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P42127 (ASIP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Agouti-signaling protein

Short name=ASP
Alternative name(s):
Agouti switch protein
Gene names
Name:ASIP
Synonyms:AGTI, AGTIL, ASP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length132 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (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 variants in ASIP define the skin/hair/eye pigmentation variation locus 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.

Sequence similarities

Contains 1 agouti domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Chain23 – 132110Agouti-signaling protein
PRO_0000001028

Regions

Domain93 – 13240Agouti
Compositional bias57 – 8630Arg/Lys-rich (basic)

Amino acid modifications

Glycosylation391N-linked (GlcNAc...) Potential
Disulfide bond93 ↔ 108 Ref.5
Disulfide bond100 ↔ 114 Ref.5
Disulfide bond107 ↔ 125 Ref.5
Disulfide bond111 ↔ 132 Ref.5
Disulfide bond116 ↔ 123 Ref.5

Natural variations

Natural variant131V → A.
Corresponds to variant rs2296151 [ dbSNP | Ensembl ].
VAR_022125
Natural variant611Q → P.
Corresponds to variant rs1129414 [ dbSNP | Ensembl ].
VAR_005003

Secondary structure

......... 132
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P42127 [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: AF82CC3C747F2BE6

FASTA13214,515
        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 

« Hide

References

« Hide 'large scale' references
[1]"Molecular structure and chromosomal mapping of the human homolog of the agouti gene."
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.
Proc. Natl. Acad. Sci. U.S.A. 91:9760-9764(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Structure and function of ASP, the human homolog of the mouse agouti gene."
Wilson B.D., Ollmann M.M., Kang L., Stoffel M., Bell G.I., Barsh G.S.
Hum. Mol. Genet. 4:223-230(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"The DNA sequence and comparative analysis of human chromosome 20."
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. expand/collapse author list , 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.
Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"Structures of the agouti signaling protein."
McNulty J.C., Jackson P.J., Thompson D.A., Chai B., Gantz I., Barsh G.S., Dawson P.E., Millhauser G.L.
J. Mol. Biol. 346:1059-1070(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 80-132, DISULFIDE BONDS.
[6]"A polymorphism in the agouti signaling protein gene is associated with human pigmentation."
Kanetsky P.A., Swoyer J., Panossian S., Holmes R., Guerry D., Rebbeck T.R.
Am. J. Hum. Genet. 70:770-775(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SHEP9.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U12775, U12770, U12774 Genomic DNA. Translation: AAB61247.1.
L37019 Genomic DNA. Translation: AAA89208.1.
AL035458 Genomic DNA. Translation: CAB96679.1.
BC104238 mRNA. Translation: AAI04239.1.
BC104239 mRNA. Translation: AAI04240.1.
PIRI37143.
RefSeqNP_001663.2. NM_001672.2.
UniGeneHs.659995.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1Y7JNMR-A80-132[»]
1Y7KNMR-A80-132[»]
2IQWmodel-B93-132[»]
2KZANMR-A80-132[»]
2L1JNMR-A93-126[»]
ProteinModelPortalP42127.
SMRP42127. Positions 93-126.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000364092.

PTM databases

PhosphoSiteP42127.

Polymorphism databases

DMDM1168389.

Proteomic databases

PRIDEP42127.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000374954; ENSP00000364092; ENSG00000101440.
ENST00000568305; ENSP00000454804; ENSG00000101440.
GeneID434.
KEGGhsa:434.
UCSCuc002xah.1. human.

Organism-specific databases

CTD434.
GeneCardsGC20P032785.
HGNCHGNC:745. ASIP.
HPAHPA048636.
MIM600201. gene.
611742. phenotype.
neXtProtNX_P42127.
PharmGKBPA25045.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG309706.
HOGENOMHOG000111779.
HOVERGENHBG050593.
InParanoidP42127.
KOK08725.
OMACSCRVLN.
OrthoDBEOG79PJRV.
PhylomeDBP42127.
TreeFamTF330729.

Gene expression databases

BgeeP42127.
CleanExHS_ASIP.
GenevestigatorP42127.

Family and domain databases

Gene3D4.10.760.10. 1 hit.
InterProIPR007733. Agouti.
IPR027300. Agouti_dom.
[Graphical view]
PANTHERPTHR16551. PTHR16551. 1 hit.
PfamPF05039. Agouti. 1 hit.
[Graphical view]
SMARTSM00792. Agouti. 1 hit.
[Graphical view]
SUPFAMSSF57055. SSF57055. 1 hit.
PROSITEPS60024. AGOUTI_1. 1 hit.
PS51150. AGOUTI_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP42127.
GenomeRNAi434.
NextBio1817.
PROP42127.
SOURCESearch...

Entry information

Entry nameASIP_HUMAN
AccessionPrimary (citable) accession number: P42127
Secondary accession number(s): Q3SXL2
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: March 19, 2014
This is version 126 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM