P21146

PR
Gene name
GRK2
Protein name
Beta-adrenergic receptor kinase 1
Names
Beta-ARK-1, G-protein-coupled receptor kinase 2
Species
Bos taurus (Bovine)
KEGG Pathway
bta:282682
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)

1-63 (Predicted disordered autoinhibitory region) PR

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

References

Autoinhibited structure

Activated structure

16 structures for P21146

Entry ID Method Resolution Chain Position Source
1OMW X-ray 250 A A 1-689 PDB
1YM7 X-ray 450 A A/B/C/D 1-689 PDB
2BCJ X-ray 306 A A 1-689 PDB
3PSC X-ray 267 A A 1-689 PDB
3PVU X-ray 248 A A 1-689 PDB
3PVW X-ray 249 A A 1-689 PDB
3UZS X-ray 452 A A 1-681 PDB
3UZT X-ray 351 A A 1-689 PDB
5HE0 X-ray 256 A A 30-670 PDB
5HE2 X-ray 279 A A 30-670 PDB
5HE3 X-ray 274 A A 30-670 PDB
5UKM X-ray 303 A A 1-689 PDB
8JPB EM 307 A G 2-689 PDB
8JPC EM 307 A G 2-689 PDB
8JPD EM 281 A G 2-689 PDB
AF-P21146-F1 Predicted AlphaFoldDB

