GRK4 G protein-coupled receptor kinase 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: GRK4provided by HGNC
Official Full Name: G protein-coupled receptor kinase 4provided by HGNC
Primary source: HGNC:HGNC:4543
See related: Ensembl:ENSG00000125388 MIM:137026; AllianceGenome:HGNC:4543
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: IT11; GPRK4; GRK4a; GPRK2L
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 its deactivation. This gene has been linked to both genetic and acquired hypertension. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]
Expression: Biased expression in testis (RPKM 14.6) and brain (RPKM 0.7) See more
Orthologs: mouse all
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Genomic context

Location:: 4p16.3

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (2963571..3040760)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (2962247..3039448)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (2965298..3042487)

Chromosome 4 - NC_000004.12 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: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Downregulation of G protein-coupled receptor kinase 4 protects against kidney ischemia-reperfusion injury.
Title: Downregulation of G protein-coupled receptor kinase 4 protects against kidney ischemia-reperfusion injury.
Comprehensive insights in GRK4 and hypertension: From mechanisms to potential therapeutics.
Title: Comprehensive insights in GRK4 and hypertension: From mechanisms to potential therapeutics.
Genetic variants of GRK4 influence circadian rhythm of blood pressure and response to candesartan in hypertensive patients.
Title: Genetic variants of GRK4 influence circadian rhythm of blood pressure and response to candesartan in hypertensive patients.
Associations of SUCNR1, GRK4, CAMK1D gene polymorphisms and the susceptibility of type 2 diabetes mellitus and essential hypertension in a northern Chinese Han population.
Title: Associations of SUCNR1, GRK4, CAMK1D gene polymorphisms and the susceptibility of type 2 diabetes mellitus and essential hypertension in a northern Chinese Han population.
Renal Dopamine Receptors and Oxidative Stress: Role in Hypertension.
Title: Renal Dopamine Receptors and Oxidative Stress: Role in Hypertension.
Targeted capture sequencing identifies genetic variations of GRK4 and RDH8 in Han Chinese with essential hypertension in Xinjiang.
Title: Targeted capture sequencing identifies genetic variations of GRK4 and RDH8 in Han Chinese with essential hypertension in Xinjiang.
The role of G protein-coupled receptor kinase 4 in cardiomyocyte injury after myocardial infarction.
Title: The role of G protein-coupled receptor kinase 4 in cardiomyocyte injury after myocardial infarction.
Proteomics analysis of G protein-coupled receptor kinase 4-inhibited cellular growth of HEK293 cells.
Title: Proteomics analysis of G protein-coupled receptor kinase 4-inhibited cellular growth of HEK293 cells.
GRK4 gene variants in humans (GRK4 A>65L, A>142V, and A>486V) are associated with Hypertension in several but not all ethnic groups. GRK4 gene variants impair the function of D1R and D3R and abet the function of AT1R. These lead to enhancement of renal sodium reabsorption and impaired ability to excrete a sodium load that eventually leads to hypertension. Acknowledgments
Title: Gastrorenal Axis.
On normal salt diet, renal CuZnSOD and ECSOD proteins were similar but renal MnSOD was lower in hGRK4g486V than Non-T mice and remained low on high salt diet. hGRK4gammawild-type mice were normotensive and hGRK4g142V mice were hypertensive but both were salt-resistant and in normal redox balance. Chronic tempol treatment partially prevented the salt-sensitivity of hGRK4g486V mice.
Title: Increased renal oxidative stress in salt-sensitive human GRK4γ486V transgenic mice.

Submit: New GeneRIF Correction See all GeneRIFs (46)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

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

SHGC-67218 (e-PCR)
- UniSTS:8710

D4S95 (e-PCR)
- UniSTS:147271

GDB:230300 (e-PCR)
- UniSTS:156271

D4S127 (e-PCR)
- UniSTS:147092

STS-N23898 (e-PCR)
- UniSTS:78261

STS-AA024498 (e-PCR)
- UniSTS:82107

RH70602 (e-PCR)
- UniSTS:14023

D4S127 (e-PCR)
- UniSTS:149984

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables rhodopsin kinase activity	TAS Traceable Author Statement more info

Process	Evidence Code	Pubs
involved_in receptor internalization	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of G protein-coupled receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in regulation of opsin-mediated signaling pathway	TAS Traceable Author Statement 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
located_in cell cortex	IEA Inferred from Electronic Annotation more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in photoreceptor disc membrane	TAS Traceable Author Statement more info
located_in plasma membrane	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: G protein-coupled receptor kinase 4

