AiPD: Autoinhibited Protein Database

P43250

Gene name	GRK6 (GPRK6)
Protein name	G protein-coupled receptor kinase 6
Names	G protein-coupled receptor kinase GRK6
Species	Homo sapiens (Human)
KEGG Pathway	hsa:2870
EC number	2.7.11.16: Protein-serine/threonine kinases
Protein Class	G PROTEIN-COUPLED RECEPTOR KINASE/RIBOSOMAL PROTEIN S6 KINASE (PTHR24355)

Descriptions

GRK6 (G protein-coupled receptor kinase 6) seems to be involved in the desensitization of D2-like dopamine receptors in striatum and chemokine receptor CXCR4 which is critical for CXCL12-induced cell chemotaxis. GRK5 possesses an autoinhibitory domain, because its deletion increases GRK5 affinity for both phospholipids and receptor. However, a similar sequence is not found within GRK6.

Autoinhibitory domains (AIDs)

Target domain	186-448 (Protein kinase domain)
Relief mechanism	PTM
Assay	Mutagenesis experiment

AID

557-576 (C-terminal extension)

Target domain

186-448 (Protein kinase domain)

Relief mechanism

PTM (Phosphorylation in C-terminal extension)

Assay

Mutagenesis experiment

Accessory elements

328-350 (Activation loop from InterPro)

Target domain	186-448 (Protein kinase domain)
Relief mechanism
Assay

References

Pronin AN et al. (1998) "Structure-function analysis of G protein-coupled receptor kinase-5. Role of the carboxyl terminus in kinase regulation", The Journal of biological chemistry, 273, 31510-8

Vatter P et al. (2005) "The variable C-terminal extension of G-protein-coupled receptor kinase 6 constitutes an accessorial autoregulatory domain", The FEBS journal, 272, 6039-51

Autoinhibited structure

Activated structure

4 structures for P43250

Entry ID	Method	Resolution	Chain	Position	Source
2ACX	X-ray	260 A	A/B	1-576	PDB
3NYN	X-ray	272 A	A/B	2-576	PDB
3NYO	X-ray	292 A	A/B	2-576	PDB
AF-P43250-F1	Predicted				AlphaFoldDB

