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Protein

G protein-coupled receptor kinase 2

Gene

grk-2

Organism
Caenorhabditis elegans
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Specifically phosphorylates the activated forms of G protein-coupled receptors (By similarity). Required in adult sensory neurons for chemotaxis (PubMed:15157420). Plays a role in the ASH sensory neurons in the chemotaxis response to NaCl where it is likely to modulate the strength of the NaCl avoidance response which occurs at high NaCl concentrations (PubMed:16407969). Required in the HSN motor neurons for normal egg laying by promoting phosphorylation of amine oxidase amx-2 which inhibits amx-2 activity, preventing metabolism of serotonin (PubMed:28213524). Acts in head acetylcholine neurons to positively regulate locomotion (PubMed:28968387). Inactivates dopamine receptor dop-3 which leads to inactivation of guanine nucleotide-binding protein G(o) subunit goa-1 and activation of the unc-77/nca-1 and nca-2 ion channel proteins (PubMed:28968387).By similarity4 Publications

Catalytic activityi

ATP + [G-protein-coupled receptor] = ADP + [G-protein-coupled receptor] phosphate.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei3Required for receptor phosphorylationBy similarity1
Sitei4Required for receptor phosphorylationBy similarity1
Sitei10Required for receptor phosphorylationBy similarity1
Binding sitei220ATPPROSITE-ProRule annotation1
Active sitei318Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi197 – 205ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • chemotaxis Source: WormBase
  • hyperosmotic response Source: WormBase
  • multicellular organismal process Source: WormBase
  • negative regulation of dopamine receptor signaling pathway Source: UniProtKB
  • olfactory behavior Source: WormBase
  • positive regulation of cation channel activity Source: UniProtKB
  • positive regulation of chemotaxis Source: UniProtKB
  • positive regulation of growth rate Source: WormBase
  • positive regulation of locomotion Source: UniProtKB
  • positive regulation of oviposition Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • response to salt Source: UniProtKB
  • serotonin catabolic process Source: UniProtKB
  • signal transduction Source: InterPro

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processChemotaxis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-CEL-111933 Calmodulin induced events
R-CEL-416476 G alpha (q) signalling events
SignaLinkiQ09639

Names & Taxonomyi

Protein namesi
Recommended name:
G protein-coupled receptor kinase 2 (EC:2.7.11.16)
Gene namesi
Name:grk-2
ORF Names:W02B3.2
OrganismiCaenorhabditis elegans
Taxonomic identifieri6239 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaNematodaChromadoreaRhabditidaRhabditoideaRhabditidaePeloderinaeCaenorhabditis
Proteomesi
  • UP000001940 Componenti: Chromosome III

