P07550 · ADRB2_HUMAN
- ProteinBeta-2 adrenergic receptor
- GeneADRB2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids413 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 113 | (S)-carazolol (UniProtKB | ChEBI); inverse agonist | ||||
Sequence: D | ||||||
Binding site | 113 | (S)-timolol (UniProtKB | ChEBI); inverse agonist | ||||
Sequence: D | ||||||
Binding site | 118 | (S)-timolol (UniProtKB | ChEBI); inverse agonist | ||||
Sequence: T | ||||||
Binding site | 203 | (S)-carazolol (UniProtKB | ChEBI); inverse agonist | ||||
Sequence: S | ||||||
Binding site | 293 | (S)-timolol (UniProtKB | ChEBI); inverse agonist | ||||
Sequence: N | ||||||
Binding site | 312 | (S)-carazolol (UniProtKB | ChEBI); inverse agonist | ||||
Sequence: N | ||||||
Binding site | 312 | (S)-timolol (UniProtKB | ChEBI); inverse agonist | ||||
Sequence: N | ||||||
Binding site | 316 | (S)-timolol (UniProtKB | ChEBI); inverse agonist | ||||
Sequence: Y |
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Keywords
- Molecular function
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameBeta-2 adrenergic receptor
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP07550
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-34 | Extracellular | ||||
Sequence: MGQPGNGSAFLLAPNGSHAPDHDVTQERDEVWVV | ||||||
Transmembrane | 35-58 | Helical; Name=1 | ||||
Sequence: GMGIVMSLIVLAIVFGNVLVITAI | ||||||
Topological domain | 59-71 | Cytoplasmic | ||||
Sequence: AKFERLQTVTNYF | ||||||
Transmembrane | 72-95 | Helical; Name=2 | ||||
Sequence: ITSLACADLVMGLAVVPFGAAHIL | ||||||
Topological domain | 96-106 | Extracellular | ||||
Sequence: MKMWTFGNFWC | ||||||
Transmembrane | 107-129 | Helical; Name=3 | ||||
Sequence: EFWTSIDVLCVTASIETLCVIAV | ||||||
Topological domain | 130-150 | Cytoplasmic | ||||
Sequence: DRYFAITSPFKYQSLLTKNKA | ||||||
Transmembrane | 151-174 | Helical; Name=4 | ||||
Sequence: RVIILMVWIVSGLTSFLPIQMHWY | ||||||
Topological domain | 175-196 | Extracellular | ||||
Sequence: RATHQEAINCYANETCCDFFTN | ||||||
Transmembrane | 197-220 | Helical; Name=5 | ||||
Sequence: QAYAIASSIVSFYVPLVIMVFVYS | ||||||
Topological domain | 221-274 | Cytoplasmic | ||||
Sequence: RVFQEAKRQLQKIDKSEGRFHVQNLSQVEQDGRTGHGLRRSSKFCLKEHKALKT | ||||||
Transmembrane | 275-298 | Helical; Name=6 | ||||
Sequence: LGIIMGTFTLCWLPFFIVNIVHVI | ||||||
Topological domain | 299-305 | Extracellular | ||||
Sequence: QDNLIRK | ||||||
Transmembrane | 306-329 | Helical; Name=7 | ||||
Sequence: EVYILLNWIGYVNSGFNPLIYCRS | ||||||
Topological domain | 330-413 | Cytoplasmic | ||||
Sequence: PDFRIAFQELLCLRRSSLKAYGNGYSSNGNTGEQSGYHVEQEKENKLLCEDLPGTEDFVGHQGTVPSDNIDSQGRNCSTNDSLL |
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_049373 | 15 | in dbSNP:rs33973603 | |||
Sequence: N → S | ||||||
Natural variant | VAR_003452 | 16 | in dbSNP:rs1042713 | |||
Sequence: G → R | ||||||
Natural variant | VAR_003453 | 27 | in dbSNP:rs1042714 | |||
Sequence: E → Q | ||||||
Natural variant | VAR_003454 | 34 | in dbSNP:rs990810566 | |||
Sequence: V → M | ||||||
Mutagenesis | 79 | Affects binding of catecholamines, and produces an uncoupling between the receptor and stimulatory G proteins. | ||||
Sequence: D → N | ||||||
Mutagenesis | 141 | Abolishes insulin-induced tyrosine phosphorylation and insulin-induced receptor supersensitization. | ||||
Sequence: Y → F | ||||||
Natural variant | VAR_009125 | 159 | ||||
Sequence: I → F | ||||||
Natural variant | VAR_009124 | 159 | ||||
Sequence: I → L | ||||||
Natural variant | VAR_003455 | 164 | in dbSNP:rs1800888 | |||
Sequence: T → I | ||||||
Natural variant | VAR_025101 | 220 | in dbSNP:rs3729943 | |||
Sequence: S → C | ||||||
Mutagenesis | 265 | Loss of ligand-induced palmitoylation. | ||||
Sequence: C → A | ||||||
Mutagenesis | 341 | Loss of basal palmitoylation. | ||||
Sequence: C → A | ||||||
Mutagenesis | 341 | Uncoupled receptor. | ||||
Sequence: C → G | ||||||
