GRK5 (G protein-coupled receptor kinase 5)

Gene

• Entrez ID: 2869
• Gene name: G protein-coupled receptor kinase 5
• Gene symbol: GRK5
• Synonyms (NCBI Gene): FP2025, GPRK5
• Chromosome: 10
• Chromosome location: 10q26.11
• 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 de

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT036566	hsa-miR-941	CLASH	23622248
MIRT487507	hsa-miR-570-3p	PAR-CLIP	23592263
MIRT487505	hsa-miR-4481	PAR-CLIP	23592263
MIRT487506	hsa-miR-4745-5p	PAR-CLIP	23592263
MIRT487504	hsa-miR-1238-5p	PAR-CLIP	23592263
MIRT487503	hsa-miR-4758-5p	PAR-CLIP	23592263
MIRT487507	hsa-miR-570-3p	PAR-CLIP	23592263
MIRT487505	hsa-miR-4481	PAR-CLIP	23592263
MIRT487506	hsa-miR-4745-5p	PAR-CLIP	23592263
MIRT487504	hsa-miR-1238-5p	PAR-CLIP	23592263
MIRT487503	hsa-miR-4758-5p	PAR-CLIP	23592263
MIRT1034929	hsa-miR-129-5p	CLIP-seq
MIRT1034930	hsa-miR-23a	CLIP-seq
MIRT1034931	hsa-miR-23b	CLIP-seq
MIRT1034932	hsa-miR-23c	CLIP-seq
MIRT1034933	hsa-miR-3161	CLIP-seq
MIRT1034934	hsa-miR-627	CLIP-seq
MIRT2239367	hsa-miR-1285	CLIP-seq
MIRT2239368	hsa-miR-132	CLIP-seq
MIRT2239369	hsa-miR-135a	CLIP-seq
MIRT2239370	hsa-miR-135b	CLIP-seq
MIRT2239371	hsa-miR-1587	CLIP-seq
MIRT2239372	hsa-miR-1909	CLIP-seq
MIRT2239373	hsa-miR-212	CLIP-seq
MIRT2239374	hsa-miR-2278	CLIP-seq
MIRT2239375	hsa-miR-3187-5p	CLIP-seq
MIRT2239376	hsa-miR-378g	CLIP-seq
MIRT2239377	hsa-miR-4283	CLIP-seq
MIRT2239378	hsa-miR-4486	CLIP-seq
MIRT2239379	hsa-miR-4492	CLIP-seq
MIRT2239380	hsa-miR-4498	CLIP-seq
MIRT2239381	hsa-miR-4656	CLIP-seq
MIRT2239382	hsa-miR-4675	CLIP-seq
MIRT2239383	hsa-miR-4741	CLIP-seq
MIRT2239384	hsa-miR-4804-3p	CLIP-seq
MIRT2239385	hsa-miR-604	CLIP-seq
MIRT2239386	hsa-miR-612	CLIP-seq
MIRT2239387	hsa-miR-647	CLIP-seq
MIRT2239388	hsa-miR-762	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0004672	Function	Protein kinase activity	IBA
GO:0004672	Function	Protein kinase activity	IEA
GO:0004674	Function	Protein serine/threonine kinase activity	IDA	20124405
GO:0004674	Function	Protein serine/threonine kinase activity	IEA
GO:0004703	Function	G protein-coupled receptor kinase activity	IEA
GO:0005080	Function	Protein kinase C binding	TAS	9813065
GO:0005515	Function	Protein binding	IPI	17986524, 19008357, 19661922, 20124405
GO:0005524	Function	ATP binding	IEA
GO:0005543	Function	Phospholipid binding	TAS	9813065
GO:0005634	Component	Nucleus	IEA
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IEA
GO:0005737	Component	Cytoplasm	TAS	7685906
GO:0005829	Component	Cytosol	IDA
GO:0005886	Component	Plasma membrane	IDA	14976207, 17986524
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0006915	Process	Apoptotic process	IEA
GO:0007165	Process	Signal transduction	IEA
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS
GO:0007188	Process	Adenylate cyclase-modulating G protein-coupled receptor signaling pathway	TAS	8626574
GO:0007217	Process	Tachykinin receptor signaling pathway	IDA	17986524
GO:0008277	Process	Regulation of G protein-coupled receptor signaling pathway	IEA
GO:0008277	Process	Regulation of G protein-coupled receptor signaling pathway	TAS	8288567
GO:0008284	Process	Positive regulation of cell population proliferation	IMP	22099983
GO:0008289	Function	Lipid binding	IEA
GO:0009966	Process	Regulation of signal transduction	IBA
GO:0016020	Component	Membrane	IEA
GO:0016055	Process	Wnt signaling pathway	IEA
GO:0016301	Function	Kinase activity	IEA
GO:0016607	Component	Nuclear speck	IDA
GO:0016740	Function	Transferase activity	IEA
GO:0031965	Component	Nuclear membrane	IDA
GO:0043066	Process	Negative regulation of apoptotic process	IDA	20124405
GO:0045444	Process	Fat cell differentiation	IEA
GO:0046777	Process	Protein autophosphorylation	IDA	14976207
GO:0047696	Function	Beta-adrenergic receptor kinase activity	IMP	20038610
GO:0047696	Function	Beta-adrenergic receptor kinase activity	TAS
GO:0051726	Process	Regulation of cell cycle	IMP	22099983