Organism-specific databases

WormBaseiW02B3.2 ; CE32946 ; WBGene00001709 ; grk-2

Pathology & Biotechi

Disruption phenotypei

Defective egg-laying with mutants retaining 35 eggs compared to 13-14 eggs in wild-type worms (PubMed:28213524, PubMed:28968387). Reduced serotonin levels, increased levels of the serotonin metabolite 5-hydroxyindoleacetic acid, increased levels of amine oxidase amx-2 in early adult stages and reduced levels of phosphorylated amx-2 (PubMed:28213524). Defective locomotion and reduced body length (PubMed:28968387).2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi3D → K: Failure to restore locomotion or avoidance to the aversive compounds octanol and quinine in animals lacking endogenous grk-2. 2 Publications1
Mutagenesisi4L → K: Failure to restore locomotion or avoidance to the aversive compounds octanol and quinine in animals lacking endogenous grk-2. 2 Publications1
Mutagenesisi7 – 8VL → AA: Failure to restore locomotion or avoidance to the aversive compounds octanol and quinine in animals lacking endogenous grk-2. 2 Publications2
Mutagenesisi10D → A: Failure to restore locomotion or avoidance to the aversive compounds octanol and quinine in animals lacking endogenous grk-2. 2 Publications1
Mutagenesisi106R → A: No effect on ability to restore locomotion or avoidance to the aversive compounds octanol and quinine in animals lacking endogenous grk-2. 2 Publications1
Mutagenesisi109Y → I: No effect on ability to restore locomotion or avoidance to the aversive compounds octanol and quinine in animals lacking endogenous grk-2. 2 Publications1
Mutagenesisi110D → A: No effect on ability to restore locomotion or avoidance to the aversive compounds octanol and quinine in animals lacking endogenous grk-2. 2 Publications1
Mutagenesisi195R → A: Failure to restore locomotion or avoidance to the aversive compounds octanol and quinine in animals lacking endogenous grk-2. 2 Publications1
Mutagenesisi220K → R: Failure to restore avoidance to the aversive compounds octanol and quinine in animals lacking endogenous grk-2. Failure to rescue defective egg laying in grk-2 mutants. 2 Publications1
Mutagenesisi354T → I in rt97; dramatic decrease in grk-2 protein levels, defective egg laying, reduced serotonin levels, increased levels of the serotonin metabolite 5-hydroxyindoleacetic acid, increased levels of amine oxidase amx-2 in early adult stages, reduced levels of phosphorylated amx-2, severe defect in octanol avoidance and severely impaired chemotaxis to attractive compounds including 0.1-100 mM NaCl although mutants show avoidance to 25 mM NaCl after pre-exposure to 100 mM NaCl. 3 Publications1
Mutagenesisi379G → E in yak18; decreased body length, slow locomotion and defective egg laying. 1 Publication1
Mutagenesisi567K → E: Failure to restore locomotion in animals lacking endogenous grk-2. Significantly restored avoidance of aversive compounds octanol and quinine in animals lacking endogenous grk-2. Failure to restore avoidance to octanol and quinine in animals lacking endogenous grk-2; when associated with Q-587. 2 Publications1
Mutagenesisi587R → Q: Failure to restore locomotion in animals lacking endogenous grk-2. Reduced ability to restore avoidance to the aversive compounds octanol and quinine in animals lacking endogenous grk-2. Failure to restore avoidance to octanol and quinine in animals lacking endogenous grk-2; when associated with E-567. 2 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000868411 – 707G protein-coupled receptor kinase 2Add BLAST707

Proteomic databases

EPDiQ09639
PaxDbiQ09639
PeptideAtlasiQ09639
PRIDEiQ09639

Expressioni

Tissue specificityi

Expressed in many neurons in the adult including the ASH neurons and other sensory neurons, many interneurons, and motor neurons of the ventral nerve cord (PubMed:15157420). Expressed broadly in head neurons and is detected in several head actetylcholine neurons including the AVA, AVB, AVD and AVE premotor interneurons, the SMD and RMD head motor neurons, and the AIN, AIY, SIA, SIB and SAA interneurons (PubMed:28968387). Expressed in HSN motor neurons and VC4/VC5 motor neurons (PubMed:28213524). Also expressed in vulval muscle cells (PubMed:15157420, PubMed:28213524).3 Publications

Developmental stagei

Expression is observed in embryos as early as the 20-30 cell stage and persists throughout development and into adulthood.1 Publication

Gene expression databases

BgeeiWBGene00001709

Interactioni

Subunit structurei

Interacts with amx-2; the interaction promotes phosphorylation of amx-2.1 Publication

Protein-protein interaction databases

IntActiQ09639, 2 interactors
MINTiQ09639
STRINGi6239.W02B3.2

Structurei

3D structure databases

ProteinModelPortaliQ09639
SMRiQ09639
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini54 – 175RGSPROSITE-ProRule annotationAdd BLAST122
Domaini191 – 455Protein kinasePROSITE-ProRule annotationAdd BLAST265
Domaini456 – 523AGC-kinase C-terminalAdd BLAST68
Domaini558 – 658PHPROSITE-ProRule annotationAdd BLAST101

