ID   AGRP_MOUSE              Reviewed;         131 AA.
AC   P56473; O35967;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   15-JUL-1998, sequence version 1.
DT   24-JAN-2024, entry version 158.
DE   RecName: Full=Agouti-related protein;
DE   Flags: Precursor;
GN   Name=Agrp; Synonyms=Agrt, Art;
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.
RC   STRAIN=129;
RX   PubMed=9311920; DOI=10.1126/science.278.5335.135;
RA   Ollmann M.M., Wilson B.D., Yang Y.K., Kerns J.A., Chen Y., Gantz I.,
RA   Barsh G.S.;
RT   "Antagonism of central melanocortin receptors in vitro and in vivo by
RT   agouti-related protein.";
RL   Science 278:135-138(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE.
RX   PubMed=9119224; DOI=10.1101/gad.11.5.593;
RA   Shutter J.R., Graham M., Kinsey A.C., Scully S., Luethy R., Stark K.L.;
RT   "Hypothalamic expression of ART, a novel gene related to agouti, is up-
RT   regulated in obese and diabetic mutant mice.";
RL   Genes Dev. 11:593-602(1997).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Eye;
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   [4]
RP   FUNCTION, AND INTERACTION WITH MELANOCORTIN RECEPTORS MC3R; MC4R AND MC5R.
RX   PubMed=9892020; DOI=10.1210/mend.13.1.0223;
RA   Yang Y.K., Thompson D.A., Dickinson C.J., Wilken J., Barsh G.S., Kent S.B.,
RA   Gantz I.;
RT   "Characterization of Agouti-related protein binding to melanocortin
RT   receptors.";
RL   Mol. Endocrinol. 13:148-155(1999).
CC   -!- FUNCTION: Plays a role in weight homeostasis. Involved in the control
CC       of feeding behavior through the central melanocortin system. Acts as
CC       alpha melanocyte-stimulating hormone antagonist by inhibiting cAMP
CC       production mediated by stimulation of melanocortin receptors within the
CC       hypothalamus and adrenal gland. Has very low activity with MC5R. Is an
CC       inverse agonist for MC3R and MC4R being able to suppress their
CC       constitutive activity (By similarity). It promotes MC3R and MC4R
CC       endocytosis in an arrestin-dependent manner (By similarity).
CC       {ECO:0000250, ECO:0000269|PubMed:9892020}.
CC   -!- SUBUNIT: Interacts with melanocortin receptors MC3R, MC4R and MC5R.
CC       {ECO:0000269|PubMed:9892020}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:O00253}. Golgi
CC       apparatus lumen {ECO:0000250|UniProtKB:O00253}.
CC   -!- TISSUE SPECIFICITY: Expressed in arcuate nucleus and median eminence,
CC       adrenal gland (medulla), hypothalamus, testis, and lung.
CC   -!- INDUCTION: Hypothalamic expression is elevated circa 10-fold in ob/ob
CC       and db/db mice.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin.
CC       {ECO:0000250|UniProtKB:O00253}.
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DR   EMBL; U89484; AAB68620.1; -; mRNA.
DR   EMBL; U89486; AAB68622.1; -; Genomic_DNA.
DR   EMBL; BC079902; AAH79902.1; -; mRNA.
DR   CCDS; CCDS22605.1; -.
DR   RefSeq; NP_001258735.1; NM_001271806.1.
DR   RefSeq; NP_031453.1; NM_007427.3.
DR   AlphaFoldDB; P56473; -.
DR   SMR; P56473; -.
DR   STRING; 10090.ENSMUSP00000142044; -.
DR   PaxDb; 10090-ENSMUSP00000005849; -.
DR   ProteomicsDB; 282043; -.
DR   Antibodypedia; 29554; 345 antibodies from 32 providers.
DR   DNASU; 11604; -.
DR   Ensembl; ENSMUST00000005849.11; ENSMUSP00000005849.6; ENSMUSG00000005705.11.
DR   Ensembl; ENSMUST00000194091.6; ENSMUSP00000142044.2; ENSMUSG00000005705.11.
DR   GeneID; 11604; -.
DR   KEGG; mmu:11604; -.
DR   UCSC; uc009ndh.2; mouse.
DR   AGR; MGI:892013; -.
DR   CTD; 181; -.
DR   MGI; MGI:892013; Agrp.
DR   VEuPathDB; HostDB:ENSMUSG00000005705; -.
DR   eggNOG; ENOG502S7K0; Eukaryota.
DR   GeneTree; ENSGT00940000154258; -.
DR   HOGENOM; CLU_103790_0_0_1; -.
DR   InParanoid; P56473; -.
DR   OMA; SWAMLQG; -.
DR   OrthoDB; 4017051at2759; -.
DR   PhylomeDB; P56473; -.
DR   TreeFam; TF330729; -.
