AiPD: Autoinhibited Protein Database

P34947

Gene name	GRK5 (GPRK5)
Protein name	G protein-coupled receptor kinase 5
Names	G protein-coupled receptor kinase GRK5
Species	Homo sapiens (Human)
KEGG Pathway	hsa:2869
EC number	2.7.11.16: Protein-serine/threonine kinases
Protein Class	G PROTEIN-COUPLED RECEPTOR KINASE/RIBOSOMAL PROTEIN S6 KINASE (PTHR24355)

Descriptions

GRK5(G protein-coupled receptor kinase 5) phosphorylates a variety of GPCRs, including adrenergic receptors, muscarinic acetylcholine receptors (more specifically Gi-coupled M2/M4 subtypes), dopamine receptors and opioid receptors. In addition to GPCRs, GRK5 also phosphorylates various substrates: Hsc70-interacting protein/ST13, TP53/p53, HDAC5, and arrestin-1/ARRB1. GRK5 has an autoinhibitory domain, because its deletion increases GRK5 affinity for both phospholipids and receptor by 3-4 fold. The efficacy of the autoinhibition is enhanced by PKC phosphorylation or calmodulin-stimulated autophosphorylation within the autoinhibitory domain.

Autoinhibitory domains (AIDs)

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

AID

563-590 (Autoinhibitory domain)

Target domain

186-448 (Protein kinase domain)

Relief mechanism

Assay

Deletion assay

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

Autoinhibited structure

Activated structure

6 structures for P34947

Entry ID	Method	Resolution	Chain	Position	Source
4TNB	X-ray	211 A	A	1-590	PDB
4TND	X-ray	180 A	A	1-590	PDB
6PJX	X-ray	196 A	A	1-590	PDB
8UAP	X-ray	250 A	A	1-590	PDB
8UAQ	X-ray	280 A	A	1-590	PDB
AF-P34947-F1	Predicted				AlphaFoldDB

