Reviewed, UniProtKB/Swiss-Prot P32298 (GRK4_HUMAN)

Names and origin

Protein names

Recommended name:
    G protein-coupled receptor kinase 4
    EC=2.7.11.16
Alternative name(s):
    G protein-coupled receptor kinase GRK4
    ITI1

Gene names

Name:	GRK4
Synonyms:	GPRK2L, GPRK4

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	578 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Specifically phosphorylates the activated forms of G protein-coupled receptors. GRK4-alpha can phosphorylate rhodopsin and its activity is inhibited by calmodulin; the other three isoforms do not phosphorylate rhodopsin and do not interact with calmodulin.
Catalytic activity	ATP + [G-protein-coupled receptor] = ADP + [G-protein-coupled receptor] phosphate.
Tissue specificity	Testis, and in a lower extent in other tissues including brain cortex and striatum.
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	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
Gene Ontology (GO)
Biological process	regulation of G-protein coupled receptor protein signaling pathway Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P32298-1)

Also known as: GRK4-alpha; GRK4D;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P32298-2)

Also known as: GRK4-beta; GRK4C;

The sequence of this isoform differs from the canonical sequence as follows:
     18-49: Missing.

Isoform 3 (identifier: P32298-3)

Also known as: GRK4-delta; GRK4A;

The sequence of this isoform differs from the canonical sequence as follows:
     18-49: Missing.
     516-561: Missing.

Isoform 4 (identifier: P32298-4)

Also known as: GRK4-gamma; GRK4B;