180 variants for P21146

Variant ID(s) Position Change Description Diseaes Association Provenance
rs137641318 33 L>M No EVA
rs475910647 40 R>G No EVA
rs461369859 42 V>A No EVA
rs444400836 42 V>I No EVA
rs442731876 49 D>V No EVA
rs459611908 53 V>A No EVA
rs479652263 54 T>A No EVA
rs465024416 55 F>Y No EVA
rs481726315 58 I>S No EVA
rs450368252 59 F>C No EVA
rs450368252 59 F>Y No EVA
rs478130710 78 E>A No EVA
rs449162634 89 I>S No EVA
rs459765920 90 K>E No EVA
rs479899731 96 E>A No EVA
rs447527496 96 E>D No EVA
rs479899731 96 E>G No EVA
rs464506517 99 E>* No EVA
rs449914433 105 S>G No EVA
rs469847055 106 R>P No EVA
rs435290110 110 D>A No EVA
rs469959387 134 G>C No EVA
rs465864711 141 V>A No EVA
rs465864711 141 V>G No EVA
rs448965885 141 V>L No EVA
rs434332338 146 F>I No EVA
rs448990885 161 V>G No EVA
rs437904896 186 L>V No EVA
rs448318428 190 D>A No EVA
rs468372300 192 S>G No EVA
rs453818918 199 R>* No EVA
rs432700845 205 V>A No EVA
rs432700845 205 V>G No EVA
rs456153064 206 Y>S No EVA
rs476905443 214 G>C No EVA
rs442292457 215 K>T No EVA
rs435034304 241 I>M No EVA
rs451916619 245 L>F No EVA
rs437422558 246 V>D No EVA
rs457397896 247 S>C No EVA
rs457397896 247 S>G No EVA
rs474313876 248 T>P No EVA
rs459703844 249 G>R No EVA
rs436470335 279 L>M No EVA
rs453458402 282 H>R No EVA
rs473391477 288 V>D No EVA
rs457983578 293 D>A No EVA
rs471694582 297 Y>F No EVA
rs443379162 300 E>A No EVA
rs463504103 301 I>L No EVA
rs480474288 302 I>S No EVA
rs459322013 305 L>R No EVA
rs479171078 310 N>D No EVA
rs444804495 313 V>L No EVA
rs465472832 316 R>W No EVA
rs437504113 317 D>A No EVA
rs475640773 321 A>P No EVA
rs437667931 328 H>D No EVA
rs437667931 328 H>N No EVA
rs474590390 328 H>Q No EVA
rs454587136 328 H>R No EVA
rs443407549 343 S>P No EVA
rs440040309 345 K>R No EVA
rs466678806 386 R>Q No EVA
rs449450941 396 T>A No EVA
rs466305122 402 I>N No EVA
rs466305122 402 I>T No EVA
rs434921814 409 M>K No EVA
rs475438439 412 E>G No EVA
rs461684610 415 D>A No EVA
rs461684610 415 D>G No EVA
rs481565903 418 S>C No EVA
rs481565903 418 S>F No EVA
rs876384852 418 S>P No EVA
rs460564483 420 E>A No EVA
rs477521328 420 E>D No EVA
rs446128748 421 L>I No EVA
rs469397504 422 R>P No EVA
rs438026437 423 S>A No EVA
rs467507217 426 E>Q No EVA
rs436125021 428 L>M No EVA
rs453005745 431 R>K No EVA
rs453005745 431 R>M No EVA
rs432037258 433 V>L No EVA
rs452163655 434 N>T No EVA
rs475437682 436 R>G No EVA
rs475312309 437 L>Q No EVA
rs455196561 437 L>V No EVA
rs455663194 450 S>I No EVA
rs460054500 466 Y>F No EVA
rs460054500 466 Y>S No EVA
rs445442072 476 E>G No EVA
rs465558307 477 V>G No EVA
rs437273612 478 N>K No EVA
rs451065895 480 A>P No EVA
rs436388005 481 D>A No EVA
rs455506764 483 F>L No EVA
rs472559004 484 D>E No EVA
rs434548021 485 I>L No EVA
rs451456740 486 G>V No EVA
rs443272633 489 D>Y No EVA
rs473553956 490 E>* No EVA
rs442397797 490 E>G No EVA
rs473553956 490 E>Q No EVA
rs480132976 492 D>V No EVA
rs459962266 492 D>Y No EVA
rs482456663 496 I>L No EVA
rs440446975 501 S>I No EVA
rs481711281 501 S>R No EVA
rs460601414 505 L>P No EVA
rs455625484 513 I>F No EVA
rs477409040 517 W>G No EVA
rs446020094 521 V>A No EVA
rs469242176 524 T>A No EVA
rs481901942 525 V>I No EVA
rs450740129 528 T>S No EVA
rs467398817 534 D>H No EVA
rs436187973 535 R>L No EVA
rs452937100 537 E>G No EVA
rs452102125 547 L>F No EVA
rs431922252 547 L>V No EVA
rs475430723 550 E>Q No EVA
rs445724776 553 Y>F No EVA
rs437564733 555 L>M No EVA
rs468229441 561 M>I No EVA
rs454458704 562 H>P No EVA
rs434267832 562 H>Y No EVA
rs464677405 564 Y>F No EVA
rs433359151 568 M>K No EVA
rs456439405 570 N>H No EVA
rs476533802 570 N>T No EVA
rs442101132 574 T>P No EVA
rs455635646 574 T>S No EVA
rs472671479 582 Y>S No EVA
rs440288722 585 P>T No EVA
rs460466329 587 R>P No EVA
rs439452065 593 E>G No EVA
rs135667933 595 E>G No EVA
rs448209777 597 P>A No EVA
rs1118121007 602 T>I No EVA
rs453915636 606 I>N No EVA
rs439567360 607 Q>P No EVA
rs462739886 619 C>W No EVA
rs463216647 636 S>G No EVA
rs480938005 636 S>N No EVA
rs449544052 636 S>R No EVA
rs445316120 637 D>E No EVA
rs480074390 637 D>G No EVA
rs459948191 637 D>Y No EVA
rs465481296 638 P>T No EVA
rs450898490 639 E>Q No EVA
rs435464045 640 L>P No EVA
rs467776165 640 L>V No EVA
rs465929754 641 V>A No EVA
rs465929754 641 V>G No EVA
rs434553360 642 Q>E No EVA
rs471291120 642 Q>H No EVA
rs451272822 642 Q>P No EVA
rs451272822 642 Q>R No EVA
rs456913624 643 W>C No EVA
rs443321391 643 W>G No EVA
rs443321391 643 W>R No EVA
rs473850736 644 K>E No EVA
rs443066527 644 K>T No EVA
rs460007293 645 K>E No EVA
rs480017001 646 E>V No EVA
rs439045087 647 L>R No EVA
rs482299077 648 R>L No EVA
rs481478504 649 D>G No EVA
rs467787464 649 D>N No EVA
rs466038743 658 V>G No EVA
rs434676569 661 V>E No EVA
rs434676569 661 V>G No EVA
rs451384893 663 K>Q No EVA
rs465041357 669 R>P No EVA
rs436858715 672 V>L No EVA
rs456980734 673 V>G No EVA
rs473788321 678 V>G No EVA
rs453559274 684 G>C No EVA
rs473669511 690 L>C No EVA