Other IDs

• MIM: 600870
• HGNC: 4544
• e!Ensembl: ENSG00000198873

Protein

• UniProt ID: P34947
• Protein name: G protein-coupled receptor kinase 5 (EC 2.7.11.16) (G protein-coupled receptor kinase GRK5)
• Protein function: Serine/threonine kinase that phosphorylates preferentially the activated forms of a variety of G-protein-coupled receptors (GPCRs). Such receptor phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and sig
• PDB: 4TNB, 4TND, 6PJX, 8UAP, 8UAQ, 9BRE, 9BRG, 9BRH, 9BRI, 9BRJ
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00615	RGS	52 → 170	Regulator of G protein signaling domain	Domain
  PF00069	Pkinase	186 → 448	Protein kinase domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Highest levels in heart, placenta, lung > skeletal muscle > brain, liver, pancreas > kidney. {ECO:0000269|PubMed:7685906}.
• Sequence:

  MELENIVANTVLLKAREGGGGKRKGKSKKWKEILKFPHISQCEDLRRTIDRDYCSLCDKQ
  PIGRLLFRQFCETRPGLECYIQFLDSVAEYEVTPDEKLGEKGKEIMTKYLTPKSPVFIAQ
  VGQDLVSQTEEKLLQKPCKELFSACAQSVHEYLRGEPFHEYLDSMFFDRFLQWKWLERQP
  VTKNTFRQYRVLGKGGFGEVCACQVRATGKMYACKRLEKKRIKKRKGESMALNEKQILEK
  VNSQFVVNLAYAYETKDALCLVLTIMNGGDLKFHIYNMGNPGFEEERALFYAAEILCGLE
  DLHRENTVYRDLKPENILLDDYGHIRISDLGLAVKIPEGDLIRGRVGTVGYMAPEVLNNQ
  RYGLSPDYWGLGCLIYEMIEGQSPFRGRKEKVKREEVDRRVLETEEVYSHKFSEEAKSIC
  KMLLTKDAKQRLGCQEEGAAEVKRHPFFRNMNFKRLEAGMLDPPFVPDPRAVYCKDVLDI
  EQFSTVKGVNLDHTDDDFYSKFSTGSVSIPWQNEMIETECFKELNVFGPNGTLPPDLNRN
  HPPEPPKKGLLQRLFKRQHQNNSKSSPSSKTSFNHHINSNHVSSNSTGSS

• Sequence length: 590

Pathways

KEGG:

Chemokine signaling pathway
Endocytosis
Morphine addiction

Reactome:

