P28327 (RK_BOVIN) 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

Bos taurus (Bovine) [Reference proteome]

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length	561 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 By similarity.
Catalytic activity	ATP + [rhodopsin] = ADP + [rhodopsin] phosphate.
Enzyme regulation	Inhibited by phosphorylation of Ser-21 By similarity.
Subcellular location	Membrane; Lipid-anchor.
Tissue specificity	Retinal and pineal gland.
Post-translational modification	Autophosphorylated, Ser-21 is a minor site of autophosphorylation compared to Ser-488 and Thr-489. Phosphorylation at Ser-21 is regulated by light and activated by cAMP Probable. Ref.3 Ref.4 Farnesylation is required for full activity.
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
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Lipoprotein Methylation Phosphoprotein Prenylation
Technical term	3D-structure Complete proteome Direct protein sequencing 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 sequence or structural similarity. Source: UniProtKB regulation of rhodopsin mediated signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB response to light stimulus Inferred from electronic annotation. Source: Compara 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: InterPro rhodopsin kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 558

558

Rhodopsin kinase

PRO_0000024373

Propeptide

559 – 561

3

Removed in mature form

PRO_0000024374

Regions

Domain

58 – 172

115

RGS

Domain

187 – 452

266

Protein kinase

Domain

453 – 518

66

AGC-kinase C-terminal

Nucleotide binding

193 – 201

9

ATP By similarity

Region

1 – 186

186

N-terminal

Region

453 – 561

109

C-terminal

Sites

Active site

314

1

Proton acceptor By similarity

Binding site

216

1

ATP By similarity

Amino acid modifications

Modified residue

5

1

Phosphoserine Ref.4

Modified residue

8

1

Phosphothreonine Ref.4

Modified residue

21

1

Phosphoserine; by PKA and autocatalysis Probable

Modified residue

488

1

Phosphoserine; by autocatalysis Ref.3 Ref.4

Modified residue

489

1

Phosphothreonine; by autocatalysis Ref.3 Ref.4

Modified residue

558

1

Cysteine methyl ester

Lipidation

558

1

S-farnesyl cysteine Ref.2

Experimental info

Mutagenesis

558

1

C → S: 75% decrease in enzymatic activity. Ref.2

Secondary structure

1

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561

Helix Strand Turn

Details...

