GRK6 G protein-coupled receptor kinase 6 [Homo sapiens (human)] - Gene

Summary

Official Symbol: GRK6provided by HGNC
Official Full Name: G protein-coupled receptor kinase 6provided by HGNC
Primary source: HGNC:HGNC:4545
See related: Ensembl:ENSG00000198055 MIM:600869; AllianceGenome:HGNC:4545
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: GPRK6
Summary: This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase subfamily of the Ser/Thr protein kinase family. The protein phosphorylates the activated forms of G protein-coupled receptors thus initiating their deactivation. Several transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]
Expression: Broad expression in bone marrow (RPKM 27.2), lymph node (RPKM 19.5) and 23 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 5q35.3

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (177425523..177442891)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (177968774..177986142)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (176853677..176869892)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The Role of G Protein-Coupled Receptor Kinase 6 Regulation in Inflammation and Pain.
Title: The Role of G Protein-Coupled Receptor Kinase 6 Regulation in Inflammation and Pain.
M2 macrophages-derived exosomal miR-3917 promotes the progression of lung cancer via targeting GRK6.
Title: M2 macrophages-derived exosomal miR-3917 promotes the progression of lung cancer via targeting GRK6.
Multisite NHERF1 phosphorylation controls GRK6A regulation of hormone-sensitive phosphate transport.
Title: Multisite NHERF1 phosphorylation controls GRK6A regulation of hormone-sensitive phosphate transport.
Characterization of the G protein-coupled receptor kinase 6 promoter reveals a functional CREB binding site.
Title: Characterization of the G protein-coupled receptor kinase 6 promoter reveals a functional CREB binding site.
GRK6 S-nitrosylation at cys 474 enhances its kinase activity toward alpha-syn phosphorylation at S129.
Title: S-Nitrosylation of G protein-coupled receptor kinase 6 and Casein kinase 2 alpha modulates their kinase activity toward alpha-synuclein phosphorylation in an animal model of Parkinson's disease.
MiR-19b-3p attenuates IL-1beta induced extracellular matrix degradation and inflammatory injury in chondrocytes by targeting GRK6.
Title: MiR-19b-3p attenuates IL-1β induced extracellular matrix degradation and inflammatory injury in chondrocytes by targeting GRK6.
Hypermethylation of the GRK6 gene promoter suppressed binding of C/EBPalpha, thereby contributing to the promotion of cell migration and invasion.
Title: Hypermethylation of the G protein-coupled receptor kinase 6 (GRK6) promoter inhibits binding of C/EBPα, and GRK6 knockdown promotes cell migration and invasion in lung adenocarcinoma cells.
GRK6 overexpression can significantly enhance tumor proliferation and invasion, which was consistent with clinical findings.
Title: Overexpression of G Protein-Coupled Receptor Kinase 6 (GRK6) Is Associated with Progression and Poor Prognosis of Papillary Thyroid Carcinoma.
demonstrate for the first time exosomal enrichment of G-protein-coupled receptor kinase (GRK) 5 and GRK6, both of which regulate Src and IGF-IR signaling and have been implicated in cancer.
Title: c-Src, Insulin-Like Growth Factor I Receptor, G-Protein-Coupled Receptor Kinases and Focal Adhesion Kinase are Enriched Into Prostate Cancer Cell Exosomes.
Genetic variation in OXTR and GRK6 is associated with the amount of oxytocin required as well as the duration of labor and risk for cesarean delivery among women undergoing induction of labor near term.
Title: The association of single-nucleotide polymorphisms in the oxytocin receptor and G protein-coupled receptor kinase 6 (GRK6) genes with oxytocin dosing requirements and labor outcomes.

Submit: New GeneRIF Correction See all GeneRIFs (31)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genetic associations for activated partial thromboplastin time and prothrombin time, their gene expression profiles, and risk of coronary artery disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
New loci associated with kidney function and chronic kidney disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel Loci for metabolic networks and multi-tissue expression studies reveal genes for atherosclerosis. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

WI-18758 (e-PCR)
- UniSTS:29200

RH70522 (e-PCR)
- UniSTS:10055

D13S662E (e-PCR)
- UniSTS:153193

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables G protein-coupled receptor kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables beta-adrenergic receptor kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables beta-adrenergic receptor kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables beta-adrenergic receptor kinase activity	TAS Traceable Author Statement more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in G protein-coupled receptor signaling pathway	TAS Traceable Author Statement more info
involved_in Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in protein phosphorylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of G protein-coupled receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in regulation of signal transduction	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in membrane	HDA more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: G protein-coupled receptor kinase 6