373 variants for P34947

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
RCV001262995 rs1848415086	11	V>F	Neurodevelopmental disorder [ClinVar]	Yes	ClinVar dbSNP
CA5715068 rs776373760	13	L>V		No	ClinGen ExAC TOPMed gnomAD
rs1168556943 CA378270190	16	R>S		No	ClinGen gnomAD
rs1424610264 CA378270193	17	E>*		No	ClinGen gnomAD
rs985394764 CA214155486	17	E>G		No	ClinGen TOPMed
rs1403848685 CA378270198	18	G>R		No	ClinGen TOPMed
rs201715604 CA5715091	19	G>R		No	ClinGen ExAC TOPMed gnomAD
rs201715604 CA5715090	19	G>S		No	ClinGen ExAC TOPMed gnomAD
rs761548495 CA5715093	20	G>E		No	ClinGen ExAC gnomAD
CA5715092 rs148368301	20	G>R		No	ClinGen ESP ExAC TOPMed gnomAD
CA214617737 rs1023421469	23	R>C		No	ClinGen TOPMed
rs767144498 CA5715094	23	R>H		No	ClinGen ExAC TOPMed gnomAD
rs755630855 CA5715096	24	K>E		No	ClinGen ExAC gnomAD
CA378355785 rs1564892090	27	S>N		No	ClinGen Ensembl
rs1177966090 CA378355792	28	K>E		No	ClinGen TOPMed gnomAD
CA378355841 rs1216070478	34	L>P		No	ClinGen TOPMed
CA5715097 rs780564165	36	F>L		No	ClinGen ExAC gnomAD
rs1355404509 CA378355869	38	H>R		No	ClinGen TOPMed
CA5715099 rs199919771	39	I>N		No	ClinGen 1000Genomes ExAC gnomAD
rs576302427 CA5715098	39	I>V		No	ClinGen 1000Genomes ExAC gnomAD
rs2230345 CA5715100 VAR_040517	41	Q>L	exerts a protective effect in heart failure and ischemia [UniProt]	No	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs1244210867 CA378355895	42	C>Y		No	ClinGen TOPMed
rs1394632002 CA378355913	44	D>G		No	ClinGen gnomAD
CA5715101 rs377304963	46	R>Q		No	ClinGen ESP ExAC TOPMed gnomAD
CA5715102 rs772304616	47	R>G		No	ClinGen ExAC gnomAD
CA5715103 rs777904638	48	T>N		No	ClinGen ExAC gnomAD
rs747058699 CA5715104	49	I>L		No	ClinGen ExAC TOPMed gnomAD
CA214617824 rs991578886	49	I>T		No	ClinGen TOPMed gnomAD
CA378355938 rs747058699	49	I>V		No	ClinGen ExAC TOPMed gnomAD
CA378355964 rs1423435801	50	D>G		No	ClinGen gnomAD
CA5715155 rs150876579	52	D>E		No	ClinGen ESP ExAC TOPMed gnomAD
CA378355976 rs1163077540	52	D>H		No	ClinGen gnomAD
rs561959438 CA5715154	52	D>V		No	ClinGen 1000Genomes ExAC gnomAD
CA378355998 rs1399440730	55	S>G		No	ClinGen gnomAD
CA214659673 rs1040210830	58	D>E		No	ClinGen TOPMed
rs1306030442 CA378356068	64	R>S		No	ClinGen TOPMed gnomAD
rs549815612 CA5715158	66	L>F		No	ClinGen 1000Genomes ExAC gnomAD
rs201278015 CA5715160	68	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs766100398 COSM271759 CA5715159	68	R>W	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs1217848349 CA378356090	69	Q>K		No	ClinGen gnomAD
rs1336212199 CA378356093	69	Q>P		No	ClinGen gnomAD
CA5715161 rs767801735	73	T>N		No	ClinGen ExAC gnomAD
rs1326861121 CA378356122	73	T>S		No	ClinGen TOPMed
rs377486443 CA5715163	74	R>G		No	ClinGen ESP ExAC TOPMed gnomAD
CA214659714 rs35412666	76	G>A		No	ClinGen Ensembl
CA214659721 rs35412666	76	G>V		No	ClinGen Ensembl
CA5715164 rs143531840	76	G>W		No	ClinGen ESP ExAC TOPMed gnomAD
CA5715166 rs758236985	78	E>K		No	ClinGen ExAC TOPMed
CA5715167 rs777814696	79	C>Y		No	ClinGen ExAC gnomAD
CA378356161 rs1195985390	80	Y>N		No	ClinGen Ensembl
rs147153472 CA378356181	82	Q>H		No	ClinGen ESP ExAC TOPMed gnomAD
rs770742028 CA5715169	82	Q>L		No	ClinGen ExAC
rs756729559 CA214659785	87	V>M		No	ClinGen gnomAD
rs769402461 CA5715190	88	A>V		No	ClinGen ExAC gnomAD
CA5715191 rs779808867	90	Y>C		No	ClinGen ExAC gnomAD
rs1306031893 CA378274694	90	Y>D		No	ClinGen gnomAD
rs527735295 CA378274885	95	D>E		No	ClinGen 1000Genomes ExAC gnomAD
rs1449026634 CA378275032	98	L>V		No	ClinGen gnomAD
CA214150203 rs866256506	102	G>E		No	ClinGen Ensembl
CA214150185 rs1013337392	102	G>R		No	ClinGen TOPMed gnomAD
rs1191706517 CA378275163	103	K>E		No	ClinGen gnomAD
rs1406031089 CA378275260	104	E>D		No	ClinGen gnomAD
CA378275206 rs1396611064	104	E>K		No	ClinGen gnomAD
CA214150210 rs547806195	106	M>V		No	ClinGen 1000Genomes
