KISS1_MOUSE
ID KISS1_MOUSE Reviewed; 130 AA.
AC Q6Y4S4; Q149Z8; Q68Y93; Q80XF6;
DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Metastasis-suppressor KiSS-1;
DE AltName: Full=Kisspeptin-1;
DE Contains:
DE RecName: Full=Metastin;
DE AltName: Full=Kisspeptin-52;
DE Contains:
DE RecName: Full=Kisspeptin-10;
DE AltName: Full=Metastin45-54;
DE Flags: Precursor;
GN Name=Kiss1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION, AND TISSUE
RP SPECIFICITY.
RC STRAIN=129S6/SvEvTac; TISSUE=Brain;
RX PubMed=12359743;
RA Stafford L.J., Xia C., Ma W., Cai Y., Liu M.;
RT "Identification and characterization of mouse metastasis-suppressor KiSS1
RT and its G-protein-coupled receptor.";
RL Cancer Res. 62:5399-5404(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Embryo;
RX PubMed=15157736; DOI=10.1016/j.bbaexp.2004.02.005;
RA Terao Y., Kumano S., Takatsu Y., Hattori M., Nishimura A., Ohtaki T.,
RA Shintani Y.;
RT "Expression of KiSS-1, a metastasis suppressor gene, in trophoblast giant
RT cells of the rat placenta.";
RL Biochim. Biophys. Acta 1678:102-110(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC STRAIN=ICR; TISSUE=Brain;
RA Ohsawa M., Chi M., Ohtsubo Y., Brailoiu G.C., Yang J., Chang J., Dun N.J.;
RT "Identification and characterization of metastin in the mouse spinal
RT cord.";
RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Placenta;
RA Xie H., Bonaldo M.F., Soares M.B.;
RT "The genesis of the human KISS1.";
RL Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP TISSUE SPECIFICITY, AND ROLE IN THE REGULATION OF GONADOTROPIN SECRETION.
RX PubMed=15217982; DOI=10.1210/en.2004-0431;
RA Gottsch M.L., Cunningham M.J., Smith J.T., Popa S.M., Acohido B.V.,
RA Crowley W.F., Seminara S., Clifton D.K., Steiner R.A.;
RT "A role for kisspeptins in the regulation of gonadotropin secretion in the
RT mouse.";
RL Endocrinology 145:4073-4077(2004).
RN [7]
RP INVOLVEMENT IN REGULATION OF GONADOTROPIN SECRETION.
RX PubMed=15665556; DOI=10.1159/000083140;
RA Irwig M.S., Fraley G.S., Smith J.T., Acohido B.V., Popa S.M.,
RA Cunningham M.J., Gottsch M.L., Clifton D.K., Steiner R.A.;
RT "Kisspeptin activation of gonadotropin releasing hormone neurons and
RT regulation of KiSS-1 mRNA in the male rat.";
RL Neuroendocrinology 80:264-272(2004).
RN [8]
RP FUNCTION.
RX PubMed=15486019; DOI=10.1113/jphysiol.2004.072298;
RA Navarro V.M., Fernandez-Fernandez R., Castellano J.M., Roa J., Mayen A.,
RA Barreiro M.L., Gaytan F., Aguilar E., Pinilla L., Dieguez C.,
RA Tena-Sempere M.;
RT "Advanced vaginal opening and precocious activation of the reproductive
RT axis by KiSS-1 peptide, the endogenous ligand of GPR54.";
RL J. Physiol. (Lond.) 561:379-386(2004).
RN [9]
RP ROLE IN LUTEINIZING HORMONE SECRETION.
RX PubMed=15375028; DOI=10.1210/en.2004-0836;
RA Navarro V.M., Castellano J.M., Fernandez-Fernandez R., Tovar S., Roa J.,
RA Mayen A., Nogueiras R., Vazquez M.J., Barreiro M.L., Magni P., Aguilar E.,
RA Dieguez C., Pinilla L., Tena-Sempere M.;
RT "Characterization of the potent luteinizing hormone-releasing activity of
RT KiSS-1 peptide, the natural ligand of GPR54.";
RL Endocrinology 146:156-163(2005).
RN [10]
RP DIRECT STIMULATION OF GONADOTROPIN-RELEASING HORMONE RELEASE.
