UniProt Accession

 GRK4_HUMAN; P32298; O00641; O00642; Q13293; Q13294; Q13295; Q14453; Q14725; Q15313; Q15314; Q15315; Q15316; Q17RH6; Q53EQ8 

Genbank Protein ID

 L03718; X97879; X97880; X97881; U33054; U33055; U33056; U33168; U33153; U33155; U33156; U33157; U33158; U33159; U33160; U33161; U33162; U33163; U33164; U33165; U33166; U33167; U33168; U33153; U33154; U33155; U33156; U33157; U33158; U33159; U33160; U33161; U33162; U33163; U33164; U33165; U33166; U33167; U33168; U33153; U33154; U33155; U33156; U33157; U33158; U33159; U33160; U33161; U33162; U33163; U33164; U33165; U33166; U33168; U33153; U33155; U33156; U33157; U33158; U33159; U33160; U33161; U33162; U33163; U33164; U33165; U33166; AK223581; X98118; X75897; Z68192; BC117320 

Genbank Nucleotide ID

 AAB04045.1; CAA66468.1; CAA66469.1; CAA66470.1; AAC50406.1; AAC50407.1; AAC50408.1; AAC50409.1; AAC50409.1; AAC50409.1; AAC50409.1; AAC50409.1; AAC50409.1; AAC50409.1; AAC50409.1; AAC50409.1; AAC50409.1; AAC50409.1; AAC50409.1; AAC50409.1; AAC50409.1; AAC50409.1; AAC50410.1; AAC50410.1; AAC50410.1; AAC50410.1; AAC50410.1; AAC50410.1; AAC50410.1; AAC50410.1; AAC50410.1; AAC50410.1; AAC50410.1; AAC50410.1; AAC50410.1; AAC50410.1; AAC50410.1; AAC50410.1; AAC50411.1; AAC50411.1; AAC50411.1; AAC50411.1; AAC50411.1; AAC50411.1; AAC50411.1; AAC50411.1; AAC50411.1; AAC50411.1; AAC50411.1; AAC50411.1; AAC50411.1; AAC50411.1; AAC50411.1; AAC50412.1; AAC50412.1; AAC50412.1; AAC50412.1; AAC50412.1; AAC50412.1; AAC50412.1; AAC50412.1; AAC50412.1; AAC50412.1; AAC50412.1; AAC50412.1; AAC50412.1; AAC50412.1; BAD97301.1; CAA66802.1; CAA53506.1; CAA92341.1; AAI17321.1 

Protein Name

 G protein-coupled receptor kinase 4 

Protein Synonyms/Alias

 G protein-coupled receptor kinase GRK4; ITI1 

Gene Name

 GRK4 

Gene Synonyms/Alias

 GPRK2L; GPRK4 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
14	VANSLLLKARQGGYG	ubiquitination	[1]
184	LERQPVTKNTFRHYR	ubiquitination	[1]
195	RHYRVLGKGGFGEVC	acetylation	[2]
195	RHYRVLGKGGFGEVC	ubiquitination	[1]
216	TGKMYACKKLQKKRI	ubiquitination	[3, 4]
217	GKMYACKKLQKKRIK	ubiquitination	[3, 4]
227	KKRIKKRKGEAMALN	ubiquitination	[1]

Reference

 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [3] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [4] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789] 

Functional Description

 Specifically phosphorylates the activated forms of G protein-coupled receptors. GRK4-alpha can phosphorylate rhodopsin and its activity is inhibited by calmodulin; the other three isoforms do not phosphorylate rhodopsin and do not interact with calmodulin. GRK4-alpha and GRK4-gamma phosphorylate DRD3. Phosphorylates ADRB2. 

Sequence Annotation

 DOMAIN 52 172 RGS.
 DOMAIN 187 449 Protein kinase.
 DOMAIN 450 515 AGC-kinase C-terminal.
 NP_BIND 193 201 ATP (By similarity).
 REGION 1 154 N-terminal.
 ACT_SITE 312 312 Proton acceptor (By similarity).
 BINDING 216 216 ATP (By similarity).  

Keyword

 Alternative splicing; ATP-binding; Complete proteome; Cytoplasm; Kinase; Lipoprotein; Nucleotide-binding; Palmitate; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 578 AA 

Protein Sequence

Gene Ontology

 GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
 GO:0005829; C:cytosol; IEA:Compara.
 GO:0030425; C:dendrite; IEA:Compara.
 GO:0043025; C:neuronal cell body; IEA:Compara.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004703; F:G-protein coupled receptor kinase activity; IEA:EC.
 GO:0050254; F:rhodopsin kinase activity; IEA:Compara.
 GO:0002031; P:G-protein coupled receptor internalization; IEA:Compara.
 GO:0031623; P:receptor internalization; IDA:UniProtKB.
 GO:0008277; P:regulation of G-protein coupled receptor protein signaling pathway; TAS:ProtInc.
 GO:0007165; P:signal transduction; IEA:InterPro.
 GO:0038032; P:termination of G-protein coupled receptor signaling pathway; IEA:InterPro. 

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. 

Pfam

 PF00069; Pkinase
 PF00615; RGS 

SMART

 SM00315; RGS
 SM00133; S_TK_X
 SM00220; S_TKc 

PROSITE

 PS51285; AGC_KINASE_CTER
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST
 PS50132; RGS 

PRINTS

 PR00717; GPCRKINASE.