CA214150212 rs1025183445	107	T>A		No	ClinGen gnomAD
rs969072084 CA214150214	110	L>F		No	ClinGen TOPMed gnomAD
CA378284316 rs1207468140	114	S>F		No	ClinGen TOPMed
rs1207468140 CA378284313	114	S>Y		No	ClinGen TOPMed
CA5715215 rs773876361	115	P>R		No	ClinGen ExAC TOPMed
CA214171371 rs201054122	118	I>T		No	ClinGen Ensembl
CA5715217 RCV000952953 rs55980792 VAR_040518	119	A>V		No	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA378284406 rs1235194267	121	V>A		No	ClinGen TOPMed gnomAD
VAR_040519 CA5715218 rs55902633	122	G>S		No	ClinGen UniProt 1000Genomes ExAC TOPMed dbSNP gnomAD
rs1374406715 CA378284421	122	G>V		No	ClinGen TOPMed
CA214171412 rs938534143	123	Q>E		No	ClinGen TOPMed
CA378284472 rs1195189085	126	V>I		No	ClinGen gnomAD
rs765439908 CA214171452	128	Q>H		No	ClinGen ExAC TOPMed gnomAD
rs34679178 VAR_040520 CA5715221	129	T>M		No	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA214171483 rs768260715	130	E>V		No	ClinGen Ensembl
CA378284564 rs1474054850	131	E>K		No	ClinGen gnomAD
CA378284645 rs1418002514	135	Q>*		No	ClinGen gnomAD
rs750394682 CA5715224	137	P>L		No	ClinGen ExAC gnomAD
CA378284710 rs1410887954	138	C>Y		No	ClinGen gnomAD
RCV000973451 VAR_040521 rs56254855 CA5715226	141	L>I		No	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs188222479 CA5715227	143	S>A		No	ClinGen 1000Genomes ExAC gnomAD
rs1292679179 CA378285508	149	V>F		No	ClinGen TOPMed
rs142641433 CA5715253	151	E>K		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs142641433 CA5715252	151	E>Q		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1193580833 CA378285617	155	G>E		No	ClinGen gnomAD
CA378285667 rs1564929829	158	F>S		No	ClinGen Ensembl
CA214173070 rs189973518	159	H>Q		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1174730931 CA378285711	160	E>D		No	ClinGen gnomAD
CA5715256 rs780185768	160	E>K		No	ClinGen ExAC gnomAD
rs1363425843 CA378285719	161	Y>H		No	ClinGen gnomAD
CA5715258 rs542137819	167	F>L		No	ClinGen 1000Genomes ExAC gnomAD
CA378285851 rs1435666968	168	D>Y		No	ClinGen TOPMed gnomAD
rs774485072 CA5715259	169	R>C		No	ClinGen ExAC TOPMed gnomAD
COSM3375400 rs763588844 CA5715260	169	R>H	pancreas [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs763588844 CA378285881	169	R>L		No	ClinGen ExAC TOPMed gnomAD
rs61733303 CA214173087	178	R>K		No	ClinGen Ensembl
rs1222988591 CA378288070	179	Q>L		No	ClinGen gnomAD
rs369944660 CA5715280	180	P>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA214177419 rs920143365	181	V>M		No	ClinGen Ensembl
rs1314770270 CA378288131	182	T>I		No	ClinGen TOPMed
CA378288138 rs1475038952	183	K>E		No	ClinGen gnomAD
CA378288147 rs1168594162	183	K>R		No	ClinGen gnomAD
CA378288167 rs1185853375	184	N>S		No	ClinGen gnomAD
CA378288207 rs1406966316	186	F>L		No	ClinGen TOPMed gnomAD
rs1406966316 CA378288205	186	F>L		No	ClinGen TOPMed gnomAD
rs1460272093 CA378288230	188	Q>H		No	ClinGen gnomAD
CA5715285 rs762887108	188	Q>R		No	ClinGen ExAC gnomAD
rs1424467925 CA378288249	190	R>*		No	ClinGen Ensembl
CA5715286 rs763787676	190	R>Q		No	ClinGen ExAC gnomAD
CA378288343 rs1345851560	198	G>R		No	ClinGen TOPMed
CA378288540 rs1216855787	205	V>A		No	ClinGen gnomAD
rs769828788 CA214178298	206	R>G		No	ClinGen ExAC gnomAD
CA378288544 rs1347619240 COSM3358661	206	R>Q	kidney [Cosmic]	No	ClinGen cosmic curated gnomAD
CA5715300 rs769828788 COSM1644213	206	R>W	urinary_tract [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA378288558 rs1232297123	207	A>G		No	ClinGen gnomAD
CA378288574 rs1443281425	208	T>M		No	ClinGen gnomAD
rs967398207 CA214178308	210	K>Q		No	ClinGen TOPMed gnomAD
CA378288594 rs1240482113	210	K>R		No	ClinGen gnomAD
COSM1209002 rs564130593 CA5715305	216	R>C	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs774000868 CA5715306	216	R>H		No	ClinGen ExAC gnomAD
CA214178345 rs528343617	220	K>M		No	ClinGen gnomAD
