Reviewed,
UniProtKB/Swiss-Prot P32298 (GRK4_HUMAN)
Last modified
November 3, 2009.
Version 104.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
Customize display | text xml rdf/xml gff fasta |
Names and origin
| Protein names | Recommended name: G protein-coupled receptor kinase 4 EC=2.7.11.16 Alternative name(s): G protein-coupled receptor kinase GRK4 ITI1 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 578 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | 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. Ref.3 Ref.9 |
| Catalytic activity | ATP + [G-protein-coupled receptor] = ADP + [G-protein-coupled receptor] phosphate. |
| Enzyme regulation | Inhibited by heparine. Ref.9 |
| Subunit structure | Interacts with DRD3. Ref.9 |
| Subcellular location | Cytoplasm. Cytoplasm › cell cortex. Note: Both at the cell surface and dispersed in the cytoplasm under basal conditions. Receptor stimulation results in the internalization of GRK4 to the perinuclear area, where co-localization with DRD3 is observed strongly at 5 and 15 minutes. DRD3 and GRK4 co-localize in lipid rafts of renal proximal tubule cells. Ref.3 Ref.9 |
| Tissue specificity | Testis, and in a lower extent in other tissues including brain cortex and striatum. Has a widespread but low level of expression. Also expressed in myometrium; namely the GRK4-gamma isoform. Ref.3 Ref.8 |
| Post-translational modification | Palmitoylated. Ref.3 |
| 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 | |
|---|---|
| Cellular component | Cytoplasm |
| Coding sequence diversity | Alternative splicing Polymorphism |
| Ligand | ATP-binding Nucleotide-binding |
| Molecular function | Kinase Serine/threonine-protein kinase Transferase |
| PTM | Lipoprotein Palmitate |
| Technical term | Complete proteome |
| Gene Ontology (GO) | |
| Biological process | protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro regulation of G-protein coupled receptor protein signaling pathway Ref.1Traceable author statement. Source: ProtInc signal transductionInferred from electronic annotation. Source: InterPro |
| Molecular function | ATP binding Inferred from electronic annotation. Source: UniProtKB-KW G-protein coupled receptor kinase activityInferred from electronic annotation. Source: EC signal transducer activityInferred from electronic annotation. Source: InterPro |
| Complete GO annotation... | |
Alternative products
| This entry describes 4 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: P32298-1) Also known as: GRK4-alpha; GRK4D; This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: P32298-2) Also known as: GRK4-beta; GRK4C; The sequence of this isoform differs from the canonical sequence as follows: 18-49: Missing. | ||||||
| Isoform 3 (identifier: P32298-3) Also known as: GRK4-delta; GRK4A; The sequence of this isoform differs from the canonical sequence as follows: 18-49: Missing. 516-561: Missing. | ||||||
| Isoform 4 (identifier: P32298-4) Also known as: GRK4-gamma; GRK4B; The sequence of this isoform differs from the canonical sequence as follows: 516-561: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 578 | 578 | G protein-coupled receptor kinase 4 | PRO_0000085967 | |||||
Regions | |||||||||
| Domain | 52 – 172 | 121 | RGS | ||||||
| Domain | 187 – 449 | 263 | Protein kinase | ||||||
| Domain | 450 – 515 | 66 | AGC-kinase C-terminal | ||||||
| Nucleotide binding | 193 – 201 | 9 | ATP By similarity | ||||||
| Region | 1 – 154 | 154 | N-terminal | ||||||
Sites | |||||||||
| Active site | 312 | 1 | Proton acceptor By similarity | ||||||
