KISS1R
entrez
84634
canonical
uniprot
Q969F8
canonical
ensembl
ENSG00000116014
resolver
ensp
ENSP00000234371
resolver
enst
ENST00000234371
resolver
genesymbol
KISS1R
resolver
genesymbol_syn
AXOR12
resolver
genesymbol_syn
GPR54
resolver
hgnc
HGNC:4510
resolver
uniprot
A5D8U2
resolver
uniprot
B2RTV1
resolver
uniprot
Q96QG0
resolver
uniprot_entry
KISSR_HUMAN
resolver
uniprot_sec
A5D8U2
resolver
uniprot_sec
B2RTV1
resolver
uniprot_sec
Q96QG0
resolver
amino_acid_sequence
MHTVATSGPNASWGAPANASGCPGCGANASDGPVPSPRAVDAWLVPLFFAALMLLGLVGNSLVIYVICRHKPMRTVTNFYIANLAATDVTFLLCCVPFTALLYPLPGWVLGDFMCKFVNYIQQVSVQATCATLTAMSVDRWYVTVFPLRALHRRTPRLALAVSLSIWVGSAAVSAPVLALHRLSPGPRAYCSEAFPSRALERAFALYNLLALYLLPLLATCACYAAMLRHLGRVAVRPAPADSALQGQVLAERAGAVRAKVSRLVAAVVLLFAACWGPIQLFLVLQALGPAGSWHPRSYAAYALKTWAHCMSYSNSALNPLLYAFLGSHFRQAFRRVCPCAPRRPRRPRRPGPSDPAAPHAELLRLGSHPAPARAQKPGSSGLAARGLCVLGEDNAPL
uniprot
proteins
disease_involvement
DISEASE: 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). HH8 inheritance pattern is autosomal recessive. {ECO:0000269|PubMed:12944565, ECO:0000269|PubMed:14573733, ECO:0000269|PubMed:15598687, ECO:0000269|PubMed:17164310, ECO:0000269|PubMed:18772143, ECO:0000269|PubMed:23643382, ECO:0000269|PubMed:25077900, ECO:0000269|PubMed:25147978}. Note=The disease is caused by variants 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:0000269|PubMed:23643382}.; DISEASE: 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:0000269|PubMed:18272894}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Receptor for kisspeptins (kisspeptin-10, kisspeptin-13, kisspeptin-14 and metastin/kisspeptin-54) (PubMed:11457843, PubMed:11527393, PubMed:15020672, PubMed:15596153). The hypothalamic KISS1/KISS1R signaling system plays a central role in the regulation of the hypothalamic-pituitary-gonadal reproductive axis by modulating the secretion of gonadotropin-releasing hormone (GnRH) from GnRH neurons (PubMed:12944565, PubMed:14573733, PubMed:15598687, PubMed:17164310, PubMed:18272894). In these neurons, kisspeptin binding to its receptor activates G(q)-dependent signaling, leading to phospholipase C (PLC) activation, and hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) (PubMed:14573733, PubMed:15598687, PubMed:39151001). The subsequent rise in intracellular calcium levels results in the inhibition of inward rectifier potassium channels and activation of TRPC-like cation channels, leading to GnRH neurons depolarization and stimulation (By similarity). In addition to this pathway, kisspeptin also triggers G(q)-independent signaling via beta-arrestin, leading to MAPK cascade activation and ERK1/ERK2 phosphorylation (PubMed:25147978). Furthermore, activation of KISS1R by kisspeptin-10 recruits phosphatase DUSP18 and SRC to the KISS1R C-terminus through a G(q)-dependent signaling pathway, leading to DUSP18-mediated dephosphorylation of SRC (PubMed:38346942). In bone tissue, this results in down-regulation of osteoclast differentiation and activity, and consequently suppression of bone resorption (By similarity). KISS1R is also involved in the regulation of other processes, including cell proliferation and cell migration (PubMed:11457843, PubMed:11527393, PubMed:15020672, PubMed:15596153, PubMed:38512807). {ECO:0000250|UniProtKB:Q91V45, ECO:0000269|PubMed:11457843, ECO:0000269|PubMed:11527393, ECO:0000269|PubMed:12944565, ECO:0000269|PubMed:14573733, ECO:0000269|PubMed:15020672, ECO:0000269|PubMed:15596153, ECO:0000269|PubMed:15598687, ECO:0000269|PubMed:17164310, ECO:0000269|PubMed:18272894, ECO:0000269|PubMed:25147978, ECO:0000269|PubMed:38346942, ECO:0000269|PubMed:38512807, ECO:0000269|PubMed:39151001}.