366 variants for P43250

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
rs1581670221 CA362339033	4	E>*		No	ClinGen Ensembl
rs1183935895 CA362339070	6	I>V		No	ClinGen TOPMed gnomAD
rs1342261475 CA362339141	11	V>L		No	ClinGen gnomAD
rs749276819 CA362339162	13	L>F		No	ClinGen ExAC gnomAD
CA3581676 rs749276819	13	L>I		No	ClinGen ExAC gnomAD
rs866691666 CA132856693	16	R>L		No	ClinGen Ensembl
rs962185664 CA132856696	18	G>S		No	ClinGen TOPMed
rs182443546 CA3581700	20	G>S		No	ClinGen 1000Genomes ExAC gnomAD
rs780589980 CA3581701	20	G>V		No	ClinGen ExAC TOPMed gnomAD
rs1432684474 CA362340089	23	R>C		No	ClinGen TOPMed gnomAD
CA3581702 rs547540433	23	R>H		No	ClinGen 1000Genomes ExAC gnomAD
rs1286629194 CA362340276	28	K>R		No	ClinGen gnomAD
CA362340316 rs1581675103	30	W>G		No	ClinGen Ensembl
COSM20611 CA3581705 VAR_040524 rs141014084	31	R>Q	a gastric adenocarcinoma sample; somatic mutation stomach [UniProt, Cosmic]	No	ClinGen cosmic curated UniProt ESP ExAC TOPMed dbSNP gnomAD
CA3581706 rs769290182	32	Q>R		No	ClinGen ExAC gnomAD
rs772643880 CA3581707	33	M>L		No	ClinGen ExAC gnomAD
CA3581709 rs766253396	36	F>L		No	ClinGen ExAC TOPMed gnomAD
rs1581675135 CA362340546	36	F>S		No	ClinGen Ensembl
CA362340585 rs1280059046	37	P>L		No	ClinGen gnomAD
rs1056305094 CA132858605	39	I>T		No	ClinGen TOPMed
rs539625494 CA3581711	39	I>V		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1276585111 CA362340687	41	Q>*		No	ClinGen TOPMed
rs764426194 CA362340705	41	Q>L		No	ClinGen ExAC gnomAD
rs764426194 CA3581712	41	Q>R		No	ClinGen ExAC gnomAD
CA3581713 rs557978680	43	E>K		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA362340769 rs1255171494	44	E>K		No	ClinGen gnomAD
rs1452808977 CA362340822	46	R>W		No	ClinGen gnomAD
CA362340854 rs1172850043	48	S>N		No	ClinGen gnomAD
rs757475827 CA3581715	48	S>R		No	ClinGen ExAC gnomAD
CA3581717 rs576317155	50	E>*		No	ClinGen 1000Genomes ExAC gnomAD
rs945261941 CA132859193	50	E>G		No	ClinGen TOPMed
rs576317155 CA362340918	50	E>K		No	ClinGen 1000Genomes ExAC gnomAD
rs576317155 CA132858636	50	E>Q		No	ClinGen 1000Genomes ExAC gnomAD
CA362342428 rs1464315015	51	R>C		No	ClinGen TOPMed
CA3581760 rs370990784	51	R>H		No	ClinGen ESP ExAC TOPMed gnomAD
CA362342520 rs1581676842	54	H>P		No	ClinGen Ensembl
CA362342543 rs1419280955	55	S>C		No	ClinGen gnomAD
rs754735690 CA3581761	57	C>*		No	ClinGen ExAC gnomAD
rs1581676854 CA362342571	57	C>G		No	ClinGen Ensembl
CA3581763 rs756444285	58	E>K		No	ClinGen ExAC TOPMed gnomAD
rs777455959 CA3581764	59	R>Q		No	ClinGen ExAC gnomAD
rs1479264805 CA362342614	59	R>W		No	ClinGen TOPMed
CA362342656 rs1414689508	60	Q>L		No	ClinGen gnomAD
rs1328207317 CA362342704	62	I>T		No	ClinGen TOPMed gnomAD
CA3581766 rs756867006	64	R>C		No	ClinGen ExAC gnomAD
rs778299335 CA3581767	64	R>H		No	ClinGen ExAC gnomAD
rs1250689247 CA362342829	68	R>G		No	ClinGen TOPMed
rs780019731 CA3581770	68	R>Q		No	ClinGen ExAC gnomAD
CA3581771 rs746859263	69	E>K		No	ClinGen ExAC gnomAD
CA362342900 rs1561653552	72	A>T		No	ClinGen Ensembl
rs56382815 CA3581772 VAR_040525	73	T>M		No	ClinGen UniProt ExAC TOPMed dbSNP gnomAD
CA3581775 rs771139234	75	P>L		No	ClinGen ExAC gnomAD
rs1253280454 CA362342956	76	E>K		No	ClinGen gnomAD
rs951515058 CA132859295	76	E>V		No	ClinGen Ensembl
rs767954531 CA3581778	79	R>C		No	ClinGen ExAC TOPMed gnomAD
rs571235637 CA3581779	79	R>H		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA3581780 rs761090950	80	C>R		No	ClinGen ExAC TOPMed gnomAD
CA362343112 rs538655077	80	C>W		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs747788540 CA3581782	81	V>I		No	ClinGen ExAC TOPMed gnomAD
COSM3783897 rs778598612 COSM3783896 CA3581784	82	A>T	prostate [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs1444794813 CA362343291	86	G>R		No	ClinGen TOPMed
CA3581807 rs755000045	88	A>V		No	ClinGen ExAC gnomAD
rs747940046 CA3581809	89	E>K		No	ClinGen ExAC TOPMed gnomAD
CA362343639 rs1418697636	93	T>I		No	ClinGen gnomAD
rs755921293 CA3581810	94	P>L		No	ClinGen ExAC TOPMed gnomAD
CA3581812 rs746103199 COSM1736194	96	D>E	central_nervous_system [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA3581814 rs775567957	98	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs772223816 CA3581813	98	R>W		No	ClinGen ExAC TOPMed gnomAD
rs1393973668 CA362343828	99	K>N		No	ClinGen TOPMed gnomAD
rs747049926 CA3581815	100	A>T		No	ClinGen ExAC gnomAD
CA3581816 rs769189900	101	C>Y		No	ClinGen ExAC gnomAD
