Q969F8 · KISSR_HUMAN
- ProteinKiSS-1 receptor
- GeneKISS1R
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids398 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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.
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | cell surface | |
Cellular Component | cilium | |
Cellular Component | intracellular membrane-bounded organelle | |
Cellular Component | membrane | |
Cellular Component | plasma membrane | |
Molecular Function | G protein-coupled peptide receptor activity | |
Molecular Function | neuropeptide receptor activity | |
Biological Process | G protein-coupled receptor signaling pathway | |
Biological Process | neuropeptide signaling pathway |
Keywords
- Molecular function
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameKiSS-1 receptor
- Short namesKiSS-1R
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ969F8
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-46 | Extracellular | ||||
Sequence: MHTVATSGPNASWGAPANASGCPGCGANASDGPVPSPRAVDAWLVP | ||||||
Transmembrane | 47-67 | Helical; Name=1 | ||||
Sequence: LFFAALMLLGLVGNSLVIYVI | ||||||
Topological domain | 68-78 | Cytoplasmic | ||||
Sequence: CRHKPMRTVTN | ||||||
Transmembrane | 79-101 | Helical; Name=2 | ||||
Sequence: FYIANLAATDVTFLLCCVPFTAL | ||||||
Topological domain | 102-120 | Extracellular | ||||
Sequence: LYPLPGWVLGDFMCKFVNY | ||||||
Transmembrane | 121-138 | Helical; Name=3 | ||||
Sequence: IQQVSVQATCATLTAMSV | ||||||
Topological domain | 139-157 | Cytoplasmic | ||||
Sequence: DRWYVTVFPLRALHRRTPR | ||||||
Transmembrane | 158-178 | Helical; Name=4 | ||||
Sequence: LALAVSLSIWVGSAAVSAPVL | ||||||
Topological domain | 179-202 | Extracellular | ||||
Sequence: ALHRLSPGPRAYCSEAFPSRALER | ||||||
Transmembrane | 203-223 | Helical; Name=5 | ||||
Sequence: AFALYNLLALYLLPLLATCAC | ||||||
Topological domain | 224-263 | Cytoplasmic | ||||
Sequence: YAAMLRHLGRVAVRPAPADSALQGQVLAERAGAVRAKVSR | ||||||
Transmembrane | 264-284 | Helical; Name=6 | ||||
Sequence: LVAAVVLLFAACWGPIQLFLV | ||||||
Topological domain | 285-305 | Extracellular | ||||
Sequence: LQALGPAGSWHPRSYAAYALK | ||||||
Transmembrane | 306-328 | Helical; Name=7 | ||||
Sequence: TWAHCMSYSNSALNPLLYAFLGS | ||||||
Topological domain | 329-398 | Cytoplasmic | ||||
Sequence: HFRQAFRRVCPCAPRRPRRPRRPGPSDPAAPHAELLRLGSHPAPARAQKPGSSGLAARGLCVLGEDNAPL |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Hypogonadotropic hypogonadism 8 with or without anosmia (HH8)
- Note
- 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 alsoMIM:614837
Natural variants in HH8
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_043906 | 102 | L>P | in HH8; absence of inositol phosphate accumulation under kisspeptin challenge; normal affinity for kisspeptin; dbSNP:rs104894703 | |
VAR_021392 | 148 | L>S | in HH8; 65% reduction of inositol phosphate production; dbSNP:rs28939719 | |
VAR_069961 | 189 | A>T | in HH8; benign; the patient also carries a mutation in FGFR1; phenotype consistent with normosmic idiopathic hypogonadotropic hypogonadism; dbSNP:rs73507527 | |
VAR_069962 | 194 | A>D | in HH8; phenotype consistent with Kallmann syndrome; the patient also carries a mutation in IL17RD; dbSNP:rs397514699 | |
VAR_021393 | 223 | C>R | in HH8; exhibit profoundly impaired signaling; dbSNP:rs2037102475 | |
VAR_072975 | 262 | S>L | in HH8; dbSNP:rs745580229 | |
VAR_021394 | 297 | R>L | in HH8; mild reduction in ligand-stimulated activity across the ligand dose range; dbSNP:rs144670595 |
Precocious puberty, central 1 (CPPB1)
- Note
- 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 alsoMIM:176400
Natural variants in CPPB1
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_043907 | 386 | R>P | in CPPB1; reduced rate of decline in inositol phosphate accumulation after kisspeptin stimulation; prolonged phosphorylation of ERK; dbSNP:rs121908499 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_043906 | 102 | in HH8; absence of inositol phosphate accumulation under kisspeptin challenge; normal affinity for kisspeptin; dbSNP:rs104894703 | |||