NP_001004105.1

EC 2.7.11.16

NP_001004106.1

EC 2.7.11.16

NP_001351093.1

EC 2.7.11.16

NP_002073.2

EC 2.7.11.16

XP_006714921.1

EC 2.7.11.16

XP_006714922.1

EC 2.7.11.16

XP_011532840.1

EC 2.7.11.16

XP_047273082.1

EC 2.7.11.16

XP_054208434.1

EC 2.7.11.16

XP_054208435.1

EC 2.7.11.16

XP_054208436.1

EC 2.7.11.16

XP_054208437.1

EC 2.7.11.16

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_031981.1 RefSeqGene

Range

4991..21206

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001004105.3 → NP_001004105.1 G protein-coupled receptor kinase 6 isoform C

See identical proteins and their annotated locations for NP_001004105.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) contains an alternate 3' terminal exon, compared to variant 2, resulting in a shorter isoform (C) with a distinct C-terminus compared to isoform B.

Source sequence(s)

AC145098, AF040752, BC009277, BI258860

Consensus CDS

CCDS43406.1

UniProtKB/TrEMBL

Q96AD6

Related

ENSP00000348230.5, ENST00000355958.9

Conserved Domains (3) summary

smart00220
Location:186 → 448

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd05630
Location:185 → 469

STKc_GRK6; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6

cl02565
Location:35 → 179

RGS; Regulator of G protein signaling (RGS) domain superfamily
NM_001004106.3 → NP_001004106.1 G protein-coupled receptor kinase 6 isoform A

See identical proteins and their annotated locations for NP_001004106.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) uses an alternate acceptor splice site in the last exon, compared to variant 2, resulting in a shorter isoform (A) compared to isoform B.

Source sequence(s)

AC145098, BC009277, BI258860

Consensus CDS

CCDS34303.1

UniProtKB/Swiss-Prot

O60541, P43250, Q13652

UniProtKB/TrEMBL

F8W9W2

Related

ENSP00000347655.5, ENST00000355472.10

Conserved Domains (2) summary

cd05630
Location:185 → 469

STKc_GRK6; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6

cl02565
Location:35 → 179

RGS; Regulator of G protein signaling (RGS) domain superfamily
NM_001364164.2 → NP_001351093.1 G protein-coupled receptor kinase 6 isoform D

Status: REVIEWED

Source sequence(s)

AC145098

Conserved Domains (1) summary

cl21453
Location:1 → 259

PKc_like; Protein Kinases, catalytic domain
NM_002082.4 → NP_002073.2 G protein-coupled receptor kinase 6 isoform B

See identical proteins and their annotated locations for NP_002073.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) represents the longest transcript and encodes the longest isoform (B).

Source sequence(s)

AC145098, AF040751, BC009277, BI258860

UniProtKB/TrEMBL

Q96AD6

Conserved Domains (3) summary

smart00220
Location:186 → 448

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd05630
Location:185 → 469

STKc_GRK6; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6

cl02565
Location:35 → 179

RGS; Regulator of G protein signaling (RGS) domain superfamily

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000005.10 Reference GRCh38.p14 Primary Assembly

Range

177425523..177442891

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047417126.1 → XP_047273082.1 G protein-coupled receptor kinase 6 isoform X3
XM_006714859.3 → XP_006714922.1 G protein-coupled receptor kinase 6 isoform X2

UniProtKB/TrEMBL

Q96AD6

Conserved Domains (3) summary

smart00220
Location:154 → 416

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd05630
Location:153 → 437

STKc_GRK6; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6

cl02565
Location:3 → 147

RGS; Regulator of G protein signaling (RGS) domain superfamily
XM_006714858.4 → XP_006714921.1 G protein-coupled receptor kinase 6 isoform X1

See identical proteins and their annotated locations for XP_006714921.1

UniProtKB/TrEMBL

B3KPS5, Q96AD6

Conserved Domains (3) summary

smart00220
Location:156 → 418

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd05630
Location:155 → 439

STKc_GRK6; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6

cl02565
Location:20 → 149

RGS; Regulator of G protein signaling (RGS) domain superfamily
XM_011534538.2 → XP_011532840.1 G protein-coupled receptor kinase 6 isoform X4

Conserved Domains (2) summary

smart00220
Location:1 → 183

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl21453
Location:1 → 204

PKc_like; Protein Kinases, catalytic domain

Alternate T2T-CHM13v2.0

Genomic

NC_060929.1 Alternate T2T-CHM13v2.0

Range

177968774..177986142

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054352461.1 → XP_054208436.1 G protein-coupled receptor kinase 6 isoform X3
XM_054352460.1 → XP_054208435.1 G protein-coupled receptor kinase 6 isoform X2
XM_054352459.1 → XP_054208434.1 G protein-coupled receptor kinase 6 isoform X1

UniProtKB/TrEMBL

B3KPS5
XM_054352462.1 → XP_054208437.1 G protein-coupled receptor kinase 6 isoform X4