rs1186612780 CA362343912	102	G>V		No	ClinGen TOPMed
rs377541049 CA132859474	103	R>Q		No	ClinGen TOPMed
rs113773107 CA132859472	103	R>W		No	ClinGen Ensembl
CA3581818 rs777110947	104	Q>E		No	ClinGen ExAC gnomAD
rs777110947 CA3581817	104	Q>K		No	ClinGen ExAC gnomAD
rs79664864 CA132859479	104	Q>R		No	ClinGen Ensembl
CA362343982 rs1292119336	105	L>V		No	ClinGen TOPMed gnomAD
rs76705113 CA3581820	106	T>M		No	ClinGen ExAC TOPMed gnomAD
CA132859486 rs1028723194	112	H>Y		No	ClinGen TOPMed gnomAD
CA3581823 rs149694282	113	T>K		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs149694282 CA3581822	113	T>M		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs759181391 CA3581843	114	G>D		No	ClinGen ExAC gnomAD
CA132859695 rs898692878	115	P>S		No	ClinGen Ensembl
CA362344432 rs1194042659	116	D>E		No	ClinGen gnomAD
CA362344518 rs1396590384	121	V>F		No	ClinGen TOPMed gnomAD
CA362344541 rs1396590384	121	V>I		No	ClinGen TOPMed gnomAD
rs767137153 CA362344561	123	R>G		No	ClinGen ExAC TOPMed gnomAD
CA132859704 rs139248624	123	R>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs139248624 CA3581845	123	R>Q		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA3581844 rs767137153	123	R>W		No	ClinGen ExAC TOPMed gnomAD
rs1345694316 CA362344653	127	T>A		No	ClinGen gnomAD
CA3581846 rs756099579	127	T>M		No	ClinGen ExAC TOPMed gnomAD
CA362344760 rs1358671049	130	T>I		No	ClinGen TOPMed
CA3581848 rs2230881	132	R>Q		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA362344811 rs1472581488	132	R>W		No	ClinGen TOPMed gnomAD
CA362344856 rs1581678189	134	E>G		No	ClinGen Ensembl
rs780323605 CA3581850	136	G>C		No	ClinGen ExAC gnomAD
CA362344947 rs1318012383	137	P>L		No	ClinGen gnomAD
CA3581851 rs751784930	138	C>F		No	ClinGen ExAC TOPMed gnomAD
rs1218120581 CA362344949	138	C>R		No	ClinGen gnomAD
CA362344956 rs1464617742	138	C>W		No	ClinGen TOPMed gnomAD
CA132859717 rs1050231684	146	T>A		No	ClinGen TOPMed
rs1050231684 CA362345131	146	T>P		No	ClinGen TOPMed
CA3581853 rs781358837	147	R>Q		No	ClinGen ExAC gnomAD
CA3581852 rs755136029	147	R>W		No	ClinGen ExAC gnomAD
rs779438253 CA3581880	151	E>D		No	ClinGen ExAC TOPMed gnomAD
rs771503581 CA3581878	151	E>G		No	ClinGen ExAC gnomAD
rs528670739 CA3581877	151	E>K		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA362345412 rs1318519863	153	L>P		No	ClinGen gnomAD
rs542185009 CA3581882	155	V>M		No	ClinGen ExAC TOPMed gnomAD
rs1354488266 CA362345525	158	F>L		No	ClinGen TOPMed
rs760288504 CA3581883	160	D>N		No	ClinGen ExAC TOPMed gnomAD
rs768056681 CA3581885	162	L>I		No	ClinGen ExAC gnomAD
rs750263792 CA362345669	163	D>E		No	ClinGen ExAC gnomAD
rs1189516663 CA362345661	163	D>G		No	ClinGen TOPMed gnomAD
rs144732874 CA3581888	163	D>H		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA3581887 rs144732874	163	D>N		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA3581890 rs762636724	165	I>V		No	ClinGen ExAC TOPMed gnomAD
rs767841378 CA3581891	168	N>S		No	ClinGen ExAC gnomAD
rs200416754 CA3581892	169	R>C		No	ClinGen 1000Genomes ExAC gnomAD
CA3581893 rs201293306	177	E>G		No	ClinGen ExAC gnomAD
rs750960883 CA3581916	178	R>S		No	ClinGen ExAC gnomAD
rs764091020 CA3581894	178	R>T		No	ClinGen ExAC gnomAD
rs1581679280 CA362346400	185	T>S		No	ClinGen Ensembl
rs1279474823 CA362346528	190	R>*		No	ClinGen TOPMed
CA362346578 rs1205269101	193	G>V		No	ClinGen gnomAD
rs758884458 CA3581917	196	G>S		No	ClinGen ExAC gnomAD
CA362346653 rs1247817464	199	E>K		No	ClinGen gnomAD
rs1183115320 CA362346740	201	C>R		No	ClinGen gnomAD
rs751921361 CA3581938	202	A>G		No	ClinGen ExAC gnomAD
rs755326265 CA3581939	203	C>R		No	ClinGen ExAC gnomAD
rs752353702 CA3581941	206	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA3581940 rs780891929	206	R>W		No	ClinGen ExAC TOPMed gnomAD
CA362346822 rs1330865468	209	G>D		No	ClinGen gnomAD
rs748787453 CA3581944	210	K>R		No	ClinGen ExAC TOPMed gnomAD
rs1481279014 CA362346920	217	L>V		No	ClinGen TOPMed gnomAD
rs1242074801 CA362346941	219	K>E		No	ClinGen gnomAD
rs771986333 CA3581948	220	K>R		No	ClinGen ExAC gnomAD
CA3581950 rs762149337	221	R>Q		No	ClinGen ExAC gnomAD
CA3581949 rs530467814	221	R>W		No	ClinGen ExAC gnomAD
rs1254678919 CA362347010	225	R>Q		No	ClinGen gnomAD
rs773206129 CA3581952	229	A>D		No	ClinGen ExAC gnomAD
rs1241727233 CA362347049	229	A>T		No	ClinGen TOPMed gnomAD
CA3581953 rs763068007 COSM449396	231	A>V	breast [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA362347121 rs1368087871	236	Q>*		No	ClinGen gnomAD
