P43249

SS
Gene name
GRK5 (GPRK5)
Protein name
G protein-coupled receptor kinase 5
Names
G protein-coupled receptor kinase GRK5
Species
Bos taurus (Bovine)
KEGG Pathway
bta:281801
EC number
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.

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

References

Autoinhibited structure

Activated structure

2 structures for P43249

Entry ID Method Resolution Chain Position Source
4WNK X-ray 242 A A 1-590 PDB
AF-P43249-F1 Predicted AlphaFoldDB

119 variants for P43249

Variant ID(s) Position Change Description Diseaes Association Provenance
rs461393951 2 E>G No Ensembl
rs479820452 6 I>M No Ensembl
rs440293616 9 N>H No Ensembl
rs458746377 10 T>P No Ensembl
rs477284582 11 V>G No Ensembl
rs462743966 12 L>F No Ensembl
rs481151594 15 A>G No Ensembl
rs465020286 51 R>Q No Ensembl
rs467138053 79 S>A No Ensembl
rs479200498 83 F>C No Ensembl
rs444315255 92 V>G No Ensembl
rs456373251 93 T>S No Ensembl
rs449844522 104 E>G No Ensembl
rs447226333 114 S>A No Ensembl
rs446329956 124 D>Y No Ensembl
rs464784750 128 Q>E No Ensembl
rs450112341 131 E>V No Ensembl
rs468689711 132 K>* No Ensembl
rs453958013 135 Q>L No Ensembl
rs472336827 140 E>D No Ensembl
rs433063171 141 L>P No Ensembl
rs380560534 143 S>L No Ensembl
rs520419993 146 V>M No Ensembl
rs477280978 175 W>C No Ensembl
rs458790388 175 W>L No Ensembl
rs440337336 175 W>R No Ensembl
rs450507769 178 R>S No Ensembl
rs462473469 180 P>Q No Ensembl
rs480865799 197 F>Y No Ensembl
rs451816441 200 V>G No Ensembl
rs476566453 203 C>* No Ensembl
rs462072359 227 G>A No Ensembl
rs519184505 228 E>* No Ensembl
rs441166655 238 L>R No Ensembl
rs459678164 239 E>G No Ensembl
rs459678164 239 E>V No Ensembl
rs478166678 241 V>A No Ensembl
rs469979642 242 N>H No Ensembl
rs481974218 242 N>I No Ensembl
rs480098452 247 V>A No Ensembl
rs465496762 270 D>G No Ensembl
rs432449956 271 L>V No Ensembl
rs457388685 277 N>K No Ensembl
rs469418252 278 M>I No Ensembl
rs436377554 284 E>G No Ensembl
rs454773362 285 E>G No Ensembl
rs473316368 286 E>G No Ensembl
rs440258102 289 L>M No Ensembl
rs470554325 294 E>D No Ensembl
rs452301156 294 E>Q No Ensembl
rs444105338 297 C>W No Ensembl
rs523596810 304 H>R No Ensembl
rs434373369 329 D>G No Ensembl
rs447916697 340 D>G No Ensembl
rs451816298 349 V>A No Ensembl
rs437293662 352 M>K No Ensembl
rs468653475 362 Y>N No Ensembl
rs466305548 366 P>R No Ensembl
rs451687113 384 P>H No Ensembl
rs443589868 389 K>Q No Ensembl
rs455605255 392 V>G No Ensembl
rs441060077 393 K>N No Ensembl
rs474025238 393 K>R No Ensembl
rs459453221 396 E>G No Ensembl
rs477950298 397 V>G No Ensembl
rs481872437 406 E>* No Ensembl
rs450325483 407 V>G No Ensembl
rs447798865 417 K>* No Ensembl
rs466284252 419 I>T No Ensembl
rs433306981 420 C>R No Ensembl
rs470224556 422 M>I No Ensembl
rs470224556 422 M>I No Ensembl
rs445285919 422 M>R No Ensembl
rs437140774 423 L>P No Ensembl
rs455607475 424 L>I No Ensembl
rs467628053 424 L>P No Ensembl
rs453055257 437 E>G No Ensembl
rs716774424 440 A>T No Ensembl
rs456815906 442 V>D No Ensembl
rs456815906 442 V>G No Ensembl
rs475206298 447 F>L No Ensembl
rs462437860 457 E>G No Ensembl
rs480921420 460 M>R No Ensembl
rs441391648 461 L>M No Ensembl
rs445352853 468 D>V No Ensembl
rs519091291 472 V>G No Ensembl
rs468994905 480 I>T No Ensembl
rs436132631 483 F>V No Ensembl
rs448147686 493 H>P No Ensembl
rs466558949 494 T>K No Ensembl
rs451984774 495 D>A No Ensembl
rs433584174 495 D>N No Ensembl
rs451984774 495 D>V No Ensembl
rs471705866 496 D>Y No Ensembl
rs472090839 498 F>S No Ensembl
rs432603464 499 Y>S No Ensembl
rs457572777 502 F>L No Ensembl
rs516120499 506 S>Y No Ensembl
rs468674431 520 C>G No Ensembl
rs447627978 530 H>P No Ensembl
rs466159168 532 T>P No Ensembl
rs466159168 532 T>S No Ensembl
rs451602614 541 H>Q No Ensembl
rs470041195 550 L>P No Ensembl
rs455475235 553 R>S No Ensembl
rs473913879 555 F>I No Ensembl
rs481736795 562 N>T No Ensembl
rs448632093 570 K>R No Ensembl
rs478960877 572 S>R No Ensembl
rs446095927 573 F>L No Ensembl
rs464625539 573 F>S No Ensembl
rs437989628 574 N>T No Ensembl
rs456489895 576 H>P No Ensembl
rs468458880 577 I>T No Ensembl
rs435463320 578 N>I No Ensembl
rs453952194 580 N>K No Ensembl
rs439364565 584 S>T No Ensembl
rs451300447 585 N>I No Ensembl
rs476322498 585 N>K No Ensembl

