g protein-coupled receptor kinase 3 g protein-coupled receptor kinase 3 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. grk3identifiersaliasesgrk3, bark2, adrbk2, beta adrenergic receptor kinase-2, g protein-coupled receptor kinase 3external idsomim: 109636 mgi: 87941 homologene: 21072 genecards: grk3 gene location (human)chr.chromosome 22 (human)band22q12.1start25,564,675 bpend25,729,294 bpgene location (mouse)chr.chromosome 5 (mouse)band5 f|5 55.29 cmstart113,058,348 bpend113,163,657 bprna expression patternbgeehumanmouse (ortholog)top expressed inbrodmann area 23middle temporal gyrusendothelial cellparietal pleuramonocyteparietal lobepostcentral gyrusentorhinal cortexspermsuperior frontal gyrustop expressed insubiculumsubstantia nigrasubmandibular glandmedial dorsal nucleuscerebellar vermismedial geniculate nucleusparotid glandcingulate gyruslateral geniculate nucleussuperior colliculusmore reference expression databiogpsmore reference expression datagene ontologymolecular function g protein-coupled receptor kinase activity atp binding transferase activity protein kinase activity nucleotide binding protein serine/threonine kinase activity kinase activity beta-adrenergic receptor kinase activity cellular component plasma membrane cytosol biological process protein phosphorylation receptor internalization phosphorylation signal transduction g protein-coupled receptor signaling pathway sources:amigo / quickgoorthologsspecieshumanmouseentrez157320129ensemblensg00000100077ensmusg00000042249uniprotp35626q3uyh7refseq (mrna)nm_005160nm_001362778nm_001035531nm_001285806nm_177078refseq (protein)np_005151np_001349707np_001272735np_796052location (ucsc)chr 22: 25.56 – 25.73 mbchr 5: 113.06 – 113.16 mbpubmed searchwikidataview/edit humanview/edit mouse function g protein-coupled receptor kinases phosphorylate activated g protein-coupled receptors, which promotes the binding of an arrestin protein to the receptor. arrestin binding to phosphorylated, active receptor prevents receptor stimulation of heterotrimeric g protein transducer proteins, blocking their cellular signaling and resulting in receptor desensitization. arrestin binding also directs receptors to specific cellular internalization pathways, removing the receptors from the cell surface and also preventing additional activation. arrestin binding to phosphorylated, active receptor also enables receptor signaling through arrestin partner proteins. as a result, the g protein-coupled receptors' complicated signaling switch is the grk/arrestin system. grk3 and the closely related grk2 phosphorylate receptors at sites that encourage arrestin-mediated receptor desensitization, internalization and trafficking rather than arrestin-mediated signaling (in contrast to grk5 and grk6, which have the opposite effect). this difference is one basis for pharmacological biased agonism (also called functional selectivity), where a drug binding to a receptor may bias that receptor’s signaling toward a particular subset of the actions stimulated by that receptor. grk3 is expressed broadly in tissues, but generally at lower levels than the related grk2. grk3 has particularly high expression in olfactory neurons, and mice lacking the adrbk2 gene exhibit defects in olfaction. gene linkage techniques were used to identify a polymorphism in the promoter of the human adrbk2 gene as a possible cause of up to 10% of cases of bipolar disorder. however, the significance of grk3 in bipolar disorder has been controversial due to conflicting reports. grk3 has also been implicated in regulation of dopamine receptors in parkinson disease in animal models. reduced expression of grk3 has been associated with the immunodeficient whim syndrome in humans, and appears causative in a mouse model of the disease.