Q8VEB1

SS
Gene name
Grk5 (Gprk5)
Protein name
G protein-coupled receptor kinase 5
Names
EC 2.7.11.16 , G protein-coupled receptor kinase GRK5
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:14773
EC number
2.7.11.16: Protein-serine/threonine kinases
Protein Class

Descriptions

GRK5(G protein-coupled receptor kinase 5) phosphorylates a variety of GPCRs, including adrenergic receptors, muscarinic acetylcholine receptors (more specifically Gi-coupled M2/M4 subtypes), dopamine receptors and opioid receptors. In addition to GPCRs, GRK5 also phosphorylates various substrates: Hsc70-interacting protein/ST13, TP53/p53, HDAC5, and arrestin-1/ARRB1. GRK5 has an autoinhibitory domain, because its deletion increases GRK5 affinity for both phospholipids and receptor by 3-4 fold. The efficacy of the autoinhibition is enhanced by PKC phosphorylation or calmodulin-stimulated autophosphorylation within the autoinhibitory domain.

Autoinhibitory domains (AIDs)

563-590 (Autoinhibitory domain) SS

Target domain

186-448 (Protein kinase domain)

Relief mechanism

Assay

Accessory elements

328-350 (Activation loop from InterPro)

Target domain

186-448 (Protein kinase domain)

Relief mechanism

Assay

328-350 (Activation loop from InterPro)

Target domain

186-448 (Protein kinase domain)

Relief mechanism

Assay

References

Autoinhibited structure

Activated structure

1 structures for Q8VEB1

Entry ID Method Resolution Chain Position Source
AF-Q8VEB1-F1 Predicted AlphaFoldDB

28 variants for Q8VEB1

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3389550111 19 G>C No EVA
rs3389562020 32 E>D No EVA
rs3389566009 40 S>R No EVA
rs3389458125 51 R>I No EVA
rs3389458125 51 R>T No EVA
rs3389529230 120 Q>* No EVA
rs3389506325 131 K>R No EVA
rs3389516300 133 L>F No EVA
rs3389559863 166 Y>F No EVA
rs3389458145 170 F>V No EVA
rs3389506352 210 K>R No EVA
rs3389545274 212 Y>D No EVA
rs3389545227 218 E>G No EVA
rs3389562043 252 A>V No EVA
rs3389562013 264 T>I No EVA
rs3389549595 291 Y>H No EVA
rs3389458116 382 Q>* No EVA
rs3389529211 405 E>A No EVA
rs3389562086 406 E>G No EVA
rs3389550166 453 F>L No EVA
rs3389497982 482 Q>R No EVA
rs3408386142 519 E>* No EVA
rs3409065848 519 E>D No EVA
rs3409364529 519 E>V No EVA
rs3409457868 522 K>* No EVA
rs3407426300 522 K>N No EVA
rs3409691261 523 E>Q No EVA
rs48502943 545 P>L No EVA

No associated diseases with Q8VEB1

4 regional properties for Q8VEB1

Type Name Position InterPro Accession
domain Protein kinase domain 186 - 448 IPR000719
domain AGC-kinase, C-terminal 449 - 528 IPR000961
domain RGS domain 52 - 171 IPR016137
binding_site Protein kinase, ATP binding site 192 - 224 IPR017441

Functions

Description
EC Number 2.7.11.16 Protein-serine/threonine kinases
Subcellular Localization
  • Cytoplasm
  • Nucleus
  • Cell membrane; Peripheral membrane protein
  • Predominantly localized at the plasma membrane, targeted to the cell surface through the interaction with phospholipids
  • Nucleus localization is regulated in a GPCR and Ca(2+)/calmodulin-dependent fashion (By similarity)
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

5 GO annotations of cellular component

Name Definition
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.
nuclear membrane Either of the lipid bilayers that surround the nucleus and form the nuclear envelope; excludes the intermembrane space.
nuclear speck A discrete extra-nucleolar subnuclear domain, 20-50 in number, in which splicing factors are seen to be localized by immunofluorescence microscopy.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.