No associated diseases with P43249

5 regional properties for P43249

Type Name Position InterPro Accession
domain Protein kinase domain 186 - 448 IPR000719
domain AGC-kinase, C-terminal 449 - 528 IPR000961
active_site Serine/threonine-protein kinase, active site 307 - 319 IPR008271
domain RGS domain 52 - 171 IPR016137
binding_site Protein kinase, ATP binding site 192 - 224 IPR017441

Functions

Description
EC Number
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: ATP + beta-adrenergic receptor = ADP + phospho-beta-adrenergic receptor.
G protein-coupled receptor kinase activity Catalysis of the reaction: ATP + G protein-coupled receptor = ADP + G protein-coupled receptor phosphate.
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: 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.

9 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.
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).
protein phosphorylation The process of introducing a phosphate group on to a protein.
regulation of cell cycle Any process that modulates the rate or extent of progression through the cell cycle.
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.

19 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
P21146 GRK2 Beta-adrenergic receptor kinase 1 Bos taurus (Bovine) PR
P26818 GRK3 Beta-adrenergic receptor kinase 2 Bos taurus (Bovine) PR
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
O70293 Grk6 G protein-coupled receptor kinase 6 Mus musculus (Mouse) SS
Q99MK8 Grk2 Beta-adrenergic receptor kinase 1 Mus musculus (Mouse) PR
Q9WVL4 Grk1 Rhodopsin kinase GRK1 Mus musculus (Mouse) PR
Q3UYH7 Adrbk2 Beta-adrenergic receptor kinase 2 Mus musculus (Mouse) PR
Q8VEB1 Grk5 G protein-coupled receptor kinase 5 Mus musculus (Mouse) SS
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
O48963 PHOT1 Phototropin-1 Arabidopsis thaliana (Mouse-ear cress) PR
10 20 30 40 50 60
MELENIVANT VLLKAREGGG GKRKGKSKKW KEILKFPHIN QCEDLRRTID RDYCSLCDKQ
70 80 90 100 110 120
PVGRLLFRQF CETRPGLESY IQFLDSVAEY EVTPDEKLGE KGKEIMTKYL TPKSPVFITQ
130 140 150 160 170 180
VGRDLVSQTE EKLLQKPCKE LFSACVQSVH DYLRGEPFHE YLDSMYFDRF LQWKWLERQP
190 200 210 220 230 240
VTKNTFRQYR VLGKGGFGEV CACQVRATGK MYACKRLEKK RIKKRKGESM ALNEKQILEK
250 260 270 280 290 300
VNSRFVVNLA YAYETKDALC LVLTIMNGGD LKFHIYNMGN PGFEEERALF YAAEILCGLE
310 320 330 340 350 360
DLHHENIVYR DLKPENILLD DYGHIRISDL GLAVKIPEGD LIRGRVGTVG YMAPEVLNNQ
370 380 390 400 410 420
RYGLSPDYWG LGCLIYEMIE GQSPFRGRKE KVKREEVDRR VLETEEVYSH KFSEEAKSIC
430 440 450 460 470 480
KMLLTKDAKQ RLGCQEEGAA EVKRHPFFRN MNFKRLEAGM LDPPFVPDPR AVYCKDVLDI
490 500 510 520 530 540
EQFSTVKGVN LDHTDDDFYS KFSTGSVPIP WQSEMIETEC FKELNVFGPH GTLSPDLNRS
550 560 570 580
HPPEPPKKGL LQRLFKRQHQ NNSKSSPNSK TSFNHHINSN HVSSNSTGSS