The sequence of this isoform differs from the canonical sequence as follows:
     516-561: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 578	578	G protein-coupled receptor kinase 4
Regions
	Domain	52 – 172	121	RGS
	Domain	187 – 449	263	Protein kinase
	Domain	450 – 515	66	AGC-kinase C-terminal
	Nucleotide binding	193 – 201	9	ATP By similarity
	Region	1 – 154	154	N-terminal
Sites
	Active site	312	1	Proton acceptor By similarity
	Binding site	216	1	ATP By similarity
Natural variations
	Alternative sequence	18 – 49	32	Missing in isoform 2 and isoform 3.
	Alternative sequence	516 – 561	46	Missing in isoform 3 and isoform 4.
	Natural variant	65	1	R → L: dbSNP rs2960306.
	Natural variant	116	1	A → T
	Natural variant	142	1	A → V: dbSNP rs1024323.
	Natural variant	247	1	V → I
	Natural variant	383	1	H → Q
	Natural variant	425	1	L → P
	Natural variant	473	1	V → I
	Natural variant	486	1	V → A: dbSNP rs1801058.
	Natural variant	495	1	A → T
Experimental info
	Sequence conflict	562	1	G → D in CAA66468 and CAA66802. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (GRK4-alpha) (GRK4D) [UniParc]. Last modified April 3, 2007. Version 3. Checksum: 72FCF94ED551F2D0	FASTA	578	66,583
	10 20 30 40 50 60 MELENIVANS LLLKARQGGY GKKSGRSKKW KEILTLPPVS QCSELRHSIE KDYSSLCDKQ 70 80 90 100 110 120 PIGRRLFRQF CDTKPTLKRH IEFLDAVAEY EVADDEDRSD CGLSILDRFF NDKLAAPLPE 130 140 150 160 170 180 IPPDVVTECR LGLKEENPSK KAFEECTRVA HNYLRGEPFE EYQESSYFSQ FLQWKWLERQ 190 200 210 220 230 240 PVTKNTFRHY RVLGKGGFGE VCACQVRATG KMYACKKLQK KRIKKRKGEA MALNEKRILE 250 260 270 280 290 300 KVQSRFVVSL AYAYETKDAL CLVLTIMNGG DLKFHIYNLG NPGFDEQRAV FYAAELCCGL 310 320 330 340 350 360 EDLQRERIVY RDLKPENILL DDRGHIRISD LGLATEIPEG QRVRGRVGTV GYMAPEVVNN 370 380 390 400 410 420 EKYTFSPDWW GLGCLIYEMI QGHSPFKKYK EKVKWEEVDQ RIKNDTEEYS EKFSEDAKSI 430 440 450 460 470 480 CRMLLTKNPS KRLGCRGEGA AGVKQHPVFK DINFRRLEAN MLEPPFCPDP HAVYCKDVLD 490 500 510 520 530 540 IEQFSVVKGI YLDTADEDFY ARFATGCVSI PWQNEMIESG CFKDINKSES EEALPLDLDK 550 560 570 NIHTPVSRPN RGFFYRLFRR GGCLTMVPSE KEVEPKQC
	Isoform 2 (GRK4-beta) (GRK4C) [UniParc]. Checksum: AD60D125A5839CA3		546	63,030
	10 20 30 40 50 60 MELENIVANS LLLKARQEKD YSSLCDKQPI GRRLFRQFCD TKPTLKRHIE FLDAVAEYEV 70 80 90 100 110 120 ADDEDRSDCG LSILDRFFND KLAAPLPEIP PDVVTECRLG LKEENPSKKA FEECTRVAHN 130 140 150 160 170 180 YLRGEPFEEY QESSYFSQFL QWKWLERQPV TKNTFRHYRV LGKGGFGEVC ACQVRATGKM 190 200 210 220 230 240 YACKKLQKKR IKKRKGEAMA LNEKRILEKV QSRFVVSLAY AYETKDALCL VLTIMNGGDL 250 260 270 280 290 300 KFHIYNLGNP GFDEQRAVFY AAELCCGLED LQRERIVYRD LKPENILLDD RGHIRISDLG 310 320 330 340 350 360 LATEIPEGQR VRGRVGTVGY MAPEVVNNEK YTFSPDWWGL GCLIYEMIQG HSPFKKYKEK 370 380 390 400 410 420 VKWEEVDQRI KNDTEEYSEK FSEDAKSICR MLLTKNPSKR LGCRGEGAAG VKQHPVFKDI 430 440 450 460 470 480 NFRRLEANML EPPFCPDPHA VYCKDVLDIE QFSVVKGIYL DTADEDFYAR FATGCVSIPW 490 500 510 520 530 540 QNEMIESGCF KDINKSESEE ALPLDLDKNI HTPVSRPNRG FFYRLFRRGG CLTMVPSEKE VEPKQC
	Isoform 3 (GRK4-delta) (GRK4A) [UniParc]. Checksum: 6AF0953E8D1F7A06		500	57,663
	10 20 30 40 50 60 MELENIVANS LLLKARQEKD YSSLCDKQPI GRRLFRQFCD TKPTLKRHIE FLDAVAEYEV 70 80 90 100 110 120 ADDEDRSDCG LSILDRFFND KLAAPLPEIP PDVVTECRLG LKEENPSKKA FEECTRVAHN 130 140 150 160 170 180 YLRGEPFEEY QESSYFSQFL QWKWLERQPV TKNTFRHYRV LGKGGFGEVC ACQVRATGKM 190 200 210 220 230 240 YACKKLQKKR IKKRKGEAMA LNEKRILEKV QSRFVVSLAY AYETKDALCL VLTIMNGGDL 250 260 270 280 290 300 KFHIYNLGNP GFDEQRAVFY AAELCCGLED LQRERIVYRD LKPENILLDD RGHIRISDLG 310 320 330 340 350 360 LATEIPEGQR VRGRVGTVGY MAPEVVNNEK YTFSPDWWGL GCLIYEMIQG HSPFKKYKEK 370 380 390 400 410 420 VKWEEVDQRI KNDTEEYSEK FSEDAKSICR MLLTKNPSKR LGCRGEGAAG VKQHPVFKDI 430 440 450 460 470 480 NFRRLEANML EPPFCPDPHA VYCKDVLDIE QFSVVKGIYL DTADEDFYAR FATGCVSIPW 490 500 QNEGCLTMVP SEKEVEPKQC
	Isoform 4 (GRK4-gamma) (GRK4B) [UniParc]. Checksum: 1DD49402FCB381E5		532	61,216
	10 20 30 40 50 60 MELENIVANS LLLKARQGGY GKKSGRSKKW KEILTLPPVS QCSELRHSIE KDYSSLCDKQ 70 80 90 100 110 120 PIGRRLFRQF CDTKPTLKRH IEFLDAVAEY EVADDEDRSD CGLSILDRFF NDKLAAPLPE 130 140 150 160 170 180 IPPDVVTECR LGLKEENPSK KAFEECTRVA HNYLRGEPFE EYQESSYFSQ FLQWKWLERQ 190 200 210 220 230 240 PVTKNTFRHY RVLGKGGFGE VCACQVRATG KMYACKKLQK KRIKKRKGEA MALNEKRILE 250 260 270 280 290 300 KVQSRFVVSL AYAYETKDAL CLVLTIMNGG DLKFHIYNLG NPGFDEQRAV FYAAELCCGL 310 320 330 340 350 360 EDLQRERIVY RDLKPENILL DDRGHIRISD LGLATEIPEG QRVRGRVGTV GYMAPEVVNN 370 380 390 400 410 420 EKYTFSPDWW GLGCLIYEMI QGHSPFKKYK EKVKWEEVDQ RIKNDTEEYS EKFSEDAKSI 430 440 450 460 470 480 CRMLLTKNPS KRLGCRGEGA AGVKQHPVFK DINFRRLEAN MLEPPFCPDP HAVYCKDVLD 490 500 510 520 530 IEQFSVVKGI YLDTADEDFY ARFATGCVSI PWQNEGCLTM VPSEKEVEPK QC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel G protein-coupled receptor kinase gene cloned from 4p16.3." Ambrose C., James M., Barnes G., Lin C., Bates G., Altherr M., Duyao M., Groot N., Church D., Wasmuth J.J., Lehrach H., Housman D., Buckler A.J., Gusella J.F., McDonald M.E. Hum. Mol. Genet. 1:697-703(1992) [PubMed: 1338872] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 3), VARIANT ALA-486.
