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P04274

- ADRB2_MESAU

UniProt

P04274 - ADRB2_MESAU

Protein

Beta-2 adrenergic receptor

Gene

ADRB2

Organism
Mesocricetus auratus (Golden hamster)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 108 (01 Oct 2014)
      Sequence version 1 (20 Mar 1987)
      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. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei113 – 1131Agonist or antagonistBy similarity
    Binding sitei118 – 1181Agonist or antagonistBy similarity

    GO - Molecular functioni

    1. beta2-adrenergic receptor activity Source: HGNC
    2. norepinephrine binding Source: HGNC
    3. 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: InterPro
    3. adrenergic receptor signaling pathway Source: GOC
    4. desensitization of G-protein coupled receptor protein signaling pathway by arrestin Source: HGNC
    5. positive regulation of MAPK cascade Source: HGNC
    6. receptor-mediated endocytosis Source: HGNC
    7. regulation of smooth muscle contraction Source: InterPro
    8. regulation of vasodilation Source: InterPro

    Keywords - Molecular functioni

    G-protein coupled receptor, Receptor, Transducer

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Beta-2 adrenergic receptor
    Alternative name(s):
    Beta-2 adrenoreceptor
    Short name:
    Beta-2 adrenoceptor
    Gene namesi
    Name:ADRB2
    OrganismiMesocricetus auratus (Golden hamster)
    Taxonomic identifieri10036 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaCricetidaeCricetinaeMesocricetus

    Subcellular locationi

    Cell membrane By similarity; Multi-pass membrane protein By similarity
    Note: Colocalizes with VHL on cell membranes.By similarity

    GO - Cellular componenti

    1. integral component of membrane Source: UniProtKB-KW
    2. plasma membrane Source: UniProtKB-SubCell
    3. receptor complex Source: HGNC

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi79 – 791D → A: Small decrease in agonist binding. No effect on antagonist binding. 2 Publications
    Mutagenesisi113 – 1131D → A: Drastic decrease in agonist and antagonist binding. Stimulates adenylyl cyclase activity. 2 Publications
    Mutagenesisi204 – 2041S → A: Decrease in catechol agonist binding. 2 Publications
    Mutagenesisi207 – 2071S → A: Decrease in catechol agonist binding. 2 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 418418Beta-2 adrenergic receptorPRO_0000069133Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi6 – 61N-linked (GlcNAc...)
    Glycosylationi15 – 151N-linked (GlcNAc...)
    Disulfide bondi106 ↔ 191PROSITE-ProRule annotation
    Modified residuei141 – 1411PhosphotyrosineBy similarity
    Disulfide bondi184 ↔ 190PROSITE-ProRule annotation
    Modified residuei261 – 2611Phosphoserine; by PKASequence Analysis
    Modified residuei262 – 2621Phosphoserine; by PKASequence Analysis
    Lipidationi341 – 3411S-palmitoyl cysteineBy similarity
    Modified residuei345 – 3451Phosphoserine; by PKABy similarity
    Modified residuei346 – 3461Phosphoserine; by PKABy similarity
    Modified residuei355 – 3551Phosphoserine; by BARKCurated
    Modified residuei356 – 3561Phosphoserine; by BARKCurated
    Modified residuei387 – 38714-hydroxyprolineBy similarity
    Modified residuei400 – 40014-hydroxyprolineBy similarity