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 190N-terminalAdd BLAST190

Domaini

The kinase domain is required for chemotaxis activity.1 Publication

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0986 Eukaryota
ENOG410YRQZ LUCA
GeneTreeiENSGT00860000133699
HOGENOMiHOG000006742
InParanoidiQ09639
KOiK00910
OMAiPLCHRNS
OrthoDBiEOG091G0AEI
PhylomeDBiQ09639

Family and domain databases

Gene3Di2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR000961 AGC-kinase_C
IPR000239 GPCR_kinase
IPR011009 Kinase-like_dom_sf
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR016137 RGS
IPR036305 RGS_sf
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PF00615 RGS, 1 hit
PRINTSiPR00717 GPCRKINASE
SMARTiView protein in SMART
SM00233 PH, 1 hit
SM00315 RGS, 1 hit
SM00133 S_TK_X, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF48097 SSF48097, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51285 AGC_KINASE_CTER, 1 hit
PS50003 PH_DOMAIN, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
PS50132 RGS, 1 hit

Sequencei

Sequence statusi: Complete.

Q09639-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MADLEAVLAD VSYLMAMEKS RSQPAARASK RIVLPDPSVR SIMQKFLEKS
60 70 80 90 100
GDMKFDKIFN QKLGFLLLKD YAENVSESPC PQIKFYEAIK EYEKMETPDE
110 120 130 140 150
RLTKAREIYD HHIMVEMLAH AHNYSKESLQ HVQYHLLKQN VPPDLFHRYV
160 170 180 190 200
LEICDQLRGD IFQRFLESDK FTRFCQWKNL ELNMQLTMND FSVHRIIGRG
210 220 230 240 250
GFGEVYGCRK ADTGKMYAMK CLDKKRIKMK QGETLALNER IMLSLVSTGQ
260 270 280 290 300
DCPFIVCMTY AFQSPDKLCF ILDLMNGGDL HYHLSQHGVF TEQEMIFYAS
310 320 330 340 350
EVILGLEHMH NRFVVYRDLK PANILLDENG HVRVSDLGLA CDYSKKKPHA
360 370 380 390 400
SVGTHGYMAP EVLAKGVAYD SSADWFSLGC MLYKLLKGHS PFRQHKSKDK
410 420 430 440 450
NEIDKMTLTQ DIELPNEGLS KDCRDLLEGL LKRDVPDRLG CRGKGPTEVK
460 470 480 490 500
EHPFFKDVDW QTVYLRRMTP PLIPPRGEVN AADAFDIGNF DDDEVKGVKL
510 520 530 540 550
QDGDSDLYKN FNIVISERWQ NEIAETIFEV VNQDADKAES KKRSKQKIKV
560 570 580 590 600
AVEEKDSDVI VHGYIKKLGG PFTSAWQTKY GKLYPSRLEL YPESLTAKPE
610 620 630 640 650
LVFMDQIEDV CAEMQTIKGE TAIIVKLRDG FKEPKICLTN SDEISLKEWH
660 670 680 690 700
TSLRTAHKVS QELLQRMGRK AIKIYGVNHD PMLSESERPG SVTRAFLNRA

SSVDSGV
Length:707
Mass (Da):80,978
Last modified:April 23, 2003 - v2
Checksum:iD37F03260F324939
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
FO080476 Genomic DNA Translation: CCD63981.1
PIRiT26096
RefSeqiNP_497235.2, NM_064834.4
UniGeneiCel.9949

Genome annotation databases

EnsemblMetazoaiW02B3.2; W02B3.2; WBGene00001709
GeneIDi175223
KEGGicel:CELE_W02B3.2
UCSCiW02B3.2 c. elegans

Similar proteinsi

Entry informationi

Entry nameiGRK2_CAEEL
AccessioniPrimary (citable) accession number: Q09639
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: April 23, 2003
Last modified: May 23, 2018
This is version 145 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programCaenorhabditis annotation project

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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