Reviewed, UniProtKB/Swiss-Prot P42127 (ASIP_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

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.

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.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Knottin Signal
PTM	Disulfide bond 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 hormone-mediated signaling Inferred from electronic annotation. Source: InterPro
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...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Potential

Chain

23 – 132

110

Agouti-signaling protein

PRO_0000001028

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

93 ↔ 108

Ref.5

Disulfide bond

100 ↔ 114

Ref.5

Disulfide bond

107 ↔ 125

Ref.5

Disulfide bond

111 ↔ 132

Ref.5

Disulfide bond

116 ↔ 123

Ref.5

Natural variations

Natural variant

13

1

V → A: dbSNP rs2296151.

VAR_022125

Natural variant

61

1

Q → P: dbSNP rs1129414.

VAR_005003

Secondary structure

1

.

.

.

.

.

.

.

132

Helix Strand Turn

Details...

Beta strand

102 – 105

4

Beta strand

113 – 116

4

Beta strand

123 – 126

4

Sequences

	Sequence		Length	Mass (Da)
	P42127-1 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: AF82CC3C747F2BE6	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

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. , 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: 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.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

IPI

IPI00030037.

PIR

I37143.

RefSeq

NP_001663.2.

UniGene

Hs.659995

3D structure databases

PDBPDBe

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

ModBase

Search...

Proteomic databases

PRIDE

P42127.

Genome annotation databases

Ensembl

ENSG00000101440. Homo sapiens. [Contig view]

GeneID

434.

KEGG

hsa:434.

Organism-specific databases

GeneCards

GC20P032312.

H-InvDB

HIX0040611.

HGNC

HGNC:745. ASIP.

MIM

600201. gene.
611742. phenotype.

PharmGKB

PA25045.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P42127.

HOVERGEN

P42127.

OMA

P42127. CSCRVLN.

Enzyme and pathway databases

Pathway_Interaction_DB

insulin_glucose_pathway. Insulin-mediated glucose transport.

Gene expression databases

ArrayExpress

P42127.

Bgee

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]

ProtoNet

Search...

Other Resources

NextBio

1817.

SOURCE

Search...

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:	May 5, 2009
This is version 83 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)