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FLASH GENE
Symbol KISS1 contributors: npt/mct/pgu - updated : 08-03-2018
HGNC name KISS-1 metastasis-suppressor
HGNC id 6341
Location 1q32      Physical location : 204.159.469 - 204.165.619
Synonym name
  • metastin
  • malignant melanoma metastasis-suppressor
  • kisspeptin
  • Synonym symbol(s) KIS1, MGC39258, KiSS-1, HH13
    DNA
    TYPE functioning gene
    STRUCTURE 6.15 kb     3 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    C1orf37 1q31.1 chromosome 1 open reading frame 37 PPFIA4 1q32.1 protein tyrosine phosphatase, receptor type, f polypeptide (PTPRF), interacting protein (liprin), alpha 4 MYOG 1q31-q41 myogenin (myogenic factor 4) ADORA1 1q32.1 adenosine A1 receptor MYBPH 1q32.1 myosin binding protein H CHI3L1 1q31-q32 chitinase 3-like 1 (cartilage glycoprotein-39) CHIT1 1q31-q32 chitinase 1 (chitotriosidase) LOC388729 1 LOC388729 BTG2 1q32 BTG family, member 2 FMOD 1q32.1 fibromodulin ATP2B4 1q32 ATPase, Ca++ transporting, plasma membrane 4 MGC5457 1q32.1 hypothetical protein MGC5457 LAX 1q32.1 hypothetical protein FLJ20340 KIAA0663 1q32.1 hypothetical protein FLJ20340 SNRPE 1q32 small nuclear ribonucleoprotein polypeptide E LOC391155 1 similar to KRT8 protein FLJ40343 1q32.1 hypothetical protein FLJ40343 SOX13 1q31.3-q32.1 SRY (sex determining region Y)-box 13 FLJ10761 1q32.1 putative ethanolamine kinase REN 1q32 renin KISS1 1q32 KiSS-1 metastasis-suppressor FLJ42654 1q32.1 FLJ42654 protein PEPP3 1q32.1 phosphoinositol 3-phosphate-binding protein-3 PPP1R15B 1q32.1 protein phosphatase 1, regulatory (inhibitor) subunit 15B PIK3C2B 1q32 phosphoinositide-3-kinase, class 2, beta polypeptide MDM4 1q32 Mdm4, transformed 3T3 cell double minute 4, p53 binding protein (mouse) GAC1 NFASC 1q32.1 Mdm4, transformed 3T3 cell double minute 4, p53 binding protein (mouse) CNTN2 1q32.1 contactin 2 (axonal) LOC388730 1 similar to RIKEN cDNA 4930429O20 RBBP5 1q32 retinoblastoma binding protein 5 KIAA0472
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 731 14.6 138 - 1998 9806840
    variant 1 isoform 1
    - - - - 54 - 2001 11385580
    C terminally amidated peptide
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinepancreas    
    Nervousbraindiencephalonamygdala   Homo sapiens
    Reproductivefemale systemplacenta    Homo sapiens
     male systemtestis    Homo sapiens
    Urinarykidney    
    cell lineage
    cell lines amelanotic melanoma cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    HOMOLOGY
    Homologene
    FAMILY
  • KISS1 family
  • CATEGORY tumor suppressor , receptor membrane
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm
    basic FUNCTION
  • regulation of cancer metastasis in malignant melanomas
  • regulating events downstream of cell-matrix adhesion, perhaps involving cytoskeletal reorganization
  • directly stimulating gonadotrophin-releasing hormone release via KISS1R, and as a relevant downstream element in the neuroendocrine network governing LH secretion
  • activates a receptor coupled to Galphaq subunits, KISS1R (activation of KISS1R signaling may negatively regulate the role of CXCR4 in programming tumor metastasis)
  • strong suppressant of metastasis
  • having a potential autocrine metastasis suppression effect on KISS1R-positive tumor cells
  • being pivotal regulator of the hypothalamic-pituitary-gonadal axis and reproduction, with the ability to integrate signals from both internal and external sources
  • functional kisspeptin is important for puberty and reproduction in humans
  • is a key locus of integration for circadian and steroidal signaling necessary for the initiation of ovulation
  • KISS1, KISS1R play a major role in trophoblast invasion, and progesterone-induced blocking factor (PIBF1) is needed for maintaining pregnancy
