Q8WTQ7 (GRK7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
G protein-coupled receptor kinase 7
EC=2.7.11.14
EC=2.7.11.16

Alternative name(s):
G protein-coupled receptor kinase GRK7

Gene names

Name:	GRK7
Synonyms:	GPRK7

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	553 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Retina-specific kinase involved in the shutoff of the photoresponse and adaptation to changing light conditions via cone opsin phosphorylation, including rhodopsin (RHO). Ref.4
Catalytic activity	ATP + [G-protein-coupled receptor] = ADP + [G-protein-coupled receptor] phosphate. Ref.4 ATP + [rhodopsin] = ADP + [rhodopsin] phosphate. Ref.4
Enzyme regulation	Inhibited by phosphorylation of Ser-36 By similarity. Ref.4
Subcellular location	Membrane; Lipid-anchor.
Tissue specificity	Retinal cones, outer and inner segments. Ref.1 Ref.5
Post-translational modification	Autophosphorylated in vitro at Ser-490. Phosphorylation at Ser-36 is regulated by light and activated by cAMP. Ref.4 Ref.5
Miscellaneous	Although the protein is present in a diversity of vertebrates ranging from bony fish to mammals, the mouse and rat orthologous proteins do not exist.
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.
Biophysicochemical properties	Kinetic parameters: KM=1.9 µM for rhodopsin Ref.4 KM=21.4 µM for ATP Vmax=915 nmol/min/mg enzyme

