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P18762

- ADRB2_MOUSE

UniProt

P18762 - ADRB2_MOUSE

Protein

Beta-2 adrenergic receptor

Gene

Adrb2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 144 (01 Oct 2014)
      Sequence version 2 (27 Jul 2011)
      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. adenylate cyclase binding Source: BHF-UCL
    2. beta2-adrenergic receptor activity Source: MGI
    3. enzyme binding Source: BHF-UCL
    4. norepinephrine binding Source: HGNC
    5. potassium channel regulator activity Source: Ensembl
    6. protein binding Source: MGI
    7. 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: MGI
    3. adrenergic receptor signaling pathway Source: GOC
    4. bone resorption Source: MGI
    5. brown fat cell differentiation Source: MGI
    6. desensitization of G-protein coupled receptor protein signaling pathway by arrestin Source: HGNC
    7. diet induced thermogenesis Source: MGI
    8. heat generation Source: MGI
    9. negative regulation of multicellular organism growth Source: MGI
    10. negative regulation of smooth muscle contraction Source: MGI
    11. positive regulation of bone mineralization Source: MGI
    12. positive regulation of MAPK cascade Source: HGNC
    13. positive regulation of protein ubiquitination Source: Ensembl
    14. positive regulation of transcription from RNA polymerase II promoter Source: MGI
    15. receptor-mediated endocytosis Source: HGNC
    16. regulation of sodium ion transport Source: MGI
    17. regulation of systemic arterial blood pressure by norepinephrine-epinephrine Source: MGI
    18. regulation of vasodilation Source: InterPro
    19. response to cold Source: MGI
    20. vasodilation by norepinephrine-epinephrine involved in regulation of systemic arterial blood pressure Source: MGI

    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
    Synonyms:Adrb2r
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 18

    Organism-specific databases

    MGIiMGI:87938. Adrb2.

    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. apical plasma membrane Source: MGI
    2. integral component of plasma membrane Source: Ensembl
    3. membrane Source: MGI
    4. nucleus Source: MGI
    5. plasma membrane Source: MGI
    6. receptor complex Source: HGNC

    Keywords - Cellular componenti

    Cell membrane, Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 418418Beta-2 adrenergic receptorPRO_0000069134Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi6 – 61N-linked (GlcNAc...)Curated
    Glycosylationi15 – 151N-linked (GlcNAc...)Curated
    Disulfide bondi106 ↔ 191PROSITE-ProRule annotation
    Modified residuei141 – 1411PhosphotyrosineBy similarity
    Disulfide bondi184 ↔ 190PROSITE-ProRule annotation
    Modified residuei246 – 2461PhosphoserineBy similarity
    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.
    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

    Proteomic databases

    PRIDEiP18762.

    PTM databases

    PhosphoSiteiP18762.

    Expressioni

    Gene expression databases

    ArrayExpressiP18762.
    BgeeiP18762.
    CleanExiMM_ADRB2.
    GenevestigatoriP18762.

    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

    DIPiDIP-59568N.
    IntActiP18762. 5 interactions.
    MINTiMINT-1793203.

    Structurei

    3D structure databases

    ProteinModelPortaliP18762.
    SMRiP18762. Positions 7-342.
    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

    eggNOGiNOG262978.
    GeneTreeiENSGT00720000108411.
    HOGENOMiHOG000239242.
    HOVERGENiHBG106962.
    InParanoidiQ8BH38.
    KOiK04142.
    OMAiRVFQVAK.
    OrthoDBiEOG7BS4BS.
    TreeFamiTF316350.

    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.