  • may function in decidualized endometrium to prepare for adequate placentation but this autocrine secretion of KISS1 is deregulated during oncogenesis to enable tumor cells to spread
  • KISS1/KISS1R signaling is critical for regulating the activity of gonadotropin-releasing hormone (GNRH1) neurons in mammals
  • is a crucial activator of reproductive function
  • is a 'master regulator' of reproductive physiology, integrating limbic circuits with the regulation of gonadotropin-releasing hormone neurons and reproductive hormone secretion
  • plays an important role in regulating very early pregnancy events such as embryo implantation
  • KISS1 is a metastasis suppressor gene of pancreatic cancer, and this suppression is not dependent on the expression levels of KISS1R
  • CD82 and KISS1 are implicated in the pathogenesis and maintenance of endometriosis
  • KISS1 has a role in male sexual behavior, which is specific to the medial amygdala (MePD)
  • potential involvement of KISS1 protein in the pathogenesis and maintenance of adenomyosis
  • regulates osteosarcoma apoptosis and autophagy processes
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    Signaling between KISS1/KISS1R is now recognized as being essential for normal fertility
    a component kisspeptin/KISS1R system appears to play an important role in the regulation of reproduction
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • metastin, ligand for KISS1R (AXOR12)(KISS1/KISS1R signalling may suppress the invasive phenotype of epithelial ovarian cancer)
  • MED23 is a key regulator in KISS1 transactivation in normal tissue, and the loss of MED23 expression, provokes increased tumor metastasis
  • cleaved by matrix metalloproteinases
  • associated with its receptor GPR54
  • binds directly to the kisspeptin (KISS1) promoter and stimulates KISS1 transcription
  • FURIN appears to be the essential enzyme for the generation of kisspeptin (KISS1)
  • interaction of KISS1 with KISS1R suppresses metastasis and also regulates release of gonadotropin-releasing hormone, which promotes secretion of estradiol (E2) and progesterone (P4)
  • regulates reproduction by stimulating GNRH1 secretion
  • cell & other
    REGULATION
    Other intraovarian KISS1 is likely regulated by sympathetic nerves via a beta-adrenergic receptor and participates locally in ovarian follicular development in reproductive aging
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in malignant skin melanoma, and breast cancer metastatic
    tumoral     --low  
    in metastatic melanoma and in breast cancer compared with their nonmetastatic counterparts
    tumoral     --low  
    in uveal melanoma, associated with a higher risk of metastatic disease
    tumoral     --low  
    in pancreatic cancer is associated with cancer metastasis
    tumoral     --over  
    KISS1/KISS1R expression was found to be significantly higher in breast cancer compared to non-malignant mammary tissues
    constitutional     --low  
    decreased KISS1 and PIBF1 expressions in trophoblasts and deciduas are associated with recurrent spontaneous abortion (RSA)
    constitutional     --over  
    expression level of KISS1 was higher in trophoblasts from women with preeclampsia as compared to normal controls
    Susceptibility to central precocious puberty
    Variant & Polymorphism other p.P74S and p.H90D, were identified inchildren with idiopathic central precocious puberty
    Candidate gene prognostic marker in uveal melanoma
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancermetastases 
    target for antimetastatic therapeutic (antimetastatic agent in combination with MMP inhibitor)
    cancermetastases 
    soluble KISS1, kisspeptins, or mimetics could be used to maintain tumor dormancy, rendering treatment of already disseminated tumor cells (i.e., micrometastases) a legitimate target
    cancerdigestivepancreas
    KISS1 is potentially a novel target for gene therapy
    ANIMAL & CELL MODELS