    Post-translational modificationi

    Palmitoylated; may reduce accessibility of Ser-345 and Ser-346 by anchoring Cys-341 to the plasma membrane. Agonist stimulation promotes depalmitoylation and further allows Ser-345 and Ser-346 phosphorylation By similarity.By similarity
    Phosphorylated by PKA and BARK upon agonist stimulation, which mediates homologous desensitization of the receptor. PKA-mediated phosphorylation seems to facilitate phosphorylation by BARK By similarity.By similarity
    Phosphorylation of Tyr-141 is induced by insulin and leads to supersensitization of the receptor.By similarity
    Polyubiquitinated. Agonist-induced ubiquitination leads to sort internalized receptors to the lysosomes for degradation. Deubiquitination by USP20 and USP33, leads to ADRB2 recycling and resensitization after prolonged agonist stimulation. USP20 and USP33 are constitutively associated and are dissociated immediately after agonist stimulation. Ubiquitination by the VHL-E3 ligase complex is oxygen-dependent By similarity.By similarity
    Hydroxylation by EGLN3 occurs only under normoxia and increases the interaction with VHL and the subsequent ubiquitination and degradation of ADRB2.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Hydroxylation, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

    Interactioni

    Subunit structurei

    Binds SLC9A3R1 and GPRASP1. Interacts with ARRB1 and ARRB2. Interacts with SRC, USP20 and USP33. Interacts with VHL; the interaction, which is increased on hydroxylation of ADRB2, ubiquitinates ADRB2 leading to its degradation. Interacts with EGLN3; the interaction hydroxylates ADRB2 facilitating VHL-E3 ligase-mediated ubiquitination. Interacts (via PDZ-binding motif) with SNX27 (via PDZ domain); the interaction is required when endocytosed to prevent degradation in lysosomes and promote recycling to the plasma membrane By similarity.By similarity

    Protein-protein interaction databases

    MINTiMINT-194411.

    Structurei

    3D structure databases

    ProteinModelPortaliP04274.
    SMRiP04274. Positions 29-348.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 3434ExtracellularBy similarityAdd
    BLAST
    Topological domaini59 – 7113CytoplasmicBy similarityAdd
    BLAST
    Topological domaini96 – 10611ExtracellularBy similarityAdd
    BLAST
    Topological domaini130 – 15021CytoplasmicBy similarityAdd
    BLAST
    Topological domaini175 – 19622ExtracellularBy similarityAdd
    BLAST
    Topological domaini221 – 27454CytoplasmicBy similarityAdd
    BLAST
    Topological domaini299 – 3057ExtracellularBy similarity
    Topological domaini330 – 41889CytoplasmicBy similarityAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei35 – 5824Helical; Name=1By similarityAdd
    BLAST
    Transmembranei72 – 9524Helical; Name=2By similarityAdd
    BLAST
    Transmembranei107 – 12923Helical; Name=3By similarityAdd
    BLAST
    Transmembranei151 – 17424Helical; Name=4By similarityAdd
    BLAST
    Transmembranei197 – 22024Helical; Name=5By similarityAdd
    BLAST
    Transmembranei275 – 29824Helical; Name=6By similarityAdd
    BLAST
    Transmembranei306 – 32924Helical; Name=7By similarityAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni193 – 20715Agonist and antagonist bindingBy similarityAdd
    BLAST
    Regioni286 – 2938Agonist and antagonist bindingBy similarity
    Regioni312 – 3165Agonist and antagonist bindingBy similarity

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi415 – 4184PDZ-binding

    Sequence similaritiesi

    Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRB2 sub-subfamily.PROSITE-ProRule annotation

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    HOVERGENiHBG106962.

    Family and domain databases

    Gene3Di1.20.1070.10. 1 hit.
    InterProiIPR002233. ADR_fam.
    IPR000332. ADRB2_rcpt.
    IPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    [Graphical view]
    PANTHERiPTHR24248:SF21. PTHR24248:SF21. 1 hit.
    PfamiPF00001. 7tm_1. 1 hit.
    [Graphical view]
    PRINTSiPR01103. ADRENERGICR.
    PR00562. ADRENRGCB2AR.
    PR00237. GPCRRHODOPSN.
    PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
    PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P04274-1 [UniParc]FASTAAdd to Basket

