ID   ASIP_MOUSE              Reviewed;         131 AA.
AC   Q03288; A2ALT3; Q80ST0;
DT   01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT   28-JUN-2011, sequence version 2.
DT   03-AUG-2022, entry version 157.
DE   RecName: Full=Agouti-signaling protein;
DE            Short=ASP;
DE   AltName: Full=Agouti coat color protein;
DE   AltName: Full=Agouti switch protein;
DE   Flags: Precursor;
GN   Name=Asip; Synonyms=a;
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].
RX   PubMed=8449404; DOI=10.1101/gad.7.3.454;
RA   Miller M.W., Duhl D.M., Vrieling H., Cordes S.P., Ollmann M.M.,
RA   Winkes B.M., Barsh G.S.;
RT   "Cloning of the mouse agouti gene predicts a secreted protein ubiquitously
RT   expressed in mice carrying the lethal yellow mutation.";
RL   Genes Dev. 7:454-467(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=1473152; DOI=10.1016/s0092-8674(05)80067-4;
RA   Bultman S.J., Michaud E.J., Woychik R.P.;
RT   "Molecular characterization of the mouse agouti locus.";
RL   Cell 71:1195-1204(1992).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=129; TISSUE=Mammary gland;
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   NUCLEOTIDE SEQUENCE [MRNA] OF 1-70.
RX   PubMed=8319910; DOI=10.1101/gad.7.7a.1203;
RA   Michaud E.J., Bultman S.J., Stubbs L.J., Woychik R.P.;
RT   "The embryonic lethality of homozygous lethal yellow mice (Ay/Ay) is
RT   associated with the disruption of a novel RNA-binding protein.";
RL   Genes Dev. 7:1203-1213(1993).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-16.
RC   STRAIN=C57BL/6J; TISSUE=Spleen;
RX   PubMed=7987393; DOI=10.1038/ng0994-59;
RA   Duhl D.M., Vrieling H., Miller K.A., Wolff G.L., Barsh G.S.;
RT   "Neomorphic agouti mutations in obese yellow mice.";
RL   Nat. Genet. 8:59-65(1994).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-16.
RX   PubMed=8202545; DOI=10.1073/pnas.91.12.5667;
RA   Vrieling H., Duhl D.M., Millar S.E., Miller K.A., Barsh G.S.;
RT   "Differences in dorsal and ventral pigmentation result from regional
RT   expression of the mouse agouti gene.";
RL   Proc. Natl. Acad. Sci. U.S.A. 91:5667-5671(1994).
CC   -!- FUNCTION: Involved in the regulation of melanogenesis. The binding of
CC       ASP to MC1R precludes alpha-MSH initiated signaling and thus blocks
CC       production of cAMP, leading to a down-regulation of eumelanogenesis
CC       (brown/black pigment) and thus increasing synthesis of pheomelanin
CC       (yellow/red pigment). Causes hair follicle melanocytes to synthesize
CC       phaeomelanin instead of black or brown pigment eumelanin and produces
CC       hairs with a subapical yellow band on an otherwise black or brown
CC       background when expressed during the mid-portion of hair growth.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Epithelial cells of the hair follicles and the
CC       epidermis.
CC   -!- DEVELOPMENTAL STAGE: Widely expressed in embryonic and neonatal skin.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin. {ECO:0000250}.
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DR   EMBL; L06451; AAA37201.1; -; mRNA.
DR   EMBL; L06941; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; AL805955; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH466551; EDL06105.1; -; Genomic_DNA.
DR   EMBL; CH466551; EDL06106.1; -; Genomic_DNA.
DR   EMBL; BC009122; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; S63413; AAA15908.1; -; mRNA.
DR   EMBL; S70320; AAP19635.1; -; mRNA.
DR   EMBL; S70326; AAP19636.1; -; mRNA.
DR   EMBL; S70394; AAP19637.1; -; mRNA.
DR   EMBL; S74479; AAP31517.1; -; mRNA.
DR   EMBL; S74489; AAP31519.1; -; mRNA.
DR   EMBL; S74493; AAP31520.1; -; mRNA.
DR   CCDS; CCDS16941.1; -.
DR   PIR; A46298; A46298.
DR   RefSeq; NP_056585.2; NM_015770.3.
DR   AlphaFoldDB; Q03288; -.
DR   SMR; Q03288; -.
DR   STRING; 10090.ENSMUSP00000029123; -.
DR   GlyGen; Q03288; 1 site.
DR   iPTMnet; Q03288; -.
DR   PhosphoSitePlus; Q03288; -.
DR   PaxDb; Q03288; -.
DR   PRIDE; Q03288; -.
