Grk6 G protein-coupled receptor kinase 6 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Grk6provided by MGI
Official Full Name: G protein-coupled receptor kinase 6provided by MGI
Primary source: MGI:MGI:1347078
See related: Ensembl:ENSMUSG00000074886 AllianceGenome:MGI:1347078
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Gprk6
Summary: Enables protein kinase activity. Involved in protein phosphorylation. Predicted to be located in cytosol. Predicted to be active in cytoplasm and plasma membrane. Is expressed in several structures, including genitourinary system; liver; lung; spleen; and submandibular gland primordium. Human ortholog(s) of this gene implicated in Parkinson's disease. Orthologous to human GRK6 (G protein-coupled receptor kinase 6). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in spleen adult (RPKM 77.5), thymus adult (RPKM 59.5) and 27 other tissues See more
Orthologs: human all
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Genomic context

Location:: 13 B1; 13 30.06 cM

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	13	NC_000079.7 (55592865..55608740)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	13	NC_000079.6 (55445072..55460927)

Chromosome 13 - NC_000079.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

G protein-coupled receptor kinase 6 (GRK6) regulates insulin processing and secretion via effects on proinsulin conversion to insulin.
Title: G protein-coupled receptor kinase 6 (GRK6) regulates insulin processing and secretion via effects on proinsulin conversion to insulin.
Role of GRK6 in the Regulation of Platelet Activation through Selective G Protein-Coupled Receptor (GPCR) Desensitization.
Title: Role of GRK6 in the Regulation of Platelet Activation through Selective G Protein-Coupled Receptor (GPCR) Desensitization.
These data indicate that GRK2, GRK5 and GRK6 redundantly modulate Smo-GATA crosstalk in fetal mouse hearts, orchestrating transcriptional pathways previously linked to clinical and experimental atrioventricular canal defects
Title: G-protein receptor kinases 2, 5 and 6 redundantly modulate Smoothened-GATA transcriptional crosstalk in fetal mouse hearts.
findings show that chemerin-activated CMKLR1 regulation in inflammatory macrophages is largely GRK6 and beta-arrestin mediated, which may impact innate immunity and have therapeutic implications in rheumatic disease.
Title: Chemerin-activated functions of CMKLR1 are regulated by G protein-coupled receptor kinase 6 (GRK6) and β-arrestin 2 in inflammatory macrophages.
Conditions for optimal dendritic cells guidance are perfectly provided by the CCL21 gradients measured in vivo. Furthermore, CCR7 signal termination by the G-protein-coupled receptor kinase 6 (GRK6) is crucial for haptotactic but dispensable for chemotactic CCL21 gradient sensing in vitro and confirm those observations in vivo.
Title: Dendritic Cells Interpret Haptotactic Chemokine Gradients in a Manner Governed by Signal-to-Noise Ratio and Dependent on GRK6.
These studies suggest a previously unrecognized and novel role for GRK6 in neutrophil migration specific to pulmonary tissue during bacterial infection.
Title: Role of G protein-coupled receptor kinase-6 in Escherichia coli lung infection model in mice.
Silencing of GRK6 expression by siRNA impairs CXCR4-serine 339 phosphorylation and migration of cardiac stem cellss caused by SCF. In vivo, knockdown of GRK6 impairs the ability of CSCs to migrate into peri-infarcted areas.
Title: SCF/c-kit transactivates CXCR4-serine 339 phosphorylation through G protein-coupled receptor kinase 6 and regulates cardiac stem cell migration.
This work demonstrates the importance of GRK6 in regulation of hematopoietic stem cell self-renewal and reveals its potential role in participation of stress response.
Title: GRK6 regulates ROS response and maintains hematopoietic stem cell self-renewal.
GRK6-mediated OXTR desensitization in labor is necessary for normal uterine contractile patterns and optimal fetal outcome.
Title: Enhanced Uterine Contractility and Stillbirth in Mice Lacking G Protein-Coupled Receptor Kinase 6 (GRK6): Implications for Oxytocin Receptor Desensitization.
It regulates apoptotic engulfment in phagocytes. (review)
Title: [Research on Molecular Mechanisms of Engulfment of Apoptotic Cells].

Submit: New GeneRIF Correction See all GeneRIFs (24)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Gene trapped (1)
Targeted (2) 1 citation
Endonuclease-mediated (2)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Grk6 (e-PCR), detects polymorphism
- UniSTS:527372

Y15798 (e-PCR)
- UniSTS:160304

Gprk6 (e-PCR), detects polymorphism
- UniSTS:186227

RH141163 (e-PCR)
- UniSTS:223159

Gene Ontology Provided by MGI

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 G protein-coupled receptor kinase activity	ISO Inferred from Sequence Orthology more info
enables beta-adrenergic receptor kinase activity	ISO Inferred from Sequence Orthology more info
enables kinase activity	IEA Inferred from Electronic Annotation more info
enables nucleotide binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
enables transferase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in desensitization of G protein-coupled receptor signaling pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within 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 signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in signal transduction	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: G protein-coupled receptor kinase 6

Names: g protein-coupled receptor kinase GRK6

NP_001033107.1

EC 2.7.11.16

NP_001106182.1

EC 2.7.11.16

NP_001272992.1

EC 2.7.11.16

NP_001272993.1

EC 2.7.11.16

NP_001272994.1

EC 2.7.11.16

NP_001272995.1

EC 2.7.11.16

NP_001364005.1

EC 2.7.11.16

NP_001364006.1

EC 2.7.11.16

NP_036068.2

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.

mRNA and Protein(s)

NM_001038018.5 → NP_001033107.1 G protein-coupled receptor kinase 6 isoform a

See identical proteins and their annotated locations for NP_001033107.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).

