KISS1
Function
Metastasis suppressor protein in malignant melanomas and in some breast cancers. May regulate events downstream of cell-matrix adhesion, perhaps involving cytoskeletal reorganization. Generates a C-terminally amidated peptide, metastin which functions as the endogenous ligand of the G-protein coupled receptor GPR54. Activation of the receptor inhibits cell proliferation and cell migration, key characteristics of tumor metastasis. Kp-10 is a decapeptide derived from the primary translation product, isolated in conditioned medium of first trimester trophoblast. Kp-10, but not other kisspeptins, increased intracellular Ca(2+) levels in isolated first trimester trophoblasts. Kp-10 is a paracrine/endocrine regulator in fine-tuning trophoblast invasion generated by the trophoblast itself. The receptor is also essential for normal gonadotropin-released hormone physiology and for puberty. The hypothalamic KiSS1/GPR54 system is a pivotal factor in central regulation of the gonadotropic axis at puberty and in adulthood.
Involvement in disease
Hypogonadotropic hypogonadism 13 with or without anosmia
HH13
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 the gene represented in this entry.
Post-translational modifications
Processed by MMP2 and MMP9.
Sequence Similarities
Belongs to the KISS1 family.
Tissue Specificity
Very high expression in placenta, with the next highest level in testis and moderate levels in pancreas, liver, small intestine and brain at much lower levels. Expression levels increased in both early placentas and molar pregnancies and are reduced in choriocarcinoma cells. Expressed at higher levels in first trimester trophoblasts than at term of gestation, but only expressed in the villous trophoblast.
Cellular localization
- Secreted
Alternative names
PP5098, KISS1, Metastasis-suppressor KiSS-1, Kisspeptin-1