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Protein

Agouti-related protein

Gene

AGRP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  1. neuropeptide hormone activity Source: UniProtKB
  2. receptor binding Source: ProtInc

GO - Biological processi

  1. adult feeding behavior Source: Ensembl
  2. eating behavior Source: Ensembl
  3. feeding behavior Source: ProtInc
  4. hormone-mediated signaling pathway Source: InterPro
  5. maternal process involved in female pregnancy Source: Ensembl
  6. neuropeptide signaling pathway Source: UniProtKB
  7. photoperiodism Source: Ensembl
  8. positive regulation of feeding behavior Source: Ensembl
  9. regulation of feeding behavior Source: UniProtKB
  10. response to insulin Source: Ensembl
Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
Agouti-related protein
Gene namesi
Name:AGRP
Synonyms:AGRT, ART
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 16

Organism-specific databases

HGNCiHGNC:330. AGRP.

Subcellular locationi

Secreted 1 Publication. Golgi apparatus lumen 1 Publication

GO - Cellular componenti

  1. extracellular space Source: UniProtKB
  2. extracellular vesicular exosome Source: UniProtKB
  3. Golgi lumen Source: UniProtKB
  4. neuronal cell body Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Golgi apparatus, Secreted

Pathology & Biotechi

Involvement in diseasei

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)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi111 – 1111R → A: Abolishes inhibition of cAMP production in response to melanocortin receptor stimulation. 1 Publication

Keywords - Diseasei

Disease mutation, Obesity

Organism-specific databases

MIMi601665. phenotype.
PharmGKBiPA24627.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2020Sequence AnalysisAdd
BLAST
Chaini21 – 132112Agouti-related proteinPRO_0000001034Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi87 ↔ 102
Disulfide bondi94 ↔ 108
Disulfide bondi101 ↔ 119
Disulfide bondi105 ↔ 129
Disulfide bondi110 ↔ 117

Keywords - PTMi

Disulfide bond

Proteomic databases

PaxDbiO00253.
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

BgeeiO00253.
CleanExiHS_AGRP.
ExpressionAtlasiO00253. baseline.
GenevestigatoriO00253.

Organism-specific databases

HPAiHPA041017.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi106688. 1 interaction.
STRINGi9606.ENSP00000290953.

Structurei

Secondary structure

1
132
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi95 – 973Combined sources
Beta strandi101 – 1033Combined sources
Beta strandi107 – 1159Combined sources
Beta strandi117 – 1204Combined sources
Beta strandi125 – 1273Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1HYKNMR-A87-132[»]
1MR0NMR-A87-120[»]
2IQVmodel-B87-132[»]
ProteinModelPortaliO00253.
SMRiO00253. Positions 87-132.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO00253.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini87 – 12943AgoutiPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni111 – 1133Interaction with melanocortin receptors

Domaini

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

Sequence similaritiesi

Contains 1 agouti domain.PROSITE-ProRule annotation

Keywords - Domaini

Knottin, Signal

Phylogenomic databases

eggNOGiNOG44906.
GeneTreeiENSGT00510000048590.
HOGENOMiHOG000033861.
HOVERGENiHBG050467.
InParanoidiO00253.
KOiK05231.
OMAiMQGAQMG.
OrthoDBiEOG74TX1T.
PhylomeDBiO00253.
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.

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti6 – 61V → L in AAB68621 (PubMed:9311920).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti67 – 671A → T Polymorphism that may play a role in obesity in an age-dependent manner; apparently no effect on activity. 3 Publications
Corresponds to variant rs5030980 [ dbSNP | Ensembl ].
VAR_015385

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.

Cross-referencesi

Web resourcesi

SeattleSNPs

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1HYKNMR-A87-132[»]
1MR0NMR-A87-120[»]
2IQVmodel-B87-132[»]
ProteinModelPortaliO00253.
SMRiO00253. Positions 87-132.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106688. 1 interaction.
STRINGi9606.ENSP00000290953.

Proteomic databases

PaxDbiO00253.
PRIDEiO00253.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi181.
GeneCardsiGC16M067516.
HGNCiHGNC:330. AGRP.
HPAiHPA041017.
MIMi601665. phenotype.
602311. gene.
neXtProtiNX_O00253.
PharmGKBiPA24627.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG44906.
GeneTreeiENSGT00510000048590.
HOGENOMiHOG000033861.
HOVERGENiHBG050467.
InParanoidiO00253.
KOiK05231.
OMAiMQGAQMG.
OrthoDBiEOG74TX1T.
PhylomeDBiO00253.
TreeFamiTF330729.

