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Protein

Agouti-signaling protein

Gene

ASIP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

GO - Biological processi

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000101440.9
HGNCiHGNC:745 ASIP
MIMi600201 gene
neXtProtiNX_P42127

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi434
MalaCardsiASIP
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...) asparagineSequence 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
PeptideAtlasiP42127
PRIDEiP42127
ProteomicsDBi55487

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

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.

Keywords - Domaini

Knottin, Signal

Phylogenomic databases

eggNOGiENOG410J1GH Eukaryota
ENOG410ZCK9 LUCA
GeneTreeiENSGT00510000048661
HOGENOMiHOG000111779
HOVERGENiHBG050593
InParanoidiP42127
KOiK08725
OMAiCSCRVLN
OrthoDBiEOG09370HSB
PhylomeDBiP42127
TreeFamiTF330729

Family and domain databases

Gene3Di4.10.760.10, 1 hit
InterProiView protein in InterPro
IPR007733 Agouti
IPR027300 Agouti_dom
IPR036836 Agouti_dom_sf
PANTHERiPTHR16551 PTHR16551, 1 hit
PfamiView protein in Pfam
PF05039 Agouti, 1 hit
SMARTiView protein in SMART
SM00792 Agouti, 1 hit
SUPFAMiSSF57055 SSF57055, 1 hit
PROSITEiView protein in PROSITE
PS60024 AGOUTI_1, 1 hit
PS51150 AGOUTI_2, 1 hit

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 dbSNP:rs2296151Ensembl.1
Natural variantiVAR_00500361Q → P. Corresponds to variant dbSNP:rs1129414Ensembl.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 No translation available.
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

Similar proteinsi

Entry informationi

Entry nameiASIP_HUMAN
AccessioniPrimary (citable) accession number: P42127
Secondary accession number(s): Q3SXL2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: June 20, 2018
This is version 155 of the entry and version 1 of the sequence. See 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

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