Reviewed, UniProtKB/Swiss-Prot P34947 (GRK5_HUMAN)

Names and origin

Protein names

Recommended name:
    G protein-coupled receptor kinase 5
    EC=2.7.11.16
Alternative name(s):
    G protein-coupled receptor kinase GRK5

Gene names

Name:	GRK5
Synonyms:	GPRK5

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	590 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Specifically phosphorylates the activated forms of G protein-coupled receptors.
Catalytic activity	ATP + [G-protein-coupled receptor] = ADP + [G-protein-coupled receptor] phosphate.
Tissue specificity	Highest levels in heart, placenta, lung > skeletal muscle > brain, liver, pancreas > kidney.
Sequence similarities	Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. GPRK subfamily. Contains 1 AGC-kinase C-terminal domain. Contains 1 protein kinase domain. Contains 1 RGS domain.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	G-protein signaling, coupled to cAMP nucleotide second messenger Traceable author statement. Source: ProtInc protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro regulation of G-protein coupled receptor protein signaling pathway Traceable author statement. Source: ProtInc tachykinin receptor signaling pathway Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Ref.1 Traceable author statement. Source: ProtInc plasma membrane Inferred from direct assay. Source: UniProtKB soluble fraction Ref.1 Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW G-protein coupled receptor kinase activity Inferred from electronic annotation. Source: EC phospholipid binding Traceable author statement. Source: ProtInc protein kinase C binding Traceable author statement. Source: ProtInc signal transducer activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 590	590	G protein-coupled receptor kinase 5		PRO_0000085971
Regions
	Domain	53 – 171	119	RGS
	Domain	186 – 448	263	Protein kinase
	Domain	449 – 514	66	AGC-kinase C-terminal
	Nucleotide binding	192 – 200	9	ATP By similarity
	Region	1 – 185	185	N-terminal
Sites
	Active site	311	1	Proton acceptor By similarity
	Binding site	215	1	ATP By similarity
Amino acid modifications
	Modified residue	484	1	Phosphoserine; by autocatalysis By similarity
	Modified residue	485	1	Phosphothreonine; by autocatalysis By similarity
Natural variations
	Natural variant	41	1	Q → L: dbSNP rs17098707. Ref.7		VAR_040517
	Natural variant	119	1	A → V: dbSNP rs55980792. Ref.7		VAR_040518
	Natural variant	122	1	G → S: dbSNP rs55902633. Ref.7		VAR_040519
	Natural variant	129	1	T → M: dbSNP rs34679178. Ref.7		VAR_040520
	Natural variant	141	1	L → I: dbSNP rs56254855. Ref.7		VAR_040521
	Natural variant	163	1	D → E in a lung neuroendocrine carcinoma sample; somatic mutation. Ref.7		VAR_040522
	Natural variant	172	1	Q → H: dbSNP rs45630572.		VAR_059766
	Natural variant	304	1	R → H: dbSNP rs2230349. Ref.7		VAR_040523

