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Protein

G protein-coupled receptor kinase 6

Gene

GRK6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Specifically phosphorylates the activated forms of G protein-coupled receptors. Such receptor phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events leading to their desensitization. Seems to be involved in the desensitization of D2-like dopamine receptors in striatum and chemokine receptor CXCR4 which is critical for CXCL12-induced cell chemotaxis (By similarity). Phosphorylates rhodopsin (RHO) (in vitro) and a non G-protein-coupled receptor: LRP6 during Wnt signaling (in vitro).By similarity2 Publications

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei215ATP1
Active sitei311Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi192 – 200ATP9
Nucleotide bindingi264 – 270ATP7
Nucleotide bindingi315 – 318ATP4

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processWnt signaling pathway
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.16 2681
ReactomeiR-HSA-418555 G alpha (s) signalling events
SignaLinkiP43250
SIGNORiP43250

Names & Taxonomyi

Protein namesi
Recommended name:
G protein-coupled receptor kinase 6 (EC:2.7.11.16)
Alternative name(s):
G protein-coupled receptor kinase GRK6
Gene namesi
Name:GRK6
Synonyms:GPRK6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000198055.10
HGNCiHGNC:4545 GRK6
MIMi600869 gene
neXtProtiNX_P43250

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi6I → A: 12-13 fold defects in kinase activity; 180-fold defects in kinase activity; when associated with A-7. 1 Publication1
Mutagenesisi7V → A: 12-13 fold defects in kinase activity; 180-fold defects in kinase activity; when associated with A-6. 1 Publication1
Mutagenesisi9N → A: 140-fold defects in kinase activity. 1 Publication1
Mutagenesisi12L → A: 1100-fold defects in kinase activity. 1 Publication1
Mutagenesisi561C → S: Abolishes palmitoylation; when associated with S-562 and S-565. 1 Publication1
Mutagenesisi562C → S: Abolishes palmitoylation; when associated with S-561 and S-565. 1 Publication1
Mutagenesisi565C → S: Abolishes palmitoylation; when associated with S-561 and S-562. 1 Publication1

Organism-specific databases

DisGeNETi2870
OpenTargetsiENSG00000198055
PharmGKBiPA28942

Chemistry databases

ChEMBLiCHEMBL6144
GuidetoPHARMACOLOGYi1470

Polymorphism and mutation databases

BioMutaiGRK6
DMDMi20141386

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000859741 – 576G protein-coupled receptor kinase 6Add BLAST576

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei484PhosphoserineCombined sources1
Modified residuei485PhosphothreonineCombined sources1
Lipidationi561S-palmitoyl cysteine1 Publication1
Lipidationi562S-palmitoyl cysteine1 Publication1
Lipidationi565S-palmitoyl cysteine1 Publication1
Modified residuei566PhosphoserineBy similarity1
Modified residuei568PhosphoserineBy similarity1

Post-translational modificationi

It is uncertain whether palmitoylation is on Cys-561 and/or Cys-562 and/or Cys-565.1 Publication

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

MaxQBiP43250
PaxDbiP43250
PeptideAtlasiP43250
PRIDEiP43250
ProteomicsDBi55602
55603 [P43250-2]
55604 [P43250-3]

PTM databases

CarbonylDBiP43250
iPTMnetiP43250
PhosphoSitePlusiP43250
SwissPalmiP43250

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiENSG00000198055 Expressed in 228 organ(s), highest expression level in blood
CleanExiHS_GRK6
ExpressionAtlasiP43250 baseline and differential
GenevisibleiP43250 HS

Organism-specific databases

HPAiHPA015327
HPA018903

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
ROM1P522059EBI-722747,EBI-8176947From Bos taurus.

Protein-protein interaction databases

BioGridi109128, 30 interactors
IntActiP43250, 8 interactors
MINTiP43250
STRINGi9606.ENSP00000433511

Chemistry databases

BindingDBiP43250

Structurei

Secondary structure

1576
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP43250
SMRiP43250
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP43250

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini53 – 171RGSPROSITE-ProRule annotationAdd BLAST119
Domaini186 – 448Protein kinasePROSITE-ProRule annotationAdd BLAST263
Domaini449 – 514AGC-kinase C-terminalAdd BLAST66

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 185N-terminalAdd BLAST185

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0986 Eukaryota
ENOG410YRQZ LUCA
GeneTreeiENSGT00860000133699
HOGENOMiHOG000006742
HOVERGENiHBG004532
InParanoidiP43250
KOiK08291
OMAiNFKRLGA
OrthoDBiEOG091G062G
PhylomeDBiP43250
TreeFamiTF313940