Source sequence(s)

AK051405, AW048460, CT009762, Y15799

UniProtKB/TrEMBL

O70296

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_001112711.2 → NP_001106182.1 G protein-coupled receptor kinase 6 isoform c

See identical proteins and their annotated locations for NP_001106182.1

Status: VALIDATED

Description

Transcript Variant: This variant (3) uses an alternate splice site in the 3' coding region, which results in a frameshift, compared to variant 1. The encoded isoform (c) has a shorter and distinct C-terminus, compared to isoform a.

Source sequence(s)

AK051405, AW048460, CT009762, Y15799

Consensus CDS

CCDS88457.1

UniProtKB/Swiss-Prot

O70293, O70294, O70295, Q6DI67

UniProtKB/TrEMBL

Q792R0

Related

ENSMUSP00000152968.2, ENSMUST00000224118.2

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_001286063.2 → NP_001272992.1 G protein-coupled receptor kinase 6 isoform d

Status: VALIDATED

Description

Transcript Variant: This variant (4) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (d) has a shorter N-terminus, compared to isoform a.

Source sequence(s)

AK051405, AW048460, CT009762, Y15799

UniProtKB/TrEMBL

A0A286YDZ5, O70296

Related

ENSMUSP00000153623.2, ENSMUST00000224653.2

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
NM_001286064.2 → NP_001272993.1 G protein-coupled receptor kinase 6 isoform e

Status: VALIDATED

Description

Transcript Variant: This variant (5) uses an alternate in-frame splice site in the central coding region, compared to variant 1. The encoded isoform (e) is shorter, compared to isoform a.

Source sequence(s)

AK051405, AW048460, CT009762, Y15799

UniProtKB/TrEMBL

A0A286YDA5, O70296

Conserved Domains (3) summary

smart00220
Location:186 → 443

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd05630
Location:185 → 464

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_001286065.1 → NP_001272994.1 G protein-coupled receptor kinase 6 isoform f

Status: VALIDATED

Description

Transcript Variant: This variant (6) uses an alternate in-frame splice site in the central coding region, and uses an alternate splice site in the 3' coding region, which results in a frameshift, compared to variant 1. The encoded isoform (f) is shorter and has a distinct C-terminus, compared to isoform a.

Source sequence(s)

AK051405, AW048460, CT009762, Y15799

Consensus CDS

CCDS88458.1

UniProtKB/TrEMBL

A0A286YE10, Q3UK88

Related

ENSMUSP00000153668.2, ENSMUST00000225925.2

Conserved Domains (3) summary

smart00220
Location:186 → 414

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl02565
Location:35 → 179

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

cl21453
Location:185 → 435

PKc_like; Protein Kinases, catalytic domain
NM_001286066.2 → NP_001272995.1 G protein-coupled receptor kinase 6 isoform g

Status: VALIDATED

Description

Transcript Variant: This variant (7) has multiple differences compared to variant 1. These differences result in a distinct 5' UTR, 3' UTR, and 3' coding region, and cause translation initiation from a downstream start codon. The encoded isoform (g) has a shorter N-terminus and a distinct and shorter C-terminus, compared to isoform a.

Source sequence(s)

CT009762

UniProtKB/TrEMBL

Q9EP84

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
NM_001377076.1 → NP_001364005.1 G protein-coupled receptor kinase 6 isoform h

Status: VALIDATED

Source sequence(s)

CT009762

UniProtKB/TrEMBL

Q792R0

Conserved Domains (2) summary

cd05630
Location:180 → 464

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

cl02565
Location:30 → 174

RGS; Regulator of G protein signaling (RGS) domain superfamily
NM_001377077.1 → NP_001364006.1 G protein-coupled receptor kinase 6 isoform i

Status: VALIDATED

Source sequence(s)

CT009762

Conserved Domains (1) summary

cl21453
Location:1 → 204

PKc_like; Protein Kinases, catalytic domain
NM_011938.5 → NP_036068.2 G protein-coupled receptor kinase 6 isoform b

See identical proteins and their annotated locations for NP_036068.2

Status: VALIDATED

Description

Transcript Variant: This variant (2) differs in the 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (b) has a shorter and distinct C-terminus, compared to isoform a.

Source sequence(s)

CT009762

Consensus CDS

CCDS36676.1

UniProtKB/TrEMBL

Q792R0, Q9EP84

Related

ENSMUSP00000097081.4, ENSMUST00000099482.5

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