CA362347137 rs1561655353	237	I>T		No	ClinGen Ensembl
rs1313328721 CA362347164	240	K>E		No	ClinGen TOPMed
CA362347168 rs1368691441	240	K>R		No	ClinGen gnomAD
rs1461331281 CA362347291	247	V>L		No	ClinGen TOPMed
CA362347329 rs1458507263	250	A>V		No	ClinGen gnomAD
CA3581995 rs551229599	252	A>T		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA132860536 rs770127017	253	Y>C		No	ClinGen Ensembl
CA3581997 rs761093075	254	E>Q		No	ClinGen ExAC
rs764524369 CA3581998	255	T>A		No	ClinGen ExAC gnomAD
rs1370382342 CA362347378	255	T>I		No	ClinGen gnomAD
CA362347403 rs966033174	257	D>E		No	ClinGen TOPMed gnomAD
CA362347409 rs35270792	258	A>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA3581999 rs35270792	258	A>T		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA132860554 rs865781391	258	A>V		No	ClinGen TOPMed gnomAD
CA3582002 rs750004797	265	L>Q		No	ClinGen ExAC gnomAD
rs766494289 CA3582004	268	G>R		No	ClinGen ExAC TOPMed gnomAD
rs781067073 CA3582007	270	D>N		No	ClinGen ExAC gnomAD
rs985885225 CA132860620	271	L>I		No	ClinGen TOPMed
CA3582009 rs371992461	275	I>V		No	ClinGen ESP ExAC TOPMed gnomAD
rs1434976954 CA362347614	277	H>R		No	ClinGen gnomAD
CA132860626 rs948045373	278	M>T		No	ClinGen TOPMed
CA3582011 rs746003217	282	G>S		No	ClinGen ExAC gnomAD
CA3582013 rs566558526	284	P>L		No	ClinGen 1000Genomes ExAC gnomAD
rs1291786462 CA362348562	286	A>G		No	ClinGen TOPMed gnomAD
rs1229062176 CA362347801	286	A>T		No	ClinGen gnomAD
CA362348556 rs1291786462	286	A>V		No	ClinGen TOPMed gnomAD
CA3582017 rs762062818	287	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs777094286 CA3582016	287	R>W		No	ClinGen ExAC gnomAD
CA3582018 rs551864050	289	V>I		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs74796961 CA3582020	292	A>T		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs368436043 CA3582022	293	A>T		No	ClinGen ESP ExAC TOPMed gnomAD
CA362348686 rs1238605234	294	E>K		No	ClinGen TOPMed
rs150356729 CA3582024	301	D>A		No	ClinGen ESP ExAC TOPMed gnomAD
CA362348866 rs1306292755	301	D>N		No	ClinGen gnomAD
CA3582028 rs376251838	304	R>L		No	ClinGen ESP ExAC TOPMed gnomAD
rs376251838 CA3582027	304	R>Q		No	ClinGen ESP ExAC TOPMed gnomAD
CA3582026 rs749603773	304	R>W		No	ClinGen ExAC gnomAD
rs1297991606 CA362348962	305	E>*		No	ClinGen gnomAD
rs138392836 CA3582029	306	R>C		No	ClinGen ESP ExAC TOPMed gnomAD
CA3582030 rs780128630	306	R>H		No	ClinGen ExAC TOPMed gnomAD
CA362348995 rs1485741470	307	I>V		No	ClinGen TOPMed gnomAD
rs888876754 CA132860694	308	V>L		No	ClinGen TOPMed gnomAD
CA362349018 rs888876754	308	V>M		No	ClinGen TOPMed gnomAD
rs1397207765 CA362349371	323	G>S		No	ClinGen TOPMed
CA3582068 rs560434892	324	H>R		No	ClinGen 1000Genomes ExAC gnomAD
rs375225364 CA132861290	326	R>H		No	ClinGen ESP
rs1357556111 CA362349472	329	D>E		No	ClinGen gnomAD
rs1303713360 CA362349500	332	L>P		No	ClinGen Ensembl
rs143935970 CA3582070	334	V>M		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA362349515 rs1490326033	335	H>Y		No	ClinGen gnomAD
CA362349549 rs1386651105	338	E>A		No	ClinGen TOPMed
CA3582073 rs373013135	338	E>D		No	ClinGen ESP ExAC TOPMed gnomAD
rs200924933 CA3582072	338	E>K		No	ClinGen ESP ExAC TOPMed gnomAD
CA362349559 rs1181418041	339	G>C		No	ClinGen gnomAD
CA3582074 rs778398556	339	G>D		No	ClinGen ExAC gnomAD
rs749724882 CA3582075	342	I>V		No	ClinGen ExAC TOPMed gnomAD
rs1161225469 CA362349602	343	K>R		No	ClinGen gnomAD
CA362349622 rs1387832979	345	R>H		No	ClinGen TOPMed
rs1167534488 CA362349627	346	V>M		No	ClinGen TOPMed
COSM1195888 rs376452319 CA3582076	349	V>M	lung [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
CA362349697 rs1266199948	352	M>I		No	ClinGen TOPMed gnomAD
rs1221060405 CA362349688	352	M>V		No	ClinGen gnomAD
rs1309358090 CA362349701	353	A>T		No	ClinGen gnomAD
rs764280672 CA3582110	354	P>L		No	ClinGen ExAC gnomAD
CA3582115 rs200876617	361	R>Q		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA3582114 rs750801806	361	R>W		No	ClinGen ExAC TOPMed gnomAD
CA3582116 rs200013126	363	T>M		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA132862009 rs1039278539	365	S>G		No	ClinGen Ensembl
rs149423489 CA362350378	365	S>I		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs149423489 CA3582118	365	S>T		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA132862019 rs769672004	370	A>G		No	ClinGen ExAC TOPMed gnomAD
rs769672004 CA3582121	370	A>V		No	ClinGen ExAC TOPMed gnomAD
