Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

O00253 (AGRP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Agouti-related protein
Gene names
Name:AGRP
Synonyms:AGRT, ART
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length132 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.8 Ref.9 Ref.10 Ref.11 Ref.15

Subunit structure

Interacts with melanocortin receptors MC3R, MC4R and MC5R. Ref.8

Subcellular location

Secreted. Golgi apparatus lumen Ref.15.

Tissue specificity

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

Domain

The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin. Ref.12

Involvement in disease

Obesity (OBESITY) [MIM:601665]: A 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.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.14

Sequence similarities

Contains 1 agouti domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020 Potential
Chain21 – 132112Agouti-related protein
PRO_0000001034

Regions

Domain87 – 12943Agouti
Region111 – 1133Interaction with melanocortin receptors

Amino acid modifications

Disulfide bond87 ↔ 102 Ref.7 Ref.11 Ref.12
Disulfide bond94 ↔ 108 Ref.7 Ref.11 Ref.12
Disulfide bond101 ↔ 119 Ref.7 Ref.11 Ref.12
Disulfide bond105 ↔ 129 Ref.7 Ref.11 Ref.12
Disulfide bond110 ↔ 117 Ref.7 Ref.11 Ref.12

Natural variations

Natural variant671A → T Polymorphism that may play a role in obesity in an age-dependent manner; apparently no effect on activity. Ref.3 Ref.14 Ref.15
Corresponds to variant rs5030980 [ dbSNP | Ensembl ].
VAR_015385

Experimental info

Mutagenesis1111R → A: Abolishes inhibition of cAMP production in response to melanocortin receptor stimulation. Ref.11
Sequence conflict61V → L in AAB68621. Ref.2

Secondary structure

........... 132
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O00253 [UniParc].

Last modified July 1, 1997. Version 1.
Checksum: 1CCBE112C3EB10F5

FASTA13214,440
        10         20         30         40         50         60 
MLTAAVLSCA LLLALPATRG AQMGLAPMEG IRRPDQALLP ELPGLGLRAP LKKTTAEQAE 

        70         80         90        100        110        120 
EDLLQEAQAL AEVLDLQDRE PRSSRRCVRL HESCLGQQVP CCDPCATCYC RFFNAFCYCR 

       130 
KLGTAMNPCS RT 

« Hide

References

« Hide 'large scale' references
[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]"Association between an agouti-related protein gene polymorphism and anorexia nervosa."
Vink T., Hinney A., van Elburg A.A., van Goozen S.H., Sandkuijl L.A., Sinke R.J., Herpertz-Dahlmann B.M., Hebebrand J., Remschmidt H., van Engeland H., Adan R.A.
Mol. Psychiatry 6:325-328(2001) [PubMed] [Europe PMC] [Abstract]
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]"A polymorphism in the human agouti-related protein is associated with late-onset obesity."
Argyropoulos G., Rankinen T., Neufeld D.R., Rice T., Province M.A., Leon A.S., Skinner J.S., Wilmore J.H., Rao D.C., Bouchard C.
J. Clin. Endocrinol. Metab. 87:4198-4202(2002) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS10839.1.
RefSeqNP_001129.1. NM_001138.1.
UniGeneHs.104633.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1HYKNMR-A87-132[»]
1MR0NMR-A87-120[»]
2IQVmodel-B87-132[»]
ProteinModelPortalO00253.
SMRO00253. Positions 87-132.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106688. 1 interaction.
STRING9606.ENSP00000290953.

Proteomic databases

PaxDbO00253.
PRIDEO00253.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000290953; ENSP00000290953; ENSG00000159723.
GeneID181.
KEGGhsa:181.
UCSCuc002etg.1. human.

Organism-specific databases

CTD181.
GeneCardsGC16M067516.
HGNCHGNC:330. AGRP.
HPAHPA041017.
MIM601665. phenotype.
602311. gene.
neXtProtNX_O00253.
PharmGKBPA24627.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG44906.
HOGENOMHOG000033861.
HOVERGENHBG050467.
InParanoidO00253.
KOK05231.
OMADPEGREP.
OrthoDBEOG74TX1T.
PhylomeDBO00253.
TreeFamTF330729.

Gene expression databases

ArrayExpressO00253.
BgeeO00253.
CleanExHS_AGRP.
GenevestigatorO00253.

Family and domain databases

Gene3D4.10.760.10. 1 hit.
InterProIPR007733. Agouti.
IPR027300. Agouti_dom.
[Graphical view]
PANTHERPTHR16551. PTHR16551. 1 hit.
PfamPF05039. Agouti. 1 hit.
[Graphical view]
SMARTSM00792. Agouti. 1 hit.
[Graphical view]
SUPFAMSSF57055. SSF57055. 1 hit.
PROSITEPS60024. AGOUTI_1. 1 hit.
PS51150. AGOUTI_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO00253.
GeneWikiAgouti-related_peptide.
GenomeRNAi181.
NextBio738.
PROO00253.
SOURCESearch...

Entry information

Entry nameAGRP_HUMAN
AccessionPrimary (citable) accession number: O00253
Secondary accession number(s): O15459, Q2TBD9
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 1, 1997
Last modified: July 9, 2014
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM