Recombinant Human Beta-2 adrenergic receptor (ADRB2), partial

Function

G protein-coupled receptor for catecholamines that couples to both G(s) and G(i) proteins, activating bifurcated signaling pathways (PubMed:2831218, PubMed:7915137). ADRB2 binds epinephrine (Epi) with an approximately 30-fold greater affinity than norepinephrine (NE) (PubMed:2831218, PubMed:33093660, PubMed:7915137). In the heart, Epi- and NE-activated ADRB2 induces rapid and slow cardiomyocyte contraction rate, respectively (By similarity). Both NE and Epi promote coupling to G(s)/PKA pathway to regulate myocyte contraction rate (By similarity). Epi also promotes ADRB2 coupling to G(i) proteins to exert cardioprotective effects especially in the conditions of hypoxia and oxidative stress through the G(i)/PI3K/Akt signaling pathway (By similarity). ADRB2-G(s) signaling delivers proapoptotic signals in cardiomyocytes although G(i)-mediated survival effect appears to predominate (By similarity). ADRB2 also transduces signals independently of PKA to regulate cellular pH by modulating Na(+)/H(+) exchanger SLC9A3 function (PubMed:9560162)

Subcellular Location

Cell membrane (Multi-pass membrane protein); Golgi apparatus

Subunit

Binds NHERF1 and GPRASP1 (PubMed:9560162). 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)

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