Reviewed, UniProtKB/Swiss-Prot Q15835 (RK_HUMAN)

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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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	Phosphorylates rhodopsin thereby initiating its deactivation.
Catalytic activity	ATP + [rhodopsin] = ADP + [rhodopsin] phosphate.
Subcellular location	Membrane; Lipid-anchor.
Tissue specificity	Retina and pineal gland By similarity.
Post-translational modification	Autophosphorylated By similarity. Farnesylation is required for full activity By similarity.
Involvement in disease	Defects in GRK1 are the cause of Oguchi disease 2 [MIM:258100]; also known as stationary night blindness Oguchi type-2. It is a form of recessively inherited stationary night blindness due to malfunction of the rod photoreceptor mechanism. The characteristics of this disease are congenital, static hemeralopia and diffuse yellow or gray coloration of the fundus. After 2 or 3 hours in total darkness, the normal color of the fundus returns.
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
Biological process	Sensory transduction Vision
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Lipoprotein Methylation Phosphoprotein Prenylation
Gene Ontology (GO)
Biological process	regulation of G-protein coupled receptor protein signaling pathway Traceable author statement. Source: ProtInc rhodopsin mediated phototransduction Traceable author statement. Source: ProtInc rhodopsin mediated signaling pathway Ref.1 Traceable author statement. Source: ProtInc
Molecular function	protein kinase activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 560	560	Rhodopsin kinase
	Propeptide	561 – 563	3	Removed in mature form By similarity
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	21	1	Phosphoserine; by autocatalysis By similarity
	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 in one patient with autosomal dominant retinitis pigmentosa; probably not pathogenic.
	Natural variant	298	1	T → M in patients with autosomal recessive retinitis pigmentosa; unclear pathological significance.
	Natural variant	330	1	N → S in patients with autosomal dominant retinitis pigmentosa; probably not pathogenic.
	Natural variant	380	1	V → D in Oguchi disease 2.
	Natural variant	391	1	P → H in Oguchi disease 2.
	Natural variant	438	1	R → H in one patient with autosomal dominant retinitis pigmentosa; probably not pathogenic.
	Natural variant	514	1	C → S in one patient with autosomal dominant retinitis pigmentosa; probably not pathogenic.
	Natural variant	522	1	M → T in patients with autosomal recessive retinitis pigmentosa; unclear pathological significance.
	Natural variant	536	1	S → L in one patient with autosomal dominant retinitis pigmentosa; probably not pathogenic.

Sequences

	Sequence		Length	Mass (Da)
	Q15835-1 [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

[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: 9147475] [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: 8812493] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"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: 9268593] [Abstract] Cited for: VARIANTS GLN-136; MET-298; SER-330; HIS-438; SER-514; THR-522 AND LEU-536.
[4]	"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: 9020843] [Abstract] Cited for: VARIANT OGUCHI DISEASE-2 ASP-380.
[5]	"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: 17070587] [Abstract] Cited for: VARIANT OGUCHI DISEASE 2 HIS-391.
+	Additional computationally mapped references.

Web resources

Mutations of the RHOK gene

Retina International's Scientific Newsletter

Cross-references

Sequence databases
EMBLGenBankDDBJ	U63973 mRNA. Translation: AAB05929.1. L77503 mRNA. Translation: AAG50439.1.
RefSeq	NP_002920.1.
UniGene	Hs.103501
3D structure databases
HSSP	HSSP built from PDB template 1GZK based on UniProtKB P31751.
ModBase	Search...
PTM databases
PhosphoSite	Q15835.
Genome annotation databases
Ensembl	ENSG00000185974. Homo sapiens. [Contig view]
GeneID	6011.
KEGG	hsa:6011.
Organism-specific databases
H-InvDB	HIX0037605. HIX0060255.
HGNC	HGNC:10013. GRK1.
MIM	180381. gene. 258100. phenotype.
Orphanet	75382. Oguchi disease.
PharmGKB	PA34391.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	Q15835.
HOVERGEN	Q15835.
Gene expression databases
CleanEx	HS_GRK1.
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

RK_HUMAN

Accession

Primary (citable) accession number: Q15835

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	July 22, 2008
This is version 88 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)