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Protein

G protein-coupled receptor kinase 7

Gene

GRK7

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Retina-specific kinase involved in the shutoff of the photoresponse and adaptation to changing light conditions via cone opsin phosphorylation, including rhodopsin (RHO).1 Publication

Catalytic activityi

ATP + [G-protein-coupled receptor] = ADP + [G-protein-coupled receptor] phosphate.1 Publication
ATP + [rhodopsin] = ADP + [rhodopsin] phosphate.1 Publication

Enzyme regulationi

Inhibited by phosphorylation of Ser-36.By similarity

Kineticsi

  1. KM=1.9 µM for rhodopsin1 Publication
  2. KM=21.4 µM for ATP1 Publication
  1. Vmax=915 nmol/min/mg enzyme1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei220 – 2201ATPPROSITE-ProRule annotation
Active sitei316 – 3161Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi197 – 2059ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • G-protein coupled receptor kinase activity Source: UniProtKB-EC
  • rhodopsin kinase activity Source: UniProtKB

GO - Biological processi

  • protein autophosphorylation Source: UniProtKB
  • signal transduction Source: InterPro
  • termination of G-protein coupled receptor signaling pathway Source: InterPro
  • visual perception Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Sensory transduction, Vision

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.14. 2681.
SignaLinkiQ8WTQ7.

Names & Taxonomyi

Protein namesi
Recommended name:
G protein-coupled receptor kinase 7 (EC:2.7.11.141 Publication, EC:2.7.11.16)
Alternative name(s):
G protein-coupled receptor kinase GRK7
Gene namesi
Name:GRK7
Synonyms:GPRK7
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:17031. GRK7.

Subcellular locationi

  • Membrane By similarity; Lipid-anchor By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi23 – 231S → A: No effect on kinase activity. Increase kinase activity; when associated with A-36. 1 Publication
Mutagenesisi36 – 361S → A: No effect on kinase activity. Increase kinase activity; when associated with A-23. 1 Publication

Organism-specific databases

PharmGKBiPA38433.

Polymorphism and mutation databases

BioMutaiGRK7.
DMDMi21263659.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 550550G protein-coupled receptor kinase 7PRO_0000024332Add
BLAST
Propeptidei551 – 5533Removed in mature formBy similarityPRO_0000024333

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei36 – 361Phosphoserine; by PKA1 Publication
Modified residuei550 – 5501Cysteine methyl esterSequence Analysis
Lipidationi550 – 5501S-geranylgeranyl cysteineSequence Analysis

Post-translational modificationi

Autophosphorylated in vitro at Ser-490. Phosphorylation at Ser-36 is regulated by light and activated by cAMP.1 Publication

Keywords - PTMi

Lipoprotein, Methylation, Phosphoprotein, Prenylation

Proteomic databases

PaxDbiQ8WTQ7.
PRIDEiQ8WTQ7.

PTM databases

PhosphoSiteiQ8WTQ7.

Expressioni

Tissue specificityi

Retinal cones, outer and inner segments.2 Publications

Gene expression databases

BgeeiQ8WTQ7.
CleanExiHS_GRK7.
GenevisibleiQ8WTQ7. HS.

Organism-specific databases

HPAiHPA040138.

Interactioni

Subunit structurei

Interacts (when prenylated) with PDE6D; this promotes release from membranes.By similarity

Protein-protein interaction databases

BioGridi126297. 2 interactions.
IntActiQ8WTQ7. 1 interaction.
STRINGi9606.ENSP00000264952.

Structurei

3D structure databases

ProteinModelPortaliQ8WTQ7.
SMRiQ8WTQ7. Positions 26-531.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini56 – 176121RGSPROSITE-ProRule annotationAdd
BLAST
Domaini191 – 454264Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini455 – 52066AGC-kinase C-terminalAdd
BLAST

Sequence similaritiesi

Contains 1 AGC-kinase C-terminal domain.Curated
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 RGS domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00770000120493.
HOGENOMiHOG000006742.
HOVERGENiHBG004532.
InParanoidiQ8WTQ7.
KOiK00909.
OMAiESKSHLC.
OrthoDBiEOG7V1FQK.
PhylomeDBiQ8WTQ7.
TreeFamiTF313940.

