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Protein

KiSS-1 receptor

Gene

KISS1R

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Complete GO annotation...

Keywords - Molecular functioni

G-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

HGNCiHGNC:4510. KISS1R.

Subcellular locationi

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

GO - Cellular componenti

Complete GO annotation...

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 rs104894703dbSNPEnsembl.1
Natural variantiVAR_021392148L → S in HH8; 65% reduction of inositol phosphate production. 1 PublicationCorresponds to variant rs28939719dbSNPEnsembl.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 rs73507527dbSNPEnsembl.1
Natural variantiVAR_069962194A → D in HH8; phenotype consistent with Kallmann syndrome; the patient also carries a mutation in IL17RD. 1 PublicationCorresponds to variant rs397514699dbSNPEnsembl.1
Natural variantiVAR_021393223C → R in HH8; exhibit profoundly impaired signaling. 1 Publication1
Natural variantiVAR_072975262S → L in HH8. 1 PublicationCorresponds to variant rs745580229dbSNPEnsembl.1
Natural variantiVAR_021394297R → L in HH8; mild reduction in ligand-stimulated activity across the ligand dose range. 1 PublicationCorresponds to variant rs144670595dbSNPEnsembl.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 rs121908499dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation, Hypogonadotropic hypogonadism

Organism-specific databases

DisGeNETi84634.
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...)Sequence analysis1
Glycosylationi18N-linked (GlcNAc...)Sequence analysis1
Glycosylationi28N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi115 ↔ 191PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ969F8.
PeptideAtlasiQ969F8.
PRIDEiQ969F8.

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. 2 interactors.
IntActiQ969F8. 1 interactor.
STRINGi9606.ENSP00000234371.

Chemistry databases

BindingDBiQ969F8.

Structurei

3D structure databases

ProteinModelPortaliQ969F8.
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.
GeneTreeiENSGT00860000133695.
HOGENOMiHOG000230487.
HOVERGENiHBG106952.
InParanoidiQ969F8.
KOiK08374.
OMAiFVICRHK.
OrthoDBiEOG091G0HEN.
PhylomeDBiQ969F8.
TreeFamiTF315737.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR008103. KiSS_1_rcpt.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR01728. KISS1RECEPTR.
PROSITEiPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

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 rs104894703dbSNPEnsembl.1
Natural variantiVAR_021392148L → S in HH8; 65% reduction of inositol phosphate production. 1 PublicationCorresponds to variant rs28939719dbSNPEnsembl.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 rs73507527dbSNPEnsembl.1
Natural variantiVAR_069962194A → D in HH8; phenotype consistent with Kallmann syndrome; the patient also carries a mutation in IL17RD. 1 PublicationCorresponds to variant rs397514699dbSNPEnsembl.1
Natural variantiVAR_021393223C → R in HH8; exhibit profoundly impaired signaling. 1 Publication1
Natural variantiVAR_072975262S → L in HH8. 1 PublicationCorresponds to variant rs745580229dbSNPEnsembl.1
Natural variantiVAR_021394297R → L in HH8; mild reduction in ligand-stimulated activity across the ligand dose range. 1 PublicationCorresponds to variant rs144670595dbSNPEnsembl.1
Natural variantiVAR_021395364L → H.7 PublicationsCorresponds to variant rs350132dbSNPEnsembl.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 rs121908499dbSNPEnsembl.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

Cross-referencesi

Web resourcesi

Protein Spotlight

Tintin's blight - Issue 58 of May 2005

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.

3D structure databases

ProteinModelPortaliQ969F8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124162. 2 interactors.
IntActiQ969F8. 1 interactor.
STRINGi9606.ENSP00000234371.

Chemistry databases

BindingDBiQ969F8.
ChEMBLiCHEMBL5413.
GuidetoPHARMACOLOGYi266.

Protein family/group databases

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

PTM databases

iPTMnetiQ969F8.
PhosphoSitePlusiQ969F8.

Polymorphism and mutation databases

BioMutaiKISS1R.
DMDMi125987836.

Proteomic databases

PaxDbiQ969F8.
PeptideAtlasiQ969F8.
PRIDEiQ969F8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi84634.
DisGeNETi84634.
GeneCardsiKISS1R.
GeneReviewsiKISS1R.
HGNCiHGNC:4510. KISS1R.
HPAiHPA071913.
MalaCardsiKISS1R.
MIMi176400. phenotype.
604161. gene.
614837. phenotype.
neXtProtiNX_Q969F8.
OpenTargetsiENSG00000116014.
Orphaneti478. Kallmann syndrome.
432. Normosmic congenital hypogonadotropic hypogonadism.
PharmGKBiPA28899.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00860000133695.
HOGENOMiHOG000230487.
HOVERGENiHBG106952.
InParanoidiQ969F8.
KOiK08374.
OMAiFVICRHK.
OrthoDBiEOG091G0HEN.
PhylomeDBiQ969F8.
TreeFamiTF315737.

Enzyme and pathway databases

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

Miscellaneous databases

GeneWikiiKiSS1-derived_peptide_receptor.
GenomeRNAii84634.
PROiQ969F8.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000116014.
CleanExiHS_KISS1R.
ExpressionAtlasiQ969F8. baseline and differential.
GenevisibleiQ969F8. HS.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR008103. KiSS_1_rcpt.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR01728. KISS1RECEPTR.
PROSITEiPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKISSR_HUMAN
AccessioniPrimary (citable) accession number: Q969F8
Secondary accession number(s): A5D8U2, B2RTV1, Q96QG0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 2005
Last sequence update: February 6, 2007
Last modified: November 30, 2016
This is version 132 of the entry and version 2 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.