Mutagenesis | 345-346 | Delayed agonist-promoted desensitization. | ||||
Sequence: SS → AA | ||||||
Mutagenesis | 350 | Does not affect insulin-induced tyrosine phosphorylation or insulin-induced receptor supersensitization. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 354 | Does not affect insulin-induced tyrosine phosphorylation or insulin-induced receptor supersensitization. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 366 | Does not affect insulin-induced tyrosine phosphorylation or insulin-induced receptor supersensitization. | ||||
Sequence: Y → F | ||||||
Natural variant | VAR_009394 | 375 | in dbSNP:rs771585355 | |||
Sequence: K → R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 410 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, glycosylation, disulfide bond, modified residue, modified residue (large scale data), lipidation.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000069130 | 1-413 | UniProt | Beta-2 adrenergic receptor | |||
Sequence: MGQPGNGSAFLLAPNGSHAPDHDVTQERDEVWVVGMGIVMSLIVLAIVFGNVLVITAIAKFERLQTVTNYFITSLACADLVMGLAVVPFGAAHILMKMWTFGNFWCEFWTSIDVLCVTASIETLCVIAVDRYFAITSPFKYQSLLTKNKARVIILMVWIVSGLTSFLPIQMHWYRATHQEAINCYANETCCDFFTNQAYAIASSIVSFYVPLVIMVFVYSRVFQEAKRQLQKIDKSEGRFHVQNLSQVEQDGRTGHGLRRSSKFCLKEHKALKTLGIIMGTFTLCWLPFFIVNIVHVIQDNLIRKEVYILLNWIGYVNSGFNPLIYCRSPDFRIAFQELLCLRRSSLKAYGNGYSSNGNTGEQSGYHVEQEKENKLLCEDLPGTEDFVGHQGTVPSDNIDSQGRNCSTNDSLL | |||||||
Glycosylation | 6 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Glycosylation | 15 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Disulfide bond | 106↔191 | UniProt | |||||
Sequence: CEFWTSIDVLCVTASIETLCVIAVDRYFAITSPFKYQSLLTKNKARVIILMVWIVSGLTSFLPIQMHWYRATHQEAINCYANETCC | |||||||
Modified residue | 141 | UniProt | Phosphotyrosine | ||||
Sequence: Y | |||||||
Disulfide bond | 184↔190 | UniProt | |||||
Sequence: CYANETC | |||||||
Modified residue | 246 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 246 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 261 | UniProt | Phosphoserine; by PKA | ||||
Sequence: S | |||||||
Modified residue | 262 | UniProt | Phosphoserine; by PKA | ||||
Sequence: S | |||||||
Lipidation | 265 | UniProt | S-palmitoyl cysteine | ||||
Sequence: C | |||||||
Lipidation | 341 | UniProt | S-palmitoyl cysteine | ||||
Sequence: C | |||||||
Modified residue | 345 | UniProt | Phosphoserine; by PKA | ||||
Sequence: S | |||||||
Modified residue | 346 | UniProt | Phosphoserine; by PKA | ||||
Sequence: S | |||||||
Modified residue | 355 | UniProt | Phosphoserine; by BARK | ||||
Sequence: S | |||||||
Modified residue | 356 | UniProt | Phosphoserine; by BARK | ||||
Sequence: S | |||||||
Modified residue | 382 | UniProt | 4-hydroxyproline | ||||
Sequence: P | |||||||
Modified residue | 395 | UniProt | 4-hydroxyproline | ||||
Sequence: P |
Post-translational modification
Palmitoylated (PubMed:11146000, PubMed:17962520, PubMed:18547522, PubMed:2540197, PubMed:27481942).
Mainly palmitoylated at Cys-341 (PubMed:17962520, PubMed:18547522, PubMed:2540197).
Palmitoylation may reduce accessibility of phosphorylation sites by anchoring the receptor to the plasma membrane. Agonist stimulation promotes depalmitoylation and further allows Ser-345 and Ser-346 phosphorylation (PubMed:11146000).
Also undergoes transient, ligand-induced palmitoylation at Cys-265 probably by ZDHHC9, ZDHHC14 and ZDHHC18 within the Golgi (PubMed:27481942).
Palmitoylation at Cys-265 requires phosphorylation by PKA and receptor internalization and stabilizes the receptor (PubMed:27481942).
Could be depalmitoylated by LYPLA1 at the plasma membrane (PubMed:27481942).
Mainly palmitoylated at Cys-341 (PubMed:17962520, PubMed:18547522, PubMed:2540197).
Palmitoylation may reduce accessibility of phosphorylation sites by anchoring the receptor to the plasma membrane. Agonist stimulation promotes depalmitoylation and further allows Ser-345 and Ser-346 phosphorylation (PubMed:11146000).