Names: G protein-coupled receptor kinase 2-like

NP_001004056.1

EC 2.7.11.16

NP_001004057.1

EC 2.7.11.16

NP_001337102.1

EC 2.7.11.16

NP_005298.2

EC 2.7.11.16

NP_892027.2

EC 2.7.11.16

XP_005248019.1

EC 2.7.11.16

XP_011511749.1

EC 2.7.11.16

XP_011511750.1

EC 2.7.11.16

XP_011511751.1

EC 2.7.11.16

XP_011511752.1

EC 2.7.11.16

XP_011511753.1

EC 2.7.11.16

XP_011511754.1

EC 2.7.11.16

XP_011511755.1

EC 2.7.11.16

XP_011511756.1

EC 2.7.11.16

XP_011511757.1

EC 2.7.11.16

XP_011511758.1

EC 2.7.11.16

XP_011511759.1

EC 2.7.11.16

XP_016863541.1

EC 2.7.11.16

XP_016863542.1

EC 2.7.11.16

XP_016863543.1

EC 2.7.11.16

XP_016863544.1

EC 2.7.11.16

XP_016863545.1

EC 2.7.11.16

XP_047306080.1

EC 2.7.11.16

XP_047306081.1

EC 2.7.11.16

XP_047306082.1

EC 2.7.11.16

XP_047306083.1

EC 2.7.11.16

XP_047306084.1

EC 2.7.11.16

XP_054205768.1

EC 2.7.11.16

XP_054205769.1

EC 2.7.11.16

XP_054205770.1

EC 2.7.11.16

XP_054205771.1

EC 2.7.11.16

XP_054205772.1

EC 2.7.11.16

XP_054205773.1

EC 2.7.11.16

XP_054205774.1

EC 2.7.11.16

XP_054205775.1

EC 2.7.11.16

XP_054205776.1

EC 2.7.11.16

XP_054205777.1

EC 2.7.11.16

XP_054205778.1

EC 2.7.11.16

XP_054205779.1

EC 2.7.11.16

XP_054205780.1

EC 2.7.11.16

XP_054205781.1

EC 2.7.11.16

XP_054205782.1

EC 2.7.11.16

XP_054205783.1

EC 2.7.11.16

XP_054205784.1

EC 2.7.11.16

XP_054205785.1

EC 2.7.11.16

XP_054205786.1

EC 2.7.11.16

XP_054205787.1

EC 2.7.11.16

XP_054205788.1

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_029102.1 RefSeqGene

Range

4956..82145

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001004056.2 → NP_001004056.1 G protein-coupled receptor kinase 4 isoform beta

See identical proteins and their annotated locations for NP_001004056.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (beta) has the same N- and C-termini but is shorter compared to isoform alpha.

Source sequence(s)

AL390065, BC027597, BI465220, BM725978, U33054

Consensus CDS

CCDS47002.1

UniProtKB/TrEMBL

A8K8M5

Related

ENSP00000264764.8, ENST00000345167.10

Conserved Domains (3) summary

cd05631
Location:154 → 438

STKc_GRK4; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4

smart00220
Location:155 → 417

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl02565
Location:20 → 152

RGS; Regulator of G protein signaling (RGS) domain superfamily
NM_001004057.2 → NP_001004057.1 G protein-coupled receptor kinase 4 isoform gamma

See identical proteins and their annotated locations for NP_001004057.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (gamma) has the same N- and C-termini but is shorter compared to isoform alpha.

Source sequence(s)

AL390065, BC027597, BI465220, BM725978

Consensus CDS

CCDS33947.1

UniProtKB/TrEMBL

A8K8M5

Related

ENSP00000427445.1, ENST00000504933.1

Conserved Domains (3) summary

cd05631
Location:186 → 470

STKc_GRK4; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4

smart00220
Location:187 → 449

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl02565
Location:52 → 184

RGS; Regulator of G protein signaling (RGS) domain superfamily
NM_001350173.2 → NP_001337102.1 G protein-coupled receptor kinase 4 isoform 5

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs in the 5' UTR, lacks a portion of the 5' coding region and initiates translation at an alternate start codon, compared to variant 1. It encodes isoform 5, which has a shorter and distinct N-terminus, compared to isoform alpha.

Source sequence(s)

AK223581, AK292390, AL390065, BI792406, N23898, X97881

Conserved Domains (1) summary

cl21453
Location:5 → 276

PKc_like; Protein Kinases, catalytic domain
NM_005307.3 → NP_005298.2 G protein-coupled receptor kinase 4 isoform delta

See identical proteins and their annotated locations for NP_005298.2

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks two alternate in-frame exons compared to variant 1. The resulting isoform (delta) has the same N- and C-termini but is shorter compared to isoform alpha.