RX PubMed=15665093; DOI=10.1073/pnas.0409330102;
RA Messager S., Chatzidaki E.E., Ma D., Hendrick A.G., Zahn D., Dixon J.,
RA Thresher R.R., Malinge I., Lomet D., Carlton M.B., Colledge W.H.,
RA Caraty A., Aparicio S.A.J.R.;
RT "Kisspeptin directly stimulates gonadotropin-releasing hormone release via
RT G protein-coupled receptor 54.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:1761-1766(2005).
RN [11]
RP ROLE IN FOLLICLE-STIMULATING HORMONE SECRETION.
RX PubMed=15637288; DOI=10.1210/en.2004-1353;
RA Navarro V.M., Castellano J.M., Fernandez-Fernandez R., Tovar S., Roa J.,
RA Mayen A., Barreiro M.L., Casanueva F.F., Aguilar E., Dieguez C.,
RA Pinilla L., Tena-Sempere M.;
RT "Effects of KiSS-1 peptide, the natural ligand of GPR54, on follicle-
RT stimulating hormone secretion in the rat.";
RL Endocrinology 146:1689-1697(2005).
RN [12]
RP DISRUPTION PHENOTYPE.
RX PubMed=17563351; DOI=10.1073/pnas.0704114104;
RA d'Anglemont de Tassigny X., Fagg L.A., Dixon J.P., Day K., Leitch H.G.,
RA Hendrick A.G., Zahn D., Franceschini I., Caraty A., Carlton M.B.,
RA Aparicio S.A., Colledge W.H.;
RT "Hypogonadotropic hypogonadism in mice lacking a functional Kiss1 gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:10714-10719(2007).
CC -!- FUNCTION: Metastasis suppressor protein. May regulate events downstream
CC of cell-matrix adhesion, perhaps involving cytoskeletal reorganization.
CC Generates a C-terminally amidated peptide, metastin which functions as
CC the endogenous ligand of the G-protein coupled receptor GPR54.
CC Activation of the receptor inhibits cell proliferation and cell
CC migration, key characteristics of tumor metastasis. The receptor is
CC also essential for normal gonadotropin-released hormone physiology and
CC for puberty. The hypothalamic KiSS1/GPR54 system is a pivotal factor in
CC central regulation of the gonadotropic axis at puberty and in
CC adulthood. Intracerebroventricular administration induces an increase
CC in serum LH and FSH levels in prepubertal male and female as well as in
CC adult animals. {ECO:0000269|PubMed:15217982,
CC ECO:0000269|PubMed:15375028, ECO:0000269|PubMed:15486019,
CC ECO:0000269|PubMed:15637288}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6Y4S4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6Y4S4-2; Sequence=VSP_012957;
CC -!- TISSUE SPECIFICITY: Weak in all tissue types with highest levels in
CC lung and 15- 17-day embryos. Expressed in areas of the hypothalamus
CC implicated in the neuroendocrine regulation of gonadotropin secretion,
CC including the anteroventral periventricular nucleus, the
CC periventricular nucleus, and the arcuate nucleus.
CC {ECO:0000269|PubMed:12359743, ECO:0000269|PubMed:15217982}.
CC -!- DISRUPTION PHENOTYPE: Animals are viable and healthy with no apparent
CC abnormalities but fail to undergo sexual maturation. Mutant female do
CC not progress through the estrous cycle, have thread-like uteri and
CC small ovaries, and do not produce mature Graffian follicles. Mutant
CC males have small testes, and spermatogenesis arrested mainly at the
CC early haploid spermatid stage. Both sexes have low circulating
CC gonadotropin (LH and FSH) and sex steroid (beta-estradiol or
CC testosterone) hormone levels. Migration of GnRH neurons into the
CC hypothalamus appears normal with appropriate axonal connections to the
CC median eminence and total GnRH content. The hypothalamic-pituitary axis
CC is functional, as shown by robust LH secretion after peripheral
CC administration of kisspeptin. {ECO:0000269|PubMed:17563351}.
CC -!- SIMILARITY: Belongs to the KISS1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAO64981.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF472576; AAP13356.1; -; mRNA.
DR EMBL; AY182231; AAO64981.1; ALT_INIT; mRNA.
DR EMBL; AB162440; BAD36756.1; -; mRNA.
DR EMBL; AY707858; AAW34131.1; -; mRNA.
DR EMBL; BC117046; AAI17047.1; -; mRNA.
DR EMBL; BC119348; AAI19349.1; -; mRNA.
