Reviewed, UniProtKB/Swiss-Prot O70293 (GRK6_MOUSE)

Names and origin

Protein names

Recommended name:
    G protein-coupled receptor kinase 6
    EC=2.7.11.16
Alternative name(s):
    G protein-coupled receptor kinase GRK6

Gene names

Name:	Grk6
Synonyms:	Gprk6

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	576 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	Specifically phosphorylates the activated forms of G protein-coupled receptors By similarity.
Catalytic activity	ATP + [G-protein-coupled receptor] = ADP + [G-protein-coupled receptor] phosphate.
Subcellular location	Membrane; Lipid-anchor.
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	Membrane
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Lipoprotein Palmitate Phosphoprotein
Gene Ontology (GO)
None. [Check GOA]

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform GRK6A (identifier: O70293-1)

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 GRK6B (identifier: O70293-2)

The sequence of this isoform differs from the canonical sequence as follows:
     560-576: DCCGNCSDSEEELPTRL → RIAVGTAATVRKSSPPASSPQAEAPTGGWR

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 576	576	G protein-coupled receptor kinase 6
Regions
	Domain	53 – 171	119	RGS
	Domain	186 – 448	263	Protein kinase
	Domain	449 – 514	66	AGC-kinase C-terminal
	Nucleotide binding	192 – 200	9	ATP By similarity
	Region	1 – 185	185	N-terminal
Sites
	Active site	311	1	Proton acceptor By similarity
	Binding site	215	1	ATP By similarity
Amino acid modifications
	Modified residue	484	1	Phosphoserine; by autocatalysis By similarity
	Modified residue	485	1	Phosphothreonine; by autocatalysis By similarity
	Lipidation	561	1	S-palmitoyl cysteine By similarity
	Lipidation	562	1	S-palmitoyl cysteine By similarity
	Lipidation	565	1	S-palmitoyl cysteine By similarity
Natural variations
	Alternative sequence	560 – 576	17	DCCGN…LPTRL → RIAVGTAATVRKSSPPASSP QAEAPTGGWR in isoform GRK6B.
Experimental info
	Sequence conflict	98	1	R → Q in AAC09265. Ref.1
	Sequence conflict	571	1	E → K in AAC09265. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform GRK6A [UniParc]. Last modified August 1, 1998. Version 1. Checksum: 91EEC2028CAF4B91	FASTA	576	65,979
	10 20 30 40 50 60 MELENIVANT VLLKAREGGG GNRKGKSKKW RQMLQFPHIS QCEELRLSLE RDYHSLCERQ 70 80 90 100 110 120 PIGRLLFREF CATRPELTRC TAFLDGVSEY EVTPDEKRKA CGRRLMQNFL SHTGPDLIPE 130 140 150 160 170 180 VPRQLVSNCA QRLEQGPCKD LFQELTRLTH EYLSTAPFAD YLDSIYFNRF LQWKWLERQP 190 200 210 220 230 240 VTKNTFRQYR VLGKGGFGEV CACQVRATGK MYACKKLEKK RIKKRKGEAM ALNEKQILEK 250 260 270 280 290 300 VNSRFVVSLA YAYETKDALC LVLTLMNGGD LKFHIYHMGQ AGFPEARAVF YAAEICCGLE 310 320 330 340 350 360 DLHRERIVYR DLKPENILLD DHGHIRISDL GLAVHVPEGQ TIKGRVGTVG YMAPEVVRNE 370 380 390 400 410 420 RYTFSPDWWA LGCLLYEMIA GQSPFQQRKK KIKREEVERL VKEVAEEYTD RFSSQARSLC 430 440 450 460 470 480 SQLLSKDPAE RLGCRGGGAR EVKEHPLFKK LNFKRLGAGM LEPPFKPDPQ AIYCKDVLDI 490 500 510 520 530 540 EQFSTVKGVD LEPTDQDFYQ KFATGSVSIP WQNEMVETEC FQELNVFGLD GSVPPDLDWK 550 560 570 GQPTAPPKKG LLQRLFSRQD CCGNCSDSEE ELPTRL
	Isoform GRK6B [UniParc]. Checksum: C08443E7CB2B714D		589	67,115
	10 20 30 40 50 60 MELENIVANT VLLKAREGGG GNRKGKSKKW RQMLQFPHIS QCEELRLSLE RDYHSLCERQ 70 80 90 100 110 120 PIGRLLFREF CATRPELTRC TAFLDGVSEY EVTPDEKRKA CGRRLMQNFL SHTGPDLIPE 130 140 150 160 170 180 VPRQLVSNCA QRLEQGPCKD LFQELTRLTH EYLSTAPFAD YLDSIYFNRF LQWKWLERQP 190 200 210 220 230 240 VTKNTFRQYR VLGKGGFGEV CACQVRATGK MYACKKLEKK RIKKRKGEAM ALNEKQILEK 250 260 270 280 290 300 VNSRFVVSLA YAYETKDALC LVLTLMNGGD LKFHIYHMGQ AGFPEARAVF YAAEICCGLE 310 320 330 340 350 360 DLHRERIVYR DLKPENILLD DHGHIRISDL GLAVHVPEGQ TIKGRVGTVG YMAPEVVRNE 370 380 390 400 410 420 RYTFSPDWWA LGCLLYEMIA GQSPFQQRKK KIKREEVERL VKEVAEEYTD RFSSQARSLC 430 440 450 460 470 480 SQLLSKDPAE RLGCRGGGAR EVKEHPLFKK LNFKRLGAGM LEPPFKPDPQ AIYCKDVLDI 490 500 510 520 530 540 EQFSTVKGVD LEPTDQDFYQ KFATGSVSIP WQNEMVETEC FQELNVFGLD GSVPPDLDWK 550 560 570 580 GQPTAPPKKG LLQRLFSRQR IAVGTAATVR KSSPPASSPQ AEAPTGGWR