CA132862026 rs374983204	372	G>S		No	ClinGen ESP TOPMed
CA132862041 rs17851507	374	L>F		No	ClinGen Ensembl
rs1290827677 CA362350541	374	L>P		No	ClinGen TOPMed
rs553986214 CA362350606	376	Y>*		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA362350615 rs371241210	377	E>*		No	ClinGen ESP ExAC TOPMed
CA3582126 rs371241210	377	E>K		No	ClinGen ESP ExAC TOPMed
CA362350632 rs1294588961	378	M>L		No	ClinGen Ensembl
CA362350674 rs202175190	380	A>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA3582128 rs202175190	380	A>T		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs997169774 CA132862063	380	A>V		No	ClinGen gnomAD
rs1458423902 CA362350687	381	G>S		No	ClinGen TOPMed gnomAD
rs1161861827 CA362350751	383	S>L		No	ClinGen TOPMed gnomAD
rs1412602319 CA362350769	384	P>L		No	ClinGen TOPMed
rs761929808 CA3582129	386	Q>*		No	ClinGen ExAC gnomAD
rs141934602 CA362350874	388	R>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs750946000 CA362350898	389	K>N		No	ClinGen ExAC TOPMed gnomAD
CA3582133 rs763312755	390	K>E		No	ClinGen ExAC gnomAD
rs1351342998 CA362350926	391	K>M		No	ClinGen gnomAD
CA362350933 rs1230421764	391	K>N		No	ClinGen TOPMed gnomAD
CA362350956 rs1288899529	392	I>M		No	ClinGen TOPMed gnomAD
CA362350963 rs766754458	393	K>*		No	ClinGen ExAC TOPMed gnomAD
CA132862094 rs374190468	393	K>N		No	ClinGen ESP TOPMed
CA3582134 rs766754458	393	K>Q		No	ClinGen ExAC TOPMed gnomAD
CA3582137 rs750720659	394	R>*		No	ClinGen ExAC
rs754668753 CA3582138	394	R>Q		No	ClinGen ExAC gnomAD
rs751883117 CA3582136	394	R>W		No	ClinGen ExAC gnomAD
rs752211378 CA3582141	395	E>D		No	ClinGen ExAC TOPMed gnomAD
rs1486432563 CA362351011	395	E>V		No	ClinGen TOPMed
CA362351053 rs1251853641	398	E>K		No	ClinGen gnomAD
rs200870863 CA3582143	399	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs866606233 CA132862116	399	R>W		No	ClinGen TOPMed gnomAD
rs1027826479 CA3582146	401	V>G		No	ClinGen gnomAD
CA3582150 rs76969408	402	K>E		No	ClinGen ExAC gnomAD
rs1352136406 CA362351152	402	K>R		No	ClinGen gnomAD
rs745629556 CA3582151	403	E>G		No	ClinGen ExAC gnomAD
CA3582152 rs201683213	404	V>D		No	ClinGen ExAC gnomAD
CA3582153 rs201683213	404	V>G		No	ClinGen ExAC gnomAD
rs1372858560 CA362351235	407	E>G		No	ClinGen gnomAD
rs200401278 CA3582161	410	E>K		No	ClinGen ESP ExAC TOPMed gnomAD
rs146135301 CA3582162	411	R>C		No	ClinGen ESP ExAC TOPMed gnomAD
COSM1066382 CA3582163 rs200351023	411	R>H	endometrium [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
rs146135301 CA362351306	411	R>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA3582165 rs753249774	414	P>L		No	ClinGen ExAC TOPMed gnomAD
rs778973062 CA3582167	416	A>S		No	ClinGen ExAC TOPMed gnomAD
rs543441456 CA3582168	417	R>C		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA3582169 rs776311701	417	R>H		No	ClinGen ExAC TOPMed gnomAD
CA362351446 rs776311701	417	R>L		No	ClinGen ExAC TOPMed gnomAD
CA3582171 rs748423472	419	L>F		No	ClinGen ExAC gnomAD
rs1312458885 CA362351524	420	C>G		No	ClinGen gnomAD
rs769865602 CA3582172	421	S>L		No	ClinGen ExAC gnomAD
rs267600570 CA132862201	422	Q>*		No	ClinGen Ensembl
CA362351734 rs1581684798	423	L>P		No	ClinGen Ensembl
rs1329367782 CA362351782	425	C>F		No	ClinGen TOPMed
CA3582191 rs779929443	425	C>W		No	ClinGen ExAC gnomAD
CA362351814 rs1192525477	426	K>R		No	ClinGen gnomAD
rs1371439948 CA362351836	427	D>N		No	ClinGen gnomAD
CA362351850 rs1322322899	427	D>V		No	ClinGen gnomAD
CA3582192 rs751278575	429	A>V		No	ClinGen ExAC gnomAD
rs749433938 CA362351918	430	E>*		No	ClinGen ExAC TOPMed gnomAD
rs749433938 CA3582195	430	E>K		No	ClinGen ExAC TOPMed gnomAD
CA132862297 rs909306347	431	R>C		No	ClinGen TOPMed gnomAD
COSM3827783 rs770999265 CA3582196 COSM3827782	431	R>H	breast [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs1581684886 CA362352013	434	C>G		No	ClinGen Ensembl
rs374437384 CA3582197	435	R>C		No	ClinGen ESP ExAC TOPMed gnomAD
CA3582198 rs746400339	435	R>H		No	ClinGen ExAC TOPMed gnomAD
CA3582199 rs746400339	435	R>L		No	ClinGen ExAC TOPMed gnomAD
CA132862328 rs41275337	436	G>R		No	ClinGen TOPMed
CA362352040 rs41275337	436	G>R		No	ClinGen TOPMed
rs760926294 CA3582201	437	G>D		No	ClinGen ExAC TOPMed gnomAD
rs1469426932 CA362352066	437	G>S		No	ClinGen gnomAD
rs1390503488 CA362352105	439	A>S		No	ClinGen gnomAD
rs1317606599 CA362352125	440	R>C		No	ClinGen TOPMed gnomAD
CA3582203 rs199662008	440	R>H		No	ClinGen ExAC TOPMed gnomAD
CA362352168 rs749911063	441	E>D		No	ClinGen ExAC gnomAD