rs528343617 CA378289226	220	K>R		No	ClinGen gnomAD
rs1414718692 CA378289240	221	R>K		No	ClinGen gnomAD
rs1342961278 CA378289264	222	I>N		No	ClinGen gnomAD
CA214178347 rs925928770	223	K>E		No	ClinGen TOPMed
rs1321826625 CA378289361	228	E>K		No	ClinGen gnomAD
CA214178349 rs866759998	229	S>F		No	ClinGen Ensembl
rs1589806968 CA378289405	230	M>V		No	ClinGen Ensembl
rs767270791 CA5715308	238	L>F		No	ClinGen ExAC gnomAD
CA5715309 rs140965782	238	L>P		No	ClinGen ESP ExAC TOPMed
CA378289629 rs1345950962	239	E>G		No	ClinGen TOPMed gnomAD
COSM3806561 rs766824009 CA378289620	239	E>K	breast [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA5715311 rs766824009	239	E>Q		No	ClinGen ExAC gnomAD
CA214178424 rs112871819	241	V>A		No	ClinGen gnomAD
CA378289679 rs112871819	241	V>G		No	ClinGen gnomAD
rs202120111 CA214178416	241	V>L		No	ClinGen TOPMed gnomAD
CA378289727 rs1004387219	244	Q>E		No	ClinGen gnomAD
rs1004387219 CA214178430	244	Q>K		No	ClinGen gnomAD
CA378289771 rs1468028276	245	F>L		No	ClinGen TOPMed gnomAD
rs1460301401 CA378290761	250	A>S		No	ClinGen gnomAD
rs1165512799 CA378290773	252	A>T		No	ClinGen gnomAD
CA378290785 rs1391833873	253	Y>F		No	ClinGen gnomAD
rs371156667 CA5715334	254	E>K		No	ClinGen ESP ExAC TOPMed gnomAD
CA214182164 rs745516627	255	T>I		No	ClinGen gnomAD
rs1554922628 CA378290853	263	L>R		No	ClinGen Ensembl
CA5715337 rs568383324	265	I>M		No	ClinGen 1000Genomes ExAC gnomAD
CA214182194 rs758430522	266	M>I		No	ClinGen Ensembl
rs1211979303 CA378290870	266	M>T		No	ClinGen TOPMed
rs1242450120 CA378290867	266	M>V		No	ClinGen gnomAD
CA214182197 rs200072822	268	G>W		No	ClinGen Ensembl
CA5715338 rs750601695	269	G>D		No	ClinGen ExAC gnomAD
CA378290909 rs1357052784	272	K>R		No	ClinGen gnomAD
CA378290947 rs1194983488	277	N>T		No	ClinGen gnomAD
CA5715341 rs747849563	281	P>L		No	ClinGen ExAC TOPMed gnomAD
rs771934392 CA5715342	282	G>S		No	ClinGen ExAC gnomAD
CA378290997 rs1369544710	284	E>A		No	ClinGen gnomAD
CA5715344 rs368432841	284	E>K		No	ClinGen ESP ExAC TOPMed gnomAD
rs770635665 CA5715345	285	E>K		No	ClinGen ExAC TOPMed gnomAD
CA5715347 rs759135424	286	E>*		No	ClinGen ExAC gnomAD
CA378291007 rs759135424	286	E>K		No	ClinGen ExAC gnomAD
rs372032697 CA5715349	287	R>Q		No	ClinGen ESP ExAC TOPMed gnomAD
CA5715348 rs770147450	287	R>W		No	ClinGen ExAC
rs763157287 CA5715350	289	L>S		No	ClinGen ExAC gnomAD
rs146569660 CA378291048	292	A>E		No	ClinGen ESP TOPMed gnomAD
rs146569660 CA214182284 COSM357485	292	A>V	lung large_intestine [Cosmic]	No	ClinGen cosmic curated ESP TOPMed gnomAD
CA5715353 rs762125001	294	E>Q		No	ClinGen ExAC TOPMed gnomAD
CA5715354 rs767895963	295	I>T		No	ClinGen ExAC gnomAD
CA214182292 rs914468006	297	C>R		No	ClinGen TOPMed gnomAD
rs140946236 CA5715357	298	G>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1256304771 CA378291096	300	E>*		No	ClinGen gnomAD
rs758323171 CA378291105	301	D>A		No	ClinGen ExAC TOPMed
rs758323171 CA5715360	301	D>V		No	ClinGen ExAC TOPMed
rs145397190 CA5715362	304	R>C		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs2230349 VAR_040523 CA5715363	304	R>H		No	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA214182340 rs2230349	304	R>P		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA378291124 rs145397190	304	R>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA5715364 rs780840740	305	E>K		No	ClinGen ExAC gnomAD
CA378291149 rs1203150330	308	V>A		No	ClinGen gnomAD
COSM537490 CA5715366 rs769347901	308	V>I	lung endometrium [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA378291161 rs1467819775	310	R>*		No	ClinGen TOPMed gnomAD
rs775799901 CA5715367	310	R>Q		No	ClinGen ExAC TOPMed
rs1246731473 CA378291181	311	D>Y		No	ClinGen TOPMed
CA5715385 rs374620668	316	N>S		No	ClinGen ESP ExAC gnomAD
CA5715386 rs755778274	317	I>V		No	ClinGen ExAC gnomAD
