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Protein

Metastasis-suppressor KiSS-1

Gene

KISS1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Metastasis suppressor protein in malignant melanomas and in some breast cancers. May regulate events downstream of cell-matrix adhesion, perhaps involving cytoskeletal reorganization. Generates a C-terminally amidated peptide, metastin which functions as the endogenous ligand of the G-protein coupled receptor GPR54. Activation of the receptor inhibits cell proliferation and cell migration, key characteristics of tumor metastasis. Kp-10 is a decapeptide derived from the primary translation product, isolated in conditioned medium of first trimester trophoblast. Kp-10, but not other kisspeptins, increased intracellular Ca2+ levels in isolated first trimester trophoblasts. Kp-10 is a paracrine/endocrine regulator in fine-tuning trophoblast invasion generated by the trophoblast itself. The receptor is also essential for normal gonadotropin-released hormone physiology and for puberty. The hypothalamic KiSS1/GPR54 system is a pivotal factor in central regulation of the gonadotropic axis at puberty and in adulthood.4 Publications

GO - Biological processi

Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:ENSG00000170498-MONOMER.
ReactomeiR-HSA-375276. Peptide ligand-binding receptors.
R-HSA-416476. G alpha (q) signalling events.
SIGNORiQ15726.

Names & Taxonomyi

Protein namesi
Recommended name:
Metastasis-suppressor KiSS-1
Alternative name(s):
Kisspeptin-1
Cleaved into the following 4 chains:
Alternative name(s):
Kisspeptin-54
Gene namesi
Name:KISS1
ORF Names:PP5098
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:6341. KISS1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Hypogonadotropic hypogonadism 13 with or without anosmia (HH13)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
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:614842
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069179115N → K in HH13; significantly reduced efficacy as well as potency. 1 Publication1

Keywords - Diseasei

Disease mutation, Hypogonadotropic hypogonadism

Organism-specific databases

DisGeNETi3814.
MalaCardsiKISS1.
MIMi614842. phenotype.
OpenTargetsiENSG00000170498.
Orphaneti432. Normosmic congenital hypogonadotropic hypogonadism.
PharmGKBiPA30127.

Polymorphism and mutation databases

BioMutaiKISS1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
ChainiPRO_000002154420 – 138Metastasis-suppressor KiSS-1Add BLAST119
PeptideiPRO_000002154568 – 121MetastinAdd BLAST54
PeptideiPRO_0000021546108 – 121Kisspeptin-14Add BLAST14
PeptideiPRO_0000021547109 – 121Kisspeptin-13Add BLAST13
PeptideiPRO_0000021548112 – 121Kisspeptin-1010

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei112PhosphotyrosineCombined sources1
Modified residuei121Phenylalanine amide1 Publication1

Post-translational modificationi

Processed by MMP2 and MMP9.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei118 – 119Cleavage; by MMP2 and MMP92

Keywords - PTMi

Amidation, Cleavage on pair of basic residues, Phosphoprotein

Proteomic databases

PaxDbiQ15726.
PeptideAtlasiQ15726.
PRIDEiQ15726.

PTM databases

iPTMnetiQ15726.
PhosphoSitePlusiQ15726.

Miscellaneous databases

PMAP-CutDBQ15726.

Expressioni

Tissue specificityi

Very high expression in placenta, with the next highest level in testis and moderate levels in pancreas, liver, small intestine and brain at much lower levels. Expression levels increased in both early placentas and molar pregnancies and are reduced in choriocarcinoma cells. Expressed at higher levels in first trimester trophoblasts than at term of gestation, but only expressed in the villous trophoblast.3 Publications

Inductioni

Down-regulated during the progression of melanoma in vivo. Diminishes MMP9 expression by effecting reduced NF-kappa-B binding to the promoter.1 Publication

Gene expression databases

BgeeiENSG00000170498.
CleanExiHS_KISS1.
ExpressionAtlasiQ15726. baseline and differential.
GenevisibleiQ15726. HS.

Organism-specific databases

HPAiCAB017775.
HPA035542.

Interactioni

Protein-protein interaction databases

BioGridi110014. 2 interactors.
STRINGi9606.ENSP00000356162.

Structurei

3D structure databases

ProteinModelPortaliQ15726.
SMRiQ15726.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni112 – 121Essential for receptor binding and receptor activation10

Sequence similaritiesi

Belongs to the KISS1 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IYVQ. Eukaryota.
ENOG41118MU. LUCA.
GeneTreeiENSGT00390000008827.
HOGENOMiHOG000013123.
HOVERGENiHBG052261.
InParanoidiQ15726.
PhylomeDBiQ15726.
TreeFamiTF338233.

