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P13945

- ADRB3_HUMAN

UniProt

P13945 - ADRB3_HUMAN

Protein

Beta-3 adrenergic receptor

Gene

ADRB3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 161 (01 Oct 2014)
      Sequence version 3 (01 Feb 1994)
      Previous versions | rss
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    Functioni

    Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. Beta-3 is involved in the regulation of lipolysis and thermogenesis.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei117 – 1171Agonist or antagonistBy similarity
    Binding sitei122 – 1221Agonist or antagonistBy similarity

    GO - Molecular functioni

    1. beta3-adrenergic receptor activity Source: HGNC
    2. beta-adrenergic receptor activity Source: HGNC
    3. epinephrine binding Source: Ensembl
    4. norepinephrine binding Source: Ensembl
    5. protein binding Source: UniProtKB
    6. protein homodimerization activity Source: HGNC

    GO - Biological processi

    1. activation of adenylate cyclase activity Source: HGNC
    2. adenylate cyclase-activating G-protein coupled receptor signaling pathway Source: Ensembl
    3. adenylate cyclase-modulating G-protein coupled receptor signaling pathway Source: ProtInc
    4. adrenergic receptor signaling pathway Source: GOC
    5. aging Source: Ensembl
    6. brown fat cell differentiation Source: Ensembl
    7. carbohydrate metabolic process Source: ProtInc
    8. diet induced thermogenesis Source: Ensembl
    9. eating behavior Source: Ensembl
    10. energy reserve metabolic process Source: ProtInc
    11. generation of precursor metabolites and energy Source: ProtInc
    12. G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger Source: ProtInc
    13. heat generation Source: Ensembl
    14. negative regulation of multicellular organism growth Source: Ensembl
    15. positive regulation of MAPK cascade Source: HGNC
    16. response to antibiotic Source: Ensembl
    17. response to cold Source: Ensembl
    18. vasodilation by norepinephrine-epinephrine involved in regulation of systemic arterial blood pressure Source: Ensembl

    Keywords - Molecular functioni

    G-protein coupled receptor, Receptor, Transducer

    Enzyme and pathway databases

    ReactomeiREACT_16927. Adrenoceptors.
    REACT_19327. G alpha (s) signalling events.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Beta-3 adrenergic receptor
    Alternative name(s):
    Beta-3 adrenoreceptor
    Short name:
    Beta-3 adrenoceptor
    Gene namesi
    Name:ADRB3
    Synonyms:ADRB3R, B3AR
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 8

    Organism-specific databases

    HGNCiHGNC:288. ADRB3.

    Subcellular locationi

    GO - Cellular componenti

    1. integral component of plasma membrane Source: ProtInc
    2. nucleus Source: Ensembl
    3. plasma membrane Source: Reactome
    4. receptor complex Source: HGNC

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Keywords - Diseasei

    Diabetes mellitus, Obesity

    Organism-specific databases

    PharmGKBiPA24598.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 408408Beta-3 adrenergic receptorPRO_0000069143Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi8 – 81N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi26 – 261N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi110 ↔ 196PROSITE-ProRule annotation
    Disulfide bondi189 ↔ 195PROSITE-ProRule annotation
    Lipidationi361 – 3611S-palmitoyl cysteineBy similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

    Proteomic databases

    PaxDbiP13945.
    PRIDEiP13945.

    Expressioni

    Tissue specificityi

    Expressed mainly in adipose tissues.

    Gene expression databases

    ArrayExpressiP13945.
    BgeeiP13945.
    CleanExiHS_ADRB3.
    GenevestigatoriP13945.

    Interactioni

    Protein-protein interaction databases

    BioGridi106664. 1 interaction.
    STRINGi9606.ENSP00000343782.

    Structurei

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2CDWmodel-A1-408[»]
    ProteinModelPortaliP13945.
    SMRiP13945. Positions 35-361.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 3636ExtracellularBy similarityAdd
    BLAST
    Topological domaini64 – 729CytoplasmicBy similarity
    Topological domaini92 – 11120ExtracellularBy similarityAdd
    BLAST
    Topological domaini134 – 15522CytoplasmicBy similarityAdd
    BLAST
    Topological domaini179 – 20325ExtracellularBy similarityAdd
    BLAST
    Topological domaini226 – 29267CytoplasmicBy similarityAdd
    BLAST
    Topological domaini315 – 32612ExtracellularBy similarityAdd
    BLAST
    Topological domaini348 – 40861CytoplasmicBy similarityAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei37 – 6327Helical; Name=1By similarityAdd
    BLAST
    Transmembranei73 – 9119Helical; Name=2By similarityAdd
    BLAST
    Transmembranei112 – 13322Helical; Name=3By similarityAdd
    BLAST
    Transmembranei156 – 17823Helical; Name=4By similarityAdd
    BLAST
    Transmembranei204 – 22522Helical; Name=5By similarityAdd
    BLAST
    Transmembranei293 – 31422Helical; Name=6By similarityAdd
    BLAST
    Transmembranei327 – 34721Helical; Name=7By similarityAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni198 – 21215Agonist and antagonist bindingBy similarityAdd
    BLAST
    Regioni305 – 3128Agonist and antagonist bindingBy similarity
    Regioni332 – 3365Agonist and antagonist bindingBy similarity

