Q99MK8
PR
Gene name |
Grk2 |
Protein name |
Beta-adrenergic receptor kinase 1 |
Names |
Beta-ARK-1, G-protein-coupled receptor kinase 2 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:110355 |
EC number |
2.7.11.15: Protein-serine/threonine kinases |
Protein Class |
|
Descriptions
The autoinhibited protein was predicted that may have potential autoinhibitory elements via cis-regPred.
Autoinhibitory domains (AIDs)
Target domain |
|
Relief mechanism |
|
Assay |
cis-regPred |
Accessory elements
334-355 (Activation loop from InterPro)
Target domain |
191-453 (Protein kinase domain) |
Relief mechanism |
|
Assay |
|
Autoinhibited structure
Activated structure
1 structures for Q99MK8
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-Q99MK8-F1 | Predicted | AlphaFoldDB |
33 variants for Q99MK8
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3389482611 | 63 | L>I | No | EVA | |
| rs37527074 | 96 | E>A | No | EVA | |
| rs3389424862 | 104 | R>C | No | EVA | |
| rs3389511802 | 128 | A>D | No | EVA | |
| rs3408718589 | 176 | Q>H | No | EVA | |
| rs3389530521 | 181 | E>V | No | EVA | |
| rs3408513455 | 224 | K>M | No | EVA | |
| rs3389495341 | 273 | L>I | No | EVA | |
| rs3389530476 | 300 | E>D | No | EVA | |
| rs3389510825 | 332 | R>I | No | EVA | |
| rs3389515888 | 343 | S>P | No | EVA | |
| rs3389482577 | 344 | K>M | No | EVA | |
| rs3389527476 | 358 | A>P | No | EVA | |
| rs3389530510 | 359 | P>L | No | EVA | |
| rs3407811222 | 360 | E>K | No | EVA | |
| rs3389495325 | 369 | D>V | No | EVA | |
| rs3389507698 | 371 | S>N | No | EVA | |
| rs3389519590 | 423 | S>T | No | EVA | |
| rs3389424854 | 442 | R>H | No | EVA | |
| rs3389424873 | 467 | P>S | No | EVA | |
| rs3408990388 | 499 | L>R | No | EVA | |
| rs3407888804 | 500 | D>Y | No | EVA | |
| rs3409275858 | 502 | D>Y | No | EVA | |
| rs3408806938 | 503 | Q>L | No | EVA | |
| rs3408887688 | 504 | E>A | No | EVA | |
| rs3407811208 | 504 | E>V | No | EVA | |
| rs3408912370 | 506 | Y>S | No | EVA | |
| rs3406960304 | 507 | R>S | No | EVA | |
| rs3389527525 | 572 | F>Y | No | EVA | |
| rs3412896549 | 589 | E>V | No | EVA | |
| rs3389495374 | 591 | R>G | No | EVA | |
| rs3389509671 | 626 | G>D | No | EVA | |
| rs3389495353 | 643 | W>R | No | EVA |
No associated diseases with Q99MK8
3 regional properties for Q99MK8
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| conserved_site | 14-3-3 protein, conserved site | 42 - 52 | IPR023409-1 |
| conserved_site | 14-3-3 protein, conserved site | 216 - 235 | IPR023409-2 |
| domain | 14-3-3 domain | 4 - 247 | IPR023410 |
Functions
| Description | ||
|---|---|---|
| EC Number | 2.7.11.15 | Protein-serine/threonine kinases |
| Subcellular Localization |
|
|
| PANTHER Family | ||
| PANTHER Subfamily | ||
| PANTHER Protein Class | ||
| PANTHER Pathway Category | No pathway information available | |
16 GO annotations of cellular component
| Name | Definition |
|---|---|
| anchoring junction | A cell junction that mechanically attaches a cell (and its cytoskeleton) to neighboring cells or to the extracellular matrix. |
| apical plasma membrane | The region of the plasma membrane located at the apical end of the cell. |
| axon | The long process of a neuron that conducts nerve impulses, usually away from the cell body to the terminals and varicosities, which are sites of storage and release of neurotransmitter. |
| basolateral plasma membrane | The region of the plasma membrane that includes the basal end and sides of the cell. Often used in reference to animal polarized epithelial membranes, where the basal membrane is the part attached to the extracellular matrix, or in plant cells, where the basal membrane is defined with respect to the zygotic axis. |
| caveola | A membrane raft that forms small pit, depression, or invagination that communicates with the outside of a cell and extends inward, indenting the cytoplasm and the cell membrane. Examples include flask-shaped invaginations of the plasma membrane in adipocytes associated with caveolin proteins, and minute pits or incuppings of the cell membrane formed during pinocytosis. Caveolae may be pinched off to form free vesicles within the cytoplasm. |
| cilium | A specialized eukaryotic organelle that consists of a filiform extrusion of the cell surface and of some cytoplasmic parts. Each cilium is largely bounded by an extrusion of the cytoplasmic (plasma) membrane, and contains a regular longitudinal array of microtubules, anchored to a basal body. |
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| dendritic shaft | Cylindric portion of the dendrite, directly stemming from the perikaryon, and carrying the dendritic spines. |
| dendritic spine | A small, membranous protrusion from a dendrite that forms a postsynaptic compartment, typically receiving input from a single presynapse. They function as partially isolated biochemical and an electrical compartments. Spine morphology is variable:they can be thin, stubby, mushroom, or branched, with a continuum of intermediate morphologies. They typically terminate in a bulb shape, linked to the dendritic shaft by a restriction. Spine remodeling is though to be involved in synaptic plasticity. |
| membrane | A lipid bilayer along with all the proteins and protein complexes embedded in it an attached to it. |
| membrane raft | Any of the small (10-200 nm), heterogeneous, highly dynamic, sterol- and sphingolipid-enriched membrane domains that compartmentalize cellular processes. Small rafts can sometimes be stabilized to form larger platforms through protein-protein and protein-lipid interactions. |
| mitochondrion | A semiautonomous, self replicating organelle that occurs in varying numbers, shapes, and sizes in the cytoplasm of virtually all eukaryotic cells. It is notably the site of tissue respiration. |
| nucleus | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. |
| presynapse | The part of a synapse that is part of the presynaptic cell. |
| synapse | The junction between an axon of one neuron and a dendrite of another neuron, a muscle fiber or a glial cell. As the axon approaches the synapse it enlarges into a specialized structure, the presynaptic terminal bouton, which contains mitochondria and synaptic vesicles. At the tip of the terminal bouton is the presynaptic membrane; facing it, and separated from it by a minute cleft (the synaptic cleft) is a specialized area of membrane on the receiving cell, known as the postsynaptic membrane. In response to the arrival of nerve impulses, the presynaptic terminal bouton secretes molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane. |
11 GO annotations of molecular function
| Name | Definition |
|---|---|
| ATP binding | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. |
| beta-adrenergic receptor kinase activity | Catalysis of the reaction: ATP + beta-adrenergic receptor = ADP + phospho-beta-adrenergic receptor. |
| delta-type opioid receptor binding | Binding to a delta-type opioid receptor. |
| Edg-2 lysophosphatidic acid receptor binding | Binding to an Edg-2 lysophosphatidic acid receptor. |
| G protein-coupled receptor binding | Binding to a G protein-coupled receptor. |
| G protein-coupled receptor kinase activity | Catalysis of the reaction: ATP + G protein-coupled receptor = ADP + G protein-coupled receptor phosphate. |
| kappa-type opioid receptor binding | Binding to a kappa-type opioid receptor. |
| protein kinase activity | Catalysis of the phosphorylation of an amino acid residue in a protein, usually according to the reaction: a protein + ATP = a phosphoprotein + ADP. |
| protein serine/threonine kinase activity | Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate. |
| scaffold protein binding | Binding to a scaffold protein. Scaffold proteins are crucial regulators of many key signaling pathways. Although not strictly defined in function, they are known to interact and/or bind with multiple members of a signaling pathway, tethering them into complexes. |
| ubiquitin protein ligase binding | Binding to a ubiquitin protein ligase enzyme, any of the E3 proteins. |
41 GO annotations of biological process
| Name | Definition |
|---|---|
| cardiac muscle contraction | Muscle contraction of cardiac muscle tissue. |
| cellular response to chemokine | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a chemokine stimulus. |
| cellular response to epidermal growth factor stimulus | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an epidermal growth factor stimulus. |
| cellular response to glucose stimulus | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a glucose stimulus. |
| desensitization of G protein-coupled receptor signaling pathway | The process that stops, prevents, or reduces the frequency, rate or extent of G protein-coupled receptor signaling pathway after prolonged stimulation with an agonist of the pathway. |
| follicle-stimulating hormone signaling pathway | A G protein-coupled receptor signaling pathway initiated by follicle-stimulating hormone binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process. |
| G protein-coupled receptor signaling pathway | The series of molecular signals initiated by a ligand binding to its receptor, in which the activated receptor promotes the exchange of GDP for GTP on the alpha-subunit of an associated heterotrimeric G-protein complex. The GTP-bound activated alpha-G-protein then dissociates from the beta- and gamma-subunits to further transmit the signal within the cell. The pathway begins with receptor-ligand interaction, and ends with regulation of a downstream cellular process. The pathway can start from the plasma membrane, Golgi or nuclear membrane. |
| heart development | The process whose specific outcome is the progression of the heart over time, from its formation to the mature structure. The heart is a hollow, muscular organ, which, by contracting rhythmically, keeps up the circulation of the blood. |
| maintenance of protein location in nucleus | Any process in which a protein is maintained in the nucleus and prevented from moving elsewhere. These include sequestration within the nucleus, protein stabilization to prevent transport elsewhere and the active retrieval of proteins that escape the nucleus. |
| negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway | Any process that stops, prevents or reduces the frequency, rate or extent of an adenylate cyclase-activating G protein-coupled receptor signaling pathway. |
| negative regulation of apoptotic process | Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process. |
| negative regulation of cellular response to insulin stimulus | Any process that stops, prevents or reduces the frequency, rate or extent of cellular response to insulin stimulus. |
| negative regulation of cysteine-type endopeptidase activity | Any process that stops, prevents, or reduces the frequency, rate or extent of cysteine-type endopeptidase activity. |
| negative regulation of G protein-coupled receptor signaling pathway | Any process that stops, prevents, or reduces the frequency, rate or extent of G protein-coupled receptor signaling pathway. |
| negative regulation of glucose import | Any process that stops, prevents, or reduces the frequency, rate or extent of the import of the hexose monosaccharide glucose into a cell or organelle. |
| negative regulation of peptidyl-serine phosphorylation | Any process that stops, prevents, or reduces the frequency, rate or extent of the phosphorylation of peptidyl-serine. |
| negative regulation of peptidyl-threonine phosphorylation | Any process that decreases the frequency, rate or extent of peptidyl-threonine phosphorylation. Peptidyl-threonine phosphorylation is the phosphorylation of peptidyl-threonine to form peptidyl-O-phospho-L-threonine. |
| negative regulation of relaxation of smooth muscle | Any process that stops, prevents or reduces the frequency, rate or extent of relaxation of smooth muscle. |
| negative regulation of striated muscle contraction | Any process that stops, prevents, or reduces the frequency, rate or extent of striated muscle contraction. |
| negative regulation of the force of heart contraction by chemical signal | Any process which decreases the force of heart muscle contraction mediated by chemical signaling, hormonal, autocrine or paracrine. |
| oligodendrocyte differentiation | The process in which a relatively unspecialized cell acquires the specialized features of an oligodendrocyte. An oligodendrocyte is a type of glial cell involved in myelinating the axons of neurons in the central nervous system. |
| peptidyl-serine phosphorylation | The phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine. |
| peptidyl-threonine phosphorylation | The phosphorylation of peptidyl-threonine to form peptidyl-O-phospho-L-threonine. |
| positive regulation of catecholamine secretion | Any process that activates or increases the frequency, rate or extent of the regulated release of a catecholamine. |
| positive regulation of excitatory postsynaptic potential | Any process that enhances the establishment or increases the extent of the excitatory postsynaptic potential (EPSP) which is a temporary increase in postsynaptic potential due to the flow of positively charged ions into the postsynaptic cell. The flow of ions that causes an EPSP is an excitatory postsynaptic current (EPSC) and makes it easier for the neuron to fire an action potential. |
| positive regulation of fibroblast proliferation | Any process that activates or increases the frequency, rate or extent of multiplication or reproduction of fibroblast cells. |
| positive regulation of interleukin-6 production | Any process that activates or increases the frequency, rate, or extent of interleukin-6 production. |
| positive regulation of muscle cell apoptotic process | Any process that increases the rate or frequency of muscle cell apoptotic process, a form of programmed cell death induced by external or internal signals that trigger the activity of proteolytic caspases whose actions dismantle a muscle cell and result in its death. |
| positive regulation of sensory perception of pain | Any process that activates or increases the frequency, rate or extent of sensory perception of pain. |
| positive regulation of vascular associated smooth muscle cell proliferation | Any process that activates or increases the frequency, rate or extent of vascular smooth muscle cell proliferation. |
| positive regulation of vasoconstriction | Any process that activates or increases the frequency, rate or extent of vasoconstriction. |
| protein phosphorylation | The process of introducing a phosphate group on to a protein. |
| receptor internalization | A receptor-mediated endocytosis process that results in the movement of receptors from the plasma membrane to the inside of the cell. The process begins when cell surface receptors are monoubiquitinated following ligand-induced activation. Receptors are subsequently taken up into endocytic vesicles from where they are either targeted to the lysosome or vacuole for degradation or recycled back to the plasma membrane. |
| regulation of signal transduction | Any process that modulates the frequency, rate or extent of signal transduction. |
| regulation of the force of heart contraction | Any process that modulates the extent of heart contraction, changing the force with which blood is propelled. |
| response to organic cyclic compound | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an organic cyclic compound stimulus. |
| response to oxidative stress | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of oxidative stress, a state often resulting from exposure to high levels of reactive oxygen species, e.g. superoxide anions, hydrogen peroxide (H2O2), and hydroxyl radicals. |
| tachykinin receptor signaling pathway | A G protein-coupled receptor signaling pathway initiated by tachykinin binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process. Tachykinin is a short peptide with the terminal sequence (Phe-X-Gly-Leu-Met-NH2). |
| vasodilation | An increase in the internal diameter of blood vessels, especially arterioles or capillaries, due to relaxation of smooth muscle cells that line the vessels, and usually resulting in a decrease in blood pressure. |
| viral entry into host cell | The process that occurs after viral attachment by which a virus, or viral nucleic acid, breaches the plasma membrane or cell envelope and enters the host cell. The process ends when the viral nucleic acid is released into the host cell cytoplasm. |
| viral genome replication | Any process involved directly in viral genome replication, including viral nucleotide metabolism. |
18 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| P26818 | GRK3 | Beta-adrenergic receptor kinase 2 | Bos taurus (Bovine) | PR |
| P43249 | GRK5 | G protein-coupled receptor kinase 5 | Bos taurus (Bovine) | SS |
| P21146 | GRK2 | Beta-adrenergic receptor kinase 1 | Bos taurus (Bovine) | PR |
| P32865 | Gprk1 | G protein-coupled receptor kinase 1 | Drosophila melanogaster (Fruit fly) | PR |
| P35626 | GRK3 | Beta-adrenergic receptor kinase 2 | Homo sapiens (Human) | PR |
| Q15835 | GRK1 | Rhodopsin kinase GRK1 | Homo sapiens (Human) | PR |
| P34947 | GRK5 | G protein-coupled receptor kinase 5 | Homo sapiens (Human) | EV |
| P32298 | GRK4 | G protein-coupled receptor kinase 4 | Homo sapiens (Human) | SS |
| P43250 | GRK6 | G protein-coupled receptor kinase 6 | Homo sapiens (Human) | EV |
| P25098 | GRK2 | Beta-adrenergic receptor kinase 1 | Homo sapiens (Human) | PR |
| Q3UYH7 | Adrbk2 | Beta-adrenergic receptor kinase 2 | Mus musculus (Mouse) | PR |
| Q8VEB1 | Grk5 | G protein-coupled receptor kinase 5 | Mus musculus (Mouse) | SS |
| O70293 | Grk6 | G protein-coupled receptor kinase 6 | Mus musculus (Mouse) | SS |
| Q9WVL4 | Grk1 | Rhodopsin kinase GRK1 | Mus musculus (Mouse) | PR |
| Q62833 | Grk5 | G protein-coupled receptor kinase 5 | Rattus norvegicus (Rat) | SS |
| P97711 | Grk6 | G protein-coupled receptor kinase 6 | Rattus norvegicus (Rat) | SS |
| P26817 | Grk2 | Beta-adrenergic receptor kinase 1 | Rattus norvegicus (Rat) | PR |
| Q09639 | grk-2 | G protein-coupled receptor kinase 2 | Caenorhabditis elegans | PR |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MADLEAVLAD | VSYLMAMEKS | KATPAARASK | KILLPEPSIR | SVMQKYLEDR | GEVTFEKIFS |
| 70 | 80 | 90 | 100 | 110 | 120 |
| QKLGYLLFRD | FCLNHLEEAK | PLVEFYEEIK | KYEKLETEEE | RVVRSREIFD | SYIMKELLAC |
| 130 | 140 | 150 | 160 | 170 | 180 |
| SHPFSKNATE | HVQGHLVKKQ | VPPDLFQPYI | EEICQNLRGD | VFQKFIESDK | FTRFCQWKNV |
| 190 | 200 | 210 | 220 | 230 | 240 |
| ELNIHLTMND | FSVHRIIGRG | GFGEVYGCRK | ADTGKMYAMK | CLDKKRIKMK | QGETLALNER |
| 250 | 260 | 270 | 280 | 290 | 300 |
| IMLSLVSTGD | CPFIVCMSYA | FHTPDKLSFI | LDLMNGGDLH | YHLSQHGVFS | EADMRFYAAE |
| 310 | 320 | 330 | 340 | 350 | 360 |
| IILGLEHMHN | RFVVYRDLKP | ANILLDEHGH | VRISDLGLAC | DFSKKRPHAS | VGTHGYMAPE |
| 370 | 380 | 390 | 400 | 410 | 420 |
| VLQKGVAYDS | SADWFSLGCM | LFKLLRGHSP | FRQHKTKDKH | EIDRMTLTMA | VELPDSFSPE |
| 430 | 440 | 450 | 460 | 470 | 480 |
| LRSLLEGLLQ | RDVNRRLGCL | GRGAQEVKES | PFFRSLDWQM | VFLQKYPPPL | IPPRGEVNAA |
| 490 | 500 | 510 | 520 | 530 | 540 |
| DAFDIGSFDE | EDTKGIKLLD | SDQELYRNFP | LTISERWQQE | VAETVFDTIN | AETDRLEARK |
| 550 | 560 | 570 | 580 | 590 | 600 |
| KAKNKQLGHE | EDYALGKDCI | VHGYMSKMGN | PFLTQWQRRY | FYLFPNRLEW | RGEGEAPQSL |
| 610 | 620 | 630 | 640 | 650 | 660 |
| LTMEEIQSVE | ETQIKERKCL | LLKIRGGKQF | VLQCDSDPEL | VQWKKELRDA | YREAQQLVQR |
| 670 | 680 | ||||
| VPKMKNKPRS | PVVELSKVPL | IQRGSANGL |