rs1361845574 CA378291242	320	D>A		No	ClinGen gnomAD
CA5715388 rs748790353	320	D>E		No	ClinGen ExAC gnomAD
CA5715389 rs769264960	322	Y>C		No	ClinGen ExAC gnomAD
CA5715410 rs778166997	325	I>M		No	ClinGen ExAC gnomAD
rs1381942896 CA378291375	338	E>K		No	ClinGen gnomAD
rs143794689 CA378291386	339	G>A		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs143794689 CA5715412	339	G>E		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA378291390 rs1295249304	340	D>Y		No	ClinGen gnomAD
rs1340481184 CA378291405	342	I>T		No	ClinGen gnomAD
CA214185900 rs1011638074	343	R>C		No	ClinGen TOPMed gnomAD
rs776745178 CA5715413	343	R>H		No	ClinGen ExAC TOPMed gnomAD
CA378291411 rs776745178	343	R>L		No	ClinGen ExAC TOPMed gnomAD
rs769875126 CA5715415	344	G>S		No	ClinGen ExAC TOPMed gnomAD
rs1414195283 CA378291420	345	R>L		No	ClinGen TOPMed
rs1414195283 CA378291418 COSM1346113	345	R>Q	large_intestine [Cosmic]	No	ClinGen cosmic curated TOPMed
rs775602615 CA5715416	345	R>W		No	ClinGen ExAC TOPMed gnomAD
CA378291444 rs1240241273	349	V>G		No	ClinGen gnomAD
rs1247120582 CA378291460	352	M>V		No	ClinGen gnomAD
rs911371616 CA214187130	354	P>L		No	ClinGen Ensembl
rs1256546469 CA378291529	360	Q>E		No	ClinGen TOPMed
CA5715443 rs765028792	361	R>K		No	ClinGen ExAC gnomAD
rs116059103 CA5715444	361	R>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs372256166 CA5715447	363	G>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA378291563 rs1450830945	365	S>I		No	ClinGen gnomAD
CA5715448 rs757839310	366	P>H		No	ClinGen ExAC gnomAD
rs374812456 CA214187161	367	D>Y		No	ClinGen ESP
CA5715450 rs746269627	368	Y>C		No	ClinGen ExAC TOPMed gnomAD
rs1289671234 CA378291594	370	G>S		No	ClinGen TOPMed
CA378291601 rs1409175659	371	L>F		No	ClinGen TOPMed gnomAD
CA214187196 rs367798791	371	L>H		No	ClinGen ESP TOPMed gnomAD
CA378291600 rs1409175659	371	L>I		No	ClinGen TOPMed gnomAD
CA214187199 rs367798791	371	L>P		No	ClinGen ESP TOPMed gnomAD
CA378291628 rs1390718974	375	I>T		No	ClinGen gnomAD
CA214187233 rs1041193982	376	Y>C		No	ClinGen TOPMed
CA378291650 rs1467181968	378	M>T		No	ClinGen gnomAD
CA5715454 rs768622874	380	E>K		No	ClinGen ExAC TOPMed gnomAD
rs746911797 CA5715456	383	S>L		No	ClinGen ExAC TOPMed gnomAD
CA378291687 rs746911797	383	S>W		No	ClinGen ExAC TOPMed gnomAD
rs776539506 CA5715458	384	P>L		No	ClinGen ExAC gnomAD
rs557203104 CA5715460	386	R>C		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA5715461 rs775281279	386	R>H		No	ClinGen ExAC gnomAD
CA5715463 rs202089063	387	G>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs267602389 CA214187286	388	R>C		No	ClinGen TOPMed gnomAD
rs751146861 CA5715465	388	R>H		No	ClinGen ExAC TOPMed gnomAD
rs751146861 CA5715464	388	R>L		No	ClinGen ExAC TOPMed gnomAD
CA378291715 rs1483743031	389	K>E		No	ClinGen gnomAD
CA378291735 rs1269487810	391	K>N		No	ClinGen TOPMed
rs1211228516 CA378291737	392	V>M		No	ClinGen TOPMed
rs750739113 CA5715467	394	R>L		No	ClinGen ExAC TOPMed gnomAD
CA378291752 rs750739113	394	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA214187301 rs1017068765	394	R>W		No	ClinGen TOPMed gnomAD
rs756503237 CA5715468	395	E>G		No	ClinGen ExAC TOPMed gnomAD
rs1165313528 CA378291754	395	E>K		No	ClinGen gnomAD
CA214187345 rs896923040	398	D>E		No	ClinGen Ensembl
rs1410507896 CA378291783	399	R>C		No	ClinGen gnomAD
CA5715471 rs143962659	399	R>H		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs748302706 CA5715474	400	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs147170538 CA5715473 COSM289689	400	R>W	large_intestine [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
rs756537427 CA5715475	404	T>M		No	ClinGen ExAC TOPMed gnomAD
CA378291835 rs1589813851	407	V>G		No	ClinGen Ensembl
rs1489816831 CA378291839	408	Y>C		No	ClinGen gnomAD
CA378291872 rs745587065	412	F>L		No	ClinGen ExAC TOPMed gnomAD