    Sequence similaritiesi

    Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRB3 sub-subfamily.PROSITE-ProRule annotation

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG262978.
    HOGENOMiHOG000239242.
    HOVERGENiHBG106962.
    InParanoidiP13945.
    KOiK04143.
    OMAiRRLLCRC.
    OrthoDBiEOG7BS4BS.
    PhylomeDBiP13945.
    TreeFamiTF316350.

    Family and domain databases

    Gene3Di1.20.1070.10. 1 hit.
    InterProiIPR002233. ADR_fam.
    IPR000681. ADRB3_rcpt.
    IPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    [Graphical view]
    PfamiPF00001. 7tm_1. 1 hit.
    [Graphical view]
    PRINTSiPR01103. ADRENERGICR.
    PR00563. ADRENRGCB3AR.
    PR00237. GPCRRHODOPSN.
    PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
    PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P13945-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAPWPHENSS LAPWPDLPTL APNTANTSGL PGVPWEAALA GALLALAVLA    50
    TVGGNLLVIV AIAWTPRLQT MTNVFVTSLA AADLVMGLLV VPPAATLALT 100
    GHWPLGATGC ELWTSVDVLC VTASIETLCA LAVDRYLAVT NPLRYGALVT 150
    KRCARTAVVL VWVVSAAVSF APIMSQWWRV GADAEAQRCH SNPRCCAFAS 200
    NMPYVLLSSS VSFYLPLLVM LFVYARVFVV ATRQLRLLRG ELGRFPPEES 250
    PPAPSRSLAP APVGTCAPPE GVPACGRRPA RLLPLREHRA LCTLGLIMGT 300
    FTLCWLPFFL ANVLRALGGP SLVPGPAFLA LNWLGYANSA FNPLIYCRSP 350
    DFRSAFRRLL CRCGRRLPPE PCAAARPALF PSGVPAARSS PAQPRLCQRL 400
    DGASWGVS 408
    Length:408
    Mass (Da):43,519
    Last modified:February 1, 1994 - v3
    Checksum:iE98BD6C130DD977B
    GO

    Polymorphismi

    The variant Arg-64 seems to be associated with weight gain (obesity) and is also associated with susceptibility to non-insulin-dependent diabetes mellitus (NIDDM).

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti64 – 641W → R.5 Publications
    Corresponds to variant rs4994 [ dbSNP | Ensembl ].
    VAR_003456
    Natural varianti249 – 2491E → K.
    Corresponds to variant rs28364012 [ dbSNP | Ensembl ].
    VAR_029205
    Natural varianti265 – 2651T → M.1 Publication
    Corresponds to variant rs4995 [ dbSNP | Ensembl ].
    VAR_014166
    Natural varianti353 – 3531R → C.1 Publication
    Corresponds to variant rs36031925 [ dbSNP | Ensembl ].
    VAR_025102

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M29932 Genomic DNA. Translation: AAA35550.1. Different termination.
    X72861 Genomic DNA. Translation: CAA51383.1.
    X70811 mRNA. Translation: CAA50141.1.
    X70812 Genomic DNA. Translation: CAA50142.1. Sequence problems.
    X70812 Genomic DNA. Translation: CAA50143.1. Sequence problems.
    AY487247 mRNA. Translation: AAR37414.1.
    DQ104441 Genomic DNA. Translation: AAY88743.1.
    BC075017 mRNA. Translation: AAH75017.1.
    S53291 mRNA. Translation: AAB24837.1.
    CCDSiCCDS6099.1.
    PIRiI57941.
    S33751. QRHUBE.
    RefSeqiNP_000016.1. NM_000025.2.
    UniGeneiHs.2549.

    Genome annotation databases

    EnsembliENST00000345060; ENSP00000343782; ENSG00000188778.
    GeneIDi155.
    KEGGihsa:155.
    UCSCiuc003xkr.2. human.

    Polymorphism databases

    DMDMi461604.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    SeattleSNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M29932 Genomic DNA. Translation: AAA35550.1 . Different termination.
    X72861 Genomic DNA. Translation: CAA51383.1 .
    X70811 mRNA. Translation: CAA50141.1 .
    X70812 Genomic DNA. Translation: CAA50142.1 . Sequence problems.
    X70812 Genomic DNA. Translation: CAA50143.1 . Sequence problems.
    AY487247 mRNA. Translation: AAR37414.1 .
    DQ104441 Genomic DNA. Translation: AAY88743.1 .
    BC075017 mRNA. Translation: AAH75017.1 .
    S53291 mRNA. Translation: AAB24837.1 .
    CCDSi CCDS6099.1.
    PIRi I57941.
    S33751. QRHUBE.
    RefSeqi NP_000016.1. NM_000025.2.
    UniGenei Hs.2549.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2CDW model - A 1-408 [» ]
    ProteinModelPortali P13945.
    SMRi P13945. Positions 35-361.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 106664. 1 interaction.
    STRINGi 9606.ENSP00000343782.