6 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
G protein-coupled receptor kinase activity Catalysis of the reaction
lipid binding Binding to a lipid.
protein kinase activity Catalysis of the phosphorylation of an amino acid residue in a protein, usually according to the reaction
protein serine/threonine kinase activity Catalysis of the reactions

12 GO annotations of biological process

Name Definition
apoptotic process A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died.
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.
fat cell differentiation The process in which a relatively unspecialized cell acquires specialized features of an adipocyte, an animal connective tissue cell specialized for the synthesis and storage of fat.
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.
positive regulation of cell population proliferation Any process that activates or increases the rate or extent of cell proliferation.
protein autophosphorylation The phosphorylation by a protein of one or more of its own amino acid residues (cis-autophosphorylation), or residues on an identical protein (trans-autophosphorylation).
regulation of cell cycle Any process that modulates the rate or extent of progression through the cell cycle.
regulation of G protein-coupled receptor signaling pathway Any process that modulates the frequency, rate or extent of G protein-coupled receptor signaling pathway.
regulation of signal transduction Any process that modulates the frequency, rate or extent of signal transduction.
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).
Wnt signaling pathway The series of molecular signals initiated by binding of a Wnt protein to a frizzled family receptor on the surface of the target cell and ending with a change in cell state.

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
P21146 GRK2 Beta-adrenergic receptor kinase 1 Bos taurus (Bovine) PR
P43249 GRK5 G protein-coupled receptor kinase 5 Bos taurus (Bovine) SS
P32865 Gprk1 G protein-coupled receptor kinase 1 Drosophila melanogaster (Fruit fly) PR
P25098 GRK2 Beta-adrenergic receptor kinase 1 Homo sapiens (Human) PR
P35626 GRK3 Beta-adrenergic receptor kinase 2 Homo sapiens (Human) PR
Q15835 GRK1 Rhodopsin kinase GRK1 Homo sapiens (Human) PR
P32298 GRK4 G protein-coupled receptor kinase 4 Homo sapiens (Human) SS
P43250 GRK6 G protein-coupled receptor kinase 6 Homo sapiens (Human) EV
P34947 GRK5 G protein-coupled receptor kinase 5 Homo sapiens (Human) EV
Q3UYH7 Adrbk2 Beta-adrenergic receptor kinase 2 Mus musculus (Mouse) PR
Q99MK8 Grk2 Beta-adrenergic receptor kinase 1 Mus musculus (Mouse) PR
O70293 Grk6 G protein-coupled receptor kinase 6 Mus musculus (Mouse) SS
Q9WVL4 Grk1 Rhodopsin kinase GRK1 Mus musculus (Mouse) PR
P26817 Grk2 Beta-adrenergic receptor kinase 1 Rattus norvegicus (Rat) PR
P97711 Grk6 G protein-coupled receptor kinase 6 Rattus norvegicus (Rat) SS
Q62833 Grk5 G protein-coupled receptor kinase 5 Rattus norvegicus (Rat) SS
Q09639 grk-2 G protein-coupled receptor kinase 2 Caenorhabditis elegans PR
10 20 30 40 50 60
MELENIVANT VLLKAREGGG GKRKGKSKKW KEILKFPHIS QCEDLRRTID RDYYSLCDKQ
70 80 90 100 110 120
PIGRLLFRQF CETRPGLECY IQFLDLVAEY EITPDENLGA KGKEIMTKYL TPKSPVFIAQ
130 140 150 160 170 180
VGQDLVSQTE KKLLQSPCKE LFSACAQSVH DYLKGDPFHE YLDSMYFDRF LQWKWLERQP
190 200 210 220 230 240
VTKNTFRQYR VLGKGGFGEV CACQVRATGK MYACKRLEKK RIKKRKGESM ALNEKQILEK
250 260 270 280 290 300
VNSQFVVNLA YAYETKDALC LVLTIMNGGD LKFHIYNMGN PGFEEERALF YAAEILCGLE
310 320 330 340 350 360
DLHRENTVYR DLKPENILLD DYGHIRISDL GLAVKIPEGD LIRGRVGTVG YMAPEVLNNQ
370 380 390 400 410 420
RYGLSPDYWG LGCLIYEMIE GQSPFRGRKE KVKREEVDRR VLETEEVYSS KFSEEAKSIC
430 440 450 460 470 480
NMLLTKDSKQ RLGCQEEGAA EVKRHPFFRN MNFKRLEAGM LDPPFVPDPR AVYCKDVLDI
490 500 510 520 530 540
EQFSTVKGVN LDHTDDDFYS KFSTGSVPIP WQNEMIETEC FKELNVFGPN GTLSPDLNRS
550 560 570 580
QPPEPPKKGL FHRLFRRQHQ SNSKSSPTPK TSCNHRINSN HINSNSTGSS