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UniProtKB/Swiss-Prot entry P42127


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name ASIP_HUMAN
Primary accession number P42127
Secondary accession number Q3SXL2
Integrated into Swiss-Prot on November 1, 1995
Sequence was last modified on November 1, 1995 (Sequence version 1)
Annotations were last modified on    June 10, 2008 (Entry version 76)
Name and origin of the protein
Protein name Agouti-signaling protein [Precursor]
Synonyms ASP
Agouti switch protein
Gene name
Name: ASIP
Synonyms: AGTI, AGTIL, ASP
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=7937887 [NCBI, ExPASy, EBI, Israel, Japan]
Kwon H.-Y., Bultman S.J., Loeffler C., Chen W.-J., Furdon P.J., Powell J.G., Usala A.-L., Wilkison W., Hansmann I., Woychik R.P.;
"Molecular structure and chromosomal mapping of the human homolog of the agouti gene.";
Proc. Natl. Acad. Sci. U.S.A. 91:9760-9764(1994).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
DOI=10.1093/hmg/4.2.223; PubMed=7757071 [NCBI, ExPASy, EBI, Israel, Japan]
Wilson B.D., Ollmann M.M., Kang L., Stoffel M., Bell G.I., Barsh G.S.;
"Structure and function of ASP, the human homolog of the mouse agouti gene.";
Hum. Mol. Genet. 4:223-230(1995).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/414865a; PubMed=11780052 [NCBI, ExPASy, EBI, Israel, Japan]
Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
"The DNA sequence and comparative analysis of human chromosome 20.";
Nature 414:865-871(2001).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
STRUCTURE BY NMR OF 80-132, AND DISULFIDE BONDS.
DOI=10.1016/j.jmb.2004.12.030; PubMed=15701517 [NCBI, ExPASy, EBI, Israel, Japan]
McNulty J.C., Jackson P.J., Thompson D.A., Chai B., Gantz I., Barsh G.S., Dawson P.E., Millhauser G.L.;
"Structures of the agouti signaling protein.";
J. Mol. Biol. 346:1059-1070(2005).
[6]
INVOLVEMENT IN SHEP9.
DOI=10.1086/339076; PubMed=11833005 [NCBI, ExPASy, EBI, Israel, Japan]
Kanetsky P.A., Swoyer J., Panossian S., Holmes R., Guerry D., Rebbeck T.R.;
"A polymorphism in the agouti signaling protein gene is associated with human pigmentation.";
Am. J. Hum. Genet. 70:770-775(2002).
Comments
  • FUNCTION: Involved in the regulation of melanogenesis. The binding of ASP to MC1R precludes alpha-MSH initiated signaling and thus blocks production of cAMP, leading to a down-regulation of eumelanogenesis (brown/black pigment) and thus increasing synthesis of pheomelanin (yellow/red pigment). In higher primates, agouti may affect the quality of hair pigmentation rather than its pattern of deposition. Could well play a role in neuroendocrine aspects of melanocortin action. May have some functional role in regulating the lipid metabolism with adipocytes.
  • SUBCELLULAR LOCATION: Secreted.
  • TISSUE SPECIFICITY: Expressed in adipose tissue, testis, ovary and heart and at lower levels in liver, kidney and foreskin.
  • DOMAIN: The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin.
  • POLYMORPHISM: Genetic variations in ASIP are associated with variation in skin/hair/eye pigmentation type 9 (SHEP9) [MIM:611742]. Hair, eye and skin pigmentation are among the most visible examples of human phenotypic variation, with a broad normal range that is subject to substantial geographic stratification. In the case of skin, individuals tend to have lighter pigmentation with increasing distance from the equator. By contrast, the majority of variation in human eye and hair color is found among individuals of European ancestry, with most other human populations fixed for brown eyes and black hair.
  • SIMILARITY: Contains 1 agouti domain.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
