Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q15835 (RK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Rhodopsin kinase

Short name=RK
EC=2.7.11.14
Alternative name(s):
G protein-coupled receptor kinase 1
Gene names
Name:GRK1
Synonyms:RHOK
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length563 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Retina-specific kinase involved in the signal turnoff via phosphorylation of rhodopsin (RHO), the G protein- coupled receptor that initiates the phototransduction cascade. This rapid desensitization is essential for scotopic vision and permits rapid adaptation to changes in illumination. Ref.6

Catalytic activity

ATP + [rhodopsin] = ADP + [rhodopsin] phosphate. Ref.6

Enzyme regulation

Inhibited by phosphorylation of Ser-21 By similarity. Ref.6

Subcellular location

Membrane; Lipid-anchor.

Tissue specificity

Retinal-specific. Expressed in rods and cones cells. Ref.5

Post-translational modification

Autophosphorylated, Ser-21 is a minor site of autophosphorylation compared to Ser-491 and Thr-492 By similarity. Phosphorylation at Ser-21 is regulated by light and activated by cAMP. Ref.6

Farnesylation is required for full activity By similarity.

Involvement in disease

Night blindness, congenital stationary, Oguchi type 2 (CSNBO2) [MIM:613411]: A non-progressive retinal disorder characterized by impaired night vision, often associated with nystagmus and myopia. Congenital stationary night blindness Oguchi type is associated with fundus discoloration and abnormally slow dark adaptation.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.9

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=3.5 µM for rhodopsin Ref.6

KM=10.6 µM for ATP

Vmax=1132 nmol/min/mg enzyme

Ontologies

Keywords
   Biological processSensory transduction
Vision
   Cellular componentMembrane
   Coding sequence diversityPolymorphism
   DiseaseCongenital stationary night blindness
Disease mutation
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMLipoprotein
Methylation
Phosphoprotein
Prenylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processnegative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

photoreceptor cell morphogenesis

Inferred from electronic annotation. Source: Ensembl

phototransduction, visible light

Traceable author statement. Source: Reactome

positive regulation of phosphorylation

Inferred from electronic annotation. Source: Ensembl

post-embryonic retina morphogenesis in camera-type eye

Inferred from electronic annotation. Source: Ensembl

protein autophosphorylation

Inferred from mutant phenotype Ref.6. Source: UniProtKB

regulation of G-protein coupled receptor protein signaling pathway

Traceable author statement PubMed 1656454. Source: ProtInc

regulation of rhodopsin mediated signaling pathway

Inferred from direct assay Ref.6. Source: UniProtKB

rhodopsin mediated signaling pathway

Traceable author statement. Source: Reactome

termination of G-protein coupled receptor signaling pathway

Inferred from electronic annotation. Source: InterPro

visual perception

Traceable author statement Ref.8. Source: ProtInc

   Cellular_componentphotoreceptor disc membrane

Traceable author statement. Source: Reactome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

G-protein coupled receptor kinase activity

Inferred from electronic annotation. Source: InterPro

protein kinase activity

Traceable author statement PubMed 1656454Ref.1. Source: ProtInc

rhodopsin kinase activity

Inferred from direct assay Ref.6. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 560560Rhodopsin kinase
PRO_0000024375
Propeptide561 – 5633Removed in mature form By similarity
PRO_0000024376

Regions

Domain58 – 175118RGS
Domain190 – 455266Protein kinase
Domain456 – 52166AGC-kinase C-terminal
Nucleotide binding196 – 2049ATP By similarity
Region1 – 189189N-terminal
Region456 – 563108C-terminal

Sites

Active site3171Proton acceptor By similarity
Binding site2191ATP By similarity

Amino acid modifications

Modified residue51Phosphoserine By similarity
Modified residue81Phosphothreonine By similarity
Modified residue211Phosphoserine; by PKA and autocatalysis Ref.6
Modified residue4911Phosphoserine; by autocatalysis By similarity
Modified residue4921Phosphothreonine; by autocatalysis By similarity
Modified residue5601Cysteine methyl ester By similarity
Lipidation5601S-farnesyl cysteine By similarity

Natural variations

Natural variant1361E → Q. Ref.7
VAR_008283
Natural variant2981T → M. Ref.7
VAR_008284
Natural variant3301N → S. Ref.7
VAR_008285
Natural variant3801V → D in CSNBO2. Ref.8
VAR_006215
Natural variant3911P → H in CSNBO2. Ref.9
VAR_037904
Natural variant4381R → H. Ref.7
VAR_008286
Natural variant5141C → S. Ref.7
VAR_008287
Natural variant5221M → T. Ref.7
VAR_008288
Natural variant5361S → L. Ref.7
VAR_008289

Experimental info

Mutagenesis211S → E: Not phosphorylated by PKA. Ref.6
Mutagenesis2191K → A: Loss of autophosphorylation and RHO phosphorylation. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Q15835 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 1244DCB97D40F53D

FASTA56363,526
        10         20         30         40         50         60 
MDFGSLETVV ANSAFIAARG SFDGSSSQPS RDKKYLAKLK LPPLSKCESL RDSLSLEFES 

        70         80         90        100        110        120 
VCLEQPIGKK LFQQFLQSAE KHLPALELWK DIEDYDTADN DLQPQKAQTI LAQYLDPQAK 

       130        140        150        160        170        180 
LFCSFLDEGI VAKFKEGPVE IQDGLFQPLL QATLAHLGQA PFQEYLGSLY FLRFLQWKWL 

