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Protein

Agouti-signaling protein

Gene

ASIP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  • receptor binding Source: ProtInc

GO - Biological processi

Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:ENSG00000101440-MONOMER.
SIGNORiP42127.

Names & Taxonomyi

Protein namesi
Recommended name:
Agouti-signaling protein
Short name:
ASP
Alternative name(s):
Agouti switch protein
Gene namesi
Name:ASIP
Synonyms:AGTI, AGTIL, ASP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:745. ASIP.

Subcellular locationi

GO - Cellular componenti

  • cell Source: GOC
  • extracellular space Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi434.
MIMi611742. phenotype.
OpenTargetsiENSG00000101440.
PharmGKBiPA25045.

Polymorphism and mutation databases

BioMutaiASIP.
DMDMi1168389.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Sequence analysisAdd BLAST22
ChainiPRO_000000102823 – 132Agouti-signaling proteinAdd BLAST110

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi39N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi93 ↔ 108PROSITE-ProRule annotation1 Publication
Disulfide bondi100 ↔ 114PROSITE-ProRule annotation1 Publication
Disulfide bondi107 ↔ 125PROSITE-ProRule annotation1 Publication
Disulfide bondi111 ↔ 132PROSITE-ProRule annotation1 Publication
Disulfide bondi116 ↔ 123PROSITE-ProRule annotation1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP42127.
PRIDEiP42127.

PTM databases

iPTMnetiP42127.
PhosphoSitePlusiP42127.

Expressioni

Tissue specificityi

Expressed in adipose tissue, testis, ovary and heart and at lower levels in liver, kidney and foreskin.

Gene expression databases

BgeeiENSG00000101440.
CleanExiHS_ASIP.
GenevisibleiP42127. HS.

Organism-specific databases

HPAiHPA048636.

Interactioni

GO - Molecular functioni

  • receptor binding Source: ProtInc

Protein-protein interaction databases

STRINGi9606.ENSP00000364092.

Structurei

Secondary structure

1132
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi96 – 98Combined sources3
Beta strandi102 – 105Combined sources4
Beta strandi113 – 116Combined sources4
Beta strandi123 – 126Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1Y7JNMR-A80-132[»]
1Y7KNMR-A80-132[»]
2IQWmodel-B93-132[»]
2KZANMR-A80-132[»]
2L1JNMR-A93-126[»]
ProteinModelPortaliP42127.
SMRiP42127.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP42127.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini93 – 132AgoutiPROSITE-ProRule annotationAdd BLAST40

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi57 – 86Arg/Lys-rich (basic)Add BLAST30

Domaini

The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin.

Sequence similaritiesi

Contains 1 agouti domain.PROSITE-ProRule annotation

Keywords - Domaini

Knottin, Signal

Phylogenomic databases

eggNOGiENOG410J1GH. Eukaryota.
ENOG410ZCK9. LUCA.
GeneTreeiENSGT00510000048661.
HOGENOMiHOG000111779.
HOVERGENiHBG050593.
InParanoidiP42127.
KOiK08725.
OMAiCSCRVLN.
PhylomeDBiP42127.
TreeFamiTF330729.

Family and domain databases

Gene3Di4.10.760.10. 1 hit.
InterProiIPR007733. Agouti.
IPR027300. Agouti_dom.
[Graphical view]
PANTHERiPTHR16551. PTHR16551. 1 hit.
PfamiPF05039. Agouti. 1 hit.
[Graphical view]
SMARTiSM00792. Agouti. 1 hit.
[Graphical view]
SUPFAMiSSF57055. SSF57055. 1 hit.
PROSITEiPS60024. AGOUTI_1. 1 hit.
PS51150. AGOUTI_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P42127-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDVTRLLLAT LLVFLCFFTA NSHLPPEEKL RDDRSLRSNS SVNLLDVPSV
60 70 80 90 100
SIVALNKKSK QIGRKAAEKK RSSKKEASMK KVVRPRTPLS APCVATRNSC
110 120 130
KPPAPACCDP CASCQCRFFR SACSCRVLSL NC
Length:132
Mass (Da):14,515
Last modified:November 1, 1995 - v1
Checksum:iAF82CC3C747F2BE6
GO

Polymorphismi

Genetic variants in ASIP define the skin/hair/eye pigmentation variation locus 9 (SHEP9) [MIMi: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.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02212513V → A.Corresponds to variant rs2296151dbSNPEnsembl.1
Natural variantiVAR_00500361Q → P.Corresponds to variant rs1129414dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS13232.1.
PIRiI37143.
RefSeqiNP_001663.2. NM_001672.2.
XP_011527122.1. XM_011528820.2.
XP_011527123.1. XM_011528821.1.
UniGeneiHs.659995.

Genome annotation databases

EnsembliENST00000374954; ENSP00000364092; ENSG00000101440.
ENST00000568305; ENSP00000454804; ENSG00000101440.
GeneIDi434.
KEGGihsa:434.
UCSCiuc002xah.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS13232.1.
PIRiI37143.
RefSeqiNP_001663.2. NM_001672.2.
XP_011527122.1. XM_011528820.2.
XP_011527123.1. XM_011528821.1.
UniGeneiHs.659995.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1Y7JNMR-A80-132[»]
1Y7KNMR-A80-132[»]
2IQWmodel-B93-132[»]
2KZANMR-A80-132[»]
2L1JNMR-A93-126[»]
ProteinModelPortaliP42127.
SMRiP42127.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000364092.

PTM databases

iPTMnetiP42127.
PhosphoSitePlusiP42127.

Polymorphism and mutation databases

BioMutaiASIP.
DMDMi1168389.

Proteomic databases

PaxDbiP42127.
PRIDEiP42127.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000374954; ENSP00000364092; ENSG00000101440.
ENST00000568305; ENSP00000454804; ENSG00000101440.
GeneIDi434.
KEGGihsa:434.
UCSCiuc002xah.2. human.

Organism-specific databases

CTDi434.
DisGeNETi434.
GeneCardsiASIP.
HGNCiHGNC:745. ASIP.
HPAiHPA048636.
MIMi600201. gene.
611742. phenotype.
neXtProtiNX_P42127.
OpenTargetsiENSG00000101440.
PharmGKBiPA25045.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J1GH. Eukaryota.
ENOG410ZCK9. LUCA.
GeneTreeiENSGT00510000048661.
HOGENOMiHOG000111779.
HOVERGENiHBG050593.
InParanoidiP42127.
KOiK08725.
OMAiCSCRVLN.
PhylomeDBiP42127.
TreeFamiTF330729.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000101440-MONOMER.
SIGNORiP42127.

Miscellaneous databases

EvolutionaryTraceiP42127.
GenomeRNAii434.
PROiP42127.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000101440.
CleanExiHS_ASIP.
GenevisibleiP42127. HS.

Family and domain databases

Gene3Di4.10.760.10. 1 hit.
InterProiIPR007733. Agouti.
IPR027300. Agouti_dom.
[Graphical view]
PANTHERiPTHR16551. PTHR16551. 1 hit.
PfamiPF05039. Agouti. 1 hit.
[Graphical view]
SMARTiSM00792. Agouti. 1 hit.
[Graphical view]
SUPFAMiSSF57055. SSF57055. 1 hit.
PROSITEiPS60024. AGOUTI_1. 1 hit.
PS51150. AGOUTI_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiASIP_HUMAN
AccessioniPrimary (citable) accession number: P42127
Secondary accession number(s): Q3SXL2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: November 2, 2016
This is version 146 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.