Family and domain databases

InterProiIPR020207. Metastasis-suppressor_KiSS-1.
[Graphical view]
PfamiPF15152. Kisspeptin. 1 hit.
[Graphical view]
ProDomiPD088121. Metastasis-suppressor_KiSS-1. 1 hit.
[Graphical view] [Entries sharing at least one domain]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q15726-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNSLVSWQLL LFLCATHFGE PLEKVASVGN SRPTGQQLES LGLLAPGEQS
60 70 80 90 100
LPCTERKPAA TARLSRRGTS LSPPPESSGS PQQPGLSAPH SRQIPAPQGA
110 120 130
VLVQREKDLP NYNWNSFGLR FGKREAAPGN HGRSAGRG
Length:138
Mass (Da):14,705
Last modified:March 23, 2010 - v4
Checksum:i0F0A1E1D66EDC22A
GO

Sequence cautioni

The sequence AAC79512 differs from that shown. Reason: Frameshift at position 138.Curated
The sequence AAM78592 differs from that shown. Reason: Frameshift at position 138.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02139620E → K.1 PublicationCorresponds to variant rs12998dbSNPEnsembl.1
Natural variantiVAR_02139736Q → R.1 PublicationCorresponds to variant rs35431622dbSNPEnsembl.1
Natural variantiVAR_02139881P → R.3 PublicationsCorresponds to variant rs4889dbSNPEnsembl.1
Natural variantiVAR_069179115N → K in HH13; significantly reduced efficacy as well as potency. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U43527 mRNA. Translation: AAC79512.1. Frameshift.
AY117143 mRNA. Translation: AAM78592.1. Frameshift.
AF218017 mRNA. Translation: AAG17259.1.
AL592114 Genomic DNA. Translation: CAH71226.1.
AK291695 mRNA. Translation: BAF84384.1.
BC022819 mRNA. Translation: AAH22819.1.
CCDSiCCDS41454.1.
RefSeqiNP_002247.3. NM_002256.3.
UniGeneiHs.95008.

Genome annotation databases

EnsembliENST00000367194; ENSP00000356162; ENSG00000170498.
GeneIDi3814.
KEGGihsa:3814.
UCSCiuc001har.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
U43527 mRNA. Translation: AAC79512.1. Frameshift.
AY117143 mRNA. Translation: AAM78592.1. Frameshift.
AF218017 mRNA. Translation: AAG17259.1.
AL592114 Genomic DNA. Translation: CAH71226.1.
AK291695 mRNA. Translation: BAF84384.1.
BC022819 mRNA. Translation: AAH22819.1.
CCDSiCCDS41454.1.
RefSeqiNP_002247.3. NM_002256.3.
UniGeneiHs.95008.

3D structure databases

ProteinModelPortaliQ15726.
SMRiQ15726.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110014. 2 interactors.
STRINGi9606.ENSP00000356162.

PTM databases

iPTMnetiQ15726.
PhosphoSitePlusiQ15726.

Polymorphism and mutation databases

BioMutaiKISS1.

Proteomic databases

PaxDbiQ15726.
PeptideAtlasiQ15726.
PRIDEiQ15726.

Protocols and materials databases

DNASUi3814.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000367194; ENSP00000356162; ENSG00000170498.
GeneIDi3814.
KEGGihsa:3814.
UCSCiuc001har.4. human.

Organism-specific databases

CTDi3814.
DisGeNETi3814.
GeneCardsiKISS1.
GeneReviewsiKISS1.
HGNCiHGNC:6341. KISS1.
HPAiCAB017775.
HPA035542.
MalaCardsiKISS1.
MIMi603286. gene.
614842. phenotype.
neXtProtiNX_Q15726.
OpenTargetsiENSG00000170498.
Orphaneti432. Normosmic congenital hypogonadotropic hypogonadism.
PharmGKBiPA30127.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IYVQ. Eukaryota.
ENOG41118MU. LUCA.
GeneTreeiENSGT00390000008827.
HOGENOMiHOG000013123.
HOVERGENiHBG052261.
InParanoidiQ15726.
PhylomeDBiQ15726.
TreeFamiTF338233.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000170498-MONOMER.
ReactomeiR-HSA-375276. Peptide ligand-binding receptors.
R-HSA-416476. G alpha (q) signalling events.
SIGNORiQ15726.

Miscellaneous databases

ChiTaRSiKISS1. human.
GeneWikiiKisspeptin.
GenomeRNAii3814.
PMAP-CutDBQ15726.
PROiQ15726.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000170498.
CleanExiHS_KISS1.
ExpressionAtlasiQ15726. baseline and differential.
GenevisibleiQ15726. HS.

Family and domain databases

InterProiIPR020207. Metastasis-suppressor_KiSS-1.
[Graphical view]
PfamiPF15152. Kisspeptin. 1 hit.
[Graphical view]
ProDomiPD088121. Metastasis-suppressor_KiSS-1. 1 hit.
[Graphical view] [Entries sharing at least one domain]
ProtoNetiSearch...

Entry informationi

Entry nameiKISS1_HUMAN
AccessioniPrimary (citable) accession number: Q15726
Secondary accession number(s): A8K6N0, Q9HBP1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: March 23, 2010
Last modified: November 2, 2016
This is version 136 of the entry and version 4 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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  6. 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.