DR   ProteomicsDB; 277077; -.
DR   Antibodypedia; 25783; 82 antibodies from 14 providers.
DR   DNASU; 50518; -.
DR   Ensembl; ENSMUST00000029123; ENSMUSP00000029123; ENSMUSG00000027596.
DR   Ensembl; ENSMUST00000109697; ENSMUSP00000105319; ENSMUSG00000027596.
DR   GeneID; 50518; -.
DR   KEGG; mmu:50518; -.
DR   UCSC; uc008njz.1; mouse.
DR   CTD; 50518; -.
DR   MGI; MGI:87853; a.
DR   VEuPathDB; HostDB:ENSMUSG00000027596; -.
DR   eggNOG; ENOG502S5XF; Eukaryota.
DR   GeneTree; ENSGT00940000154258; -.
DR   HOGENOM; CLU_138633_0_0_1; -.
DR   InParanoid; Q03288; -.
DR   OMA; TICQCLM; -.
DR   OrthoDB; 1369753at2759; -.
DR   TreeFam; TF330729; -.
DR   BioGRID-ORCS; 50518; 2 hits in 72 CRISPR screens.
DR   ChiTaRS; a; mouse.
DR   PRO; PR:Q03288; -.
DR   Proteomes; UP000000589; Chromosome 2.
DR   RNAct; Q03288; protein.
DR   Bgee; ENSMUSG00000027596; Expressed in spermatocyte and 38 other tissues.
DR   ExpressionAtlas; Q03288; baseline and differential.
DR   Genevisible; Q03288; MM.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0031779; F:melanocortin receptor binding; IPI:MGI.
DR   GO; GO:0005184; F:neuropeptide hormone activity; IBA:GO_Central.
DR   GO; GO:0031781; F:type 3 melanocortin receptor binding; IPI:MGI.
DR   GO; GO:0031782; F:type 4 melanocortin receptor binding; IPI:MGI.
DR   GO; GO:0008343; P:adult feeding behavior; IMP:MGI.
DR   GO; GO:0006091; P:generation of precursor metabolites and energy; IGI:MGI.
DR   GO; GO:0071514; P:genomic imprinting; IMP:MGI.
DR   GO; GO:0009755; P:hormone-mediated signaling pathway; IEA:InterPro.
DR   GO; GO:0042438; P:melanin biosynthetic process; IMP:MGI.
DR   GO; GO:0032438; P:melanosome organization; IMP:MGI.
DR   GO; GO:0032402; P:melanosome transport; IMP:MGI.
DR   GO; GO:0043473; P:pigmentation; IMP:MGI.
DR   GO; GO:0048023; P:positive regulation of melanin biosynthetic process; IGI:CACAO.
DR   GO; GO:0040029; P:regulation of gene expression, epigenetic; IMP:MGI.
DR   Gene3D; 4.10.760.10; -; 1.
DR   InterPro; IPR007733; Agouti.
DR   InterPro; IPR027300; Agouti_dom.
DR   InterPro; IPR036836; Agouti_dom_sf.
DR   PANTHER; PTHR16551; PTHR16551; 1.
DR   Pfam; PF05039; Agouti; 1.
DR   SMART; SM00792; Agouti; 1.
DR   SUPFAM; SSF57055; SSF57055; 1.
DR   PROSITE; PS60024; AGOUTI_1; 1.
DR   PROSITE; PS51150; AGOUTI_2; 1.
PE   2: Evidence at transcript level;
KW   Disulfide bond; Glycoprotein; Knottin; Reference proteome; Secreted;
KW   Signal.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000255"
FT   CHAIN           23..131
FT                   /note="Agouti-signaling protein"
FT                   /id="PRO_0000001029"
FT   DOMAIN          92..131
FT                   /note="Agouti"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00494"
FT   REGION          58..100
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        63..82
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        39
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        92..107
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00494"
FT   DISULFID        99..113
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00494"
FT   DISULFID        106..124
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00494"
FT   DISULFID        110..131
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00494"
FT   DISULFID        115..122
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00494"
FT   CONFLICT        13
FT                   /note="G -> S (in Ref. 1; AAA37201 and 6; AAA15908/
FT                   AAP19635/AAP19636/AAP19637/AAP31517/AAP31519/AAP31520)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   131 AA;  14313 MW;  A7544EEA26734135 CRC64;
     MDVTRLLLAT LVGFLCFFTV HSHLALEETL GDDRSLRSNS SMNSLDFSSV SIVALNKKSK
     KISRKEAEKR KRSSKKKASM KKVARPPPPS PCVATRDSCK PPAPACCDPC ASCQCRFFGS
     ACTCRVLNPN C