Helix

5 – 15

11

Helix

33 – 36

4

Helix

44 – 47

4

Helix

48 – 53

6

Helix

58 – 62

5

Helix

66 – 78

13

Helix

80 – 82

3

Helix

83 – 96

14

Turn

100 – 102

3

Helix

103 – 114

12

Beta strand

116 – 119

4

Helix

128 – 135

8

Turn

140 – 143

4

Helix

144 – 154

11

Helix

157 – 163

7

Helix

166 – 178

13

Helix

184 – 186

3

Beta strand

187 – 195

9

Beta strand

197 – 206

10

Turn

207 – 209

3

Beta strand

212 – 219

8

Helix

220 – 225

6

Helix

229 – 241

13

Beta strand

250 – 255

6

Beta strand

257 – 264

8

Beta strand

269 – 271

3

Helix

272 – 277

6

Beta strand

281 – 283

3

Helix

288 – 307

20

Helix

317 – 319

3

Beta strand

320 – 322

3

Beta strand

328 – 330

3

Turn

353 – 355

3

Helix

358 – 361

4

Helix

369 – 384

16

Beta strand

385 – 387

3

Beta strand

388 – 390

3

Helix

398 – 407

10

Helix

418 – 427

10

Helix

432 – 434

3

Helix

444 – 447

4

Helix

450 – 452

3

Helix

457 – 461

5

Beta strand

473 – 475

3

Helix

497 – 506

10

Helix

512 – 521

10

Helix

524 – 528

5

Sequences

	Sequence		Length	Mass (Da)
	P28327 [UniParc]. Last modified December 1, 1992. Version 1. Checksum: 1AC6FEC1B277DDD8	FASTA	561	62,934
	10 20 30 40 50 60 MDFGSLETVV ANSAFIAARG SFDASSGPAS RDRKYLARLK LPPLSKCEAL RESLDLGFEG 70 80 90 100 110 120 MCLEQPIGKR LFQQFLRTHE QHGPALQLWK DIEDYDTADD ALRPQKAQAL RAAYLEPQAQ 130 140 150 160 170 180 LFCSFLDAET VARARAGAGD GLFQPLLRAV LAHLGQAPFQ EFLDSLYFLR FLQWKWLEAQ 190 200 210 220 230 240 PMGEDWFLDF RVLGRGGFGE VFACQMKATG KLYACKKLNK KRLKKRKGYQ GAMVEKKILA 250 260 270 280 290 300 KVHSRFIVSL AYAFETKTDL CLVMTIMNGG DIRYHIYNVD EDNPGFQEPR AIFYTAQIVS 310 320 330 340 350 360 GLEHLHQRNI IYRDLKPENV LLDDDGNVRI SDLGLAVELK AGQTKTKGYA GTPGFMAPEL 370 380 390 400 410 420 LLGEEYDFSV DYFALGVTLY EMIAARGPFR ARGEKVENKE LKQRVLEQAV TYPDKFSPAS 430 440 450 460 470 480 KDFCEALLQK DPEKRLGFRD GSCDGLRTHP LFRDISWRQL EAGMLTPPFV PDSRTVYAKN 490 500 510 520 530 540 IQDVGAFSTV KGVAFEKADT EFFQEFASGT CPIPWQEEMI ETGVFGDLNV WRPDGQMPDD 550 560 MKGVSGQEAA PSSKSGMCVL S

References

[1]	"The receptor kinase family: primary structure of rhodopsin kinase reveals similarities to the beta-adrenergic receptor kinase." Lorenz W., Inglese J., Palczewski K., Onorato J.J., Caron M.G., Lefkowitz R.J. Proc. Natl. Acad. Sci. U.S.A. 88:8715-8719(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 268-297. Tissue: Retina.
[2]	"Isoprenylation of a protein kinase. Requirement of farnesylation/alpha-carboxyl methylation for full enzymatic activity of rhodopsin kinase." Inglese J., Glickman J.F., Lorenz W., Caron M.G., Lefkowitz R.J. J. Biol. Chem. 267:1422-1425(1992) [PubMed] [Europe PMC] [Abstract] Cited for: ISOPRENYLATION AT CYS-558, MUTAGENESIS OF CYS-558.
[3]	"Identification of the autophosphorylation sites in rhodopsin kinase." Palczewski K., Buczylko J., van Hooser P., Carr S.A., Huddleston M.J., Crabb J.W. J. Biol. Chem. 267:18991-18998(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-21; SER-488 AND THR-489.
[4]	"Structures of rhodopsin kinase in different ligand states reveal key elements involved in G protein-coupled receptor kinase activation." Singh P., Wang B., Maeda T., Palczewski K., Tesmer J.J. J. Biol. Chem. 283:14053-14062(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.84 ANGSTROMS) OF 1-535, PHOSPHORYLATION AT SER-5; THR-8; SER-21; SER-488 AND THR-489.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M73836 mRNA. Translation: AAA30752.1.

IPI

IPI00906037.

PIR

A41365.

RefSeq

NP_776598.1. NM_174173.2.

UniGene

Bt.459.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2I94	NMR	-	B	1-25	[»]
3C4W	X-ray	2.70	A/B	1-535	[»]
3C4X	X-ray	2.90	A/B	1-535	[»]
3C4Y	X-ray	7.51	A/B	1-535	[»]
3C4Z	X-ray	1.84	A	1-535	[»]
3C50	X-ray	2.60	A/B	1-535	[»]
3C51	X-ray	3.55	A/B	1-535	[»]
3QC9	X-ray	2.70	A/B/C/D	1-535	[»]
3T8O	X-ray	2.50	A	1-535	[»]

ProteinModelPortal

P28327.

SMR

P28327. Positions 30-533.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-1507451.

STRING

9913.ENSBTAP00000026589.

Proteomic databases

PRIDE

P28327.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSBTAT00000045068; ENSBTAP00000042484; ENSBTAG00000019963.

GeneID

281457.

KEGG

bta:281457.

Organism-specific databases

CTD

6011.

Phylogenomic databases

eggNOG

COG0515.

GeneTree

ENSGT00550000074318.

HOGENOM

HOG000006742.

HOVERGEN

HBG004532.

KO

K00909.

OMA

MPDDMKG.

Enzyme and pathway databases

BioCyc

MetaCyc:MONOMER-4461.

BRENDA

2.7.11.14. 908.

SABIO-RK

P28327.

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

EvolutionaryTrace

P28327.

NextBio

20805439.

Entry information

Entry name

RK_BOVIN

Accession

Primary (citable) accession number: P28327

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	December 1, 1992
Last modified:	April 3, 2013
This is version 118 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program