| Binding site | 216 | 1 | ATP By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 18 – 49 | 32 | Missing in isoform 2 and isoform 3. | VSP_004936 | |||||
| Alternative sequence | 516 – 561 | 46 | Missing in isoform 3 and isoform 4. | VSP_004937 | |||||
| Natural variant | 65 | 1 | R → L: dbSNP rs2960306. Ref.10 | VAR_024573 | |||||
| Natural variant | 95 | 1 | D → H: dbSNP rs13305979. | VAR_051621 | |||||
| Natural variant | 116 | 1 | A → T: dbSNP rs34857805. Ref.10 | VAR_046043 | |||||
| Natural variant | 142 | 1 | A → V: dbSNP rs1024323. Ref.10 | VAR_024574 | |||||
| Natural variant | 183 | 1 | T → R: dbSNP rs45538934. | VAR_051622 | |||||
| Natural variant | 247 | 1 | V → I: dbSNP rs35605687. Ref.10 | VAR_007806 | |||||
| Natural variant | 383 | 1 | H → Q | VAR_046044 | |||||
| Natural variant | 425 | 1 | L → P | VAR_040516 | |||||
| Natural variant | 440 | 1 | A → V: dbSNP rs1801058. | VAR_051623 | |||||
| Natural variant | 473 | 1 | V → I | VAR_046045 | |||||
| Natural variant | 486 | 1 | V → A: dbSNP rs1801058. Ref.3 Ref.10 Ref.1 Ref.2 Ref.4 Ref.7 | VAR_024575 | |||||
| Natural variant | 495 | 1 | A → T | VAR_046046 | |||||
Experimental info | |||||||||
| Sequence conflict | 562 | 1 | G → D in CAA66468. Ref.1 | ||||||
| Sequence conflict | 562 | 1 | G → D in CAA66802. Ref.1 | ||||||
Sequences
| ||||||||||||||||||||||||||||||||||||
References
| « Hide 'large scale' references | |
| [1] | "A novel G protein-coupled receptor kinase gene cloned from 4p16.3." Ambrose C., James M., Barnes G., Lin C., Bates G., Altherr M., Duyao M., Groot N., Church D., Wasmuth J.J., Lehrach H., Housman D., Buckler A.J., Gusella J.F., McDonald M.E. Hum. Mol. Genet. 1:697-703(1992) [PubMed: 1338872] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 3), VARIANT ALA-486. |
| [2] | "G protein-coupled receptor kinase GRK4. Molecular analysis of the four isoforms and ultrastructural localization in spermatozoa and germinal cells." Sallese M., Mariggio S., Collodel G., Moretti E., Piomboni P., Baccetti B., de Blasi A. J. Biol. Chem. 272:10188-10195(1997) [PubMed: 9092566] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), VARIANT ALA-486. Tissue: Testis. |
| [3] | "Characterization of the G protein-coupled receptor kinase GRK4. Identification of four splice variants." Premont R.T., Macrae A.D., Stoffel R.H., Chung N., Pitcher J.A., Ambrose C., Inglese J., MacDonald M.E., Lefkowitz R.J. J. Biol. Chem. 271:6403-6410(1996) [PubMed: 8626439] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], ALTERNATIVE SPLICING, FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, PALMITOYLATION, VARIANT ALA-486. Tissue: Testis. |
| [4] | "Two isoforms of G protein-coupled receptor kinase 4 identified by molecular cloning." Sallese M., Lombardi M.S., de Blasi A. Biochem. Biophys. Res. Commun. 199:848-854(1994) [PubMed: 8135832] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANT ALA-486. Tissue: Brain. |
| [5] | Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Kidney. |
| [6] | "Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. Wilson R.K.Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [7] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ALA-486. |
| [8] | "Amelioration of genetic hypertension by suppression of renal G protein-coupled receptor kinase type 4 expression." Sanada H., Yatabe J., Midorikawa S., Katoh T., Hashimoto S., Watanabe T., Xu J., Luo Y., Wang X., Zeng C., Armando I., Felder R.A., Jose P.A. Hypertension 47:1131-1139(2006) [PubMed: 16636192] [Abstract] Cited for: TISSUE SPECIFICITY. |
