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Protein

G protein-coupled receptor kinase 6

Gene

GRK6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  • regulation of G-protein coupled receptor protein signaling pathway Source: ProtInc
  • Wnt signaling pathway Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Wnt signaling pathway

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS00600-MONOMER.
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

HGNCiHGNC:4545. GRK6.

Subcellular locationi

GO - Cellular componenti

  • membrane Source: UniProtKB
  • plasma membrane Source: Reactome
Complete GO annotation...

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

EPDiP43250.
MaxQBiP43250.
PaxDbiP43250.
PeptideAtlasiP43250.
PRIDEiP43250.

PTM databases

iPTMnetiP43250.
PhosphoSitePlusiP43250.
SwissPalmiP43250.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiENSG00000198055.
CleanExiHS_GRK6.
ExpressionAtlasiP43250. baseline and differential.
GenevisibleiP43250. HS.

Organism-specific databases

HPAiHPA015327.
HPA018903.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
ROM1P522059EBI-722747,EBI-8176947From a different organism.

Protein-protein interaction databases

BioGridi109128. 29 interactors.
IntActiP43250. 8 interactors.
MINTiMINT-1425525.
STRINGi9606.ENSP00000433511.

Chemistry databases

BindingDBiP43250.

Structurei

Secondary structure

1576
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi3 – 18Combined sources16
Beta strandi23 – 25Combined sources3
Helixi30 – 33Combined sources4
Helixi40 – 42Combined sources3
Helixi43 – 48Combined sources6
Helixi53 – 57Combined sources5
Helixi61 – 71Combined sources11
Helixi75 – 91Combined sources17
Turni95 – 97Combined sources3
Helixi98 – 109Combined sources12
Beta strandi112 – 114Combined sources3
Beta strandi117 – 120Combined sources4
Helixi123 – 135Combined sources13
Turni139 – 142Combined sources4
Helixi143 – 153Combined sources11
Helixi156 – 162Combined sources7
Helixi165 – 177Combined sources13
Helixi183 – 185Combined sources3
Beta strandi186 – 195Combined sources10
Beta strandi198 – 205Combined sources8
Turni206 – 208Combined sources3
Beta strandi211 – 218Combined sources8
Helixi219 – 224Combined sources6
Helixi228 – 240Combined sources13
Beta strandi249 – 254Combined sources6
Beta strandi256 – 263Combined sources8
Helixi271 – 276Combined sources6
Beta strandi277 – 280Combined sources4
Helixi285 – 304Combined sources20
Helixi314 – 316Combined sources3
Beta strandi317 – 319Combined sources3
Beta strandi325 – 327Combined sources3
Helixi349 – 351Combined sources3
Helixi354 – 357Combined sources4
Beta strandi361 – 364Combined sources4
Helixi365 – 380Combined sources16
Beta strandi384 – 386Combined sources3
Beta strandi388 – 390Combined sources3
Helixi394 – 403Combined sources10
Beta strandi410 – 412Combined sources3
Helixi414 – 423Combined sources10
Helixi428 – 430Combined sources3
Beta strandi435 – 437Combined sources3
Helixi438 – 443Combined sources6
Helixi446 – 448Combined sources3
Helixi453 – 457Combined sources5
Helixi477 – 479Combined sources3
Helixi493 – 502Combined sources10
Helixi508 – 517Combined sources10
Helixi520 – 525Combined sources6
Beta strandi527 – 530Combined sources4
Helixi549 – 555Combined sources7

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...

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

Contains 1 AGC-kinase C-terminal domain.Curated
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 RGS domain.PROSITE-ProRule annotation

Phylogenomic databases

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

Family and domain databases

InterProiIPR000961. AGC-kinase_C.
IPR000239. GPCR_kinase.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016137. RGS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
PF00615. RGS. 1 hit.
[Graphical view]
PRINTSiPR00717. GPCRKINASE.
SMARTiSM00315. RGS. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF48097. SSF48097. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51285. 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.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

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

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 rs141014084dbSNPEnsembl.1
Natural variantiVAR_04052573T → M.1 PublicationCorresponds to variant rs56382815dbSNPEnsembl.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]
CCDS47348.1. [P43250-2]
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

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]
CCDS47348.1. [P43250-2]
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. 29 interactors.
IntActiP43250. 8 interactors.
MINTiMINT-1425525.
STRINGi9606.ENSP00000433511.

Chemistry databases

BindingDBiP43250.
ChEMBLiCHEMBL6144.
GuidetoPHARMACOLOGYi1470.

PTM databases

iPTMnetiP43250.
PhosphoSitePlusiP43250.
SwissPalmiP43250.

Polymorphism and mutation databases

BioMutaiGRK6.
DMDMi20141386.

Proteomic databases

EPDiP43250.
MaxQBiP43250.
PaxDbiP43250.
PeptideAtlasiP43250.
PRIDEiP43250.

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.
GeneCardsiGRK6.
HGNCiHGNC:4545. GRK6.
HPAiHPA015327.
HPA018903.
MIMi600869. gene.
neXtProtiNX_P43250.
OpenTargetsiENSG00000198055.
PharmGKBiPA28942.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:HS00600-MONOMER.
BRENDAi2.7.11.16. 2681.
ReactomeiR-HSA-418555. G alpha (s) signalling events.
SignaLinkiP43250.
SIGNORiP43250.

Miscellaneous databases

EvolutionaryTraceiP43250.
GeneWikiiGRK6.
GenomeRNAii2870.
PROiP43250.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000198055.
CleanExiHS_GRK6.
ExpressionAtlasiP43250. baseline and differential.
GenevisibleiP43250. HS.

Family and domain databases

InterProiIPR000961. AGC-kinase_C.
IPR000239. GPCR_kinase.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016137. RGS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
PF00615. RGS. 1 hit.
[Graphical view]
PRINTSiPR00717. GPCRKINASE.
SMARTiSM00315. RGS. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF48097. SSF48097. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51285. 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.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGRK6_HUMAN
AccessioniPrimary (citable) accession number: P43250
Secondary accession number(s): O60541, Q13652
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: January 23, 2002
Last modified: November 30, 2016
This is version 173 of the entry and version 2 of the sequence. [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 polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.