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O00253

- AGRP_HUMAN

UniProt

O00253 - AGRP_HUMAN

Protein

Agouti-related protein

Gene

AGRP

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. 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

    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: UniProt
    3. Golgi lumen Source: UniProtKB
    4. neuronal cell body Source: Ensembl

    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.

    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

    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

    1
    132
    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.
    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.
    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

    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. 2 Publications
    Corresponds to variant rs5030980 [ dbSNP | Ensembl ].
    VAR_015385

    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...
    MobiDBi 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

    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: October 1, 2014
    This is version 132 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