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O00253

- AGRP_HUMAN

UniProt

O00253 - AGRP_HUMAN

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Protein
Agouti-related protein
Gene
AGRP, AGRT, ART
Organism
Homo sapiens (Human)
Status
Reviewed - 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.5 Publications

GO - Molecular functioni

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

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. Golgi apparatus lumen 1 Publication

GO - Cellular componenti

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

Keywords - Cellular componenti

Golgi apparatus, Secreted

Pathology & Biotechi

Involvement in diseasei

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.1 Publication

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 – 2020 Reviewed prediction
Add
BLAST
Chaini21 – 132112Agouti-related protein
PRO_0000001034Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi87 ↔ 1023 Publications
Disulfide bondi94 ↔ 1083 Publications
Disulfide bondi101 ↔ 1193 Publications
Disulfide bondi105 ↔ 1293 Publications
Disulfide bondi110 ↔ 1173 Publications

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

ArrayExpressiO00253.
BgeeiO00253.
CleanExiHS_AGRP.
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

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

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1HYKNMR-A87-132[»]
1MR0NMR-A87-120[»]
2IQVmodel-B87-132[»]
ProteinModelPortaliO00253.
SMRiO00253. Positions 87-132.

Miscellaneous databases

EvolutionaryTraceiO00253.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini87 – 12943Agouti
Add
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.

Keywords - Domaini

Knottin, Signal

Phylogenomic databases

eggNOGiNOG44906.
HOGENOMiHOG000033861.
HOVERGENiHBG050467.
InParanoidiO00253.
KOiK05231.
OMAiDPEGREP.
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

MLTAAVLSCA LLLALPATRG AQMGLAPMEG IRRPDQALLP ELPGLGLRAP    50
LKKTTAEQAE EDLLQEAQAL AEVLDLQDRE PRSSRRCVRL HESCLGQQVP 100
CCDPCATCYC RFFNAFCYCR KLGTAMNPCS RT 132
Length:132
Mass (Da):14,440
Last modified:July 1, 1997 - v1
Checksum:i1CCBE112C3EB10F5
GO

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 conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti6 – 61V → L in AAB68621. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS10839.1.
RefSeqi NP_001129.1. NM_001138.1.
UniGenei Hs.104633.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1HYK NMR - A 87-132 [» ]
1MR0 NMR - A 87-120 [» ]
2IQV model - B 87-132 [» ]
ProteinModelPortali O00253.
SMRi O00253. Positions 87-132.
ModBasei Search...

Protein-protein interaction databases

BioGridi 106688. 1 interaction.
STRINGi 9606.ENSP00000290953.

Proteomic databases

PaxDbi O00253.
PRIDEi O00253.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000290953 ; ENSP00000290953 ; ENSG00000159723 .
GeneIDi 181.
KEGGi hsa:181.
UCSCi uc002etg.1. human.

Organism-specific databases

CTDi 181.
GeneCardsi GC16M067516.
HGNCi HGNC:330. AGRP.
HPAi HPA041017.
MIMi 601665. phenotype.
602311. gene.
neXtProti NX_O00253.
PharmGKBi PA24627.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG44906.
HOGENOMi HOG000033861.
HOVERGENi HBG050467.
InParanoidi O00253.
KOi K05231.
OMAi DPEGREP.
OrthoDBi EOG74TX1T.
PhylomeDBi O00253.
TreeFami TF330729.

Miscellaneous databases

EvolutionaryTracei O00253.
GeneWikii Agouti-related_peptide.
GenomeRNAii 181.
NextBioi 738.
PROi O00253.
SOURCEi Search...

Gene expression databases

ArrayExpressi O00253.
Bgeei O00253.
CleanExi HS_AGRP.
Genevestigatori O00253.

Family and domain databases

Gene3Di 4.10.760.10. 1 hit.
InterProi IPR007733. Agouti.
IPR027300. Agouti_dom.
[Graphical view ]
PANTHERi PTHR16551. PTHR16551. 1 hit.
Pfami PF05039. Agouti. 1 hit.
[Graphical view ]
SMARTi SM00792. Agouti. 1 hit.
[Graphical view ]
SUPFAMi SSF57055. SSF57055. 1 hit.
PROSITEi PS60024. AGOUTI_1. 1 hit.
PS51150. AGOUTI_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: September 3, 2014
This is version 131 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

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