    P18762-1 [UniParc]FASTAAdd to Basket

    « Hide

    MGPHGNDSDF LLAPNGSRAP DHDVTQERDE AWVVGMAILM SVIVLAIVFG    50
    NVLVITAIAK FERLQTVTNY FIISLACADL VMGLAVVPFG ASHILMKMWN 100
    FGNFWCEFWT SIDVLCVTAS IETLCVIAVD RYVAITSPFK YQSLLTKNKA 150
    RVVILMVWIV SGLTSFLPIQ MHWYRATHKK AIDCYTEETC CDFFTNQAYA 200
    IASSIVSFYV PLVVMVFVYS RVFQVAKRQL QKIDKSEGRF HAQNLSQVEQ 250
    DGRSGHGLRR SSKFCLKEHK ALKTLGIIMG TFTLCWLPFF IVNIVHVIRD 300
    NLIPKEVYIL LNWLGYVNSA FNPLIYCRSP DFRIAFQELL CLRRSSSKTY 350
    GNGYSSNSNG RTDYTGEPNT CQLGQEREQE LLCEDPPGME GFVNCQGTVP 400
    SLSVDSQGRN CSTNDSPL 418
    Length:418
    Mass (Da):46,998
    Last modified:July 27, 2011 - v2
    Checksum:i51D1EC73D7619D58
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti21 – 211D → H in CAA33664. (PubMed:2549959)Curated
    Sequence conflicti94 – 952IL → TS in CAA33664. (PubMed:2549959)Curated
    Sequence conflicti254 – 2541S → T in CAA33664. (PubMed:2549959)Curated
    Sequence conflicti347 – 3482SK → FE in CAA33664. (PubMed:2549959)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X15643 Genomic DNA. Translation: CAA33664.1.
    AK080241 mRNA. Translation: BAC37856.1.
    CH466528 Genomic DNA. Translation: EDL09746.1.
    BC032883 mRNA. Translation: AAH32883.1.
    CCDSiCCDS29289.1.
    PIRiS00260.
    RefSeqiNP_031446.2. NM_007420.3.
    UniGeneiMm.5598.

    Genome annotation databases

    EnsembliENSMUST00000053640; ENSMUSP00000062256; ENSMUSG00000045730.
    GeneIDi11555.
    KEGGimmu:11555.
    UCSCiuc008fcy.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X15643 Genomic DNA. Translation: CAA33664.1 .
    AK080241 mRNA. Translation: BAC37856.1 .
    CH466528 Genomic DNA. Translation: EDL09746.1 .
    BC032883 mRNA. Translation: AAH32883.1 .
    CCDSi CCDS29289.1.
    PIRi S00260.
    RefSeqi NP_031446.2. NM_007420.3.
    UniGenei Mm.5598.

    3D structure databases

    ProteinModelPortali P18762.
    SMRi P18762. Positions 7-342.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-59568N.
    IntActi P18762. 5 interactions.
    MINTi MINT-1793203.

    Chemistry

    BindingDBi P18762.
    ChEMBLi CHEMBL2111395.
    GuidetoPHARMACOLOGYi 29.

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei P18762.

    Proteomic databases

    PRIDEi P18762.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000053640 ; ENSMUSP00000062256 ; ENSMUSG00000045730 .
    GeneIDi 11555.
    KEGGi mmu:11555.
    UCSCi uc008fcy.1. mouse.

    Organism-specific databases

    CTDi 154.
    MGIi MGI:87938. Adrb2.

    Phylogenomic databases

    eggNOGi NOG262978.
    GeneTreei ENSGT00720000108411.
    HOGENOMi HOG000239242.
    HOVERGENi HBG106962.
    InParanoidi Q8BH38.
    KOi K04142.
    OMAi RVFQVAK.
    OrthoDBi EOG7BS4BS.
    TreeFami TF316350.

    Miscellaneous databases

    NextBioi 279054.
    PROi P18762.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P18762.
    Bgeei P18762.
    CleanExi MM_ADRB2.
    Genevestigatori P18762.

    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. "Isoproterenol response following transfection of the mouse beta 2-adrenergic receptor gene into Y1 cells."
      Allen J.M., Baetge E.E., Abrass I.B., Palmiter R.D.
      EMBO J. 7:133-138(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "Genetic regulation of beta 2-adrenergic receptors in 3T3-L1 fibroblasts."
      Nakada M.T., Haskell K.M., Ecker D.J., Stadel J.M., Crooke S.T.
      Biochem. J. 260:53-59(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    3. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    4. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
      Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "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].
      Strain: C57BL/6J.
      Tissue: Mammary gland.

    Entry informationi

    Entry nameiADRB2_MOUSE
    AccessioniPrimary (citable) accession number: P18762
    Secondary accession number(s): Q8BH38
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1990
    Last sequence update: July 27, 2011
    Last modified: October 1, 2014
    This is version 144 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. 7-transmembrane G-linked receptors
      List of 7-transmembrane G-linked receptor entries
    2. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3