Bradykinin receptor B2 is a G-protein coupled receptor for bradykinin, encoded by the BDKRB2 gene in humans.
Bradykinin receptor B2 is a G-protein coupled receptor for bradykinin, encoded by the BDKRB2 gene in humans.
The B2 receptor (B2R) is a G protein-coupled receptor, probably coupled to Gq and Gi. A 2022 Nature cryo-EM study of human B2R-Gq complexes by Jinkeng Sheng et al. investigated the proximal activation mechanisms of B2R. Sheng et al. propose that upon B2R binding bradykinin or kallidin to a "bulky orthosteric binding pocket," the phenylalanine F8 or F9 residue of bradykinin or kallidin respectively interacts with a "conserved toggle switch" W283. This hydrophobic interaction facilitates the outward movement of transmembrane domain 6 (TM6) of B2R on the cytoplasmic side of the membrane, as well as outward movement of F279, a key residue within the conserved PIF motif of GPCRs (involving proline, isoleucine and phenylalanine). This rearrangement of the PIF motif disrupts the ionic lock formed by the DRY motif and pushes the NPxxY motif towards the activated state, opening an "intracellular cleft" for insertion of the α5-helix of Gq. [5]
Gq stimulates phospholipase C to increase intracellular free calcium and Gi inhibits adenylate cyclase. Furthermore, the receptor stimulates the mitogen-activated protein kinase pathways. It is ubiquitously and constitutively expressed in healthy tissues.
The B2 receptor forms a complex with angiotensin converting enzyme (ACE), and this is thought to play a role in cross-talk between the renin-angiotensin system (RAS) and the kinin–kallikrein system (KKS). The heptapeptide angiotensin (1-7) also potentiates bradykinin action on B2 receptors. [6]
Kallidin also signals through the B2 receptor. An antagonist for the receptor is Hoe 140 (icatibant). [7]
The 9 amino acid bradykinin peptide elicits several responses including vasodilation, edema, smooth muscle spasm and nociceptor stimulation.
Alternate start codons result in two isoforms of the protein. [8]
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily related proteins that are cell surface receptors that detect molecules outside the cell and activate cellular responses. They are coupled with G proteins. They pass through the cell membrane seven times in the form of six loops of amino acid residues, which is why they are sometimes referred to as seven-transmembrane receptors. Ligands can bind either to the extracellular N-terminus and loops or to the binding site within transmembrane helices. They are all activated by agonists, although a spontaneous auto-activation of an empty receptor has also been observed.
Bradykinin (BK) (from Greek brady- 'slow' + -kinin, kīn(eîn) 'to move') is a peptide that promotes inflammation. It causes arterioles to dilate (enlarge) via the release of prostacyclin, nitric oxide, and endothelium-derived hyperpolarizing factor and makes veins constrict, via prostaglandin F2, thereby leading to leakage into capillary beds, due to the increased pressure in the capillaries. Bradykinin consists of nine amino acids, and is a physiologically and pharmacologically active peptide of the kinin group of proteins.
The angiotensin II receptors, (ATR1) and (ATR2), are a class of G protein-coupled receptors with angiotensin II as their ligands. They are important in the renin–angiotensin system: they are responsible for the signal transduction of the vasoconstricting stimulus of the main effector hormone, angiotensin II.
The H1 receptor is a histamine receptor belonging to the family of rhodopsin-like G-protein-coupled receptors. This receptor is activated by the biogenic amine histamine. It is expressed in smooth muscles, on vascular endothelial cells, in the heart, and in the central nervous system. The H1 receptor is linked to an intracellular G-protein (Gq) that activates phospholipase C and the inositol triphosphate (IP3) signalling pathway. Antihistamines, which act on this receptor, are used as anti-allergy drugs. The crystal structure of the receptor has been determined (shown on the right/below) and used to discover new histamine H1 receptor ligands in structure-based virtual screening studies.
