SPRY4

Domain

The Cys-rich domain is responsible for the localization of the protein to the membrane ruffles.

Function

Suppresses the insulin receptor and EGFR-transduced MAPK signaling pathway, but does not inhibit MAPK activation by a constitutively active mutant Ras (PubMed:12027893). Probably impairs the formation of GTP-Ras (PubMed:12027893). Inhibits Ras-independent, but not Ras-dependent, activation of RAF1 (PubMed:12717443). Represses integrin-mediated cell spreading via inhibition of TESK1-mediated phosphorylation of cofilin (PubMed:15584898).

Involvement in disease

Hypogonadotropic hypogonadism 17 with or without anosmia

HH17

A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).

None

The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. Some patients carrying mutations in SPRY4 also have a heterozygous mutation in another HH-associated gene including DUSP6 and FGFR1 (PubMed:23643382).

Sequence similarities

Belongs to the sprouty family.

Cellular localization

• Cytoplasm
• Cell projection
• Ruffle membrane
• Peripheral membrane protein
• Cytoplasmic side
• Found in the cytoplasm in unstimulated cells but is translocated to the membrane ruffles in cells stimulated with EGF (epidermal growth factor) (By similarity). Colocalizes with TESK1 in vesicular spots in the cytoplasm (PubMed:15584898).

Alternative names

• Protein sprouty homolog 4
• Spry-4
• SPRY4

Database links

• entrezGene:81848
• omim:607984
• swissprot:Q9C004

Target type

Proteins

Molecular weight

32541Da