rs1581684988 CA362352187	442	V>G		No	ClinGen Ensembl
CA362352231 rs1228567024	444	E>K		No	ClinGen gnomAD
CA132862339 rs573725258	446	P>L		No	ClinGen 1000Genomes
rs780969131 CA3582211 COSM244817	448	F>L	prostate [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs1452637308 CA362352331	449	K>E		No	ClinGen gnomAD
CA362352359 rs1224826592	450	K>R		No	ClinGen gnomAD
rs1266819208 CA362352485	455	R>Q		No	ClinGen TOPMed gnomAD
CA362352520 rs1480245854	457	G>E		No	ClinGen gnomAD
CA3582213 rs199647408	463	P>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs745918710 CA3582215	464	P>L		No	ClinGen ExAC gnomAD
CA362352648 rs1409865872	466	K>M		No	ClinGen gnomAD
CA3582259 rs751627707	480	I>L		No	ClinGen ExAC
CA362354534 rs1324798642	480	I>M		No	ClinGen TOPMed gnomAD
CA3582260 rs369487775	485	T>M		No	ClinGen ESP ExAC TOPMed gnomAD
CA3582263 rs540859187	489	V>M		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs778221007 CA3582265	492	E>K		No	ClinGen ExAC TOPMed gnomAD
rs778221007 CA3582264	492	E>Q		No	ClinGen ExAC TOPMed gnomAD
rs1489495760 CA362354664	493	P>A		No	ClinGen TOPMed
CA3582266 rs770581380	494	T>A		No	ClinGen ExAC gnomAD
CA362354689 rs1221647357	495	D>H		No	ClinGen gnomAD
rs745364019 CA3582268	496	Q>R		No	ClinGen ExAC TOPMed gnomAD
rs772058203 CA3582269	500	Q>R		No	ClinGen ExAC gnomAD
rs1581692223 CA362354827	501	K>N		No	ClinGen Ensembl
CA132866091 rs865849245	501	K>R		No	ClinGen Ensembl
rs149674824 CA132866093	504	T>I		No	ClinGen ESP
CA3582271 rs760539387	506	S>I		No	ClinGen ExAC TOPMed gnomAD
rs760539387 CA362354904	506	S>N		No	ClinGen ExAC TOPMed gnomAD
rs867783337 CA132866097	508	P>S		No	ClinGen Ensembl
rs1174752158 CA362354968	510	P>T		No	ClinGen gnomAD
CA362354993 rs1405868091	511	W>*		No	ClinGen gnomAD
CA362355051 rs375413182	513	N>K		No	ClinGen ESP ExAC TOPMed gnomAD
CA362355027 rs1454598649	513	N>Y		No	ClinGen gnomAD
CA3582291 rs776339686	519	E>K		No	ClinGen ExAC gnomAD
CA3582295 rs759772118	528	G>R		No	ClinGen ExAC gnomAD
rs752781110 CA3582298	530	D>A		No	ClinGen ExAC gnomAD
CA3582296 rs767723740	530	D>N		No	ClinGen ExAC gnomAD
CA3582297 rs752781110	530	D>V		No	ClinGen ExAC gnomAD
rs1319626844 CA362355571	532	S>L		No	ClinGen TOPMed
CA3582299 rs764644961	533	V>L		No	ClinGen ExAC gnomAD
rs148914663 CA3582301	535	P>L		No	ClinGen ESP ExAC TOPMed gnomAD
rs1387625175 CA362355735	538	D>N		No	ClinGen gnomAD
rs200510977 CA362355863 COSM3697165 COSM3697164	541	G>D	large_intestine [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
rs200510977 CA3582302	541	G>V		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA362355895 rs1438724892	542	Q>R		No	ClinGen TOPMed
rs750105777 CA3582303	543	P>L		No	ClinGen ExAC gnomAD
rs1393855840 CA362355906	543	P>T		No	ClinGen TOPMed
CA3582304 rs199969070	544	P>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA362355961 rs1581692723	545	A>E		No	ClinGen Ensembl
CA362355990 rs1444589219	546	P>L		No	ClinGen gnomAD
rs142613356 CA3582305	547	P>R		No	ClinGen ESP ExAC TOPMed gnomAD
CA3582307 rs768636126	550	G>R		No	ClinGen ExAC gnomAD
CA3582308 rs781184004	553	Q>R		No	ClinGen ExAC gnomAD
rs1357116773 CA362356186	556	F>L		No	ClinGen gnomAD
rs1244607954 CA362356220	558	R>C		No	ClinGen TOPMed gnomAD
CA362356227 rs1364435410	558	R>H		No	ClinGen gnomAD
rs1274675817 CA362356238	559	Q>*		No	ClinGen gnomAD
rs1391560036 CA362356577	561	C>F		No	ClinGen gnomAD
CA132866611 rs988901265	562	C>Y		No	ClinGen TOPMed
CA362356730 rs1378853368	567	D>E		No	ClinGen gnomAD
CA362356718 rs748162611	567	D>H		No	ClinGen ExAC TOPMed gnomAD
rs748162611 CA3582355	567	D>N		No	ClinGen ExAC TOPMed gnomAD
CA362356742 rs1561663101	568	S>G		No	ClinGen Ensembl
CA3582356 rs770397356	568	S>I		No	ClinGen ExAC gnomAD
rs559029399 CA3582359	569	E>*		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA3582358 rs559029399	569	E>K		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA3582360 rs370944775	570	E>K		No	ClinGen ESP ExAC TOPMed gnomAD
rs370944775 CA3582361	570	E>Q		No	ClinGen ESP ExAC TOPMed gnomAD
rs767052288 CA3582362	571	E>D		No	ClinGen ExAC gnomAD
CA3582364 rs760101303	572	L>P		No	ClinGen ExAC gnomAD
CA3582365 rs763634515	574	T>P		No	ClinGen ExAC gnomAD
CA3582366 rs753843240	575	R>C		No	ClinGen ExAC TOPMed gnomAD
CA3582367 rs140438014	575	R>H		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA3582368 rs778882977	576	L>F		No	ClinGen ExAC TOPMed gnomAD
CA362356979 rs1487124239	577	L>S		No	ClinGen TOPMed

