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Protein

Beta-2 adrenergic receptor

Gene

ADRB2

Organism
Mesocricetus auratus (Golden hamster)
Status
Reviewed-Annotation score: 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.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei113Agonist or antagonistBy similarity1
Binding sitei118Agonist or antagonistBy similarity1

GO - Molecular functioni

GO - Biological processi

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 1 Publication; Multi-pass membrane protein By similarity
  • Early endosome By similarity

  • Note: Colocalizes with VHL on cell membranes. Activated receptors are internalized into endosomes prior to their degradation in lysosomes.By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 34ExtracellularBy similarityAdd BLAST34
Transmembranei35 – 58Helical; Name=1By similarityAdd BLAST24
Topological domaini59 – 71CytoplasmicBy similarityAdd BLAST13
Transmembranei72 – 95Helical; Name=2By similarityAdd BLAST24
Topological domaini96 – 106ExtracellularBy similarityAdd BLAST11
Transmembranei107 – 129Helical; Name=3By similarityAdd BLAST23
Topological domaini130 – 150CytoplasmicBy similarityAdd BLAST21
Transmembranei151 – 174Helical; Name=4By similarityAdd BLAST24
Topological domaini175 – 196ExtracellularBy similarityAdd BLAST22
Transmembranei197 – 220Helical; Name=5By similarityAdd BLAST24
Topological domaini221 – 274CytoplasmicBy similarityAdd BLAST54
Transmembranei275 – 298Helical; Name=6By similarityAdd BLAST24
Topological domaini299 – 305ExtracellularBy similarity7
Transmembranei306 – 329Helical; Name=7By similarityAdd BLAST24
Topological domaini330 – 418CytoplasmicBy similarityAdd BLAST89

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi79D → A: Small decrease in agonist binding. No effect on antagonist binding. 1 Publication1
Mutagenesisi113D → A: Drastic decrease in agonist and antagonist binding. Stimulates adenylyl cyclase activity. 1 Publication1
Mutagenesisi204S → A: Decrease in catechol agonist binding. 1 Publication1
Mutagenesisi207S → A: Decrease in catechol agonist binding. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL5943.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000691331 – 418Beta-2 adrenergic receptorAdd BLAST418

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi6N-linked (GlcNAc...)1
Glycosylationi15N-linked (GlcNAc...)1
Disulfide bondi106 ↔ 191PROSITE-ProRule annotation
Modified residuei141PhosphotyrosineBy similarity1
Disulfide bondi184 ↔ 190PROSITE-ProRule annotation
Modified residuei261Phosphoserine; by PKASequence analysis1
Modified residuei262Phosphoserine; by PKASequence analysis1
Lipidationi341S-palmitoyl cysteineBy similarity1
Modified residuei345Phosphoserine; by PKABy similarity1
Modified residuei346Phosphoserine; by PKABy similarity1
Modified residuei355Phosphoserine; by BARKCurated1
Modified residuei356Phosphoserine; by BARKCurated1
Modified residuei3874-hydroxyprolineBy similarity1
Modified residuei4004-hydroxyprolineBy similarity1

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

Proteomic databases

PRIDEiP04274.

PTM databases

iPTMnetiP04274.

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. Interacts with CNIH4. Interacts with ARRDC3.By similarity

GO - Molecular functioni

Protein-protein interaction databases

MINTiMINT-194411.

Structurei

3D structure databases

ProteinModelPortaliP04274.
SMRiP04274.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni193 – 207Agonist and antagonist bindingBy similarityAdd BLAST15
Regioni286 – 293Agonist and antagonist bindingBy similarity8
Regioni312 – 316Agonist and antagonist bindingBy similarity5

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi415 – 418PDZ-binding4

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.
OrthoDBiEOG091G06VI.

Family and domain databases

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.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
Links Updated
X03804 mRNA. Translation: CAA27430.1.
RefSeqiNP_001268877.1. NM_001281948.1.

3D structure databases

ProteinModelPortaliP04274.
SMRiP04274.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-194411.

Chemistry databases

ChEMBLiCHEMBL5943.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiP04274.

Proteomic databases

PRIDEiP04274.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi101836719.

Organism-specific databases

CTDi154.

Phylogenomic databases

HOVERGENiHBG106962.
OrthoDBiEOG091G06VI.

Miscellaneous databases

PROiP04274.

Family and domain databases

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.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 2, 2016
This is version 123 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.