InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: KISS1R

Summary

InnateDB Protein

IDBP-13329.5

Last Modified

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

Gene Symbol

KISS1R

Protein Name

KISS1 receptor

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000234371

InnateDB Gene

IDBG-13327 (KISS1R)

Protein Structure

UniProt Annotation

Function

Receptor for metastin (kisspeptin-54 or kp-54), a C- terminally amidated peptide of KiSS1. KiSS1 is a metastasis suppressor protein that suppresses metastases in malignant melanomas and in some breast carcinomas without affecting tumorigenicity. The metastasis suppressor properties may be mediated in part by cell cycle arrest and induction of apoptosis in malignant cells. The receptor is essential for normal gonadotropin-released hormone physiology and for puberty. The hypothalamic KiSS1/KISS1R system is a pivotal factor in central regulation of the gonadotropic axis at puberty and in adulthood. The receptor is also probably involved in the regulation and fine- tuning of trophoblast invasion generated by the trophoblast itself. Analysis of the transduction pathways activated by the receptor identifies coupling to phospholipase C and intracellular calcium release through pertussis toxin-insensitive G(q) proteins. {ECO:0000269PubMed:15020672}.

Subcellular Localization

Cell membrane; Multi-pass membrane protein.

Disease Associations

Hypogonadotropic hypogonadism 8 with or without anosmia (HH8) [MIM:614837]: 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). {ECO:0000269PubMed:12944565, ECO:0000269PubMed:14573733, ECO:0000269PubMed:15598687, ECO:0000269PubMed:17164310, ECO:0000269PubMed:23643382}. Note=The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. The genetics of hypogonadotropic hypogonadism involves various modes of transmission. Oligogenic inheritance has been reported in some patients carrying mutations in KISS1R as well as in other HH-associated genes including FGFR1 and IL17RD (PubMed:23643382). {ECO:0000269PubMed:23643382}.Precocious puberty, central 1 (CPPB1) [MIM:176400]: A condition defined as the development of secondary sexual characteristics in boys and girls at a chronological age that is 2.5 standard deviations below the mean age at onset of puberty in the population. Central precocious puberty results from premature activation of the hypothalamic-pituitary-gonadal axis. {ECO:0000269PubMed:18272894}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Most highly expressed in the pancreas, placenta and spinal cord, with lower-level of expression in peripheral blood leukocytes, kidney, lung, fetal liver, stomach, small intestine, testes, spleen, thymus, adrenal glands and lymph nodes. In the adult brain, expressed in the superior frontal gyrus, putamen, caudate nucleus, cingulate gyrus, nucleus accumbens, hippocampus, pons and amygdala, as well as the hypothalamus and pituitary. Expression levels are higher in early (7-9 weeks) than term placentas. Expression levels were increased in both early placentas and molar pregnancies and were reduced in choriocarcinoma cells. Expressed at higher levels in first trimester trophoblasts than at term of gestation. Also found in the extravillous trophoblast suggesting endocrine/paracrine activation mechanism. {ECO:0000269PubMed:11385580, ECO:0000269PubMed:11387329, ECO:0000269PubMed:11414709, ECO:0000269PubMed:11457843, ECO:0000269PubMed:12414911, ECO:0000269PubMed:15020672}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 4 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	4 [view]
Protein-Protein	3 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004930	G-protein coupled receptor activity
GO:0005515	protein binding
GO:0008188	neuropeptide receptor activity
GO:0008528	G-protein coupled peptide receptor activity
GO:0042923	neuropeptide binding

Biological Process

GO:0000186	activation of MAPKK activity
GO:0007165	signal transduction
GO:0007186	G-protein coupled receptor signaling pathway
GO:0007218	neuropeptide signaling pathway
GO:0008285	negative regulation of cell proliferation
GO:0019722	calcium-mediated signaling
GO:0046887	positive regulation of hormone secretion
GO:0050482	arachidonic acid secretion
GO:0050806	positive regulation of synaptic transmission
GO:0051496	positive regulation of stress fiber assembly

Cellular Component

GO:0005886	plasma membrane
GO:0009986	cell surface
GO:0016020	membrane
GO:0016021	integral component of membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000276 G protein-coupled receptor, rhodopsin-like
IPR000405 Galanin receptor family
IPR000611 Neuropeptide Y receptor family
IPR008103 KiSS-1 peptide receptor
IPR017452 GPCR, rhodopsin-like, 7TM
IPR019424 7TM GPCR, olfactory receptor/chemoreceptor Srsx

PFAM

PF00001
PF10320

PRINTS

PR00237
PR00663
PR01012
PR01728

PIRSF

SMART

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q969F8