ID   ASIP_RAT                Reviewed;         131 AA.
AC   Q99JA2;
DT   01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2001, sequence version 1.
DT   25-MAY-2022, entry version 104.
DE   RecName: Full=Agouti-signaling protein;
DE            Short=ASP;
DE   AltName: Full=Agouti switch protein;
DE   Flags: Precursor;
GN   Name=Asip {ECO:0000250|UniProtKB:P42127};
GN   Synonyms=A {ECO:0000312|RGD:2003};
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1] {ECO:0000305, ECO:0000312|EMBL:BAB21579.1}
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND POLYMORPHISM.
RC   STRAIN=ACI {ECO:0000269|PubMed:11353396};
RC   TISSUE=Skin {ECO:0000269|PubMed:11353396};
RX   PubMed=11353396; DOI=10.1007/s003350020010;
RA   Kuramoto T., Nomoto T., Sugimura T., Ushijima T.;
RT   "Cloning of the rat agouti gene and identification of the rat nonagouti
RT   mutation.";
RL   Mamm. Genome 12:469-471(2001).
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).
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q03288}.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin. {ECO:0000250}.
CC   -!- POLYMORPHISM: A polymorphism exists that is responsible for the
CC       nonagouti phenotype, characterized by a plain black coat on the back
CC       and belly. This is due to a 19-bp deletion resulting in a frameshift at
CC       position 36 and a premature stop codon at position 48.
CC   -!- POLYMORPHISM: Both strain WKAH (agouti) and strain BN (nonagouti)
CC       contain a substitution at the splice donor site of intron 3, resulting
CC       in a shorter isoform lacking exon 3 which causes reduced expression
CC       levels in strain WKAH and almost undetectable levels in strain BN.
CC       {ECO:0000269|PubMed:11353396}.
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DR   EMBL; AB045587; BAB21564.1; -; mRNA.
DR   EMBL; AB045590; BAB21579.1; -; Genomic_DNA.
DR   RefSeq; NP_443211.1; NM_052979.2.
DR   AlphaFoldDB; Q99JA2; -.
DR   STRING; 10116.ENSRNOP00000023905; -.
DR   GlyGen; Q99JA2; 1 site.
DR   GeneID; 24152; -.
DR   KEGG; rno:24152; -.
DR   UCSC; RGD:2003; rat.
DR   CTD; 434; -.
DR   RGD; 2003; Asip.
DR   eggNOG; ENOG502S5XF; Eukaryota.
DR   InParanoid; Q99JA2; -.
DR   OrthoDB; 1556484at2759; -.
DR   PhylomeDB; Q99JA2; -.
DR   PRO; PR:Q99JA2; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0031779; F:melanocortin receptor binding; ISO:RGD.
DR   GO; GO:0005184; F:neuropeptide hormone activity; IBA:GO_Central.
DR   GO; GO:0031781; F:type 3 melanocortin receptor binding; ISO:RGD.
DR   GO; GO:0031782; F:type 4 melanocortin receptor binding; ISO:RGD.
DR   GO; GO:0008343; P:adult feeding behavior; ISO:RGD.
DR   GO; GO:0006091; P:generation of precursor metabolites and energy; ISO:RGD.
DR   GO; GO:0071514; P:genomic imprinting; ISO:RGD.
DR   GO; GO:0009755; P:hormone-mediated signaling pathway; IEA:InterPro.
DR   GO; GO:0042438; P:melanin biosynthetic process; ISO:RGD.
DR   GO; GO:0032438; P:melanosome organization; ISO:RGD.
DR   GO; GO:0032402; P:melanosome transport; ISO:RGD.
DR   GO; GO:0043473; P:pigmentation; ISO:RGD.
DR   GO; GO:0048023; P:positive regulation of melanin biosynthetic process; ISO:RGD.
DR   GO; GO:0040029; P:regulation of gene expression, epigenetic; ISO:RGD.
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_0000001031"
FT   DOMAIN          92..131
FT                   /note="Agouti"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00494"
FT   REGION          58..96
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"
SQ   SEQUENCE   131 AA;  14276 MW;  6E45BB22F2075AEB CRC64;
     MDVTRLLLAT LVGFLCFLTV HSHLVFEETL GDDRSLKSNS SINSLDFSSV SIVALNKKSK
     KISRKEAEKR KRSSKKKASI KKVARPPPPS PCVATRDSCK PPAPACCNPC ASCQCRFFGS
     ACTCRVLNPN C