Source sequence(s)

AK223581, AL390065, X97879

Consensus CDS

CCDS68656.1

UniProtKB/TrEMBL

A8K8M5

Related

ENSP00000381128.4, ENST00000398051.8

Conserved Domains (3) summary

cd05631
Location:154 → 438

STKc_GRK4; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4

smart00220
Location:155 → 417

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl02565
Location:20 → 152

RGS; Regulator of G protein signaling (RGS) domain superfamily
NM_182982.3 → NP_892027.2 G protein-coupled receptor kinase 4 isoform alpha

See identical proteins and their annotated locations for NP_892027.2

Status: REVIEWED

Description

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

Source sequence(s)

AL390065, BC027597, BI465220, BM725978, U33054

Consensus CDS

CCDS33946.1

UniProtKB/Swiss-Prot

O00641, O00642, P32298, Q13293, Q13294, Q13295, Q14453, Q14725, Q15313, Q15314, Q15315, Q15316, Q17RH6, Q53EQ8

UniProtKB/TrEMBL

A8K8M5

Related

ENSP00000381129.4, ENST00000398052.9

Conserved Domains (3) summary

cd05631
Location:186 → 470

STKc_GRK4; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4

smart00220
Location:187 → 449

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl02565
Location:52 → 184

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

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000004.12 Reference GRCh38.p14 Primary Assembly

Range

2963571..3040760

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011513447.3 → XP_011511749.1 G protein-coupled receptor kinase 4 isoform X1

UniProtKB/TrEMBL

A8K8M5

Conserved Domains (3) summary

cd05631
Location:186 → 509

STKc_GRK4; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4

smart00220
Location:187 → 488

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl02565
Location:52 → 184

RGS; Regulator of G protein signaling (RGS) domain superfamily
XM_011513450.3 → XP_011511752.1 G protein-coupled receptor kinase 4 isoform X6

UniProtKB/TrEMBL

A8K8M5

Conserved Domains (3) summary

cd05631
Location:186 → 509

STKc_GRK4; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4

smart00220
Location:187 → 488

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl02565
Location:52 → 184

RGS; Regulator of G protein signaling (RGS) domain superfamily
XM_011513453.3 → XP_011511755.1 G protein-coupled receptor kinase 4 isoform X10

UniProtKB/TrEMBL

A8K8M5

Conserved Domains (3) summary

smart00220
Location:187 → 488

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl02565
Location:52 → 184

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

cl21453
Location:186 → 508

PKc_like; Protein Kinases, catalytic domain
XM_011513451.3 → XP_011511753.1 G protein-coupled receptor kinase 4 isoform X7

UniProtKB/TrEMBL

A8K8M5

Conserved Domains (3) summary

smart00220
Location:187 → 462

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl02565
Location:52 → 184

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

cl21453
Location:186 → 470

PKc_like; Protein Kinases, catalytic domain
XM_011513454.3 → XP_011511756.1 G protein-coupled receptor kinase 4 isoform X9

UniProtKB/TrEMBL

A8K8M5

Conserved Domains (2) summary

cl02565
Location:52 → 184

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

cl21453
Location:186 → 470

PKc_like; Protein Kinases, catalytic domain
XM_011513455.3 → XP_011511757.1 G protein-coupled receptor kinase 4 isoform X12

Conserved Domains (3) summary

smart00220
Location:187 → 471

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl02565
Location:52 → 184

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

cl21453
Location:186 → 472

PKc_like; Protein Kinases, catalytic domain
XM_017008053.2 → XP_016863542.1 G protein-coupled receptor kinase 4 isoform X4

UniProtKB/TrEMBL

A8K8M5
XM_011513456.3 → XP_011511758.1 G protein-coupled receptor kinase 4 isoform X15

Conserved Domains (2) summary

cl02565
Location:52 → 184

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

cl21453
Location:186 → 363

PKc_like; Protein Kinases, catalytic domain
XM_017008054.2 → XP_016863543.1 G protein-coupled receptor kinase 4 isoform X11

UniProtKB/TrEMBL

A8K8M5
XM_017008056.2 → XP_016863545.1 G protein-coupled receptor kinase 4 isoform X14
XM_017008052.2 → XP_016863541.1 G protein-coupled receptor kinase 4 isoform X3

UniProtKB/TrEMBL

A8K8M5
XM_011513449.3 → XP_011511751.1 G protein-coupled receptor kinase 4 isoform X5

UniProtKB/TrEMBL

A8K8M5

Conserved Domains (3) summary

cd05631
Location:154 → 477

STKc_GRK4; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4

smart00220
Location:155 → 456

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl02565
Location:20 → 152

RGS; Regulator of G protein signaling (RGS) domain superfamily
XM_017008055.2 → XP_016863544.1 G protein-coupled receptor kinase 4 isoform X13
XM_005247962.4 → XP_005248019.1 G protein-coupled receptor kinase 4 isoform X17