References

[1]	"The GRK4 subfamily of G protein-coupled receptor kinases. Alternative splicing, gene organization, and sequence conservation." Premont R.T., Macrae A.D., Aparicio S.A., Kendall H.E., Welch J.E., Lefkowitz R.J. J. Biol. Chem. 274:29381-29389(1999) [PubMed: 10506199] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS GRK6A AND GRK6B). Strain: 129/SvJ.
[2]	"Primary structure of murine G-protein-coupled receptor kinase 6 splice variants predict differential regulation by posttranslational modifications." Moepps B., Vatter P., Frode R., Waechter F., Gierschik P. Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE (ISOFORMS GRK6A AND GRK6B). Strain: 129/SvJ and C57BL/6J. Tissue: Thymus.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF040747 mRNA. Translation: AAC09268.1. AF040748 mRNA. Translation: AAC09269.1. AF040749 mRNA. Translation: AAC09270.1. AF040754 Genomic DNA. Translation: AAC09265.1. Y17967 Genomic DNA. Translation: CAA76975.1. Y17967 Genomic DNA. Translation: CAA76976.1. Y15798 mRNA. Translation: CAA75789.1. Y15799 mRNA. Translation: CAA75790.1.
RefSeq	NP_001033107.1. NP_001106182.1. NP_036068.2.
UniGene	Mm.10193
3D structure databases
HSSP	HSSP built from PDB template 1GZK based on UniProtKB P31751.
SMR	O70293. Positions 23-532.
ModBase	Search...
PTM databases
PhosphoSite	O70293.
Genome annotation databases
Ensembl	ENSMUSG00000074886. Mus musculus. [Contig view]
GeneID	26385.
KEGG	mmu:26385.
Organism-specific databases
MGI	MGI:1347078. Grk6.
Phylogenomic databases
HOVERGEN	O70293.
Gene expression databases
ArrayExpress	O70293.
CleanEx	MM_GRK6.
GermOnline	ENSMUSG00000074886. Mus musculus.
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

GRK6_MOUSE

Accession

Primary (citable) accession number: O70293
Secondary accession number(s): O70294, O70295

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	August 1, 1998
Last modified:	July 22, 2008
This is version 84 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)