CA378291875 rs1441148901	413	S>P		No	ClinGen gnomAD
rs570225563 CA5715479	414	E>K		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA378291893 rs1449223761	415	E>D		No	ClinGen gnomAD
CA378291895 rs541514702	416	A>P		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA5715480 rs541514702	416	A>T		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA378291914 rs1211407043	418	S>F		No	ClinGen TOPMed
rs773711050 CA5715482	419	I>L		No	ClinGen ExAC TOPMed gnomAD
CA378291918 rs1223031901	419	I>T		No	ClinGen TOPMed
rs773711050 CA378291915	419	I>V		No	ClinGen ExAC TOPMed gnomAD
rs1323959596 CA378291929	421	K>Q		No	ClinGen TOPMed
COSM3382693 rs1018530689 CA214187387	422	M>T	pancreas [Cosmic]	No	ClinGen cosmic curated Ensembl
CA5715497 RCV000965865 rs77323445	425	T>M		No	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs774086762 CA378291993	428	A>E		No	ClinGen ExAC TOPMed gnomAD
CA5715498 rs149580250	428	A>T		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA5715499 rs774086762	428	A>V		No	ClinGen ExAC TOPMed gnomAD
CA5715500 rs528833332	432	L>M		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1209691928 CA378292024	433	G>D		No	ClinGen gnomAD
rs1265496637 CA378292037	435	Q>*		No	ClinGen gnomAD
COSM138785 CA5715501 rs200344195	436	E>K	skin [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC gnomAD
rs1200177458 CA378292061	438	G>E		No	ClinGen gnomAD
rs772770711 CA5715502	440	A>T		No	ClinGen ExAC TOPMed gnomAD
CA5715503 rs761170797	441	E>G		No	ClinGen ExAC gnomAD
rs1589816259 CA378292086	442	V>G		No	ClinGen Ensembl
rs1467053451 CA378292113	446	P>L		No	ClinGen TOPMed
rs766951986 CA5715504	446	P>T		No	ClinGen ExAC gnomAD
RCV000957143 CA5715505 rs139222578	448	F>L		No	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs1292763879 CA378292142	450	N>S		No	ClinGen gnomAD
rs759973613 CA5715506	451	M>I		No	ClinGen ExAC gnomAD
CA378292147 rs1388100776	451	M>V		No	ClinGen gnomAD
rs1171690251 CA378292174	454	K>R		No	ClinGen TOPMed
CA378292179 rs1303163538	455	R>C		No	ClinGen TOPMed gnomAD
CA5715507 rs765307793	457	E>K		No	ClinGen ExAC gnomAD
rs1265890823 CA378292210	460	M>L		No	ClinGen gnomAD
CA5715509 rs758748977	462	D>E		No	ClinGen ExAC gnomAD
rs1179080120 CA378292241	464	P>S		No	ClinGen TOPMed
COSM915354 rs751729008 CA5715511	466	V>I	large_intestine endometrium [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA5715512 rs756096937	467	P>A		No	ClinGen ExAC gnomAD
CA378292263 rs1238106913	468	D>N		No	ClinGen TOPMed
CA5715542 rs775975806	470	R>C		No	ClinGen ExAC gnomAD
rs369268255 CA5715543	470	R>H		No	ClinGen ESP ExAC TOPMed gnomAD
CA5715546 rs774720604	474	C>S		No	ClinGen ExAC gnomAD
rs774720604 CA5715545	474	C>Y		No	ClinGen ExAC gnomAD
CA214142788 rs372941824	477	V>M		No	ClinGen ESP TOPMed gnomAD
rs765213146 CA5715550	479	D>A		No	ClinGen ExAC TOPMed gnomAD
rs540786452 CA378268119	479	D>H		No	ClinGen 1000Genomes ExAC gnomAD
rs540786452 CA5715549	479	D>N		No	ClinGen 1000Genomes ExAC gnomAD
rs200359403 CA5715551	480	I>M		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA378268130 rs1273717795	481	E>K		No	ClinGen gnomAD
rs1481473105 CA378268141	482	Q>P		No	ClinGen TOPMed
CA378268159 rs1257119285	484	S>F		No	ClinGen Ensembl
CA378268166 rs1232107776	486	V>M		No	ClinGen TOPMed
CA5715553 rs139931883	487	K>E		No	ClinGen ESP ExAC gnomAD
rs756923300 CA5715555	489	V>I		No	ClinGen ExAC TOPMed gnomAD
CA378268191 rs1247221711	490	N>H		No	ClinGen gnomAD
CA5715560 rs200119606	496	D>N		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs774914565 CA5715562	497	D>N		No	ClinGen ExAC TOPMed gnomAD
CA378268244 rs1320259667	497	D>V		No	ClinGen gnomAD
rs986748318 CA214142806	499	Y>C		No	ClinGen TOPMed
rs762090782 CA5715563	500	S>F		No	ClinGen ExAC gnomAD
CA378268283 rs1182141595	503	S>A		No	ClinGen TOPMed gnomAD
rs1416403608 CA378268293	504	T>M		No	ClinGen gnomAD