Ontologies

Keywords
Biological process	Sensory transduction Vision
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Lipoprotein Methylation Phosphoprotein Prenylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	protein autophosphorylation Inferred from mutant phenotype Ref.4. Source: UniProtKB signal transduction Inferred from electronic annotation. Source: InterPro termination of G-protein coupled receptor signaling pathway Inferred from electronic annotation. Source: InterPro visual perception Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW G-protein coupled receptor kinase activity Inferred from electronic annotation. Source: EC rhodopsin kinase activity Inferred from direct assay Ref.4. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 550	550	G protein-coupled receptor kinase 7		PRO_0000024332
	Propeptide	551 – 553	3	Removed in mature form By similarity		PRO_0000024333
Regions
	Domain	56 – 176	121	RGS
	Domain	191 – 454	264	Protein kinase
	Domain	455 – 520	66	AGC-kinase C-terminal
	Nucleotide binding	197 – 205	9	ATP By similarity
Sites
	Active site	316	1	Proton acceptor By similarity
	Binding site	220	1	ATP By similarity
Amino acid modifications
	Modified residue	36	1	Phosphoserine; by PKA Ref.5
	Modified residue	550	1	Cysteine methyl ester Potential
	Lipidation	550	1	S-geranylgeranyl cysteine Potential
Natural variations
	Natural variant	81	1	R → H. Ref.6 Corresponds to variant rs34429284 [ dbSNP | Ensembl ].		VAR_040527
	Natural variant	113	1	C → W. Ref.6 Corresponds to variant rs56070798 [ dbSNP | Ensembl ].		VAR_040528
	Natural variant	115	1	S → C. Ref.6 Corresponds to variant rs34769632 [ dbSNP | Ensembl ].		VAR_040529
	Natural variant	127	1	S → T. Ref.6 Corresponds to variant rs35318124 [ dbSNP | Ensembl ].		VAR_040530
	Natural variant	196	1	V → G. Ref.6 Corresponds to variant rs55707760 [ dbSNP | Ensembl ].		VAR_040531
	Natural variant	196	1	V → M. Ref.6 Corresponds to variant rs56019094 [ dbSNP | Ensembl ].		VAR_040532
	Natural variant	226	1	R → W. Ref.6 Corresponds to variant rs35566288 [ dbSNP | Ensembl ].		VAR_040533
	Natural variant	253	1	S → F in a metastatic melanoma sample; somatic mutation. Ref.6		VAR_040534
	Natural variant	309	1	E → Q. Ref.6 Corresponds to variant rs55824414 [ dbSNP | Ensembl ].		VAR_040535
	Natural variant	313	1	V → I. Ref.6 Corresponds to variant rs56076641 [ dbSNP | Ensembl ].		VAR_040536
	Natural variant	443	1	E → G. Ref.6 Corresponds to variant rs36009541 [ dbSNP | Ensembl ].		VAR_040537
	Natural variant	460	1	P → T. Ref.6 Corresponds to variant rs33928105 [ dbSNP | Ensembl ].		VAR_040538
	Natural variant	461	1	R → C. Corresponds to variant rs36004830 [ dbSNP | Ensembl ].		VAR_051624
Experimental info
	Mutagenesis	23	1	S → A: No effect on kinase activity. Increase kinase activity; when associated with A-36. Ref.4
	Mutagenesis	36	1	S → A: No effect on kinase activity. Increase kinase activity; when associated with A-23. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q8WTQ7 [UniParc]. Last modified March 1, 2002. Version 1. Checksum: C502E301CF8EB688	FASTA	553	62,212
	10 20 30 40 50 60 MVDMGALDNL IANTAYLQAR KPSDCDSKEL QRRRRSLALP GLQGCAELRQ KLSLNFHSLC 70 80 90 100 110 120 EQQPIGRRLF RDFLATVPTF RKAATFLEDV QNWELAEEGP TKDSALQGLV ATCASAPAPG 130 140 150 160 170 180 NPQPFLSQAV ATKCQAATTE EERVAAVTLA KAEAMAFLQE QPFKDFVTSA FYDKFLQWKL 190 200 210 220 230 240 FEMQPVSDKY FTEFRVLGKG GFGEVCAVQV KNTGKMYACK KLDKKRLKKK GGEKMALLEK 250 260 270 280 290 300 EILEKVSSPF IVSLAYAFES KTHLCLVMSL MNGGDLKFHI YNVGTRGLDM SRVIFYSAQI 310 320 330 340 350 360 ACGMLHLHEL GIVYRDMKPE NVLLDDLGNC RLSDLGLAVE MKGGKPITQR AGTNGYMAPE 370 380 390 400 410 420 ILMEKVSYSY PVDWFAMGCS IYEMVAGRTP FKDYKEKVSK EDLKQRTLQD EVKFQHDNFT 430 440 450 460 470 480 EEAKDICRLF LAKKPEQRLG SREKSDDPRK HHFFKTINFP RLEAGLIEPP FVPDPSVVYA 490 500 510 520 530 540 KDIAEIDDFS EVRGVEFDDK DKQFFKNFAT GAVPIAWQEE IIETGLFEEL NDPNRPTGCE 550 EGNSSKSGVC LLL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of human GRK7 as a potential cone opsin kinase." Chen C.-K., Zhang K., Church-Kopish J., Huang W., Zhang H., Chen Y.-J., Frederick J.M., Baehr W. Mol. Vis. 7:305-313(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Retina.
[2]	"Species-specific differences in expression of G-protein-coupled receptor kinase (GRK) 7 and GRK1 in mammalian cone photoreceptor cells: implications for cone cell phototransduction." Weiss E.R., Ducceschi M.H., Horner T.J., Li A., Craft C.M., Osawa S. J. Neurosci. 21:9175-9184(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Retina.
[3]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Phosphorylation of GRK1 and GRK7 by cAMP-dependent protein kinase attenuates their enzymatic activities." Horner T.J., Osawa S., Schaller M.D., Weiss E.R. J. Biol. Chem. 280:28241-28250(2005) [PubMed] [Europe PMC] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY, FUNCTION IN PHOSPHORYLATION OF RHO, ENZYME REGULATION, AUTOPHOSPHORYLATION, MUTAGENESIS OF SER-23 AND SER-36.
[5]	"Phosphorylation of GRK7 by PKA in cone photoreceptor cells is regulated by light." Osawa S., Jo R., Weiss E.R. J. Neurochem. 107:1314-1324(2008) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, PHOSPHORYLATION AT SER-36.
[6]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] HIS-81; TRP-113; CYS-115; THR-127; GLY-196; MET-196; TRP-226; PHE-253; GLN-309; ILE-313; GLY-443 AND THR-460.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF439409 mRNA. Translation: AAL48216.1. AF282269 mRNA. Translation: AAL33880.1. AC112504 Genomic DNA. No translation available.
IPI	IPI00102804.
RefSeq	NP_631948.1. NM_139209.2.
UniGene	Hs.680654.
3D structure databases
ProteinModelPortal	Q8WTQ7.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8WTQ7. 1 interaction.
STRING	9606.ENSP00000264952.
PTM databases
PhosphoSite	Q8WTQ7.
Polymorphism databases
DMDM	21263659.
Proteomic databases
PaxDb	Q8WTQ7.
PRIDE	Q8WTQ7.
Protocols and materials databases
DNASU	131890.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000264952; ENSP00000264952; ENSG00000114124.
GeneID	131890.
KEGG	hsa:131890.
UCSC	uc011bnd.2. human.
Organism-specific databases
CTD	131890.
GeneCards	GC03P141496.
HGNC	HGNC:17031. GRK7.
HPA	HPA040138.
MIM	606987. gene.
neXtProt	NX_Q8WTQ7.
PharmGKB	PA38433.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000006742.
HOVERGEN	HBG004532.
InParanoid	Q8WTQ7.
KO	K00909.
OMA	ESKSHLC.
OrthoDB	EOG4TTGJ1.
PhylomeDB	Q8WTQ7.
Enzyme and pathway databases
BRENDA	2.7.11.14. 2681.
Pathway_Interaction_DB	cone_pathway. Visual signal transduction: Cones.
Gene expression databases
Bgee	Q8WTQ7.
CleanEx	HS_GRK7.
Genevestigator	Q8WTQ7.
GermOnline	ENSG00000114124. 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. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [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]
SUPFAM	SSF56112. Kinase_like. 1 hit. SSF48097. Regulat_G_prot_signal_superfam. 1 hit.
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]
ProtoNet	Search...
Other
BindingDB	Q8WTQ7.
ChEMBL	CHEMBL1075133.
GenomeRNAi	131890.
NextBio	82983.
SOURCE	Search...

Entry information

Entry name

GRK7_HUMAN

Accession

Primary (citable) accession number: Q8WTQ7

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 27, 2002
Last sequence update:	March 1, 2002
Last modified:	May 1, 2013
This is version 110 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.