Family and domain databases

InterProiView protein in InterPro
IPR000961 AGC-kinase_C
IPR000239 GPCR_kinase
IPR011009 Kinase-like_dom_sf
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
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
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
PS50132 RGS, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 7 potential isoforms that are computationally mapped.Show allAlign All

Isoform GRK6A (identifier: P43250-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MELENIVANT VLLKAREGGG GNRKGKSKKW RQMLQFPHIS QCEELRLSLE
60 70 80 90 100
RDYHSLCERQ PIGRLLFREF CATRPELSRC VAFLDGVAEY EVTPDDKRKA
110 120 130 140 150
CGRQLTQNFL SHTGPDLIPE VPRQLVTNCT QRLEQGPCKD LFQELTRLTH
160 170 180 190 200
EYLSVAPFAD YLDSIYFNRF LQWKWLERQP VTKNTFRQYR VLGKGGFGEV
210 220 230 240 250
CACQVRATGK MYACKKLEKK RIKKRKGEAM ALNEKQILEK VNSRFVVSLA
260 270 280 290 300
YAYETKDALC LVLTLMNGGD LKFHIYHMGQ AGFPEARAVF YAAEICCGLE
310 320 330 340 350
DLHRERIVYR DLKPENILLD DHGHIRISDL GLAVHVPEGQ TIKGRVGTVG
360 370 380 390 400
YMAPEVVKNE RYTFSPDWWA LGCLLYEMIA GQSPFQQRKK KIKREEVERL
410 420 430 440 450
VKEVPEEYSE RFSPQARSLC SQLLCKDPAE RLGCRGGSAR EVKEHPLFKK
460 470 480 490 500
LNFKRLGAGM LEPPFKPDPQ AIYCKDVLDI EQFSTVKGVE LEPTDQDFYQ
510 520 530 540 550
KFATGSVPIP WQNEMVETEC FQELNVFGLD GSVPPDLDWK GQPPAPPKKG
560 570
LLQRLFSRQD CCGNCSDSEE ELPTRL
Length:576
Mass (Da):65,991
Last modified:January 23, 2002 - v2
Checksum:i3BF8C3B1CDE2BD74
GO
Isoform GRK6B (identifier: P43250-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     560-576: DCCGNCSDSEEELPTRL → RIAVETAATARKSSPPASSPQPEAPTSSWR

Show »
Length:589
Mass (Da):67,257
Checksum:iBD7C24E9624DDFEC
GO
Isoform GRK6C (identifier: P43250-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     560-560: D → R
     561-576: Missing.

Show »
Length:560
Mass (Da):64,294
Checksum:i2686CECDFC7B3516
GO

Computationally mapped potential isoform sequencesi

There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6RHX8D6RHX8_HUMAN
G protein-coupled receptor kinase
GRK6
475Annotation score:
F8W9W2F8W9W2_HUMAN
G protein-coupled receptor kinase
GRK6
542Annotation score:
D6RHC7D6RHC7_HUMAN
G protein-coupled receptor kinase
GRK6
253Annotation score:
D6RDA3D6RDA3_HUMAN
G protein-coupled receptor kinase 6
GRK6
129Annotation score:
D6R9V4D6R9V4_HUMAN
G protein-coupled receptor kinase 6
GRK6
63Annotation score:
H0Y967H0Y967_HUMAN
G protein-coupled receptor kinase 6
GRK6
88Annotation score:
D6RC88D6RC88_HUMAN
G protein-coupled receptor kinase 6
GRK6
17Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti60 – 61QP → HA in AAA60175 (PubMed:8366096).Curated2
Sequence conflicti104 – 105QL → HV in AAA60175 (PubMed:8366096).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04052431R → Q in a gastric adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs141014084Ensembl.1
Natural variantiVAR_04052573T → M1 PublicationCorresponds to variant dbSNP:rs56382815Ensembl.1
Natural variantiVAR_040526275I → M in a breast infiltrating ductal carcinoma sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_004938560 – 576DCCGN…LPTRL → RIAVETAATARKSSPPASSP QPEAPTSSWR in isoform GRK6B. 1 PublicationAdd BLAST17
Alternative sequenceiVSP_041813560D → R in isoform GRK6C. 1 Publication1
Alternative sequenceiVSP_041814561 – 576Missing in isoform GRK6C. 1 PublicationAdd BLAST16