Family and domain databases

InterProiIPR000961. AGC-kinase_C.
IPR000239. GPCR_kinase.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016137. RGS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
PF00615. RGS. 1 hit.
[Graphical view]
PRINTSiPR00717. GPCRKINASE.
SMARTiSM00315. RGS. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF48097. SSF48097. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51285. 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]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q8WTQ7-1 [UniParc]FASTAAdd to basket

« Hide

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

LLL
Length:553
Mass (Da):62,212
Last modified:March 1, 2002 - v1
Checksum:iC502E301CF8EB688
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti81 – 811R → H.1 Publication
Corresponds to variant rs34429284 [ dbSNP | Ensembl ].
VAR_040527
Natural varianti113 – 1131C → W.1 Publication
Corresponds to variant rs56070798 [ dbSNP | Ensembl ].
VAR_040528
Natural varianti115 – 1151S → C.1 Publication
Corresponds to variant rs34769632 [ dbSNP | Ensembl ].
VAR_040529
Natural varianti127 – 1271S → T.1 Publication
Corresponds to variant rs35318124 [ dbSNP | Ensembl ].
VAR_040530
Natural varianti196 – 1961V → G.1 Publication
Corresponds to variant rs55707760 [ dbSNP | Ensembl ].
VAR_040531
Natural varianti196 – 1961V → M.1 Publication
Corresponds to variant rs56019094 [ dbSNP | Ensembl ].
VAR_040532
Natural varianti226 – 2261R → W.1 Publication
Corresponds to variant rs35566288 [ dbSNP | Ensembl ].
VAR_040533
Natural varianti253 – 2531S → F in a metastatic melanoma sample; somatic mutation. 1 Publication
VAR_040534
Natural varianti309 – 3091E → Q.1 Publication
Corresponds to variant rs55824414 [ dbSNP | Ensembl ].
VAR_040535
Natural varianti313 – 3131V → I.1 Publication
Corresponds to variant rs56076641 [ dbSNP | Ensembl ].
VAR_040536
Natural varianti443 – 4431E → G.1 Publication
Corresponds to variant rs36009541 [ dbSNP | Ensembl ].
VAR_040537
Natural varianti460 – 4601P → T.1 Publication
Corresponds to variant rs33928105 [ dbSNP | Ensembl ].
VAR_040538
Natural varianti461 – 4611R → C.
Corresponds to variant rs36004830 [ dbSNP | Ensembl ].
VAR_051624

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF439409 mRNA. Translation: AAL48216.1.
AF282269 mRNA. Translation: AAL33880.1.
AC112504 Genomic DNA. No translation available.
CCDSiCCDS3120.1.
RefSeqiNP_631948.1. NM_139209.2.
UniGeneiHs.680654.

Genome annotation databases

EnsembliENST00000264952; ENSP00000264952; ENSG00000114124.
GeneIDi131890.
KEGGihsa:131890.
UCSCiuc011bnd.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF439409 mRNA. Translation: AAL48216.1.
AF282269 mRNA. Translation: AAL33880.1.
AC112504 Genomic DNA. No translation available.
CCDSiCCDS3120.1.
RefSeqiNP_631948.1. NM_139209.2.
UniGeneiHs.680654.

3D structure databases

ProteinModelPortaliQ8WTQ7.
SMRiQ8WTQ7. Positions 26-531.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi126297. 2 interactions.
IntActiQ8WTQ7. 1 interaction.
STRINGi9606.ENSP00000264952.

Chemistry

BindingDBiQ8WTQ7.
ChEMBLiCHEMBL1075133.
GuidetoPHARMACOLOGYi1471.

PTM databases

PhosphoSiteiQ8WTQ7.

Polymorphism and mutation databases

BioMutaiGRK7.
DMDMi21263659.

Proteomic databases

PaxDbiQ8WTQ7.
PRIDEiQ8WTQ7.

Protocols and materials databases

DNASUi131890.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264952; ENSP00000264952; ENSG00000114124.
GeneIDi131890.
KEGGihsa:131890.
UCSCiuc011bnd.2. human.

Organism-specific databases

CTDi131890.
GeneCardsiGC03P141496.
HGNCiHGNC:17031. GRK7.
HPAiHPA040138.
MIMi606987. gene.
neXtProtiNX_Q8WTQ7.
PharmGKBiPA38433.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00770000120493.
HOGENOMiHOG000006742.
HOVERGENiHBG004532.
InParanoidiQ8WTQ7.
KOiK00909.
OMAiESKSHLC.
OrthoDBiEOG7V1FQK.
PhylomeDBiQ8WTQ7.
TreeFamiTF313940.

Enzyme and pathway databases

BRENDAi2.7.11.14. 2681.
SignaLinkiQ8WTQ7.

Miscellaneous databases

GenomeRNAii131890.
NextBioi82983.
PROiQ8WTQ7.
SOURCEiSearch...

Gene expression databases

BgeeiQ8WTQ7.
CleanExiHS_GRK7.
GenevisibleiQ8WTQ7. HS.

Family and domain databases

InterProiIPR000961. AGC-kinase_C.
IPR000239. GPCR_kinase.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016137. RGS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
PF00615. RGS. 1 hit.
[Graphical view]
PRINTSiPR00717. GPCRKINASE.
SMARTiSM00315. RGS. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF48097. SSF48097. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51285. 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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiGRK7_HUMAN
AccessioniPrimary (citable) accession number: Q8WTQ7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 27, 2002
Last sequence update: March 1, 2002
Last modified: June 24, 2015
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

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.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.