    Chemistry

    BindingDBi P13945.
    ChEMBLi CHEMBL2111388.
    DrugBanki DB00368. Norepinephrine.
    DB00960. Pindolol.
    DB00571. Propranolol.
    GuidetoPHARMACOLOGYi 30.

    Protein family/group databases

    GPCRDBi Search...

    Polymorphism databases

    DMDMi 461604.

    Proteomic databases

    PaxDbi P13945.
    PRIDEi P13945.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000345060 ; ENSP00000343782 ; ENSG00000188778 .
    GeneIDi 155.
    KEGGi hsa:155.
    UCSCi uc003xkr.2. human.

    Organism-specific databases

    CTDi 155.
    GeneCardsi GC08M037822.
    HGNCi HGNC:288. ADRB3.
    MIMi 109691. gene.
    neXtProti NX_P13945.
    PharmGKBi PA24598.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG262978.
    HOGENOMi HOG000239242.
    HOVERGENi HBG106962.
    InParanoidi P13945.
    KOi K04143.
    OMAi RRLLCRC.
    OrthoDBi EOG7BS4BS.
    PhylomeDBi P13945.
    TreeFami TF316350.

    Enzyme and pathway databases

    Reactomei REACT_16927. Adrenoceptors.
    REACT_19327. G alpha (s) signalling events.

    Miscellaneous databases

    GeneWikii Beta-3_adrenergic_receptor.
    GenomeRNAii 155.
    NextBioi 617.
    PROi P13945.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P13945.
    Bgeei P13945.
    CleanExi HS_ADRB3.
    Genevestigatori P13945.

    Family and domain databases

    Gene3Di 1.20.1070.10. 1 hit.
    InterProi IPR002233. ADR_fam.
    IPR000681. ADRB3_rcpt.
    IPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    [Graphical view ]
    Pfami PF00001. 7tm_1. 1 hit.
    [Graphical view ]
    PRINTSi PR01103. ADRENERGICR.
    PR00563. ADRENRGCB3AR.
    PR00237. GPCRRHODOPSN.
    PROSITEi PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
    PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "The promoter and intron/exon structure of the human and mouse beta 3-adrenergic-receptor genes."
      van Spronsen A., Nahmias C., Krief S., Briend-Sutren M.-M., Strosberg A.D., Emorine L.J.
      Eur. J. Biochem. 213:1117-1124(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], SEQUENCE REVISION.
    3. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    4. "cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
      Kopatz S.A., Aronstam R.S., Sharma S.V.
      Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Placenta.
    5. SeattleSNPs variation discovery resource
      Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-64 AND CYS-353.
    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. "Rodent and human beta 3-adrenergic receptor genes contain an intron within the protein-coding block."
      Granneman J.G., Lahners K.N., Rao D.D.
      Mol. Pharmacol. 42:964-970(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 392-408.
    8. "Genetic variation in the beta 3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity."
      Clement K., Vaisse C., Manning B.S.J., Basdevant A., Guy-Grand B., Ruiz J., Silver K.D., Shuldiner A.R., Froguel P., Strosberg A.D.
      N. Engl. J. Med. 333:352-354(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT ARG-64.
    9. "Association of Trp64Arg mutation of the beta3-adrenergic-receptor with NIDDM and body weight gain."
      Fujisawa T., Ikegami H., Yamato E., Takekawa K., Nakagawa Y., Hamada Y., Oga T., Ueda H., Shintani M., Fukuda M., Ogihara T.
      Diabetologia 39:349-352(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT ARG-64.
    10. "Pharmacological characterization of a recently described human beta 3-adrenergic receptor mutant."
      Candelore M.R., Deng L., Tota L.M., Kelly L.J., Cascieri M.A., Strader C.D.
      Endocrinology 137:2638-2641(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT ARG-64.
    11. "Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis."
      Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A., Cooper R., Lipshutz R., Chakravarti A.
      Nat. Genet. 22:239-247(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS ARG-64 AND MET-265.

    Entry informationi

    Entry nameiADRB3_HUMAN
    AccessioniPrimary (citable) accession number: P13945
    Secondary accession number(s): Q4JFT4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 1, 1990
    Last sequence update: February 1, 1994
    Last modified: October 1, 2014
    This is version 161 of the entry and version 3 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. 7-transmembrane G-linked receptors
      List of 7-transmembrane G-linked receptor entries
    2. Human chromosome 8
      Human chromosome 8: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3