[2]	"G protein-coupled receptor kinase GRK4. Molecular analysis of the four isoforms and ultrastructural localization in spermatozoa and germinal cells." Sallese M., Mariggio S., Collodel G., Moretti E., Piomboni P., Baccetti B., de Blasi A. J. Biol. Chem. 272:10188-10195(1997) [PubMed: 9092566] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), VARIANT ALA-486. Tissue: Testis.
[3]	"Characterization of the G protein-coupled receptor kinase GRK4. Identification of four splice variants." Premont R.T., Macrae A.D., Stoffel R.H., Chung N., Pitcher J.A., Ambrose C., Inglese J., MacDonald M.E., Lefkowitz R.J. J. Biol. Chem. 271:6403-6410(1996) [PubMed: 8626439] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], ALTERNATIVE SPLICING, VARIANT ALA-486. Tissue: Testis.
[4]	"Two isoforms of G protein-coupled receptor kinase 4 identified by molecular cloning." Sallese M., Lombardi M.S., de Blasi A. Biochem. Biophys. Res. Commun. 199:848-854(1994) [PubMed: 8135832] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANT ALA-486. Tissue: Brain.
[5]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] (ISOFORM 1), VARIANT ALA-486.
[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-65; THR-116; VAL-142; ILE-247; GLN-383; PRO-425; ILE-473; ALA-486 AND THR-495.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	L03718 Genomic DNA. Translation: AAB04045.1. X97879 mRNA. Translation: CAA66468.1. X97880 mRNA. Translation: CAA66469.1. X97881 mRNA. Translation: CAA66470.1. U33054 mRNA. Translation: AAC50406.1. U33055 mRNA. Translation: AAC50407.1. U33056 mRNA. Translation: AAC50408.1. U33168 , U33153, U33155, U33156, U33157, U33158, U33159, U33160, U33161, U33162, U33163, U33164, U33165, U33166, U33167 Genomic DNA. Translation: AAC50409.1. U33168 , U33153, U33154, U33155, U33156, U33157, U33158, U33159, U33160, U33161, U33162, U33163, U33164, U33165, U33166, U33167 Genomic DNA. Translation: AAC50410.1. U33168 , U33153, U33154, U33155, U33156, U33157, U33158, U33159, U33160, U33161, U33162, U33163, U33164, U33165, U33166 Genomic DNA. Translation: AAC50411.1. U33168 , U33153, U33155, U33156, U33157, U33158, U33159, U33160, U33161, U33162, U33163, U33164, U33165, U33166 Genomic DNA. Translation: AAC50412.1. X98118 mRNA. Translation: CAA66802.1. X75897 mRNA. Translation: CAA53506.1. Z68192 Genomic DNA. Translation: CAA92341.1. BC117320 mRNA. Translation: AAI17321.1.
PIR	I54326. JC2127.
RefSeq	NP_001004056.1. NP_001004057.1. NP_892027.2.
UniGene	Hs.32959
3D structure databases
ModBase	Search...
PTM databases
PhosphoSite	P32298.
Genome annotation databases
Ensembl	ENSG00000125388. Homo sapiens. [Contig view]
GeneID	2868.
KEGG	hsa:2868.
NMPDR	fig|9606.3.peg.23842.
Organism-specific databases
H-InvDB	HIX0031441.
HGNC	HGNC:4543. GRK4.
HPA	CAB004421.
MIM	137026. gene.
PharmGKB	PA28941.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOVERGEN	P32298.
Gene expression databases
ArrayExpress	P32298.
GermOnline	ENSG00000125388. Homo sapiens.
Family and domain databases
InterPro	IPR000239. GPCR_kinase. IPR000961. Pkinase_C. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_bd_CS. IPR000342. Regulat_G_prot_signal. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. IPR002290. Ser_thr_pkinase. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. PF00615. RGS. 1 hit. [Graphical view]
PRINTS	PR00717. GPCRKINASE.
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
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. 1 hit. PS50132. RGS. 1 hit. [Graphical view]
BLOCKS	Search...
Other Resources
SOURCE	Search...
ProtoNet	Search...

Entry information

Entry name

GRK4_HUMAN

Accession

Primary (citable) accession number: P32298
Secondary accession number(s): O00641 , O00642, Q13293, Q13294, Q13295, Q14453, Q14725, Q15313, Q15314, Q15315, Q15316, Q17RH6

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	April 3, 2007
Last modified:	September 2, 2008
This is version 90 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)