No associated diseases with P43250

5 regional properties for P43250

Type	Name	Position	InterPro Accession
domain	Protein kinase domain	186 - 448	IPR000719
domain	AGC-kinase, C-terminal	449 - 528	IPR000961
active_site	Serine/threonine-protein kinase, active site	307 - 319	IPR008271
domain	RGS domain	52 - 171	IPR016137
binding_site	Protein kinase, ATP binding site	192 - 224	IPR017441

Functions

		Description
EC Number	2.7.11.16	Protein-serine/threonine kinases
Subcellular Localization	Membrane; Lipid-anchor
PANTHER Family	PTHR24355	G PROTEIN-COUPLED RECEPTOR KINASE/RIBOSOMAL PROTEIN S6 KINASE
PANTHER Subfamily	PTHR24355:SF15	G PROTEIN-COUPLED RECEPTOR KINASE 6
PANTHER Protein Class	non-receptor serine/threonine protein kinase protein modifying enzyme
PANTHER Pathway Category	Heterotrimeric G-protein signaling pathway-Gq alpha and Go alpha mediated pathway GPRK Angiotensin II-stimulated signaling through G proteins and beta-arrestin GRK6 Inflammation mediated by chemokine and cytokine signaling pathway GPRK Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway GPRK

3 GO annotations of cellular component

Name	Definition
cytoplasm	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
membrane	A lipid bilayer along with all the proteins and protein complexes embedded in it an attached to it.
plasma membrane	The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.

