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P04274

- ADRB2_MESAU

UniProt

P04274 - ADRB2_MESAU

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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

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
Complete GO annotation...

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-KW
  3. receptor complex Source: HGNC
Complete GO annotation...

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. 1 Publication
Mutagenesisi113 – 1131D → A: Drastic decrease in agonist and antagonist binding. Stimulates adenylyl cyclase activity. 1 Publication
Mutagenesisi204 – 2041S → A: Decrease in catechol agonist binding. 1 Publication
Mutagenesisi207 – 2071S → A: Decrease in catechol agonist binding. 1 Publication

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

        10         20         30         40         50
MGPPGNDSDF LLTTNGSHVP DHDVTEERDE AWVVGMAILM SVIVLAIVFG
60 70 80 90 100
NVLVITAIAK FERLQTVTNY FITSLACADL VMGLAVVPFG ASHILMKMWN
110 120 130 140 150
FGNFWCEFWT SIDVLCVTAS IETLCVIAVD RYIAITSPFK YQSLLTKNKA
160 170 180 190 200
RMVILMVWIV SGLTSFLPIQ MHWYRATHQK AIDCYHKETC CDFFTNQAYA
210 220 230 240 250
IASSIVSFYV PLVVMVFVYS RVFQVAKRQL QKIDKSEGRF HSPNLGQVEQ
260 270 280 290 300
DGRSGHGLRR SSKFCLKEHK ALKTLGIIMG TFTLCWLPFF IVNIVHVIQD
310 320 330 340 350
NLIPKEVYIL LNWLGYVNSA FNPLIYCRSP DFRIAFQELL CLRRSSSKAY
360 370 380 390 400
GNGYSSNSNG KTDYMGEASG CQLGQEKESE RLCEDPPGTE SFVNCQGTVP
410
SLSLDSQGRN CSTNDSPL
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 29, 2014
This is version 109 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