.
Cellular localization
- Cell membrane
- Peripheral membrane protein
- Cytoplasmic side
- Cytoplasmic vesicle
- Secretory vesicle membrane
- Peripheral membrane protein
- Cytoplasmic side
- Cytoplasm
- Detected in the cytoplasm of the stratum spinosum cells, where it is associated with cytoplasmic vesicles that are supposed to be secretory granules.
Alternative names
Spred-2, SPRED2