4 GO annotations of molecular function

Name	Definition
ATP binding	Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
beta-adrenergic receptor kinase activity	Catalysis of the reaction: ATP + beta-adrenergic receptor = ADP + phospho-beta-adrenergic receptor.
G protein-coupled receptor kinase activity	Catalysis of the reaction: ATP + G protein-coupled receptor = ADP + G protein-coupled receptor phosphate.
protein kinase activity	Catalysis of the phosphorylation of an amino acid residue in a protein, usually according to the reaction: a protein + ATP = a phosphoprotein + ADP.

5 GO annotations of biological process

Name	Definition
G protein-coupled receptor signaling pathway	The series of molecular signals initiated by a ligand binding to its receptor, in which the activated receptor promotes the exchange of GDP for GTP on the alpha-subunit of an associated heterotrimeric G-protein complex. The GTP-bound activated alpha-G-protein then dissociates from the beta- and gamma-subunits to further transmit the signal within the cell. The pathway begins with receptor-ligand interaction, and ends with regulation of a downstream cellular process. The pathway can start from the plasma membrane, Golgi or nuclear membrane.
protein phosphorylation	The process of introducing a phosphate group on to a protein.
regulation of G protein-coupled receptor signaling pathway	Any process that modulates the frequency, rate or extent of G protein-coupled receptor signaling pathway.
regulation of signal transduction	Any process that modulates the frequency, rate or extent of signal transduction.
Wnt signaling pathway	The series of molecular signals initiated by binding of a Wnt protein to a frizzled family receptor on the surface of the target cell and ending with a change in cell state.

20 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
P26818	GRK3	Beta-adrenergic receptor kinase 2	Bos taurus (Bovine)	PR
P43249	GRK5	G protein-coupled receptor kinase 5	Bos taurus (Bovine)	SS
P21146	GRK2	Beta-adrenergic receptor kinase 1	Bos taurus (Bovine)	PR
P32865	Gprk1	G protein-coupled receptor kinase 1	Drosophila melanogaster (Fruit fly)	PR
Q96LW2	RSKR	Ribosomal protein S6 kinase-related protein	Homo sapiens (Human)	PR
P32298	GRK4	G protein-coupled receptor kinase 4	Homo sapiens (Human)	SS
Q15835	GRK1	Rhodopsin kinase GRK1	Homo sapiens (Human)	PR
P34947	GRK5	G protein-coupled receptor kinase 5	Homo sapiens (Human)	EV
P25098	GRK2	Beta-adrenergic receptor kinase 1	Homo sapiens (Human)	PR
P35626	GRK3	Beta-adrenergic receptor kinase 2	Homo sapiens (Human)	PR
Q8VEB1	Grk5	G protein-coupled receptor kinase 5	Mus musculus (Mouse)	SS
Q99MK8	Grk2	Beta-adrenergic receptor kinase 1	Mus musculus (Mouse)	PR
Q9WVL4	Grk1	Rhodopsin kinase GRK1	Mus musculus (Mouse)	PR
Q3UYH7	Adrbk2	Beta-adrenergic receptor kinase 2	Mus musculus (Mouse)	PR
O70293	Grk6	G protein-coupled receptor kinase 6	Mus musculus (Mouse)	SS
Q62833	Grk5	G protein-coupled receptor kinase 5	Rattus norvegicus (Rat)	SS
P26817	Grk2	Beta-adrenergic receptor kinase 1	Rattus norvegicus (Rat)	PR
P97711	Grk6	G protein-coupled receptor kinase 6	Rattus norvegicus (Rat)	SS
Q09639	grk-2	G protein-coupled receptor kinase 2	Caenorhabditis elegans	PR
O48963	PHOT1	Phototropin-1	Arabidopsis thaliana (Mouse-ear cress)	PR

10	20	30	40	50	60
MELENIVANT	VLLKAREGGG	GNRKGKSKKW	RQMLQFPHIS	QCEELRLSLE	RDYHSLCERQ
70	80	90	100	110	120
PIGRLLFREF	CATRPELSRC	VAFLDGVAEY	EVTPDDKRKA	CGRQLTQNFL	SHTGPDLIPE
130	140	150	160	170	180
VPRQLVTNCT	QRLEQGPCKD	LFQELTRLTH	EYLSVAPFAD	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	YMAPEVVKNE
370	380	390	400	410	420
RYTFSPDWWA	LGCLLYEMIA	GQSPFQQRKK	KIKREEVERL	VKEVPEEYSE	RFSPQARSLC
430	440	450	460	470	480
SQLLCKDPAE	RLGCRGGSAR	EVKEHPLFKK	LNFKRLGAGM	LEPPFKPDPQ	AIYCKDVLDI
490	500	510	520	530	540
EQFSTVKGVE	LEPTDQDFYQ	KFATGSVPIP	WQNEMVETEC	FQELNVFGLD	GSVPPDLDWK
550	560	570
GQPPAPPKKG	LLQRLFSRQD	CCGNCSDSEE	ELPTRL