Sequence: L → P | ||||||
Natural variant | VAR_021392 | 148 | in HH8; 65% reduction of inositol phosphate production; dbSNP:rs28939719 | |||
Sequence: L → S | ||||||
Natural variant | VAR_069961 | 189 | in HH8; benign; the patient also carries a mutation in FGFR1; phenotype consistent with normosmic idiopathic hypogonadotropic hypogonadism; dbSNP:rs73507527 | |||
Sequence: A → T | ||||||
Natural variant | VAR_069962 | 194 | in HH8; phenotype consistent with Kallmann syndrome; the patient also carries a mutation in IL17RD; dbSNP:rs397514699 | |||
Sequence: A → D | ||||||
Natural variant | VAR_021393 | 223 | in HH8; exhibit profoundly impaired signaling; dbSNP:rs2037102475 | |||
Sequence: C → R | ||||||
Natural variant | VAR_072975 | 262 | in HH8; dbSNP:rs745580229 | |||
Sequence: S → L | ||||||
Natural variant | VAR_021394 | 297 | in HH8; mild reduction in ligand-stimulated activity across the ligand dose range; dbSNP:rs144670595 | |||
Sequence: R → L | ||||||
Natural variant | VAR_021395 | 364 | in dbSNP:rs350132 | |||
Sequence: L → H | ||||||
Natural variant | VAR_043907 | 386 | in CPPB1; reduced rate of decline in inositol phosphate accumulation after kisspeptin stimulation; prolonged phosphorylation of ERK; dbSNP:rs121908499 | |||
Sequence: R → P |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 593 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, glycosylation, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000069695 | 1-398 | KiSS-1 receptor | |||
Sequence: MHTVATSGPNASWGAPANASGCPGCGANASDGPVPSPRAVDAWLVPLFFAALMLLGLVGNSLVIYVICRHKPMRTVTNFYIANLAATDVTFLLCCVPFTALLYPLPGWVLGDFMCKFVNYIQQVSVQATCATLTAMSVDRWYVTVFPLRALHRRTPRLALAVSLSIWVGSAAVSAPVLALHRLSPGPRAYCSEAFPSRALERAFALYNLLALYLLPLLATCACYAAMLRHLGRVAVRPAPADSALQGQVLAERAGAVRAKVSRLVAAVVLLFAACWGPIQLFLVLQALGPAGSWHPRSYAAYALKTWAHCMSYSNSALNPLLYAFLGSHFRQAFRRVCPCAPRRPRRPRRPGPSDPAAPHAELLRLGSHPAPARAQKPGSSGLAARGLCVLGEDNAPL | ||||||
Glycosylation | 10 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 18 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 28 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 115↔191 | |||||
Sequence: CKFVNYIQQVSVQATCATLTAMSVDRWYVTVFPLRALHRRTPRLALAVSLSIWVGSAAVSAPVLALHRLSPGPRAYC |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
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.
Induction
Expressed at higher levels in first trimester trophoblasts than at term of gestation.
Gene expression databases
Organism-specific databases
Interaction
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q969F8 | GNAQ P50148 | 2 | EBI-8481408, EBI-3909604 | |
BINARY | Q969F8 | PPP2CA P67775 | 3 | EBI-8481408, EBI-712311 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 341-363 | Disordered | ||||
Sequence: APRRPRRPRRPGPSDPAAPHAEL |
Sequence similarities
Belongs to the G-protein coupled receptor 1 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Protein family/group databases
Sequence
- Sequence statusComplete
- Length398
- Mass (Da)42,586
- Last updated2007-02-06 v2
- ChecksumECAE2208848F5B06
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB051065 EMBL· GenBank· DDBJ | BAB55446.1 EMBL· GenBank· DDBJ | mRNA | ||
AF343725 EMBL· GenBank· DDBJ | AAK83235.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ309020 EMBL· GenBank· DDBJ | CAC40817.1 EMBL· GenBank· DDBJ | mRNA | ||
AY029541 EMBL· GenBank· DDBJ | AAK33126.1 EMBL· GenBank· DDBJ | mRNA | ||
AY253981 EMBL· GenBank· DDBJ | AAP82929.1 EMBL· GenBank· DDBJ | mRNA | ||
AY253982 EMBL· GenBank· DDBJ | AAP82930.1 EMBL· GenBank· DDBJ | mRNA | ||
EU883577 EMBL· GenBank· DDBJ | ACG60651.1 EMBL· GenBank· DDBJ | mRNA | ||
AC005379 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471139 EMBL· GenBank· DDBJ | EAW69583.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC140825 EMBL· GenBank· DDBJ | AAI40826.1 EMBL· GenBank· DDBJ | mRNA | ||
BC141812 EMBL· GenBank· DDBJ | AAI41813.1 EMBL· GenBank· DDBJ | mRNA |