U12775; AAB61247.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U12770; AAB61247.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U12774; AAB61247.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L37019; AAA89208.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AL035458; CAB96679.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC104238; AAI04239.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC104239; AAI04240.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR I37143; I37143.
RefSeq NP_001663.2; -.
UniGene Hs.659995
3D structure databases
PDB
1Y7J; NMR; -; A=80-132.[ExPASy / RCSB / EBI]
1Y7K; NMR; -; A=80-132.[ExPASy / RCSB / EBI]
2IQW; Model; -; B=93-132.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1Y7J; -.
1Y7K; -.
2IQW; -.
ModBase P42127.
Organism-specific databases
H-InvDB HIX0040611; -.
HGNC HGNC:745; ASIP.
GeneLynx ASIP; Homo sapiens.
GenAtlas ASIP.
MIM 600201; gene. [NCBI / EBI]
611742; phenotype. [NCBI / EBI]
PharmGKB PA25045; -.
GeneCards P42127.
Gene expression databases
ArrayExpress P42127; -.
CleanEx HS_ASIP; -.
GermOnline ENSG00000101440; Homo sapiens.
Ontologies
GO
GO:0005615; Cellular component: extracellular space (traceable author statement from ProtInc).
GO:0005102; Molecular function: receptor binding (traceable author statement from ProtInc).
GO:0007267; Biological process: cell-cell signaling (traceable author statement from ProtInc).
GO:0006091; Biological process: generation of precursor metabolites and energy (traceable author statement from ProtInc).
GO:0007165; Biological process: signal transduction (traceable author statement from ProtInc).
QuickGo view.
Family and domain databases
InterPro IPR007733; Agouti.
Graphical view of domain structure.
Gene3D G3DSA:4.10.760.10; Agouti; 1.
PANTHER PTHR16551; Agouti; 1.
Pfam PF05039; Agouti; 1.
Pfam graphical view of domain structure.
SMART SM00792; Agouti; 1.
SMART graphical view of domain structure.
PROSITE PS60024; AGOUTI_1; 1.
PS51150; AGOUTI_2; 1.
PROSITE graphical view of domain structure (profiles).
BLOCKS P42127.
Genome annotation databases
Ensembl ENSG00000101440; Homo sapiens. [Contig view]
GeneID 434; -.
KEGG hsa:434; -.
Phylogenomic databases
HOGENOM P42127; -.
HOVERGEN P42127; -.
Other
SOURCE ASIP; Homo sapiens.
ProtoNet P42127.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Glycoprotein; Knottin; Polymorphism; Secreted; Signal.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
SIGNAL   1    22  22     Potential. 
CHAIN   23   132  110     Agouti-signaling protein. PRO_0000001028
DOMAIN   93   132  40     Agouti. 
COMPBIAS   57    86  30     Arg/Lys-rich (basic). 
CARBOHYD   39    39        N-linked (GlcNAc...) (Potential). 
DISULFID   93   108         
DISULFID   100   114         
DISULFID   107   125         
DISULFID   111   132         
DISULFID   116   123         
VARIANT   13    13  1     V -> A (in dbSNP:rs2296151 [NCBI]). VAR_022125 
VARIANT   61    61  1     Q -> P (in dbSNP:rs1129414 [NCBI]). VAR_005003 
STRAND   102   105  4      
STRAND   113   116  4      
STRAND   123   126  4      
Sequence information
Length: 132 AA [This is the length of the unprocessed precursor] Molecular weight: 14515 Da [This is the MW of the unprocessed precursor] CRC64: AF82CC3C747F2BE6 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MDVTRLLLAT LLVFLCFFTA NSHLPPEEKL RDDRSLRSNS SVNLLDVPSV SIVALNKKSK 

        70         80         90        100        110        120 
QIGRKAAEKK RSSKKEASMK KVVRPRTPLS APCVATRNSC KPPAPACCDP CASCQCRFFR 

       130 
SACSCRVLSL NC 

P42127 in FASTA format

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