| [9] | "G protein-coupled receptor kinase 4 (GRK4) regulates the phosphorylation and function of the dopamine D3 receptor." Villar V.A.M., Jones J.E., Armando I., Palmes-Saloma C., Yu P., Pascua A.M., Keever L., Arnaldo F.B., Wang Z., Luo Y., Felder R.A., Jose P.A. J. Biol. Chem. 284:21425-21434(2009) [PubMed: 19520868] [Abstract] Cited for: FUNCTION, ENZYME REGULATION, SUBCELLULAR LOCATION, INTERACTION WITH DRD3. |
| [10] | "Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. Stratton M.R.Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-65; THR-116; VAL-142; ILE-247; GLN-383; PRO-425; ILE-473; ALA-486 AND THR-495. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| L03718 Genomic DNA. Translation: AAB04045.1. X97879 mRNA. Translation: CAA66468.1. X97880 mRNA. Translation: CAA66469.1. X97881 mRNA. Translation: CAA66470.1. U33054 mRNA. Translation: AAC50406.1. U33055 mRNA. Translation: AAC50407.1. U33056 mRNA. Translation: AAC50408.1. U33168 U33167 Genomic DNA. Translation: AAC50409.1. U33168 U33167 Genomic DNA. Translation: AAC50410.1. U33168 U33166 Genomic DNA. Translation: AAC50411.1. U33168 U33166 Genomic DNA. Translation: AAC50412.1. AK223581 mRNA. Translation: BAD97301.1. X98118 mRNA. Translation: CAA66802.1. X75897 mRNA. Translation: CAA53506.1. Z68192 Genomic DNA. Translation: CAA92341.1. BC117320 mRNA. Translation: AAI17321.1. | |
| IPI | IPI00180426. IPI00182614. IPI00217944. IPI00337306. |
| PIR | I54326. JC2127. |
| RefSeq | NP_001004056.1. NP_001004057.1. NP_892027.2. |
| UniGene | Hs.32959 |
3D structure databases | |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | P32298. |
Proteomic databases | |
| PRIDE | P32298. |
Genome annotation databases | |
| Ensembl | ENST00000345167; ENSP00000264764; ENSG00000125388; Homo sapiens. [Genome view] ENST00000398047; ENSP00000381125; ENSG00000125388; Homo sapiens. [Genome view] ENST00000398051; ENSP00000381128; ENSG00000125388; Homo sapiens. [Genome view] ENST00000398052; ENSP00000381129; ENSG00000125388; Homo sapiens. [Genome view] ENST00000442472; ENSP00000392297; ENSG00000125388; Homo sapiens. [Genome view] ENST00000446963; ENSP00000396463; ENSG00000125388; Homo sapiens. [Genome view] |
| GeneID | 2868. |
| KEGG | hsa:2868. |
| NMPDR | fig|9606.3.peg.23842. |
| UCSC | uc003ggn.1. human. uc003ggo.1. human. uc003ggp.1. human. uc003ggq.1. human. |
Organism-specific databases | |
| CTD | 2868. |
| GeneCards | GC04P003002. |
| H-InvDB | HIX0031441. |
| HGNC | HGNC:4543. GRK4. |
| HPA | CAB004421. |
| MIM | 137026. gene. |
| PharmGKB | PA28941. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOVERGEN | P32298. |
Enzyme and pathway databases | |
| BRENDA | 2.7.11.16. 247. |
Gene expression databases | |
| ArrayExpress | P32298. |
| Bgee | P32298. |
| Genevestigator | P32298. |
| GermOnline | ENSG00000125388. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR000961. AGC-kinase_C. IPR000239. GPCR_kinase. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. 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] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 11309. |
| SOURCE | Search... |
Entry information
| Entry name | GRK4_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P32298 Secondary accession number(s): O00641 Q53EQ8 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| 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. | ||||||||
Relevant documents
| Human chromosome 4 Human chromosome 4: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| Human and mouse protein kinases Human and mouse protein kinases: classification and index |
| SIMILARITY comments Index of protein domains and families |

Clusters with