See identical proteins and their annotated locations for XP_005248019.1

Conserved Domains (2) summary

smart00220
Location:20 → 238

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl21453
Location:1 → 259

PKc_like; Protein Kinases, catalytic domain
XM_011513452.3 → XP_011511754.1 G protein-coupled receptor kinase 4 isoform X8

UniProtKB/TrEMBL

A8K8M5

Conserved Domains (2) summary

cd08750
Location:52 → 184

RGS_GRK4; Regulator of G protein signaling domain (RGS) found in G protein-coupled receptor kinase 4 (GRK4)

cl21453
Location:186 → 470

PKc_like; Protein Kinases, catalytic domain
XM_011513448.3 → XP_011511750.1 G protein-coupled receptor kinase 4 isoform X2

UniProtKB/TrEMBL

A8K8M5

Conserved Domains (2) summary

cd05631
Location:186 → 509

STKc_GRK4; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4

cd08750
Location:52 → 184

RGS_GRK4; Regulator of G protein signaling domain (RGS) found in G protein-coupled receptor kinase 4 (GRK4)
XM_047450128.1 → XP_047306084.1 G protein-coupled receptor kinase 4 isoform X19
XM_047450127.1 → XP_047306083.1 G protein-coupled receptor kinase 4 isoform X19
XM_011513457.3 → XP_011511759.1 G protein-coupled receptor kinase 4 isoform X18

Conserved Domains (2) summary

cl02565
Location:52 → 184

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

cl21453
Location:186 → 286

PKc_like; Protein Kinases, catalytic domain
XM_047450125.1 → XP_047306081.1 G protein-coupled receptor kinase 4 isoform X17
XM_047450126.1 → XP_047306082.1 G protein-coupled receptor kinase 4 isoform X17
XM_047450124.1 → XP_047306080.1 G protein-coupled receptor kinase 4 isoform X16

RNA

XR_924941.3 RNA Sequence
XR_001741210.2 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060928.1 Alternate T2T-CHM13v2.0

Range

2962247..3039448

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054349793.1 → XP_054205768.1 G protein-coupled receptor kinase 4 isoform X1

UniProtKB/TrEMBL

A8K8M5
XM_054349798.1 → XP_054205773.1 G protein-coupled receptor kinase 4 isoform X6

UniProtKB/TrEMBL

A8K8M5
XM_054349802.1 → XP_054205777.1 G protein-coupled receptor kinase 4 isoform X10

UniProtKB/TrEMBL

A8K8M5
XM_054349799.1 → XP_054205774.1 G protein-coupled receptor kinase 4 isoform X7

UniProtKB/TrEMBL

A8K8M5
XM_054349801.1 → XP_054205776.1 G protein-coupled receptor kinase 4 isoform X9

UniProtKB/TrEMBL

A8K8M5
XM_054349804.1 → XP_054205779.1 G protein-coupled receptor kinase 4 isoform X12
XM_054349796.1 → XP_054205771.1 G protein-coupled receptor kinase 4 isoform X4

UniProtKB/TrEMBL

A8K8M5
XM_054349807.1 → XP_054205782.1 G protein-coupled receptor kinase 4 isoform X15
XM_054349803.1 → XP_054205778.1 G protein-coupled receptor kinase 4 isoform X11

UniProtKB/TrEMBL

A8K8M5
XM_054349806.1 → XP_054205781.1 G protein-coupled receptor kinase 4 isoform X14
XM_054349795.1 → XP_054205770.1 G protein-coupled receptor kinase 4 isoform X3

UniProtKB/TrEMBL

A8K8M5
XM_054349797.1 → XP_054205772.1 G protein-coupled receptor kinase 4 isoform X5

UniProtKB/TrEMBL

A8K8M5
XM_054349805.1 → XP_054205780.1 G protein-coupled receptor kinase 4 isoform X13
XM_054349810.1 → XP_054205785.1 G protein-coupled receptor kinase 4 isoform X17
XM_054349800.1 → XP_054205775.1 G protein-coupled receptor kinase 4 isoform X8

UniProtKB/TrEMBL

A8K8M5
XM_054349794.1 → XP_054205769.1 G protein-coupled receptor kinase 4 isoform X2

UniProtKB/TrEMBL

A8K8M5
XM_054349813.1 → XP_054205788.1 G protein-coupled receptor kinase 4 isoform X19
XM_054349812.1 → XP_054205787.1 G protein-coupled receptor kinase 4 isoform X18
XM_054349809.1 → XP_054205784.1 G protein-coupled receptor kinase 4 isoform X17
XM_054349811.1 → XP_054205786.1 G protein-coupled receptor kinase 4 isoform X17
XM_054349808.1 → XP_054205783.1 G protein-coupled receptor kinase 4 isoform X16