Agouti-signaling protein precursor - Homo sapiens (Human)

Names and origin

Protein names

Recommended name:
    Agouti-signaling protein
      Short name=ASP
Alternative name(s):
    Agouti switch protein

Gene names

Name:	ASIP
Synonyms:	AGTI, AGTIL, ASP

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	132 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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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 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.
Sequence similarities	Contains 1 agouti domain.

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Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Knottin Signal
PTM	Glycoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cell-cell signaling Ref.2 Traceable author statement. Source: ProtInc generation of precursor metabolites and energy Ref.1 Traceable author statement. Source: ProtInc signal transduction Ref.2 Traceable author statement. Source: ProtInc
Cellular component	extracellular space Ref.1 Traceable author statement. Source: ProtInc
Molecular function	receptor binding Ref.2 Traceable author statement. Source: ProtInc
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Signal peptide

1 – 22

22

Potential

Chain

23 – 132

110

Agouti-signaling protein

Regions

Domain

93 – 132

40

Agouti

Compositional bias

57 – 86

30

Arg/Lys-rich (basic)

Amino acid modifications

Glycosylation

39

1

N-linked (GlcNAc...) Potential

Disulfide bond

Disulfide bond

Disulfide bond

Disulfide bond

Disulfide bond

Natural variations

Natural variant

13

1

V → A: dbSNP rs2296151.

Natural variant

61

1

Q → P: dbSNP rs1129414.

Secondary structure

1

.

132

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P42127-1 [UniParc].

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

132

14,515

        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

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References

	« Hide 'large scale' referencesShow '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: 7937887] [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: 7757071] [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. Rogers J. Nature 414:865-871(2001) [PubMed: 11780052] [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: 15489334] [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: 15701517] [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: 11833005] [Abstract] Cited for: INVOLVEMENT IN SHEP9.
+	Additional computationally mapped references.

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Cross-references

Sequence databases

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.

PIR

I37143.

RefSeq

NP_001663.2.

UniGene

Hs.659995

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Y7J	NMR	-	A	80-132	[»]
1Y7K	NMR	-	A	80-132	[»]
2IQW	model	-	B	93-132	[»]

ModBase

Search...

Genome annotation databases

Ensembl

ENSG00000101440. Homo sapiens. [Contig view]

GeneID

434.

KEGG

hsa:434.

Organism-specific databases

H-InvDB

HIX0040611.

HGNC

HGNC:745. ASIP.

MIM

600201. gene.
611742. phenotype.

PharmGKB

PA25045.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

P42127.

HOVERGEN

P42127.

Gene expression databases

ArrayExpress

P42127.

CleanEx

HS_ASIP.

GermOnline

ENSG00000101440. Homo sapiens.

Family and domain databases

InterPro

IPR007733. Agouti.
[Graphical view]

Gene3D

G3DSA:4.10.760.10. Agouti. 1 hit.

PANTHER

PTHR16551. Agouti. 1 hit.

Pfam

PF05039. Agouti. 1 hit.
[Graphical view]

SMART

SM00792. Agouti. 1 hit.
[Graphical view]

PROSITE

PS60024. AGOUTI_1. 1 hit.
PS51150. AGOUTI_2. 1 hit.
[Graphical view]

ProDom

P42127.
[Graphical view] [Entries sharing at least one domain]

BLOCKS

Search...

Other Resources

SOURCE

Search...

ProtoNet

Search...

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Entry information

Entry name

ASIP_HUMAN

Accession

Primary (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:	July 22, 2008
This is version 77 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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