    « Hide

    MGPPGNDSDF LLTTNGSHVP DHDVTEERDE AWVVGMAILM SVIVLAIVFG    50
    NVLVITAIAK FERLQTVTNY FITSLACADL VMGLAVVPFG ASHILMKMWN 100
    FGNFWCEFWT SIDVLCVTAS IETLCVIAVD RYIAITSPFK YQSLLTKNKA 150
    RMVILMVWIV SGLTSFLPIQ MHWYRATHQK AIDCYHKETC CDFFTNQAYA 200
    IASSIVSFYV PLVVMVFVYS RVFQVAKRQL QKIDKSEGRF HSPNLGQVEQ 250
    DGRSGHGLRR SSKFCLKEHK ALKTLGIIMG TFTLCWLPFF IVNIVHVIQD 300
    NLIPKEVYIL LNWLGYVNSA FNPLIYCRSP DFRIAFQELL CLRRSSSKAY 350
    GNGYSSNSNG KTDYMGEASG CQLGQEKESE RLCEDPPGTE SFVNCQGTVP 400
    SLSLDSQGRN CSTNDSPL 418
    Length:418
    Mass (Da):46,861
    Last modified:March 20, 1987 - v1
    Checksum:i9B20478F91FB284E
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X03804 mRNA. Translation: CAA27430.1.
    RefSeqiNP_001268877.1. NM_001281948.1.

    Genome annotation databases

    GeneIDi101836719.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X03804 mRNA. Translation: CAA27430.1 .
    RefSeqi NP_001268877.1. NM_001281948.1.

    3D structure databases

    ProteinModelPortali P04274.
    SMRi P04274. Positions 29-348.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    MINTi MINT-194411.

    Chemistry

    ChEMBLi CHEMBL5943.

    Protein family/group databases

    GPCRDBi Search...

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 101836719.

    Organism-specific databases

    CTDi 154.

    Phylogenomic databases

    HOVERGENi HBG106962.

    Family and domain databases

    Gene3Di 1.20.1070.10. 1 hit.
    InterProi IPR002233. ADR_fam.
    IPR000332. ADRB2_rcpt.
    IPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    [Graphical view ]
    PANTHERi PTHR24248:SF21. PTHR24248:SF21. 1 hit.
    Pfami PF00001. 7tm_1. 1 hit.
    [Graphical view ]
    PRINTSi PR01103. ADRENERGICR.
    PR00562. ADRENRGCB2AR.
    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 [MRNA].
      Tissue: Lung.
    2. "Mutational analysis of beta-adrenergic receptor glycosylation."
      Rands E., Candelore M.R., Cheung A.H., Will W.S., Strader C.D., Dixon R.A.F.
      J. Biol. Chem. 265:10759-10764(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS TO CONFIRM GLYCOSYLATION SITES.
    3. "Identification of two serine residues involved in agonist activation of the beta-adrenergic receptor."
      Strader C.D., Candelore M.R., Hill W.S., Sigal I.S., Dixon R.A.F.
      J. Biol. Chem. 264:13572-13578(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF SER-204 AND SER-207.
    4. "Conserved aspartic acid residues 79 and 113 of the beta-adrenergic receptor have different roles in receptor function."
      Strader C.D., Sigal I.S., Candelore M.R., Rands E., Hill W.S., Dixon R.A.F.
      J. Biol. Chem. 263:10267-10271(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF ASP-79 AND ASP-113.
    5. "Three-dimensional structure for the beta 2 adrenergic receptor protein based on computer modeling studies."
      Huss K.M., Lybrand T.P.
      J. Mol. Biol. 225:859-871(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: 3D-STRUCTURE MODELING.

    Entry informationi

    Entry nameiADRB2_MESAU
    AccessioniPrimary (citable) accession number: P04274
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 20, 1987
    Last sequence update: March 20, 1987
    Last modified: October 1, 2014
    This is version 108 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Documents

    1. 7-transmembrane G-linked receptors
      List of 7-transmembrane G-linked receptor entries
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3