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Protein

Agouti-related protein

Gene

AGRP

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

Functioni

Plays a role in weight homeostasis. Involved in the control of feeding behavior through the central melanocortin system. Acts as alpha melanocyte-stimulating hormone antagonist by inhibiting cAMP production mediated by stimulation of melanocortin receptors within the hypothalamus and adrenal gland. Has very low activity with MC5R (By similarity). Is an inverse agonist for MC3R and MC4R being able to suppress their constitutive activity. It promotes MC3R and MC4R endocytosis in an arrestin-dependent manner.By similarity5 Publications

GO - Molecular functioni

  • neuropeptide hormone activity Source: UniProtKB
  • signaling receptor binding Source: ProtInc

GO - Biological processi

Enzyme and pathway databases

SIGNORiO00253

Names & Taxonomyi

Protein namesi
Recommended name:
Agouti-related protein
Gene namesi
Name:AGRP
Synonyms:AGRT, ART
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000159723.4
HGNCiHGNC:330 AGRP
MIMi602311 gene
neXtProtiNX_O00253

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

Golgi apparatus, Secreted

Pathology & Biotechi

Involvement in diseasei

Obesity (OBESITY)
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat.
See also OMIM:601665

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi79 – 82REPR → AEPA: Cleavage is blocked. 1 Publication4
Mutagenesisi85 – 86RR → AA: No effect on cleavage. 1 Publication2
Mutagenesisi86 – 89RCVR → ACVA: No effect on cleavage. 1 Publication4
Mutagenesisi111R → A: Abolishes inhibition of cAMP production in response to melanocortin receptor stimulation. 1 Publication1

Keywords - Diseasei

Disease mutation, Obesity

Organism-specific databases

DisGeNETi181
MalaCardsiAGRP
MIMi601665 phenotype
OpenTargetsiENSG00000159723
PharmGKBiPA24627

Polymorphism and mutation databases

BioMutaiAGRP

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Sequence analysisAdd BLAST20
PropeptideiPRO_000043404421 – 822 PublicationsAdd BLAST62
ChainiPRO_000000103483 – 132Agouti-related proteinAdd BLAST50

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi87 ↔ 1023 Publications
Disulfide bondi94 ↔ 1083 Publications
Disulfide bondi101 ↔ 1193 Publications
Disulfide bondi105 ↔ 1293 Publications
Disulfide bondi110 ↔ 1173 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei82 – 83Cleavage; by PCSK11 Publication2

Keywords - PTMi

Disulfide bond

Proteomic databases

PaxDbiO00253
PeptideAtlasiO00253
PRIDEiO00253

Expressioni

Tissue specificityi

Expressed primarily in the adrenal gland, subthalamic nucleus, and hypothalamus, with a lower level of expression occurring in testis, lung, and kidney.

Gene expression databases

BgeeiENSG00000159723
CleanExiHS_AGRP
ExpressionAtlasiO00253 baseline and differential
GenevisibleiO00253 HS

Organism-specific databases

HPAiHPA041017

Interactioni

Subunit structurei

Interacts with melanocortin receptors MC3R, MC4R and MC5R.1 Publication

GO - Molecular functioni

  • neuropeptide hormone activity Source: UniProtKB
  • signaling receptor binding Source: ProtInc

Protein-protein interaction databases

BioGridi106688, 9 interactors
STRINGi9606.ENSP00000290953

Structurei

Secondary structure

1132
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi95 – 97Combined sources3
Beta strandi101 – 103Combined sources3
Beta strandi107 – 115Combined sources9
Beta strandi117 – 120Combined sources4
Beta strandi125 – 127Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1HYKNMR-A87-132[»]
1MR0NMR-A87-120[»]
2IQVmodel-B87-132[»]
ProteinModelPortaliO00253
SMRiO00253
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO00253

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini87 – 129AgoutiPROSITE-ProRule annotationAdd BLAST43

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni111 – 113Interaction with melanocortin receptors3

Domaini

The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin.1 Publication

Keywords - Domaini

Knottin, Signal

Phylogenomic databases

eggNOGiENOG410J14P Eukaryota
ENOG410Z66T LUCA
GeneTreeiENSGT00510000048590
HOGENOMiHOG000033861
HOVERGENiHBG050467
InParanoidiO00253
KOiK05231
OMAiGHQVPCC
OrthoDBiEOG091G1506
PhylomeDBiO00253
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.

O00253-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLTAAVLSCA LLLALPATRG AQMGLAPMEG IRRPDQALLP ELPGLGLRAP
60 70 80 90 100
LKKTTAEQAE EDLLQEAQAL AEVLDLQDRE PRSSRRCVRL HESCLGQQVP
110 120 130
CCDPCATCYC RFFNAFCYCR KLGTAMNPCS RT
Length:132
Mass (Da):14,440
Last modified:July 1, 1997 - v1
Checksum:i1CCBE112C3EB10F5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti6V → L in AAB68621 (PubMed:9311920).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01538567A → T Polymorphism that may play a role in obesity in an age-dependent manner; apparently no effect on activity. 3 PublicationsCorresponds to variant dbSNP:rs5030980EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U88063 mRNA Translation: AAB52240.1
U89485 mRNA Translation: AAB68621.1
AF314194 Genomic DNA Translation: AAL09457.1
AF281309 Genomic DNA Translation: AAK96256.1
DQ374394 Genomic DNA Translation: ABC88473.1
BC110443 mRNA Translation: AAI10444.1
CCDSiCCDS10839.1
RefSeqiNP_001129.1, NM_001138.1
UniGeneiHs.104633

Genome annotation databases

EnsembliENST00000290953; ENSP00000290953; ENSG00000159723
GeneIDi181
KEGGihsa:181
UCSCiuc002etg.1 human

Similar proteinsi

Entry informationi

Entry nameiAGRP_HUMAN
AccessioniPrimary (citable) accession number: O00253
Secondary accession number(s): O15459, Q2TBD9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 1, 1997
Last modified: May 23, 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

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