Also undergoes transient, ligand-induced palmitoylation at Cys-265 probably by ZDHHC9, ZDHHC14 and ZDHHC18 within the Golgi (PubMed:27481942).
Palmitoylation at Cys-265 requires phosphorylation by PKA and receptor internalization and stabilizes the receptor (PubMed:27481942).
Could be depalmitoylated by LYPLA1 at the plasma membrane (PubMed:27481942).
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.
Polyubiquitinated (PubMed:23166351).
Agonist-induced ubiquitination leads to sort internalized receptors to the lysosomes for degradation (PubMed:19424180, PubMed:20559325, PubMed:23166351).
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
Agonist-induced ubiquitination leads to sort internalized receptors to the lysosomes for degradation (PubMed:19424180, PubMed:20559325, PubMed:23166351).
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
Hydroxylation by EGLN3 occurs only under normoxia and increases the interaction with VHL and the subsequent ubiquitination and degradation of ADRB2.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Binds NHERF1 and GPRASP1. Interacts with ARRB1 and ARRB2. Interacts with SRC (PubMed:9924018).
Interacts with USP20 and USP33 (PubMed:19424180, PubMed:23166351).
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 (PubMed:24405750).
Interacts with ARRDC3 (PubMed:20559325, PubMed:25220262).
Interacts with NEDD4 (PubMed:23166351).
Interacts with MARCHF2 (PubMed:23166351).
Interacts with USP20 and USP33 (PubMed:19424180, PubMed:23166351).
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 (PubMed:24405750).
Interacts with ARRDC3 (PubMed:20559325, PubMed:25220262).
Interacts with NEDD4 (PubMed:23166351).
Interacts with MARCHF2 (PubMed:23166351).
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 392-413 | Disordered | ||||
Sequence: GTVPSDNIDSQGRNCSTNDSLL | ||||||
Compositional bias | 394-413 | Polar residues | ||||
Sequence: VPSDNIDSQGRNCSTNDSLL | ||||||
Motif | 410-413 | PDZ-binding | ||||
Sequence: DSLL |
Sequence similarities
Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRB2 sub-subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Protein family/group databases
Sequence
- Sequence statusComplete
- Length413
- Mass (Da)46,459
- Last updated2010-05-18 v3
- Checksum408C22731C6EDFBE
Sequence caution
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 71 | in Ref. 9; BAG35969 | ||||
Sequence: F → L | ||||||
Sequence conflict | 216 | in Ref. 8; AAN01267 | ||||
Sequence: V → A | ||||||
Sequence conflict | 261 | in Ref. 10; BAD96745 | ||||
Sequence: S → P | ||||||
Compositional bias | 394-413 | Polar residues | ||||
Sequence: VPSDNIDSQGRNCSTNDSLL | ||||||
Sequence conflict | 402 | in Ref. 14; AAH12481 | ||||
Sequence: Q → P |
Polymorphism
The Gly-16 allele is overrepresented in individuals affected by nocturnal asthma as compared to controls, and appears to be an important genetic factor in the expression of this asthmatic phenotype.
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X04827 EMBL· GenBank· DDBJ | CAA28511.1 EMBL· GenBank· DDBJ | mRNA | ||
Y00106 EMBL· GenBank· DDBJ | CAA68289.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M15169 EMBL· GenBank· DDBJ | AAA88015.1 EMBL· GenBank· DDBJ | mRNA | ||
J02960 EMBL· GenBank· DDBJ | AAA88017.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF022953 EMBL· GenBank· DDBJ | AAB82148.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF022954 EMBL· GenBank· DDBJ | AAB82149.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF022955 EMBL· GenBank· DDBJ | AAB82150.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF022956 EMBL· GenBank· DDBJ | AAB82151.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF169225 EMBL· GenBank· DDBJ | AAD48036.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF202305 EMBL· GenBank· DDBJ | AAF17569.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF203386 EMBL· GenBank· DDBJ | AAF20199.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AY136741 EMBL· GenBank· DDBJ | AAN01267.1 EMBL· GenBank· DDBJ | mRNA | ||
AK313151 EMBL· GenBank· DDBJ | BAG35969.1 EMBL· GenBank· DDBJ | mRNA | ||
AK223025 EMBL· GenBank· DDBJ | BAD96745.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
DQ094845 EMBL· GenBank· DDBJ | AAY88739.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
EU332834 EMBL· GenBank· DDBJ | ABY87523.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471062 EMBL· GenBank· DDBJ | EAW61798.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC012481 EMBL· GenBank· DDBJ | AAH12481.3 EMBL· GenBank· DDBJ | mRNA | ||
BC063486 EMBL· GenBank· DDBJ | AAH63486.2 EMBL· GenBank· DDBJ | mRNA | ||
BC073856 EMBL· GenBank· DDBJ | AAH73856.1 EMBL· GenBank· DDBJ | mRNA |