G alpha (s) signalling events

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ANTIPHOSPHOLIPID SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARDIOVASCULAR DISEASES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY ANEURYSM	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GASTROESOPHAGEAL REFLUX DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GRK5-related disorder	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEART DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER DISEASES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAJOR DEPRESSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Neurodevelopmental disorder	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURODEVELOPMENTAL DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OBESITY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
STROKE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VENOUS THROMBOEMBOLISM	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma	Adenocarcinoma	BEFREE	29463786		★☆☆☆☆ Found in Text Mining only
Adult Medulloblastoma	Medulloblastoma	BEFREE	24632620		★☆☆☆☆ Found in Text Mining only
Age related macular degeneration	Age-related macular degeneration	BEFREE	16080115		★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Alzheimer disease	Pubtator	34164834	Inhibit	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Alzheimer Disease, Late Onset	Alzheimer disease	BEFREE	29069820		★☆☆☆☆ Found in Text Mining only
Arthritis Infectious	Infective arthritis	Pubtator	16849637	Associate	★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	LHGDN	18622265		★☆☆☆☆ Found in Text Mining only
Atrial Fibrillation	Atrial Fibrillation	BEFREE	25049040, 26235218		★☆☆☆☆ Found in Text Mining only
Atrial Fibrillation	Atrial fibrillation	Pubtator	25049040, 26235218, 26860460	Associate	★☆☆☆☆ Found in Text Mining only
Blood Platelet Disorders	Platelet disorder	Pubtator	32649856	Associate	★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	31363957, 31664083		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Breast Neoplasms	Breast neoplasm	Pubtator	31664083, 34268929	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	36059531	Associate	★☆☆☆☆ Found in Text Mining only
Cardiomyopathies	Cardiomyopathy	BEFREE	18425130		★☆☆☆☆ Found in Text Mining only
Cardiomyopathy Dilated	Dilated cardiomyopathy	Pubtator	27711126	Associate	★☆☆☆☆ Found in Text Mining only
Cardiomyopathy, Dilated	Cardiomyopathy	BEFREE	22685168		★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Cardiovascular Diseases	CTD_human_DG	26032411		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cardiovascular Diseases	Cardiovascular Diseases	BEFREE	26248277, 30837872		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cardiovascular Diseases	Cardiovascular disease	Pubtator	32649856	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cerebral Infarction	Ischemic stroke	Pubtator	36691064, 40304040	Associate	★☆☆☆☆ Found in Text Mining only
Childhood Medulloblastoma	Medulloblastoma	BEFREE	24632620		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	21575264, 22126303	Associate	★☆☆☆☆ Found in Text Mining only
Congenital Heart Defects	Congenital heart defects	BEFREE	27618959		★☆☆☆☆ Found in Text Mining only
Congestive heart failure	Congestive Heart Failure	BEFREE	10448093, 18425130, 21622221, 21768220, 22196842, 26829117, 27618959, 28328744, 29627263, 30104167, 31186538, 31785110		★☆☆☆☆ Found in Text Mining only
Conventional (Clear Cell) Renal Cell Carcinoma	Renal Carcinoma	BEFREE	30784280		★☆☆☆☆ Found in Text Mining only
Coronary heart disease	Coronary Heart Disease	BEFREE	27618959		★☆☆☆☆ Found in Text Mining only
Craniosynostosis	Craniosynostosis	BEFREE	26149656		★☆☆☆☆ Found in Text Mining only
Crohn Disease	Crohn Disease	GWASDB_DG	17804789		★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	BEFREE	31696655		★☆☆☆☆ Found in Text Mining only
Dementia	Dementia	BEFREE	26614013		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes mellitus	Pubtator	30907055	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 2	Diabetes mellitus, type 2	Pubtator	22961080, 24594703, 29773828	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	22961080, 24594703, 26919830, 29663513, 29773828		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	GWASCAT_DG	22961080		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	GWASDB_DG	22961080		★☆☆☆☆ Found in Text Mining only
Differentiated Thyroid Gland Carcinoma	Thyroid Carcinoma	BEFREE	12107237		★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	BEFREE	29080472		★☆☆☆☆ Found in Text Mining only