DR   BioGRID-ORCS; 11604; 0 hits in 76 CRISPR screens.
DR   ChiTaRS; Agrp; mouse.
DR   PRO; PR:P56473; -.
DR   Proteomes; UP000000589; Chromosome 8.
DR   RNAct; P56473; Protein.
DR   Bgee; ENSMUSG00000005705; Expressed in median eminence of neurohypophysis and 67 other cell types or tissues.
DR   ExpressionAtlas; P56473; baseline and differential.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR   GO; GO:0005796; C:Golgi lumen; ISS:UniProtKB.
DR   GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR   GO; GO:0005184; F:neuropeptide hormone activity; IDA:MGI.
DR   GO; GO:0070996; F:type 1 melanocortin receptor binding; IBA:GO_Central.
DR   GO; GO:0031781; F:type 3 melanocortin receptor binding; ISS:UniProtKB.
DR   GO; GO:0031782; F:type 4 melanocortin receptor binding; ISS:UniProtKB.
DR   GO; GO:0008343; P:adult feeding behavior; IDA:MGI.
DR   GO; GO:0007623; P:circadian rhythm; IEA:Ensembl.
DR   GO; GO:0042755; P:eating behavior; ISO:MGI.
DR   GO; GO:0009755; P:hormone-mediated signaling pathway; IEA:InterPro.
DR   GO; GO:0048571; P:long-day photoperiodism; IEA:Ensembl.
DR   GO; GO:0060135; P:maternal process involved in female pregnancy; IEA:Ensembl.
DR   GO; GO:0007218; P:neuropeptide signaling pathway; IDA:MGI.
DR   GO; GO:2000253; P:positive regulation of feeding behavior; ISO:MGI.
DR   GO; GO:0060259; P:regulation of feeding behavior; ISS:UniProtKB.
DR   GO; GO:0032868; P:response to insulin; IEA:Ensembl.
DR   Gene3D; 4.10.760.10; Agouti domain; 1.
DR   InterPro; IPR007733; Agouti.
DR   InterPro; IPR027300; Agouti_dom.
DR   InterPro; IPR036836; Agouti_dom_sf.
DR   PANTHER; PTHR16551; AGOUTI RELATED; 1.
DR   PANTHER; PTHR16551:SF4; AGOUTI-RELATED PROTEIN; 1.
DR   Pfam; PF05039; Agouti; 1.
DR   SMART; SM00792; Agouti; 1.
DR   SUPFAM; SSF57055; Agouti-related protein; 1.
DR   PROSITE; PS60024; AGOUTI_1; 1.
DR   PROSITE; PS51150; AGOUTI_2; 1.
DR   Genevisible; P56473; MM.
PE   1: Evidence at protein level;
KW   Disulfide bond; Golgi apparatus; Knottin; Reference proteome; Secreted;
KW   Signal.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   PROPEP          21..81
FT                   /evidence="ECO:0000250|UniProtKB:O00253"
FT                   /id="PRO_0000434045"
FT   CHAIN           82..131
FT                   /note="Agouti-related protein"
FT                   /id="PRO_0000001035"
FT   DOMAIN          86..128
FT                   /note="Agouti"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00494"
FT   REGION          110..112
FT                   /note="Interaction with melanocortin receptors"
FT                   /evidence="ECO:0000250"
FT   SITE            81..82
FT                   /note="Cleavage; by PCSK1"
FT                   /evidence="ECO:0000250|UniProtKB:O00253"
FT   DISULFID        86..101
FT                   /evidence="ECO:0000250|UniProtKB:O00253,
FT                   ECO:0000255|PROSITE-ProRule:PRU00494"
FT   DISULFID        93..107
FT                   /evidence="ECO:0000250|UniProtKB:O00253,
FT                   ECO:0000255|PROSITE-ProRule:PRU00494"
FT   DISULFID        100..118
FT                   /evidence="ECO:0000250|UniProtKB:O00253,
FT                   ECO:0000255|PROSITE-ProRule:PRU00494"
FT   DISULFID        104..128
FT                   /evidence="ECO:0000250|UniProtKB:O00253,
FT                   ECO:0000255|PROSITE-ProRule:PRU00494"
FT   DISULFID        109..116
FT                   /evidence="ECO:0000250|UniProtKB:O00253,
FT                   ECO:0000255|PROSITE-ProRule:PRU00494"
SQ   SEQUENCE   131 AA;  14432 MW;  25D9766D074C6834 CRC64;
     MLTAMLLSCV LLLALPPTLG VQMGVAPLKG IRRPDQALFP EFPGLSLNGL KKTTADRAEE
     VLLQKAEALA EVLDPQNRES RSPRRCVRLH ESCLGQQVPC CDPCATCYCR FFNAFCYCRK
     LGTATNLCSR T
//