CA378268320 rs1471638238	509	I>V		No	ClinGen TOPMed
CA378268327 rs1564941775	510	P>A		No	ClinGen Ensembl
rs200305868 CA378268355	513	N>K		No	ClinGen ESP ExAC TOPMed gnomAD
rs1303534029 CA378268357	514	E>K		No	ClinGen TOPMed gnomAD
rs1270341542 CA378268379	515	M>V		No	ClinGen gnomAD
CA5715580 rs769355139	516	I>R		No	ClinGen ExAC TOPMed gnomAD
rs769355139 CA5715579	516	I>T		No	ClinGen ExAC TOPMed gnomAD
CA378268392 rs1224182831	517	E>Q		No	ClinGen TOPMed
CA5715582 rs772291983	524	L>R		No	ClinGen ExAC gnomAD
rs760745107 CA5715585	525	N>K		No	ClinGen ExAC TOPMed gnomAD
CA5715586 rs770981083	526	V>M		No	ClinGen ExAC gnomAD
rs887685206 CA378268476	529	P>A		No	ClinGen gnomAD
CA378268479 rs1409248441	529	P>R		No	ClinGen gnomAD
rs887685206 CA214142927	529	P>S		No	ClinGen gnomAD
CA5715588 rs762844113	530	N>I		No	ClinGen ExAC gnomAD
rs764064972 CA5715589	530	N>K		No	ClinGen ExAC gnomAD
CA5715591 rs761541959	531	G>D		No	ClinGen ExAC TOPMed gnomAD
rs751318677 CA5715590	531	G>S		No	ClinGen ExAC gnomAD
CA378268499 rs1412403291	533	L>H		No	ClinGen TOPMed
CA5715593 rs371520487	534	P>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA5715596 rs753440842	538	N>K		No	ClinGen ExAC gnomAD
CA5715598 rs779313655	539	R>G		No	ClinGen ExAC gnomAD
CA5715600 rs758698914	540	N>S		No	ClinGen ExAC gnomAD
CA378268549 rs1479832113	541	H>R		No	ClinGen TOPMed gnomAD
CA214142943 rs199631074	541	H>Y		No	ClinGen gnomAD
rs374258738 CA5715602	542	P>A		No	ClinGen ESP ExAC TOPMed gnomAD
rs1166747617 CA378268556	542	P>L		No	ClinGen gnomAD
COSM273646 CA5715603 rs771181138	543	P>L	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs1470033253 CA378268558	543	P>T		No	ClinGen TOPMed
rs1329438971 CA378268576	545	P>L		No	ClinGen gnomAD
rs768539745 COSM915355 CA5715606	547	K>N	endometrium [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA378268584 rs1450159932	547	K>Q		No	ClinGen gnomAD
rs1383016435 CA378268590	548	K>E		No	ClinGen gnomAD
CA5715607 rs774160810	548	K>N		No	ClinGen ExAC gnomAD
rs761610647 CA5715608	549	G>R		No	ClinGen ExAC TOPMed gnomAD
rs767203755 CA5715609	550	L>V		No	ClinGen ExAC TOPMed gnomAD
CA5715610 rs773126542	555	F>L		No	ClinGen ExAC gnomAD
rs766184775 CA378268720	557	R>L		No	ClinGen ExAC TOPMed gnomAD
rs766184775 CA5715613	557	R>P		No	ClinGen ExAC TOPMed gnomAD
rs766184775 CA5715614	557	R>Q		No	ClinGen ExAC TOPMed gnomAD
COSM268263 rs556570876 CA5715612	557	R>W	large_intestine [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
rs1589820225 CA378268962	561	N>I		No	ClinGen Ensembl
rs1329121016 CA378268972	562	N>D		No	ClinGen gnomAD
CA5715643 rs750629477	563	S>Y		No	ClinGen ExAC TOPMed gnomAD
rs141365148 CA5715645 COSM915356	566	S>L	endometrium [Cosmic]	No	ClinGen cosmic curated 1000Genomes ESP ExAC TOPMed gnomAD
CA5715647 rs372911829	567	P>R		No	ClinGen ESP ExAC gnomAD
rs1489495103 CA378269057	568	S>N		No	ClinGen TOPMed
CA378269102 rs1267113241	570	K>N		No	ClinGen gnomAD
CA5715649 rs147119258	572	S>C		No	ClinGen ESP ExAC TOPMed gnomAD
CA214143414 rs553928435	576	H>N		No	ClinGen 1000Genomes
CA5715650 rs770867919	576	H>R		No	ClinGen ExAC gnomAD
CA5715651 rs138518818	577	I>V		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1267376848 CA378269304	580	N>T		No	ClinGen TOPMed
rs769531645 CA5715653	581	H>D		No	ClinGen ExAC gnomAD
rs774811914 CA5715654	581	H>L		No	ClinGen ExAC gnomAD
rs142571352 CA5715657	584	S>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA378269402 rs1303282846	585	N>D		No	ClinGen gnomAD
CA5715658 rs762365089	585	N>I		No	ClinGen ExAC gnomAD
CA378269458 rs1322577678	587	T>S		No	ClinGen TOPMed
CA378269463 rs375507983	588	G>*		No	ClinGen ESP ExAC TOPMed gnomAD
rs375507983 CA5715660	588	G>R		No	ClinGen ESP ExAC TOPMed gnomAD
rs1336713615 COSM537486 CA378269505	590	S>I	lung [Cosmic]	No	ClinGen cosmic curated gnomAD