DR CCDS; CCDS48362.1; -. [Q6Y4S4-2]
DR RefSeq; NP_839991.2; NM_178260.3. [Q6Y4S4-2]
DR AlphaFoldDB; Q6Y4S4; -.
DR iPTMnet; Q6Y4S4; -.
DR PhosphoSitePlus; Q6Y4S4; -.
DR PaxDb; Q6Y4S4; -.
DR PRIDE; Q6Y4S4; -.
DR DNASU; 280287; -.
DR Ensembl; ENSMUST00000007433; ENSMUSP00000007433; ENSMUSG00000116158. [Q6Y4S4-2]
DR Ensembl; ENSMUST00000178033; ENSMUSP00000136746; ENSMUSG00000116158. [Q6Y4S4-2]
DR Ensembl; ENSMUST00000193888; ENSMUSP00000142234; ENSMUSG00000115958. [Q6Y4S4-2]
DR Ensembl; ENSMUST00000194044; ENSMUSP00000141501; ENSMUSG00000115958. [Q6Y4S4-2]
DR Ensembl; ENSMUST00000195286; ENSMUSP00000142264; ENSMUSG00000115958. [Q6Y4S4-2]
DR GeneID; 280287; -.
DR KEGG; mmu:280287; -.
DR CTD; 3814; -.
DR MGI; MGI:2663985; Kiss1.
DR VEuPathDB; HostDB:ENSMUSG00000115958; -.
DR VEuPathDB; HostDB:ENSMUSG00000116158; -.
DR GeneTree; ENSGT00390000008827; -.
DR HOGENOM; CLU_119112_0_0_1; -.
DR InParanoid; Q6Y4S4; -.
DR OMA; PMENPRS; -.
DR OrthoDB; 1513721at2759; -.
DR TreeFam; TF338233; -.
DR Reactome; R-MMU-375276; Peptide ligand-binding receptors.
DR Reactome; R-MMU-416476; G alpha (q) signalling events.
DR BioGRID-ORCS; 280287; 3 hits in 73 CRISPR screens.
DR PRO; PR:Q6Y4S4; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q6Y4S4; protein.
DR Bgee; ENSMUSG00000115958; Expressed in morula and 14 other tissues.
DR ExpressionAtlas; Q6Y4S4; baseline.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0031773; F:kisspeptin receptor binding; ISO:MGI.
DR GO; GO:0046697; P:decidualization; IMP:MGI.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:MGI.
DR GO; GO:0060112; P:generation of ovulation cycle rhythm; ISO:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISO:MGI.
DR GO; GO:0051482; P:positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway; ISO:MGI.
DR GO; GO:0060124; P:positive regulation of growth hormone secretion; ISO:MGI.
DR GO; GO:0033686; P:positive regulation of luteinizing hormone secretion; ISO:MGI.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:MGI.
DR GO; GO:0050806; P:positive regulation of synaptic transmission; ISO:MGI.
DR InterPro; IPR020207; Metastasis-suppressor_KiSS-1.
DR PANTHER; PTHR16955; PTHR16955; 1.
DR Pfam; PF15152; Kisspeptin; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Amidation; Cleavage on pair of basic residues;
KW Disulfide bond; Phosphoprotein; Reference proteome; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..130
FT /note="Metastasis-suppressor KiSS-1"
FT /id="PRO_0000021552"
FT PEPTIDE 68..119
FT /note="Metastin"
FT /id="PRO_0000021553"
FT PEPTIDE 110..119
FT /note="Kisspeptin-10"
FT /id="PRO_0000021554"
FT REGION 49..82
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 110..119
FT /note="Essential for receptor binding and receptor
FT activation"
FT MOD_RES 110
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q15726"
FT MOD_RES 119
FT /note="Tyrosine amide"
FT /evidence="ECO:0000250"
FT DISULFID 71..85
FT /evidence="ECO:0000255"
FT VAR_SEQ 25..28
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15157736, ECO:0000303|Ref.3,
FT ECO:0000303|Ref.4"
FT /id="VSP_012957"
SQ SEQUENCE 130 AA; 14117 MW; AC9D30CF84B4F41B CRC64;
MISMASWQLL LLLCVATYGE PLAKVAPLVK PGSTGQQSGP QELVNAWEKE SRYAESKPGS
AGLRARRSSP CPPVEGPAGR QRPLCASRSR LIPAPRGAVL VQREKDLSTY NWNSFGLRYG
RRQAARAARG