Apelin is a peptide that in humans is encoded by the APLN gene. Apelin is one of two endogenous ligands for the G-protein-coupled APJ receptor that is expressed at the surface of some cell types. It is widely expressed in various organs such as the heart, lung, kidney, liver, adipose tissue, gastrointestinal tract, brain, adrenal glands, endothelium, and human plasma.
The bradykinin receptor family is a group of G-protein coupled receptors whose principal ligand is the protein bradykinin.
The calcitonin receptor (CT) is a G protein-coupled receptor that binds the peptide hormone calcitonin and is involved in maintenance of calcium homeostasis, particularly with respect to bone formation and metabolism.
The Apelin Receptor is a G protein-coupled receptor. APLNR possesses two endogenous ligands which are APELIN and ELABELA. The structure of APLNR was resolved in 2017
Angiotensin II receptor type 1(AT1) is a Gq/11-coupled G protein-coupled receptor (GPCR) and the best characterized angiotensin receptor. It is encoded in humans by the AGTR1 gene. AT1 has vasopressor effects and regulates aldosterone secretion. It is an important effector controlling blood pressure and volume in the cardiovascular system. Angiotensin II receptor blockers are drugs indicated for hypertension, diabetic nephropathy and congestive heart failure.
Receptor tyrosine-protein kinase erbB-3, also known as HER3, is a membrane bound protein that in humans is encoded by the ERBB3 gene.
Bradykinin receptor B1 (B1) is a G-protein coupled receptor encoded by the BDKRB1 gene in humans. Its principal ligand is bradykinin, a 9 amino acid peptide generated in pathophysiologic conditions such as inflammation, trauma, burns, shock, and allergy. The B1 receptor is one of two of G protein-coupled receptors that have been found which bind bradykinin and mediate responses to these pathophysiologic conditions.
The muscarinic acetylcholine receptor, also known as cholinergic/acetylcholine receptor M3, or the muscarinic 3, is a muscarinic acetylcholine receptor encoded by the human gene CHRM3.
The alpha-1D adrenergic receptor, also known as ADRA1D, is an alpha-1 adrenergic receptor, and also denotes the human gene encoding it.
Angiotensin II receptor type 2, also known as the AT2 receptor is a protein that in humans is encoded by the AGTR2 gene.
G-protein coupled receptor 139 (GPC139) is a protein that in humans is encoded by the GPR139 gene. Research has shown that mice with loss of GCP139 experience schizophrenia-like symptomatology that is rescued with the dopamine receptor antagonist haloperidol and the μ-opioid receptor antagonist naltrexone.
Prostaglandin F receptor (FP) is a receptor belonging to the prostaglandin (PG) group of receptors. FP binds to and mediates the biological actions of prostaglandin F2α (PGF2α). It is encoded in humans by the PTGFR gene.
This gene encodes a member of the G protein-coupled receptor kinase subfamily of the Ser/Thr protein kinase family, and is most highly similar to GRK4 and GRK5. The protein phosphorylates the activated forms of G protein-coupled receptors to regulate their signaling.
G protein-coupled receptor kinase 5 is a member of the G protein-coupled receptor kinase subfamily of the Ser/Thr protein kinases, and is most highly similar to GRK4 and GRK6. The protein phosphorylates the activated forms of G protein-coupled receptors to regulate their signaling.
Serine/threonine protein kinase WNK4 also known as With No lysine (K) protein kinase 4(WNK4), is an enzyme that in humans is encoded by the WNK4 gene. Missense mutations cause a genetic form of pseudohypoaldosteronism type 2, also called Gordon syndrome or Familial Hyperkalemic Hypertension.
G-protein-coupled receptor kinase 3 (GRK3) is an enzyme that in humans is encoded by the ADRBK2 gene. GRK3 was initially called Beta-adrenergic receptor kinase 2 (βARK-2), and is a member of the G protein-coupled receptor kinase subfamily of the Ser/Thr protein kinases that is most highly similar to GRK2.
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