No associated diseases with P34947

4 regional properties for P34947

Type	Name	Position	InterPro Accession
domain	Protein kinase domain	186 - 448	IPR000719
domain	AGC-kinase, C-terminal	449 - 528	IPR000961
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	Cytoplasm Nucleus Cell membrane; Peripheral membrane protein	Predominantly localized at the plasma membrane; targeted to the cell surface through the interaction with phospholipids Nucleus localization is regulated in a GPCR and Ca(2+)/calmodulin-dependent fashion
PANTHER Family	PTHR24355	G PROTEIN-COUPLED RECEPTOR KINASE/RIBOSOMAL PROTEIN S6 KINASE
PANTHER Subfamily	PTHR24355:SF27	G PROTEIN-COUPLED RECEPTOR KINASE 5
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 GRK5 Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway GPRK

5 GO annotations of cellular component

Name	Definition
cytoplasm	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
nuclear membrane	Either of the lipid bilayers that surround the nucleus and form the nuclear envelope; excludes the intermembrane space.
nuclear speck	A discrete extra-nucleolar subnuclear domain, 20-50 in number, in which splicing factors are seen to be localized by immunofluorescence microscopy.
plasma membrane	The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.

7 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.
phospholipid binding	Binding to a phospholipid, a class of lipids containing phosphoric acid as a mono- or diester.
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.
protein kinase C binding	Binding to protein kinase C.
protein serine/threonine kinase activity	Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate.

13 GO annotations of biological process

Name	Definition
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	A G protein-coupled receptor signaling pathway in which the signal is transmitted via the activation or inhibition of adenylyl cyclase activity and a subsequent change in the intracellular concentration of cyclic AMP (cAMP).
apoptotic process	A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died.
fat cell differentiation	The process in which a relatively unspecialized cell acquires specialized features of an adipocyte, an animal connective tissue cell specialized for the synthesis and storage of fat.
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.
negative regulation of apoptotic process	Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process.
positive regulation of cell population proliferation	Any process that activates or increases the rate or extent of cell proliferation.
protein autophosphorylation	The phosphorylation by a protein of one or more of its own amino acid residues (cis-autophosphorylation), or residues on an identical protein (trans-autophosphorylation).
protein phosphorylation	The process of introducing a phosphate group on to a protein.
regulation of cell cycle	Any process that modulates the rate or extent of progression through the cell cycle.
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.
tachykinin receptor signaling pathway	A G protein-coupled receptor signaling pathway initiated by tachykinin binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process. Tachykinin is a short peptide with the terminal sequence (Phe-X-Gly-Leu-Met-NH2).
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
P21146	GRK2	Beta-adrenergic receptor kinase 1	Bos taurus (Bovine)	PR
P43249	GRK5	G protein-coupled receptor kinase 5	Bos taurus (Bovine)	SS
P32865	Gprk1	G protein-coupled receptor kinase 1	Drosophila melanogaster (Fruit fly)	PR
P25098	GRK2	Beta-adrenergic receptor kinase 1	Homo sapiens (Human)	PR
P35626	GRK3	Beta-adrenergic receptor kinase 2	Homo sapiens (Human)	PR
Q15835	GRK1	Rhodopsin kinase GRK1	Homo sapiens (Human)	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
P43250	GRK6	G protein-coupled receptor kinase 6	Homo sapiens (Human)	EV
O70293	Grk6	G protein-coupled receptor kinase 6	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
Q8VEB1	Grk5	G protein-coupled receptor kinase 5	Mus musculus (Mouse)	SS
P26817	Grk2	Beta-adrenergic receptor kinase 1	Rattus norvegicus (Rat)	PR
P97711	Grk6	G protein-coupled receptor kinase 6	Rattus norvegicus (Rat)	SS
Q62833	Grk5	G protein-coupled receptor kinase 5	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	GKRKGKSKKW	KEILKFPHIS	QCEDLRRTID	RDYCSLCDKQ
70	80	90	100	110	120
PIGRLLFRQF	CETRPGLECY	IQFLDSVAEY	EVTPDEKLGE	KGKEIMTKYL	TPKSPVFIAQ
130	140	150	160	170	180
VGQDLVSQTE	EKLLQKPCKE	LFSACAQSVH	EYLRGEPFHE	YLDSMFFDRF	LQWKWLERQP
190	200	210	220	230	240
VTKNTFRQYR	VLGKGGFGEV	CACQVRATGK	MYACKRLEKK	RIKKRKGESM	ALNEKQILEK
250	260	270	280	290	300
VNSQFVVNLA	YAYETKDALC	LVLTIMNGGD	LKFHIYNMGN	PGFEEERALF	YAAEILCGLE
310	320	330	340	350	360
DLHRENTVYR	DLKPENILLD	DYGHIRISDL	GLAVKIPEGD	LIRGRVGTVG	YMAPEVLNNQ
370	380	390	400	410	420
RYGLSPDYWG	LGCLIYEMIE	GQSPFRGRKE	KVKREEVDRR	VLETEEVYSH	KFSEEAKSIC
430	440	450	460	470	480
KMLLTKDAKQ	RLGCQEEGAA	EVKRHPFFRN	MNFKRLEAGM	LDPPFVPDPR	AVYCKDVLDI
490	500	510	520	530	540
EQFSTVKGVN	LDHTDDDFYS	KFSTGSVSIP	WQNEMIETEC	FKELNVFGPN	GTLPPDLNRN
550	560	570	580
HPPEPPKKGL	LQRLFKRQHQ	NNSKSSPSSK	TSFNHHINSN	HVSSNSTGSS