       190        200        210        220        230        240 
EAQPMGEDWF LDFRVLGKGG FGEVSACQMK ATGKLYACKK LNKKRLKKRK GYQGAMVEKK 

       250        260        270        280        290        300 
ILMKVHSRFI VSLAYAFETK ADLCLVMTIM NGGDIRYHIY NVNEENPGFP EPRALFYTAQ 

       310        320        330        340        350        360 
IICGLEHLHQ RRIVYRDLKP ENVLLDNDGN VRISDLGLAV ELLDGQSKTK GYAGTPGFMA 

       370        380        390        400        410        420 
PELLQGEEYD FSVDYFALGV TLYEMIAARG PFRARGEKVE NKELKHRIIS EPVKYPDKFS 

       430        440        450        460        470        480 
QASKDFCEAL LEKDPEKRLG FRDETCDKLR AHPLFKDLNW RQLEAGMLMP PFIPDSKTVY 

       490        500        510        520        530        540 
AKDIQDVGAF STVKGVAFDK TDTEFFQEFA TGNCPIPWQE EMIETGIFGE LNVWRSDGQM 

       550        560 
PDDMKGISGG SSSSSKSGMC LVS 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and localization of rhodopsin kinase in the mammalian pineal."
Zhao X., Haeseleer F., Fariss R.N., Huang J., Baehr W., Milam A.H., Palczewski K.
Vis. Neurosci. 14:225-232(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Retina.
[2]"Characterization and chromosomal localization of the gene for human rhodopsin kinase."
Khani S.C., Abitbol M., Yamamoto S., Maravic-Magovcevic I., Dryja T.P.
Genomics 35:571-576(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Corpus callosum.
[4]"The DNA sequence and analysis of human chromosome 13."
Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.
Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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: TISSUE SPECIFICITY.
[6]"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, PHOSPHORYLATION AT SER-21, ENZYME REGULATION, AUTOPHOSPHORYLATION, MUTAGENESIS OF SER-21 AND LYS-219.
[7]"Evaluation of the rhodopsin kinase gene in patients with retinitis pigmentosa."
Yamamoto S., Khani S.C., Berson E.L., Dryja T.P.
Exp. Eye Res. 65:249-253(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GLN-136; MET-298; SER-330; HIS-438; SER-514; THR-522 AND LEU-536.
[8]"Defects in the rhodopsin kinase gene in the Oguchi form of stationary night blindness."
Yamamoto S., Sippel K.C., Berson E.L., Dryja T.P.
Nat. Genet. 15:175-178(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CSNBO2 ASP-380.
[9]"A novel homozygous GRK1 mutation (P391H) in 2 siblings with Oguchi disease with markedly reduced cone responses."
Hayashi T., Gekka T., Takeuchi T., Goto-Omoto S., Kitahara K.
Ophthalmology 114:134-141(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CSNBO2 HIS-391.
+Additional computationally mapped references.

Web resources

Mutations of the RHOK gene

Retina International's Scientific Newsletter

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U63973 mRNA. Translation: AAB05929.1.
L77503 mRNA. Translation: AAG50439.1.
L77502 expand/collapse EMBL AC list , L77496, L77497, L77498, L77499, L77500, L77501 Genomic DNA. Translation: AAT00534.2.
AC187648 Genomic DNA. No translation available.
AK289912 mRNA. Translation: BAF82601.1.
RefSeqNP_002920.1. NM_002929.2.
UniGeneHs.103501.
Hs.721727.

3D structure databases

ProteinModelPortalQ15835.
SMRQ15835. Positions 30-535.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111943. 7 interactions.
STRING9606.ENSP00000334876.

Chemistry

BindingDBQ15835.
ChEMBLCHEMBL5607.
GuidetoPHARMACOLOGY1465.

PTM databases

PhosphoSiteQ15835.

Polymorphism databases

DMDM2833269.

Proteomic databases

PaxDbQ15835.
PRIDEQ15835.

Protocols and materials databases

DNASU6011.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000335678; ENSP00000334876; ENSG00000185974.
GeneID6011.
KEGGhsa:6011.
UCSCuc010tkf.2. human.

Organism-specific databases

CTD6011.
GeneCardsGC13P114321.
HGNCHGNC:10013. GRK1.
MIM180381. gene.
613411. phenotype.
neXtProtNX_Q15835.
Orphanet75382. Oguchi disease.
PharmGKBPA34391.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000006742.
HOVERGENHBG004532.
InParanoidQ15835.
KOK00909.
OMAMPDDMKG.
OrthoDBEOG7TF78J.
PhylomeDBQ15835.
TreeFamTF313940.

Enzyme and pathway databases

BRENDA2.7.11.14. 2681.
ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
SignaLinkQ15835.

Gene expression databases

ArrayExpressQ15835.
BgeeQ15835.
CleanExHS_GRK1.
GenevestigatorQ15835.

Family and domain databases

InterProIPR000961. AGC-kinase_C.
IPR000239. GPCR_kinase.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016137. Regulat_G_prot_signal_superfam.
IPR000342. RGS_dom.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
PF00615. RGS. 1 hit.
[Graphical view]
PRINTSPR00717. GPCRKINASE.
SMARTSM00315. RGS. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF48097. SSF48097. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS51285. 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]
ProtoNetSearch...

Other

GenomeRNAi6011.
NextBio23453.
PROQ15835.
SOURCESearch...

Entry information

Entry nameRK_HUMAN
AccessionPrimary (citable) accession number: Q15835
Secondary accession number(s): Q53X14
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: April 16, 2014
This is version 144 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 13

Human chromosome 13: entries, gene names and cross-references to MIM