ASIP_HUMAN
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 03-AUG-2022, entry version 177.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7937887; DOI=10.1073/pnas.91.21.9760;
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 the
RT agouti gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:9760-9764(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX 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 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., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., 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., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., 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 project:
RT 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., Barsh G.S.,
RA 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., Rebbeck T.R.;
RT "A polymorphism in the agouti signaling protein gene is associated with
RT human pigmentation.";
RL Am. J. Hum. Genet. 70:770-775(2002).
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). In higher primates, agouti may affect the quality
CC of hair pigmentation rather than its pattern of deposition. Could well
CC play a role in neuroendocrine aspects of melanocortin action. May have
CC some functional role in regulating the lipid metabolism with
CC 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 variants in ASIP define the skin/hair/eye
CC pigmentation variation locus 9 (SHEP9) [MIM:611742]. Hair, eye and skin
CC pigmentation are among the most visible examples of human phenotypic
CC variation, with a broad normal range that is subject to substantial
CC geographic stratification. In the case of skin, individuals tend to
CC have 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 human
CC populations fixed for brown eyes and black hair.
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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; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC104238; AAI04239.1; -; mRNA.
DR EMBL; BC104239; AAI04240.1; -; mRNA.
DR CCDS; CCDS13232.1; -.
DR PIR; I37143; I37143.
DR RefSeq; NP_001663.2; NM_001672.2.
DR RefSeq; XP_011527122.1; XM_011528820.2.
DR RefSeq; XP_011527123.1; XM_011528821.1.
DR PDB; 1Y7J; NMR; -; A=80-132.
DR PDB; 1Y7K; NMR; -; A=80-132.
DR PDB; 2KZA; NMR; -; A=80-132.
DR PDB; 2L1J; NMR; -; A=93-126.
DR PDBsum; 1Y7J; -.
DR PDBsum; 1Y7K; -.
DR PDBsum; 2KZA; -.
DR PDBsum; 2L1J; -.
DR AlphaFoldDB; P42127; -.
DR SMR; P42127; -.
DR BioGRID; 106926; 18.
DR STRING; 9606.ENSP00000454804; -.
DR GlyGen; P42127; 1 site.
DR iPTMnet; P42127; -.
DR PhosphoSitePlus; P42127; -.
DR BioMuta; ASIP; -.
DR DMDM; 1168389; -.
DR MassIVE; P42127; -.
DR PaxDb; P42127; -.
DR PeptideAtlas; P42127; -.
DR PRIDE; P42127; -.
DR Antibodypedia; 25783; 82 antibodies from 14 providers.
DR DNASU; 434; -.
DR Ensembl; ENST00000374954.4; ENSP00000364092.3; ENSG00000101440.10.
DR Ensembl; ENST00000568305.5; ENSP00000454804.1; ENSG00000101440.10.
DR GeneID; 434; -.
DR KEGG; hsa:434; -.
DR MANE-Select; ENST00000374954.4; ENSP00000364092.3; NM_001672.3; NP_001663.2.
DR UCSC; uc002xah.2; human.
DR CTD; 434; -.
DR DisGeNET; 434; -.
DR GeneCards; ASIP; -.
DR HGNC; HGNC:745; ASIP.
DR HPA; ENSG00000101440; Group enriched (epididymis, heart muscle, ovary).
DR MalaCards; ASIP; -.
DR MIM; 600201; gene.
DR MIM; 611742; phenotype.
DR neXtProt; NX_P42127; -.
DR OpenTargets; ENSG00000101440; -.
DR PharmGKB; PA25045; -.
DR VEuPathDB; HostDB:ENSG00000101440; -.
DR eggNOG; ENOG502S5XF; Eukaryota.
DR GeneTree; ENSGT00940000154258; -.
DR HOGENOM; CLU_138633_0_0_1; -.
DR InParanoid; P42127; -.
DR OMA; TICQCLM; -.
DR PhylomeDB; P42127; -.
DR TreeFam; TF330729; -.
DR PathwayCommons; P42127; -.
DR SignaLink; P42127; -.
DR SIGNOR; P42127; -.
DR BioGRID-ORCS; 434; 17 hits in 1066 CRISPR screens.
DR ChiTaRS; ASIP; human.
DR EvolutionaryTrace; P42127; -.
DR GenomeRNAi; 434; -.
DR Pharos; P42127; Tbio.
DR PRO; PR:P42127; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; P42127; protein.
DR Bgee; ENSG00000101440; Expressed in apex of heart and 96 other tissues.
DR Genevisible; P42127; HS.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0031779; F:melanocortin receptor binding; IBA:GO_Central.
DR GO; GO:0005184; F:neuropeptide hormone activity; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc.
DR GO; GO:0031781; F:type 3 melanocortin receptor binding; IEA:Ensembl.
DR GO; GO:0031782; F:type 4 melanocortin receptor binding; IEA:Ensembl.
DR GO; GO:0008343; P:adult feeding behavior; IEA:Ensembl.
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:0071514; P:genomic imprinting; IEA:Ensembl.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; IEA:InterPro.
DR GO; GO:0042438; P:melanin biosynthetic process; IEA:Ensembl.
DR GO; GO:0032438; P:melanosome organization; IBA:GO_Central.
DR GO; GO:0032402; P:melanosome transport; IEA:Ensembl.
DR GO; GO:0048023; P:positive regulation of melanin biosynthetic process; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
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 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; Glycoprotein; Knottin; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..132
FT /note="Agouti-signaling protein"
FT /id="PRO_0000001028"
FT DOMAIN 93..132
FT /note="Agouti"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00494"
FT REGION 62..85
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 39
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 93..108
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00494,
FT ECO:0000269|PubMed:15701517"
FT DISULFID 100..114
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00494,
FT ECO:0000269|PubMed:15701517"
FT DISULFID 107..125
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00494,
FT ECO:0000269|PubMed:15701517"
FT DISULFID 111..132
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00494,
FT ECO:0000269|PubMed:15701517"
FT DISULFID 116..123
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00494,
FT ECO:0000269|PubMed:15701517"
FT VARIANT 13
FT /note="V -> A (in dbSNP:rs2296151)"
FT /id="VAR_022125"
FT VARIANT 61
FT /note="Q -> P (in dbSNP:rs1129414)"
FT /id="VAR_005003"
FT STRAND 96..98
FT /evidence="ECO:0007829|PDB:2KZA"
FT STRAND 102..105
FT /evidence="ECO:0007829|PDB:1Y7J"
FT STRAND 113..116
FT /evidence="ECO:0007829|PDB:1Y7J"
FT STRAND 123..126
FT /evidence="ECO:0007829|PDB:1Y7J"
SQ SEQUENCE 132 AA; 14515 MW; AF82CC3C747F2BE6 CRC64;
MDVTRLLLAT LLVFLCFFTA NSHLPPEEKL RDDRSLRSNS SVNLLDVPSV SIVALNKKSK
QIGRKAAEKK RSSKKEASMK KVVRPRTPLS APCVATRNSC KPPAPACCDP CASCQCRFFR
SACSCRVLSL NC
