ID ASIP_HUMAN Reviewed; 132 AA. AC P42127; Q3SXL2; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 1. DT 22-JUL-2008, entry version 77. DE RecName: Full=Agouti-signaling protein; DE Short=ASP; DE AltName: Full=Agouti switch protein; DE Flags: Precursor; GN Name=ASIP; Synonyms=AGTI, AGTIL, ASP; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX MEDLINE=95024040; PubMed=7937887; RA Kwon H.-Y., Bultman S.J., Loeffler C., Chen W.-J., Furdon P.J., RA Powell J.G., Usala A.-L., Wilkison W., Hansmann I., Woychik R.P.; RT "Molecular structure and chromosomal mapping of the human homolog of RT the agouti gene."; RL Proc. Natl. Acad. Sci. U.S.A. 91:9760-9764(1994). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX MEDLINE=95276734; PubMed=7757071; DOI=10.1093/hmg/4.2.223; RA Wilson B.D., Ollmann M.M., Kang L., Stoffel M., Bell G.I., Barsh G.S.; RT "Structure and function of ASP, the human homolog of the mouse agouti RT gene."; RL Hum. Mol. Genet. 4:223-230(1995). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX MEDLINE=21638749; PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., RA Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP STRUCTURE BY NMR OF 80-132, AND DISULFIDE BONDS. RX PubMed=15701517; DOI=10.1016/j.jmb.2004.12.030; RA McNulty J.C., Jackson P.J., Thompson D.A., Chai B., Gantz I., RA Barsh G.S., Dawson P.E., Millhauser G.L.; RT "Structures of the agouti signaling protein."; RL J. Mol. Biol. 346:1059-1070(2005). RN [6] RP INVOLVEMENT IN SHEP9. RX PubMed=11833005; DOI=10.1086/339076; RA Kanetsky P.A., Swoyer J., Panossian S., Holmes R., Guerry D., RA Rebbeck T.R.; RT "A polymorphism in the agouti signaling protein gene is associated RT with human pigmentation."; RL Am. J. Hum. Genet. 70:770-775(2002). CC -!- FUNCTION: Involved in the regulation of melanogenesis. The binding CC of ASP to MC1R precludes alpha-MSH initiated signaling and thus CC blocks production of cAMP, leading to a down-regulation of CC eumelanogenesis (brown/black pigment) and thus increasing CC synthesis of pheomelanin (yellow/red pigment). In higher primates, CC agouti may affect the quality of hair pigmentation rather than its CC pattern of deposition. Could well play a role in neuroendocrine CC aspects of melanocortin action. May have some functional role in CC regulating the lipid metabolism with adipocytes. CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- TISSUE SPECIFICITY: Expressed in adipose tissue, testis, ovary and CC heart and at lower levels in liver, kidney and foreskin. CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot' CC structurally defines this protein as a knottin. CC -!- POLYMORPHISM: Genetic variations in ASIP are associated with CC variation in skin/hair/eye pigmentation type 9 (SHEP9) CC [MIM:611742]. Hair, eye and skin pigmentation are among the most CC visible examples of human phenotypic variation, with a broad CC normal range that is subject to substantial geographic CC stratification. In the case of skin, individuals tend to have CC lighter pigmentation with increasing distance from the equator. By CC contrast, the majority of variation in human eye and hair color is CC found among individuals of European ancestry, with most other CC human populations fixed for brown eyes and black hair. CC -!- SIMILARITY: Contains 1 agouti domain. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; U12775; AAB61247.1; -; Genomic_DNA. DR EMBL; U12770; AAB61247.1; JOINED; Genomic_DNA. DR EMBL; U12774; AAB61247.1; JOINED; Genomic_DNA. DR EMBL; L37019; AAA89208.1; -; Genomic_DNA. DR EMBL; AL035458; CAB96679.1; -; Genomic_DNA. DR EMBL; BC104238; AAI04239.1; -; mRNA. DR EMBL; BC104239; AAI04240.1; -; mRNA. DR PIR; I37143; I37143. DR RefSeq; NP_001663.2; -. DR UniGene; Hs.659995; -. DR PDB; 1Y7J; NMR; -; A=80-132. DR PDB; 1Y7K; NMR; -; A=80-132. DR PDB; 2IQW; Model; -; B=93-132. DR PDBsum; 1Y7J; -. DR PDBsum; 1Y7K; -. DR PDBsum; 2IQW; -. DR Ensembl; ENSG00000101440; Homo sapiens. DR GeneID; 434; -. DR KEGG; hsa:434; -. DR H-InvDB; HIX0040611; -. DR HGNC; HGNC:745; ASIP. DR MIM; 600201; gene. DR MIM; 611742; phenotype. DR PharmGKB; PA25045; -. DR HOGENOM; P42127; -. DR HOVERGEN; P42127; -. DR ArrayExpress; P42127; -. DR CleanEx; HS_ASIP; -. DR GermOnline; ENSG00000101440; Homo sapiens. DR GO; GO:0005615; C:extracellular space; TAS:ProtInc. DR GO; GO:0005102; F:receptor binding; TAS:ProtInc. DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc. DR GO; GO:0006091; P:generation of precursor metabolites and energy; TAS:ProtInc. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR InterPro; IPR007733; Agouti. DR Gene3D; G3DSA:4.10.760.10; Agouti; 1. DR PANTHER; PTHR16551; Agouti; 1. DR Pfam; PF05039; Agouti; 1. DR SMART; SM00792; Agouti; 1. DR PROSITE; PS60024; AGOUTI_1; 1. DR PROSITE; PS51150; AGOUTI_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Glycoprotein; Knottin; Polymorphism; Secreted; Signal. FT SIGNAL 1 22 Potential. FT CHAIN 23 132 Agouti-signaling protein. FT /FTId=PRO_0000001028. FT DOMAIN 93 132 Agouti. FT COMPBIAS 57 86 Arg/Lys-rich (basic). FT CARBOHYD 39 39 N-linked (GlcNAc...) (Potential). FT DISULFID 93 108 FT DISULFID 100 114 FT DISULFID 107 125 FT DISULFID 111 132 FT DISULFID 116 123 FT VARIANT 13 13 V -> A (in dbSNP:rs2296151). FT /FTId=VAR_022125. FT VARIANT 61 61 Q -> P (in dbSNP:rs1129414). FT /FTId=VAR_005003. FT STRAND 102 105 FT STRAND 113 116 FT STRAND 123 126 SQ SEQUENCE 132 AA; 14515 MW; AF82CC3C747F2BE6 CRC64; MDVTRLLLAT LLVFLCFFTA NSHLPPEEKL RDDRSLRSNS SVNLLDVPSV SIVALNKKSK QIGRKAAEKK RSSKKEASMK KVVRPRTPLS APCVATRNSC KPPAPACCDP CASCQCRFFR SACSCRVLSL NC //