uniprot
proteins
mass_dalton
42586
uniprot
proteins
mutagenesis
MUTAGEN 99; /note="T->A: Decreased sensitivity to activation by kisspeptin-54 and reduced phospholipase C-activating G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:39151001"; MUTAGEN 119; /note="N->A: Decreased sensitivity to activation by kisspeptin-54 and reduced phospholipase C-activating G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:39151001"; MUTAGEN 122; /note="Q->A: Decreased sensitivity to activation by kisspeptin-54 and reduced phospholipase C-activating G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:39151001"; MUTAGEN 123; /note="Q->A: Decreased sensitivity to activation by kisspeptin-54 and reduced phospholipase C-activating G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:39151001"; MUTAGEN 148; /note="L->A,F,T: Mildly decreased phospholipase C-activating G protein-coupled receptor signaling in response to kisspeptin-10."; /evidence="ECO:0000269|PubMed:18772143"; MUTAGEN 148; /note="L->E,R: Severely decreased phospholipase C-activating G protein-coupled receptor signaling in response to kisspeptin-10."; /evidence="ECO:0000269|PubMed:18772143"; MUTAGEN 181; /note="H->A: Decreased sensitivity to activation by kisspeptin-54 and reduced phospholipase C-activating G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:39151001"; MUTAGEN 193; /note="E->A: Loss of sensitivity to activation by kisspeptin-54 and loss of phospholipase C-activating G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:39151001"; MUTAGEN 297; /note="R->A: Decreased sensitivity to activation by kisspeptin-54 and reduced phospholipase C-activating G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:39151001"; MUTAGEN 302; /note="Y->A: Decreased sensitivity to activation by kisspeptin-54 and reduced phospholipase C-activating G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:39151001"; MUTAGEN 305; /note="K->A: Decreased sensitivity to activation by kisspeptin-54 and reduced phospholipase C-activating G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:39151001"; MUTAGEN 309; /note="H->A: Decreased sensitivity to activation by kisspeptin-54 and reduced phospholipase C-activating G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:39151001"; MUTAGEN 313; /note="Y->A: Decreased sensitivity to activation by kisspeptin-54 and reduced phospholipase C-activating G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:39151001"; MUTAGEN 336; /note="R->A: Decreased interaction with SRC; when associated in cis with A-339. Decreased interaction with DUSP18; when associated in cis with A-339."; /evidence="ECO:0000269|PubMed:38346942"; MUTAGEN 339; /note="P->A: Decreased interaction with SRC; when associated in cis with A-336. Decreased interaction with DUSP18; when associated in cis with A-336."; /evidence="ECO:0000269|PubMed:38346942
uniprot
proteins
protein_family
G protein-coupled receptor 1 family
uniprot
proteins
pubmed
11385580
uniprot
proteins
pubmed
11387329
uniprot
proteins
pubmed
11414709
uniprot
proteins
pubmed
11457843
uniprot
proteins
pubmed
11527393
uniprot
proteins
pubmed
12414911
uniprot
proteins
pubmed
12944565
uniprot
proteins
pubmed
14573733
uniprot
proteins
pubmed
15020672
uniprot
proteins
pubmed
15057824
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15519892
uniprot
proteins
pubmed
15596153
uniprot
proteins
pubmed
15598687
uniprot
proteins
pubmed
17164310
uniprot
proteins
pubmed
18272894
uniprot
proteins
pubmed
18772143
uniprot
proteins
pubmed
23643382
uniprot
proteins
pubmed
25077900
uniprot
proteins
pubmed
25147978
uniprot
proteins
pubmed
38346942
uniprot
proteins
pubmed
38512807
uniprot
proteins
pubmed
38935498
uniprot
proteins
pubmed
39151001
uniprot
proteins
pubmed
39702286
uniprot
proteins
sequence_length
398
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18772143}; Multi-pass membrane protein {ECO:0000255}.
uniprot
proteins
transmembrane_region
TRANSMEM 47..67; /note="Helical; Name=1"; /evidence="ECO:0000255"; TRANSMEM 79..101; /note="Helical; Name=2"; /evidence="ECO:0000255"; TRANSMEM 121..138; /note="Helical; Name=3"; /evidence="ECO:0000255"; TRANSMEM 158..178; /note="Helical; Name=4"; /evidence="ECO:0000255"; TRANSMEM 203..223; /note="Helical; Name=5"; /evidence="ECO:0000255"; TRANSMEM 264..284; /note="Helical; Name=6"; /evidence="ECO:0000255"; TRANSMEM 306..328; /note="Helical; Name=7"; /evidence="ECO:0000255
uniprot
proteins