Esophagitis	Esotropia	Pubtator	29628359	Associate	★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	BEFREE	30662593		★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	30662593		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	BEFREE	30662593		★☆☆☆☆ Found in Text Mining only
Heart Diseases	Heart Diseases	BEFREE	22685168		★☆☆☆☆ Found in Text Mining only
Heart failure	Heart Failure	BEFREE	18425130, 21622221, 21768220, 22196842, 26829117, 27618959, 28328744, 29627263, 30104167, 31186538, 31785110		★☆☆☆☆ Found in Text Mining only
Heart Failure	Heart failure	Pubtator	19628119, 30104167, 30978507, 31554410, 32649856, 39276349	Associate	★☆☆☆☆ Found in Text Mining only
Heart Failure Systolic	Heart failure	Pubtator	25638254	Associate	★☆☆☆☆ Found in Text Mining only
Hyperaldosteronism	Hyperaldosteronism	BEFREE	26932512		★☆☆☆☆ Found in Text Mining only
Hypertension	Hypertension	Pubtator	21127457	Associate	★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	BEFREE	21768220		★☆☆☆☆ Found in Text Mining only
Hypoglycemia	Hypoglycemia	Pubtator	24594703	Associate	★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	BEFREE	26614013		★☆☆☆☆ Found in Text Mining only
Ischemic cardiomyopathy	Ischemic myocardial dysfunction	BEFREE	22685168		★☆☆☆☆ Found in Text Mining only
Lafora Disease	Lafora Disease	BEFREE	17146290		★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	GWASCAT_DG	27903959		★☆☆☆☆ Found in Text Mining only
Lewy Body Disease	Lewy body disease	Pubtator	16957079	Associate	★☆☆☆☆ Found in Text Mining only
Lewy Body Disease	Lewy Body Disease	BEFREE	17146290		★☆☆☆☆ Found in Text Mining only
Macular Degeneration	Macular degeneration	Pubtator	16080115	Associate	★☆☆☆☆ Found in Text Mining only
Major Depressive Disorder	Mental Depression	BEFREE	20493668		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant neoplasm of breast	Breast Cancer	BEFREE	31363957, 31664083		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	24755472		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	19900276, 29463786, 30524659, 30784280, 31664083		★☆☆☆☆ Found in Text Mining only
Malnutrition	Malnutrition	BEFREE	26919830		★☆☆☆☆ Found in Text Mining only
Medulloblastoma	Medulloblastoma	BEFREE	24632620		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	12107237, 19900276, 24755472, 30662593, 30784280		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Disorders	Neurodegenerative Disorders	BEFREE	30618771		★☆☆☆☆ Found in Text Mining only
Non-Small Cell Lung Carcinoma	Lung carcinoma	BEFREE	29463786		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	29773828		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Obesity	Obesity	Pubtator	29773828	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteoarthritis, Knee	Knee osteoarthritis	BEFREE	31696655		★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	Pubtator	16957079, 40494419	Associate	★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	BEFREE	19852948, 21184589, 26614013		★☆☆☆☆ Found in Text Mining only
Periodontitis	Periodontitis	Pubtator	35179257	Associate	★☆☆☆☆ Found in Text Mining only
Presenile dementia	Senile Dementia	BEFREE	26614013		★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	24755472		★☆☆☆☆ Found in Text Mining only
Renal Cell Carcinoma	Renal Carcinoma	BEFREE	30784280		★☆☆☆☆ Found in Text Mining only
Rheumatoid Arthritis	Rheumatoid arthritis	BEFREE	10094932		★☆☆☆☆ Found in Text Mining only
Septicemia	Septicemia	BEFREE	23485819		★☆☆☆☆ Found in Text Mining only
Situs ambiguus	Situs ambiguus	BEFREE	27618959		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma	Carcinoma	BEFREE	29463786		★☆☆☆☆ Found in Text Mining only
Status Epilepticus	Status Epilepticus	BEFREE	29080472		★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	34034702	Associate	★☆☆☆☆ Found in Text Mining only
Stroke	Stroke	Pubtator	21127457, 32649856	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Stroke	Stroke	Pubtator	36691064	Stimulate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Trichohepatoenteric Syndrome	Trichohepatoenteric Syndrome	BEFREE	23794609		★☆☆☆☆ Found in Text Mining only
Triple Negative Breast Neoplasms	Triple Negative Breast Neoplasms	BEFREE	31664083		★☆☆☆☆ Found in Text Mining only
Triple Negative Breast Neoplasms	Triple negative breast cancer	Pubtator	31664083, 35412954	Associate	★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Urinary bladder neoplasms	Pubtator	34116604	Associate	★☆☆☆☆ Found in Text Mining only
Venous Thromboembolism	Venous thromboembolism	Pubtator	31420334, 32649856	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations