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Protein

KiSS-1 receptor

Gene

KISS1R

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.1 Publication

GO - Molecular functioni

  • neuropeptide receptor activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-HSA-375276 Peptide ligand-binding receptors
R-HSA-416476 G alpha (q) signalling events
SIGNORiQ969F8

Protein family/group databases

TCDBi9.A.14.13.14 the g-protein-coupled receptor (gpcr) family

Names & Taxonomyi

Protein namesi
Recommended name:
KiSS-1 receptor
Short name:
KiSS-1R
Alternative name(s):
G-protein coupled receptor 54
G-protein coupled receptor OT7T175
Short name:
hOT7T175
Hypogonadotropin-1
Kisspeptins receptor
Metastin receptor
Gene namesi
Name:KISS1R
Synonyms:AXOR12, GPR54
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000116014.9
HGNCiHGNC:4510 KISS1R
MIMi604161 gene
neXtProtiNX_Q969F8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 46ExtracellularSequence analysisAdd BLAST46
Transmembranei47 – 67Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini68 – 78CytoplasmicSequence analysisAdd BLAST11
Transmembranei79 – 101Helical; Name=2Sequence analysisAdd BLAST23
Topological domaini102 – 120ExtracellularSequence analysisAdd BLAST19
Transmembranei121 – 138Helical; Name=3Sequence analysisAdd BLAST18
Topological domaini139 – 157CytoplasmicSequence analysisAdd BLAST19
Transmembranei158 – 178Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini179 – 202ExtracellularSequence analysisAdd BLAST24
Transmembranei203 – 223Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini224 – 263CytoplasmicSequence analysisAdd BLAST40
Transmembranei264 – 284Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini285 – 305ExtracellularSequence analysisAdd BLAST21
Transmembranei306 – 328Helical; Name=7Sequence analysisAdd BLAST23
Topological domaini329 – 398CytoplasmicSequence analysisAdd BLAST70

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Hypogonadotropic hypogonadism 8 with or without anosmia (HH8)6 Publications
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).1 Publication
Disease descriptionA 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).
See also OMIM:614837
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_043906102L → P in HH8; absence of inositol phosphate accumulation under kisspeptin challenge; normal affinity for kisspeptin. 1 PublicationCorresponds to variant dbSNP:rs104894703EnsemblClinVar.1
Natural variantiVAR_021392148L → S in HH8; 65% reduction of inositol phosphate production. 1 PublicationCorresponds to variant dbSNP:rs28939719EnsemblClinVar.1
Natural variantiVAR_069961189A → T in HH8; phenotype consistent with normosmic idiopathic hypogonadotropic hypogonadism; the patient also carries a mutation in FGFR1. 1 PublicationCorresponds to variant dbSNP:rs73507527EnsemblClinVar.1
Natural variantiVAR_069962194A → D in HH8; phenotype consistent with Kallmann syndrome; the patient also carries a mutation in IL17RD. 1 PublicationCorresponds to variant dbSNP:rs397514699EnsemblClinVar.1
Natural variantiVAR_021393223C → R in HH8; exhibit profoundly impaired signaling. 1 Publication1
Natural variantiVAR_072975262S → L in HH8. 1 PublicationCorresponds to variant dbSNP:rs745580229Ensembl.1
Natural variantiVAR_021394297R → L in HH8; mild reduction in ligand-stimulated activity across the ligand dose range. 1 PublicationCorresponds to variant dbSNP:rs144670595EnsemblClinVar.1
Precocious puberty, central 1 (CPPB1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:176400
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_043907386R → P in CPPB1; reduced rate of decline in inositol phosphate accumulation after kisspeptin stimulation; prolonged phosphorylation of ERK. 1 PublicationCorresponds to variant dbSNP:rs121908499EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Hypogonadotropic hypogonadism

Organism-specific databases

DisGeNETi84634
GeneReviewsiKISS1R
MalaCardsiKISS1R
MIMi176400 phenotype
614837 phenotype
OpenTargetsiENSG00000116014
Orphaneti478 Kallmann syndrome
432 Normosmic congenital hypogonadotropic hypogonadism
PharmGKBiPA28899

Chemistry databases

ChEMBLiCHEMBL5413
GuidetoPHARMACOLOGYi266

Polymorphism and mutation databases

BioMutaiKISS1R
DMDMi125987836

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000696951 – 398KiSS-1 receptorAdd BLAST398

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi10N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi18N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi28N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi115 ↔ 191PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ969F8
PeptideAtlasiQ969F8
PRIDEiQ969F8
ProteomicsDBi75750

PTM databases

iPTMnetiQ969F8
PhosphoSitePlusiQ969F8

Expressioni

Tissue specificityi

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.6 Publications

Inductioni

Expressed at higher levels in first trimester trophoblasts than at term of gestation.

