Q15835 (RK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	563 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 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	Congenital stationary night blindness, 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 process	Sensory transduction Vision
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Congenital stationary night blindness Disease mutation
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	apoptotic process Inferred from electronic annotation. Source: Compara photoreceptor cell morphogenesis Inferred from electronic annotation. Source: Compara positive regulation of phosphorylation Inferred from electronic annotation. Source: Compara post-embryonic retina morphogenesis in camera-type eye Inferred from electronic annotation. Source: Compara protein autophosphorylation Inferred from mutant phenotype Ref.6. Source: UniProtKB regulation of rhodopsin mediated signaling pathway Inferred from direct assay Ref.6. Source: UniProtKB rhodopsin mediated signaling pathway Traceable author statement PubMed 1656454Ref.1. Source: ProtInc termination of G-protein coupled receptor signaling pathway Inferred from electronic annotation. Source: InterPro visual perception Traceable author statement Ref.8. Source: ProtInc
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: InterPro rhodopsin kinase activity Inferred from direct assay Ref.6. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 560	560	Rhodopsin kinase		PRO_0000024375
	Propeptide	561 – 563	3	Removed in mature form By similarity		PRO_0000024376
Regions
	Domain	58 – 175	118	RGS
	Domain	190 – 455	266	Protein kinase
	Domain	456 – 521	66	AGC-kinase C-terminal
	Nucleotide binding	196 – 204	9	ATP By similarity
	Region	1 – 189	189	N-terminal
	Region	456 – 563	108	C-terminal
Sites
	Active site	317	1	Proton acceptor By similarity
	Binding site	219	1	ATP By similarity
Amino acid modifications
	Modified residue	5	1	Phosphoserine By similarity
	Modified residue	8	1	Phosphothreonine By similarity
	Modified residue	21	1	Phosphoserine; by PKA and autocatalysis Ref.6
	Modified residue	491	1	Phosphoserine; by autocatalysis By similarity
	Modified residue	492	1	Phosphothreonine; by autocatalysis By similarity
	Modified residue	560	1	Cysteine methyl ester By similarity
	Lipidation	560	1	S-farnesyl cysteine By similarity
Natural variations
	Natural variant	136	1	E → Q. Ref.7		VAR_008283
	Natural variant	298	1	T → M. Ref.7		VAR_008284
	Natural variant	330	1	N → S. Ref.7		VAR_008285
	Natural variant	380	1	V → D in CSNBO2. Ref.8		VAR_006215
	Natural variant	391	1	P → H in CSNBO2. Ref.9		VAR_037904
	Natural variant	438	1	R → H. Ref.7		VAR_008286
	Natural variant	514	1	C → S. Ref.7		VAR_008287
	Natural variant	522	1	M → T. Ref.7		VAR_008288
	Natural variant	536	1	S → L. Ref.7		VAR_008289
Experimental info
	Mutagenesis	21	1	S → E: Not phosphorylated by PKA. Ref.6
	Mutagenesis	219	1	K → A: Loss of autophosphorylation and RHO phosphorylation. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Q15835 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 1244DCB97D40F53D	FASTA	563	63,526
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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 , L77496, L77497, L77498, L77499, L77500, L77501 Genomic DNA. Translation: AAT00534.2. AC187648 Genomic DNA. No translation available. AK289912 mRNA. Translation: BAF82601.1.
IPI	IPI00019980.
RefSeq	NP_002920.1. NM_002929.2.
UniGene	Hs.103501. Hs.721727.
3D structure databases
ProteinModelPortal	Q15835.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000334876.
PTM databases
PhosphoSite	Q15835.
Polymorphism databases
DMDM	2833269.
Proteomic databases
PaxDb	Q15835.
PRIDE	Q15835.
Protocols and materials databases
DNASU	6011.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000335678; ENSP00000334876; ENSG00000185974.
GeneID	6011.
KEGG	hsa:6011.
UCSC	uc010tkf.2. human.
Organism-specific databases
CTD	6011.
GeneCards	GC13P114321.
HGNC	HGNC:10013. GRK1.
MIM	180381. gene. 613411. phenotype.
neXtProt	NX_Q15835.
Orphanet	75382. Oguchi disease.
PharmGKB	PA34391.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000006742.
HOVERGEN	HBG004532.
InParanoid	Q15835.
KO	K00909.
OMA	MPDDMKG.
OrthoDB	EOG4Q84X5.
Enzyme and pathway databases
BRENDA	2.7.11.14. 2681.
Pathway_Interaction_DB	cone_pathway. Visual signal transduction: Cones. rhodopsin_pathway. Visual signal transduction: Rods.
Gene expression databases
ArrayExpress	Q15835.
Bgee	Q15835.
CleanEx	HS_GRK1.
Genevestigator	Q15835.
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	Q15835.
ChEMBL	CHEMBL5607.
GenomeRNAi	6011.
NextBio	23453.
SOURCE	Search...

Entry information

Entry name

RK_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 135 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.