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L16862 mRNA Translation: AAA60175.1
AF040751 mRNA Translation: AAC09273.1
AF040752 mRNA Translation: AAC09274.1
AC145098 Genomic DNA No translation available.
BC009277 mRNA Translation: AAH09277.1
U00686 mRNA Translation: AAA03565.1
CCDSiCCDS34303.1 [P43250-1]
CCDS43406.1 [P43250-3]
PIRiA48765
RefSeqiNP_001004105.1, NM_001004105.2 [P43250-3]
NP_001004106.1, NM_001004106.2 [P43250-1]
NP_002073.2, NM_002082.3 [P43250-2]
UniGeneiHs.235116

Genome annotation databases

EnsembliENST00000355472; ENSP00000347655; ENSG00000198055 [P43250-1]
ENST00000355958; ENSP00000348230; ENSG00000198055 [P43250-3]
ENST00000528793; ENSP00000433511; ENSG00000198055 [P43250-2]
GeneIDi2870
KEGGihsa:2870
UCSCiuc003mgq.3 human [P43250-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L16862 mRNA Translation: AAA60175.1
AF040751 mRNA Translation: AAC09273.1
AF040752 mRNA Translation: AAC09274.1
AC145098 Genomic DNA No translation available.
BC009277 mRNA Translation: AAH09277.1
U00686 mRNA Translation: AAA03565.1
CCDSiCCDS34303.1 [P43250-1]
CCDS43406.1 [P43250-3]
PIRiA48765
RefSeqiNP_001004105.1, NM_001004105.2 [P43250-3]
NP_001004106.1, NM_001004106.2 [P43250-1]
NP_002073.2, NM_002082.3 [P43250-2]
UniGeneiHs.235116

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2ACXX-ray2.60A/B1-576[»]
3NYNX-ray2.72A/B2-576[»]
3NYOX-ray2.92A/B2-576[»]
ProteinModelPortaliP43250
SMRiP43250
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109128, 30 interactors
IntActiP43250, 8 interactors
MINTiP43250
STRINGi9606.ENSP00000433511

Chemistry databases

BindingDBiP43250
ChEMBLiCHEMBL6144
GuidetoPHARMACOLOGYi1470

PTM databases

CarbonylDBiP43250
iPTMnetiP43250
PhosphoSitePlusiP43250
SwissPalmiP43250

Polymorphism and mutation databases

BioMutaiGRK6
DMDMi20141386

Proteomic databases

MaxQBiP43250
PaxDbiP43250
PeptideAtlasiP43250
PRIDEiP43250
ProteomicsDBi55602
55603 [P43250-2]
55604 [P43250-3]

Protocols and materials databases

DNASUi2870
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000355472; ENSP00000347655; ENSG00000198055 [P43250-1]
ENST00000355958; ENSP00000348230; ENSG00000198055 [P43250-3]
ENST00000528793; ENSP00000433511; ENSG00000198055 [P43250-2]
GeneIDi2870
KEGGihsa:2870
UCSCiuc003mgq.3 human [P43250-1]

Organism-specific databases

CTDi2870
DisGeNETi2870
EuPathDBiHostDB:ENSG00000198055.10
GeneCardsiGRK6
HGNCiHGNC:4545 GRK6
HPAiHPA015327
HPA018903
MIMi600869 gene
neXtProtiNX_P43250
OpenTargetsiENSG00000198055
PharmGKBiPA28942
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0986 Eukaryota
ENOG410YRQZ LUCA
GeneTreeiENSGT00860000133699
HOGENOMiHOG000006742
HOVERGENiHBG004532
InParanoidiP43250
KOiK08291
OMAiNFKRLGA
OrthoDBiEOG091G062G
PhylomeDBiP43250
TreeFamiTF313940

Enzyme and pathway databases

BRENDAi2.7.11.16 2681
ReactomeiR-HSA-418555 G alpha (s) signalling events
SignaLinkiP43250
SIGNORiP43250

Miscellaneous databases

ChiTaRSiGRK6 human
EvolutionaryTraceiP43250
GeneWikiiGRK6
GenomeRNAii2870
PROiPR:P43250
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000198055 Expressed in 228 organ(s), highest expression level in blood
CleanExiHS_GRK6
ExpressionAtlasiP43250 baseline and differential
GenevisibleiP43250 HS

Family and domain databases

InterProiView protein in InterPro
IPR000961 AGC-kinase_C
IPR000239 GPCR_kinase
IPR011009 Kinase-like_dom_sf
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
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
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
PS50132 RGS, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiGRK6_HUMAN
AccessioniPrimary (citable) accession number: P43250
Secondary accession number(s): O60541, Q13652
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: January 23, 2002
Last modified: September 12, 2018
This is version 185 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  4. SIMILARITY comments
    Index of protein domains and families
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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