Gene expression databases

BgeeiENSG00000116014
CleanExiHS_KISS1R
ExpressionAtlasiQ969F8 baseline and differential
GenevisibleiQ969F8 HS

Organism-specific databases

HPAiHPA071913

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
PPP2CAP677753EBI-8481408,EBI-712311

Protein-protein interaction databases

BioGridi124162, 4 interactors
IntActiQ969F8, 1 interactor
MINTiQ969F8
STRINGi9606.ENSP00000234371

Chemistry databases

BindingDBiQ969F8

Structurei

3D structure databases

ProteinModelPortaliQ969F8
SMRiQ969F8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3656 Eukaryota
ENOG410XRW9 LUCA
GeneTreeiENSGT00920000148959
HOGENOMiHOG000230487
HOVERGENiHBG106952
InParanoidiQ969F8
KOiK08374
OMAiIEEGYWY
OrthoDBiEOG091G0HEN
PhylomeDBiQ969F8
TreeFamiTF315737

Family and domain databases

CDDicd15095 7tmA_KiSS1R, 1 hit
InterProiView protein in InterPro
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
IPR008103 KiSS_1_rcpt
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00237 GPCRRHODOPSN
PR01728 KISS1RECEPTR
PROSITEiView protein in PROSITE
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit

Sequencei

Sequence statusi: Complete.

Q969F8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MHTVATSGPN ASWGAPANAS GCPGCGANAS DGPVPSPRAV DAWLVPLFFA
60 70 80 90 100
ALMLLGLVGN SLVIYVICRH KPMRTVTNFY IANLAATDVT FLLCCVPFTA
110 120 130 140 150
LLYPLPGWVL GDFMCKFVNY IQQVSVQATC ATLTAMSVDR WYVTVFPLRA
160 170 180 190 200
LHRRTPRLAL AVSLSIWVGS AAVSAPVLAL HRLSPGPRAY CSEAFPSRAL
210 220 230 240 250
ERAFALYNLL ALYLLPLLAT CACYAAMLRH LGRVAVRPAP ADSALQGQVL
260 270 280 290 300
AERAGAVRAK VSRLVAAVVL LFAACWGPIQ LFLVLQALGP AGSWHPRSYA
310 320 330 340 350
AYALKTWAHC MSYSNSALNP LLYAFLGSHF RQAFRRVCPC APRRPRRPRR
360 370 380 390
PGPSDPAAPH AELLRLGSHP APARAQKPGS SGLAARGLCV LGEDNAPL
Length:398
Mass (Da):42,586
Last modified:February 6, 2007 - v2
Checksum:iECAE2208848F5B06
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_043906102L → P in HH8; absence of inositol phosphate accumulation under kisspeptin challenge; normal affinity for kisspeptin. 1 PublicationCorresponds to variant dbSNP:rs104894703EnsemblClinVar.1
Natural variantiVAR_021392148L → S in HH8; 65% reduction of inositol phosphate production. 1 PublicationCorresponds to variant dbSNP:rs28939719EnsemblClinVar.1
Natural variantiVAR_069961189A → T in HH8; phenotype consistent with normosmic idiopathic hypogonadotropic hypogonadism; the patient also carries a mutation in FGFR1. 1 PublicationCorresponds to variant dbSNP:rs73507527EnsemblClinVar.1
Natural variantiVAR_069962194A → D in HH8; phenotype consistent with Kallmann syndrome; the patient also carries a mutation in IL17RD. 1 PublicationCorresponds to variant dbSNP:rs397514699EnsemblClinVar.1
Natural variantiVAR_021393223C → R in HH8; exhibit profoundly impaired signaling. 1 Publication1
Natural variantiVAR_072975262S → L in HH8. 1 PublicationCorresponds to variant dbSNP:rs745580229Ensembl.1
Natural variantiVAR_021394297R → L in HH8; mild reduction in ligand-stimulated activity across the ligand dose range. 1 PublicationCorresponds to variant dbSNP:rs144670595EnsemblClinVar.1
Natural variantiVAR_021395364L → H7 PublicationsCorresponds to variant dbSNP:rs350132EnsemblClinVar.1
Natural variantiVAR_043907386R → P in CPPB1; reduced rate of decline in inositol phosphate accumulation after kisspeptin stimulation; prolonged phosphorylation of ERK. 1 PublicationCorresponds to variant dbSNP:rs121908499EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB051065 mRNA Translation: BAB55446.1
AF343725 mRNA Translation: AAK83235.1
AJ309020 mRNA Translation: CAC40817.1
AY029541 mRNA Translation: AAK33126.1
AY253981 mRNA Translation: AAP82929.1
AY253982 mRNA Translation: AAP82930.1
EU883577 mRNA Translation: ACG60651.1
AC005379 Genomic DNA No translation available.
CH471139 Genomic DNA Translation: EAW69583.1
BC140825 mRNA Translation: AAI40826.1
BC141812 mRNA Translation: AAI41813.1
CCDSiCCDS12049.1
RefSeqiNP_115940.2, NM_032551.4
UniGeneiHs.208229

Genome annotation databases

EnsembliENST00000234371; ENSP00000234371; ENSG00000116014
GeneIDi84634
KEGGihsa:84634
UCSCiuc002lqk.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiKISSR_HUMAN
AccessioniPrimary (citable) accession number: Q969F8
Secondary accession number(s): A5D8U2, B2RTV1, Q96QG0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 1, 2005
Last sequence update: February 6, 2007
Last modified: June 20, 2018
This is version 146 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  7. SIMILARITY comments
    Index of protein domains and families

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