Miscellaneous databases

EvolutionaryTraceiO00253.
GeneWikiiAgouti-related_peptide.
GenomeRNAii181.
NextBioi738.
PROiO00253.
SOURCEiSearch...

Gene expression databases

BgeeiO00253.
CleanExiHS_AGRP.
ExpressionAtlasiO00253. baseline.
GenevestigatoriO00253.

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...

Publicationsi

« Hide 'large scale' publications
  1. "Hypothalamic expression of ART, a novel gene related to agouti, is up-regulated in obese and diabetic mutant mice."
    Shutter J.R., Graham M., Kinsey A.C., Scully S., Luethy R., Stark K.L.
    Genes Dev. 11:593-602(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein."
    Ollmann M.M., Wilson B.D., Yang Y.K., Kerns J.A., Chen Y., Gantz I., Barsh G.S.
    Science 278:135-138(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Adrenal gland.
  3. "The gene structure and minimal promoter of the human agouti related protein."
    Brown A.M., Mayfield D.K., Volaufova J., Argyropoulos G.
    Gene 277:231-238(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-67.
  4. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  5. SeattleSNPs variation discovery resource
    Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  6. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  7. "Determination of disulfide structure in agouti-related protein (AGRP) by stepwise reduction and alkylation."
    Bures E.J., Hui J.O., Young Y., Chow D.T., Katta V., Rohde M.F., Zeni L., Rosenfeld R.D., Stark K.L., Haniu M.
    Biochemistry 37:12172-12177(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISULFIDE BONDS.
  8. "Characterization of Agouti-related protein binding to melanocortin receptors."
    Yang Y.K., Thompson D.A., Dickinson C.J., Wilken J., Barsh G.S., Kent S.B., Gantz I.
    Mol. Endocrinol. 13:148-155(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH MC3R; MC4R AND MC5R.
  9. "AgRP(83-132) acts as an inverse agonist on the human-melanocortin-4 receptor."
    Nijenhuis W.A., Oosterom J., Adan R.A.
    Mol. Endocrinol. 15:164-171(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS INVERSE AGONIST FOR MC3R AND MC4R.
  10. "The natural inverse agonist agouti-related protein induces arrestin-mediated endocytosis of melanocortin-3 and -4 receptors."
    Breit A., Wolff K., Kalwa H., Jarry H., Buch T., Gudermann T.
    J. Biol. Chem. 281:37447-37456(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN MC3R AND MC4R ENDOCYTOSIS.
  11. "NMR structure of a minimized human agouti related protein prepared by total chemical synthesis."
    Bolin K.A., Anderson D.J., Trulson J.A., Thompson D.A., Wilken J., Kent S.B.H., Gantz I., Millhauser G.L.
    FEBS Lett. 451:125-131(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 87-132, FUNCTION, CIRCULAR DICHROISM, DISULFIDE BONDS, MUTAGENESIS OF ARG-111.
  12. "High-resolution NMR structure of the chemically-synthesized melanocortin receptor binding domain AGRP(87-132) of the agouti-related protein."
    McNulty J.C., Thompson D.A., Bolin K.A., Wilken J., Barsh G.S., Millhauser G.L.
    Biochemistry 40:15520-15527(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 87-132, DOMAIN, DISULFIDE BONDS.
  13. "Design, pharmacology, and NMR structure of a minimized cystine knot with agouti-related protein activity."
    Jackson P.J., McNulty J.C., Yang Y.K., Thompson D.A., Chai B., Gantz I., Barsh G.S., Millhauser G.L.
    Biochemistry 41:7565-7572(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 87-120.
  14. Cited for: VARIANT THR-67, POSSIBLE ASSOCIATION WITH OBESITY.
  15. "Functional analysis of the Ala67Thr polymorphism in agouti related protein associated with anorexia nervosa and leanness."
    de Rijke C.E., Jackson P.J., Garner K.M., van Rozen R.J., Douglas N.R., Kas M.J., Millhauser G.L., Adan R.A.
    Biochem. Pharmacol. 70:308-316(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION OF VARIANT THR-67, SUBCELLULAR LOCATION, FUNCTION.

Entry informationi

Entry nameiAGRP_HUMAN
AccessioniPrimary (citable) accession number: O00253
Secondary accession number(s): O15459, Q2TBD9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 1, 1997
Last modified: February 4, 2015
This is version 135 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 16
    Human chromosome 16: 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

External Data

Dasty 3

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 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.