No associated diseases with P21146

6 regional properties for P21146

Type Name Position InterPro Accession
domain Protein kinase domain 191 - 453 IPR000719
domain AGC-kinase, C-terminal 454 - 533 IPR000961
domain Pleckstrin homology domain 558 - 654 IPR001849
active_site Serine/threonine-protein kinase, active site 313 - 325 IPR008271
domain RGS domain 54 - 175 IPR016137
binding_site Protein kinase, ATP binding site 197 - 220 IPR017441

Functions

Description
EC Number 2.7.11.15 Protein-serine/threonine kinases
Subcellular Localization
  • Cytoplasm
  • Cell membrane
  • Postsynapse
  • Presynapse
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

8 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.
cell projection A prolongation or process extending from a cell, e.g. a flagellum or axon.
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.
membrane A lipid bilayer along with all the proteins and protein complexes embedded in it an attached to it.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
postsynapse The part of a synapse that is part of the post-synaptic cell.
presynapse The part of a synapse that is part of the presynaptic cell.

7 GO annotations of molecular function

Name Definition
alpha-2A adrenergic receptor binding Binding to an alpha-2A adrenergic receptor.
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.
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.
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.

20 GO annotations of biological process

Name Definition
cardiac muscle contraction Muscle contraction of cardiac muscle tissue.
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.
G protein-coupled acetylcholine receptor signaling pathway A G protein-coupled receptor signaling pathway initiated by a ligand binding to an acetylcholine receptor on the surface of a target cell, and ends with regulation of a downstream cellular process, e.g. transcription.
G protein-coupled receptor internalization The process that results in the uptake of a G protein-coupled receptor into an endocytic vesicle.
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.
intracellular protein transport The directed movement of proteins in a cell, including the movement of proteins between specific compartments or structures within a cell, such as organelles of a eukaryotic cell.
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.
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 protein localization to cilium Any process that activates or increases the frequency, rate or extent of protein localization to cilium.
positive regulation of smoothened signaling pathway Any process that activates or increases the frequency, rate or extent of smoothened signaling.
protein phosphorylation The process of introducing a phosphate group on to a protein.
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.
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).
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.

19 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
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
O70293 Grk6 G protein-coupled receptor kinase 6 Mus musculus (Mouse) SS
Q8VEB1 Grk5 G protein-coupled receptor kinase 5 Mus musculus (Mouse) SS
Q9WVL4 Grk1 Rhodopsin kinase GRK1 Mus musculus (Mouse) PR
Q3UYH7 Adrbk2 Beta-adrenergic receptor kinase 2 Mus musculus (Mouse) PR
Q99MK8 Grk2 Beta-adrenergic receptor kinase 1 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
O48963 PHOT1 Phototropin-1 Arabidopsis thaliana (Mouse-ear cress) PR
10 20 30 40 50 60
MADLEAVLAD VSYLMAMEKS KATPAARASK KILLPEPSIR SVMQKYLEDR GEVTFEKIFS
70 80 90 100 110 120
QKLGYLLFRD FCLKHLEEAK PLVEFYEEIK KYEKLETEEE RLVCSREIFD TYIMKELLAC
130 140 150 160 170 180
SHPFSKSAIE 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 DFSKKKPHAS 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
KTKNKQLGHE EDYALGKDCI MHGYMSKMGN PFLTQWQRRY FYLFPNRLEW RGEGEAPQSL
610 620 630 640 650 660
LTMEEIQSVE ETQIKERKCL LLKIRGGKQF VLQCDSDPEL VQWKKELRDA YREAQQLVQR
670 680
VPKMKNKPRS PVVELSKVPL IQRGSANGL