Sequences

	Sequence		Length	Mass (Da)
	P34947-1 [UniParc]. Last modified February 1, 1994. Version 1. Checksum: D363567ECFF5CF21	FASTA	590	67,787
	10 20 30 40 50 60 MELENIVANT VLLKAREGGG GKRKGKSKKW KEILKFPHIS QCEDLRRTID RDYCSLCDKQ 70 80 90 100 110 120 PIGRLLFRQF CETRPGLECY IQFLDSVAEY EVTPDEKLGE KGKEIMTKYL TPKSPVFIAQ 130 140 150 160 170 180 VGQDLVSQTE EKLLQKPCKE LFSACAQSVH EYLRGEPFHE YLDSMFFDRF LQWKWLERQP 190 200 210 220 230 240 VTKNTFRQYR VLGKGGFGEV CACQVRATGK MYACKRLEKK RIKKRKGESM ALNEKQILEK 250 260 270 280 290 300 VNSQFVVNLA YAYETKDALC LVLTIMNGGD LKFHIYNMGN PGFEEERALF YAAEILCGLE 310 320 330 340 350 360 DLHRENTVYR DLKPENILLD DYGHIRISDL GLAVKIPEGD LIRGRVGTVG YMAPEVLNNQ 370 380 390 400 410 420 RYGLSPDYWG LGCLIYEMIE GQSPFRGRKE KVKREEVDRR VLETEEVYSH KFSEEAKSIC 430 440 450 460 470 480 KMLLTKDAKQ RLGCQEEGAA EVKRHPFFRN MNFKRLEAGM LDPPFVPDPR AVYCKDVLDI 490 500 510 520 530 540 EQFSTVKGVN LDHTDDDFYS KFSTGSVSIP WQNEMIETEC FKELNVFGPN GTLPPDLNRN 550 560 570 580 590 HPPEPPKKGL LQRLFKRQHQ NNSKSSPSSK TSFNHHINSN HVSSNSTGSS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of GRK5: a member of the G protein-coupled receptor kinase family." Kunapuli P., Benovic J.L. Proc. Natl. Acad. Sci. U.S.A. 90:5588-5592(1993) [PubMed: 7685906] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Prostate.
[5]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-484 AND THR-485, MASS SPECTROMETRY.
[6]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-484 AND THR-485, MASS SPECTROMETRY. Tissue: T-cell.
[7]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-41; VAL-119; SER-122; MET-129; ILE-141; GLU-163 AND HIS-304.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L15388 mRNA. Translation: AAA58620.1. AL355273, AL355861, AL583824 Genomic DNA. Translation: CAI16487.1. AL355861, AL355273, AL583824 Genomic DNA. Translation: CAI15804.1. AL583824, AL355273, AL355861 Genomic DNA. Translation: CAI16759.1. CH471066 Genomic DNA. Translation: EAW49394.1. BC064506 mRNA. Translation: AAH64506.1.
IPI	IPI00414058.
PIR	A48277. B48682.
RefSeq	NP_005299.1.
UniGene	Hs.524625
3D structure databases
SMR	P34947. Positions 23-532.
ModBase	Search...
Protein-protein interaction databases
STRING	P34947.
PTM databases
PhosphoSite	P34947.
Proteomic databases
PRIDE	P34947.
Genome annotation databases
Ensembl	ENST00000392870; ENSP00000376609; ENSG00000198873; Homo sapiens. [Genome view]
GeneID	2869.
KEGG	hsa:2869.
UCSC	uc001led.1. human.
Organism-specific databases
CTD	2869.
GeneCards	GC10P120957.
H-InvDB	HIX0035405.
HGNC	HGNC:4544. GRK5.
HPA	CAB025579.
MIM	600870. gene.
PharmGKB	PA180.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HBG716704.
HOVERGEN	P34947.
InParanoid	P34947.
OMA	LECYIQF.
OrthoDB	EOG9Z0DR5.
PhylomeDB	P34947.
Enzyme and pathway databases
BRENDA	2.7.11.16. 247.
Pathway_Interaction_DB	alphasynuclein_pathway. Alpha-synuclein signaling.
Reactome	REACT_14797. Signaling by GPCR.
Gene expression databases
ArrayExpress	P34947.
Bgee	P34947.
CleanEx	HS_GRK5.
Genevestigator	P34947.
GermOnline	ENSG00000198873. Homo sapiens.
Family and domain databases
InterPro	IPR000961. AGC-kinase_C. IPR000239. GPCR_kinase. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR000342. Regulat_G_prot_signal. IPR016137. Regulat_G_prot_signal_superfam. IPR017442. Se/Thr_prot_kinase-like_dom. IPR002290. Ser/Thr_prot_kinase_dom. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. PF00615. RGS. 1 hit. [Graphical view]
PRINTS	PR00717. GPCRKINASE.
SMART	SM00315. RGS. 1 hit. SM00133. S_TK_X. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
PROSITE	PS51285. AGC_KINASE_CTER. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. False negative. PS50132. RGS. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	11319.
SOURCE	Search...

Entry information

Entry name

GRK5_HUMAN

Accession

Primary (citable) accession number: P34947
Secondary accession number(s): Q5T059

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	February 1, 1994
Last modified:	January 19, 2010
This is version 100 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.