AiPD: Autoinhibited Protein Database

Q13188

Gene name	STK3 (KRS1, MST2)
Protein name	Serine/threonine-protein kinase 3
Names	Mammalian STE20-like protein kinase 2, MST-2, STE20-like kinase MST2, Serine/threonine-protein kinase Krs-1
Species	Homo sapiens (Human)
KEGG Pathway	hsa:6788
EC number	2.7.11.1: Protein-serine/threonine kinases
Protein Class

Descriptions

The Mst1/2 kinases are cytosolic Ste20-related kinases activated by autophosphorylation. Designated class II GC kinases, Mst1 and Mst2, share 76% sequence identity and contain an N-terminal catalytic domain, followed successively by an autoinhibitory segment and a coiled-coil SARAH domain that mediates hetero- and homo-dimerisation. Mst1 and Mst2 also become activated in cells undergoing apoptosis from a variety of stimuli. The activation mechanism is unclear, however, once activated, both kinases undergo cleavage by caspase3 at sites just carboxy terminal to their catalytic domains. The resultant catalytic polypeptides display an altered substrate specificity and lack their autoinhibitory domain. The caspase-cleaved catalytic fragments are highly and constitutively active with unrestricted nuclear access.

Autoinhibitory domains (AIDs)

327-392 (Inhibitory domain) SS

Target domain	27-278 (Protein kinase domain)
Relief mechanism	Cleavage
Assay

AID

327-392 (Inhibitory domain)

Target domain

27-278 (Protein kinase domain)

Relief mechanism

Cleavage (Cleavage by caspase3)

Assay

Accessory elements

163-186 (Activation loop from InterPro)

Target domain	27-278 (Protein kinase domain)
Relief mechanism
Assay

References

Avruch J et al. (2011) "Mst1/2 signalling to Yap: gatekeeper for liver size and tumour development", British journal of cancer, 104, 24-32

Zhou D et al. (2011) "Mst1 and Mst2 protein kinases restrain intestinal stem cell proliferation and colonic tumorigenesis by inhibition of Yes-associated protein (Yap) overabundance", Proceedings of the National Academy of Sciences of the United States of America, 108, E1312-20

Creasy CL et al. (1996) "The Ste20-like protein kinase, Mst1, dimerizes and contains an inhibitory domain", The Journal of biological chemistry, 271, 21049-53

Autoinhibited structure

Activated structure

12 structures for Q13188

Entry ID	Method	Resolution	Chain	Position	Source
3WWS	X-ray	201 A	A/B/C/D	436-484	PDB
4HKD	X-ray	150 A	A/B/C/D	436-484	PDB
4L0N	X-ray	140 A	A/B/C/D/E/F/G/H/I/J	436-484	PDB
4LG4	X-ray	242 A	A/B/C/D/E/F	16-313	PDB
4LGD	X-ray	305 A	A/B/C/D	9-491	PDB
4OH9	X-ray	170 A	A/B	436-484	PDB
5BRM	X-ray	265 A	G/H/I/J/K/L/M/N/O	371-401	PDB
5DH3	X-ray	247 A	A/B	15-313	PDB
6AO5	X-ray	296 A	A	16-491	PDB
6AR2	X-ray	155 A	C/D	373-382	PDB
8A66	X-ray	190 A	A/B	16-312	PDB
AF-Q13188-F1	Predicted				AlphaFoldDB

311 variants for Q13188

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
CA371854923 rs1265591568	2	E>D		No	ClinGen gnomAD
CA371854914 rs1220390079	3	Q>H		No	ClinGen gnomAD
CA371854908 rs1356943297	4	P>L		No	ClinGen TOPMed gnomAD
rs1033189718 CA182835904	6	A>V		No	ClinGen TOPMed gnomAD
rs1376045996 CA371854891	7	P>L		No	ClinGen gnomAD
CA371854894 rs1240650026	7	P>S		No	ClinGen gnomAD
CA371854879 rs1340266195	9	S>N		No	ClinGen TOPMed
CA371855139 rs1157289261	9	S>R		No	ClinGen TOPMed gnomAD
rs746632419 CA4821992	14	L>V		No	ClinGen ExAC
rs1378759384 CA371855084	17	D>G		No	ClinGen gnomAD
CA371855065 rs1473562696	20	T>A		No	ClinGen TOPMed
CA371855006 rs1426866722	28	D>N		No	ClinGen gnomAD
CA371854982 rs1193956217	31	E>G		No	ClinGen gnomAD
rs1487811766 CA371854978	32	K>Q		No	ClinGen gnomAD
rs1202010149 CA371854957	35	E>K		No	ClinGen gnomAD
CA4821968 rs187757501	40	S>N		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA4821967 rs745606479	44	A>T		No	ClinGen ExAC gnomAD
rs1403140497 CA371854778	49	S>T		No	ClinGen gnomAD
rs749191480 CA4821964	50	G>S		No	ClinGen ExAC gnomAD
rs762429515 CA182822632	51	Q>H		No	ClinGen ExAC TOPMed gnomAD
rs1164638081 CA371854752	53	V>F		No	ClinGen gnomAD
rs1164638081 CA371854754	53	V>I		No	ClinGen gnomAD
rs756129319 CA4821962	54	A>G		No	ClinGen ExAC
CA371854748 rs1384400929	54	A>S		No	ClinGen gnomAD
CA4821960 rs752970275	56	K>Q		No	ClinGen ExAC
rs1228869369 CA371854727	57	Q>*		No	ClinGen TOPMed gnomAD
rs1228869369 CA371854728	57	Q>E		No	ClinGen TOPMed gnomAD
CA371854699 rs1356927652	61	E>G		No	ClinGen TOPMed
CA371854695 rs1450868524	62	S>T		No	ClinGen TOPMed
rs1345272410 CA371854646	68	I>M		No	ClinGen gnomAD
CA4821957 rs751921239	70	E>*		No	ClinGen ExAC TOPMed gnomAD
rs1226602594 CA371854598	75	Q>*		No	ClinGen TOPMed
rs77105316 CA182822618	77	C>S		No	ClinGen Ensembl
rs1268524562 CA371853775	80	P>S		No	ClinGen gnomAD
CA371853757 rs1563960978	83	V>I		No	ClinGen Ensembl
CA182818484 rs906166047	85	Y>C		No	ClinGen Ensembl
CA4821932 rs200521127	93	T>I		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA4821930 rs528318298	98	V>I		No	ClinGen 1000Genomes ExAC gnomAD
rs947958279 CA371853602	104	A>S		No	ClinGen TOPMed gnomAD
rs947958279 CA182818475	104	A>T		No	ClinGen TOPMed gnomAD
rs773157841 CA4821927	105	G>C		No	ClinGen ExAC gnomAD
rs1398850890 CA371853588	106	S>C		No	ClinGen gnomAD
rs1350908369 CA371853571	109	D>G		No	ClinGen TOPMed
CA182818470 rs920451180	110	I>M		No	ClinGen Ensembl
CA371853563 rs1427248002	110	I>T		No	ClinGen gnomAD
rs973207295 CA182818468	111	I>V		No	ClinGen Ensembl
CA182818466 rs971193348	113	L>*		No	ClinGen TOPMed gnomAD
CA4821924 COSM1726519 rs781199889	114	R>*	liver [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA182818461 rs941475589	114	R>L		No	ClinGen TOPMed gnomAD
COSM1458843 rs941475589 CA182818463	114	R>Q	large_intestine [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
CA4821923 rs768771687	115	N>I		No	ClinGen ExAC gnomAD
CA4821921 rs780352961	117	T>I		No	ClinGen ExAC TOPMed gnomAD
rs1255925875 CA371854537	119	I>M		No	ClinGen TOPMed
rs577272361 CA4821863	121	D>G		No	ClinGen 1000Genomes ExAC gnomAD
rs371706117 CA371854513	123	I>F		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs371706117 CA4821862	123	I>V		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1198258205 CA371854504	124	A>E		No	ClinGen gnomAD
rs1429473482 CA371854507	124	A>T		No	ClinGen gnomAD
rs1199182127 CA371854499	125	T>A		No	ClinGen TOPMed
rs763763606 CA4821861	125	T>S		No	ClinGen ExAC gnomAD
rs1205550787 CA371854495	126	I>V		No	ClinGen gnomAD
CA182795484 rs538970252	131	L>S		No	ClinGen gnomAD
rs767717884 CA4821858	132	K>E		No	ClinGen ExAC gnomAD
rs1554657136 CA371854421	137	L>*		No	ClinGen Ensembl
rs774457582 CA4821856	138	H>Y		No	ClinGen ExAC TOPMed gnomAD
CA371854395 rs1298163017	140	M>I		No	ClinGen gnomAD
rs575295558 CA4821855	140	M>V		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1383186928 CA371854393	141	R>G		No	ClinGen gnomAD
rs367744890 CA4821854	143	I>V		No	ClinGen ESP ExAC gnomAD
CA371854349 rs1473249180	147	I>V		No	ClinGen TOPMed
rs770128448 CA4821852	149	A>T		No	ClinGen ExAC gnomAD
rs1406203153 CA371854322	151	N>D		No	ClinGen gnomAD
rs1438380177 CA371854309	152	I>M		No	ClinGen Ensembl
CA371854292 rs1193626574	155	N>S		No	ClinGen gnomAD
rs371776932 CA4821849	156	T>I		No	ClinGen ESP ExAC TOPMed gnomAD
rs371776932 CA4821848	156	T>R		No	ClinGen ESP ExAC TOPMed gnomAD
rs753429894 CA4821845	159	H>R		No	ClinGen ExAC TOPMed gnomAD
CA371854255 rs1203171424	161	K>Q		No	ClinGen gnomAD
CA371854207 rs1275978741	168	A>P		No	ClinGen TOPMed
rs755916185 CA4821843	170	Q>*		No	ClinGen ExAC gnomAD
CA371854187 rs1587367870	171	L>V		No	ClinGen Ensembl
CA4821842 rs752687054	172	T>K		No	ClinGen ExAC
CA182795434 rs940407987	173	D>G		No	ClinGen TOPMed gnomAD
CA4821824 rs777502225	176	A>S		No	ClinGen ExAC gnomAD
CA182795433 rs913508602 COSM1102929	178	R>H	endometrium [Cosmic]	No	ClinGen cosmic curated TOPMed
rs1587366532 CA371854129	178	R>S		No	ClinGen Ensembl
rs1393938290 CA371854120	179	N>S		No	ClinGen TOPMed gnomAD
CA371854111 rs1302370737	180	T>I		No	ClinGen TOPMed
CA371854100 rs1165228727	182	I>T		No	ClinGen gnomAD
CA371854087 rs1587366422	184	T>N		No	ClinGen Ensembl
CA4821822 rs752588921	188	M>V		No	ClinGen ExAC TOPMed gnomAD
rs1344357232 CA371854047	190	P>A		No	ClinGen gnomAD
rs781102717 CA4821821	192	V>G		No	ClinGen ExAC gnomAD
rs992802416 CA182795429	192	V>M		No	ClinGen TOPMed gnomAD
rs1174551470 CA371854025	193	I>S		No	ClinGen Ensembl
CA371854015 rs1365638423	195	E>K		No	ClinGen gnomAD
CA4821820 rs755030771	196	I>M		No	ClinGen ExAC gnomAD
rs1402037240 CA371853999	197	G>D		No	ClinGen gnomAD
rs960039884 CA182795427	197	G>S		No	ClinGen Ensembl
rs775418746 CA182795426	198	Y>C		No	ClinGen TOPMed
rs1182372085 CA371853980	200	C>S		No	ClinGen TOPMed gnomAD
CA371853948 rs1262074313	204	I>M		No	ClinGen TOPMed
CA4821818 rs766490046	204	I>V		No	ClinGen ExAC TOPMed gnomAD
rs762870573 CA4821817	205	W>*		No	ClinGen ExAC gnomAD
CA371853946 rs1476706609	205	W>R		No	ClinGen TOPMed
CA4821816 rs750684813	207	L>V		No	ClinGen ExAC gnomAD
rs765399291 CA4821815	208	G>A		No	ClinGen ExAC TOPMed gnomAD
CA182795424 rs952868146	209	I>V		No	ClinGen gnomAD
rs1237780141 CA371853901	212	I>T		No	ClinGen gnomAD
CA4821812 rs764439932	214	M>I		No	ClinGen ExAC TOPMed gnomAD
rs1424205963 CA371853890	214	M>V		No	ClinGen TOPMed
CA4821811 rs761304300	215	A>V		No	ClinGen ExAC TOPMed gnomAD
CA371853870 rs1405273639	216	E>D		No	ClinGen gnomAD
rs775804009 CA4821810	218	K>Q		No	ClinGen ExAC gnomAD
CA4821809 rs779203218	219	P>T		No	ClinGen ExAC gnomAD
rs1408691717 CA371853849	220	P>S		No	ClinGen gnomAD
CA4821808 rs748708313	224	I>T		No	ClinGen ExAC gnomAD
CA4821807 rs564202745	228	R>G		No	ClinGen 1000Genomes ExAC gnomAD
rs769609076 CA4821806	228	R>M		No	ClinGen ExAC gnomAD
CA371853506 rs1357369489	229	A>T		No	ClinGen TOPMed gnomAD
CA4821787 rs776353449	235	T>A		No	ClinGen ExAC TOPMed gnomAD
CA371853449 rs1586967148	237	P>A		No	ClinGen Ensembl
CA371853440 rs1216047422	238	P>R		No	ClinGen gnomAD
rs1362425746 CA371853431	240	T>A		No	ClinGen gnomAD
CA371853384 rs1269482156	246	L>R		No	ClinGen gnomAD
CA4821785 rs746728067	247	W>*		No	ClinGen ExAC gnomAD
rs745804050 CA4821782	249	D>E		No	ClinGen ExAC TOPMed gnomAD
rs1338762257 CA371853369	249	D>N		No	ClinGen gnomAD
CA371853361 rs1393163172	250	D>N		No	ClinGen Ensembl
CA371853354 rs1485304076	251	F>I		No	ClinGen TOPMed
rs1044970778 CA182774340	252	T>I		No	ClinGen TOPMed
rs757271491 CA4821780	253	D>N		No	ClinGen ExAC gnomAD
rs1448180804 CA371853300	258	C>F		No	ClinGen gnomAD
CA4821777 rs756524585	258	C>R		No	ClinGen ExAC gnomAD
rs983939069 CA182774332	259	L>F		No	ClinGen Ensembl
rs1245573773 CA371853294	259	L>S		No	ClinGen gnomAD
CA182774330 rs763696181	260	V>L		No	ClinGen Ensembl
CA371853278 rs1422915989	262	N>H		No	ClinGen TOPMed
rs753043269 CA4821776	263	P>S		No	ClinGen ExAC gnomAD
rs753043269 CA371853270	263	P>T		No	ClinGen ExAC gnomAD
rs1235335027 CA371853231	268	T>I		No	ClinGen gnomAD
rs767919046 CA4821775	269	A>V		No	ClinGen ExAC gnomAD
rs1563784596 CA371853225	270	T>A		No	ClinGen Ensembl
CA4821774 rs760017613	271	Q>K		No	ClinGen ExAC gnomAD
CA371853173 rs1300842216	275	H>R		No	ClinGen TOPMed
CA371853175 rs1385825482	275	H>Y		No	ClinGen TOPMed
CA4821750 rs763659968	276	P>L		No	ClinGen ExAC gnomAD
CA371853168 rs547118456	276	P>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA4821751 rs547118456	276	P>T		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs760305689 CA4821749	277	F>L		No	ClinGen ExAC TOPMed gnomAD
rs527380737 CA4821748	281	A>V		No	ClinGen 1000Genomes ExAC gnomAD
rs774294377 CA4821745	283	P>R		No	ClinGen ExAC gnomAD
rs759288461 CA4821746	283	P>S		No	ClinGen ExAC TOPMed gnomAD
rs759288461 CA371853122	283	P>T		No	ClinGen ExAC TOPMed gnomAD
CA182770624 rs1045946165	284	V>I		No	ClinGen TOPMed gnomAD
rs1563760718 CA371853112	285	S>P		No	ClinGen Ensembl
rs770905353 CA371853107	286	I>L		No	ClinGen ExAC TOPMed gnomAD
CA4821743 rs749218138	286	I>T		No	ClinGen ExAC gnomAD
rs770905353 CA4821744	286	I>V		No	ClinGen ExAC TOPMed gnomAD
rs777773209 CA4821742	288	R>G		No	ClinGen ExAC gnomAD
CA4821741 rs374827150	288	R>T		No	ClinGen ESP ExAC TOPMed gnomAD
rs748322141 CA4821740	289	D>Y		No	ClinGen ExAC gnomAD
CA371853052 rs1185072443	294	A>V		No	ClinGen gnomAD
CA371853050 rs1586912764	295	M>V		No	ClinGen Ensembl
CA182770616 rs368118323	296	E>D		No	ClinGen ESP TOPMed
CA4821737 rs747423317	301	R>K		No	ClinGen ExAC gnomAD
rs1317615834 CA371852993	302	H>Q		No	ClinGen gnomAD
rs1217960466 CA371852997	302	H>R		No	ClinGen TOPMed gnomAD
rs780530727 CA4821736	304	E>K		No	ClinGen ExAC gnomAD
CA371852976 rs1174334333	305	Q>*		No	ClinGen TOPMed
CA4821735 rs759044532	306	Q>R		No	ClinGen ExAC gnomAD
CA4821733 rs763527585	307	R>*		No	ClinGen ExAC TOPMed gnomAD
rs755587989 CA4821732	307	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA371852954 rs1346113264	308	E>D		No	ClinGen TOPMed
CA371852943 rs1387321165	310	E>A		No	ClinGen gnomAD
rs752325692 CA4821731	310	E>Q		No	ClinGen ExAC gnomAD
CA182770605 rs948590957	312	E>D		No	ClinGen TOPMed
CA371852930 rs1470741154	312	E>K		No	ClinGen TOPMed gnomAD
COSM1102921 CA4821729 rs759167472	316	S>L	endometrium [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs767110089 CA4821730	316	S>T		No	ClinGen ExAC gnomAD
CA4821710 rs368388279	317	D>A		No	ClinGen ESP ExAC TOPMed gnomAD
CA371851844 rs1246183655	318	E>V		No	ClinGen gnomAD
CA371851819 rs1186674563	322	D>H		No	ClinGen gnomAD
CA371851791 rs1462719916	326	M>V		No	ClinGen gnomAD
CA371851760 rs1253429724	330	S>N		No	ClinGen gnomAD
CA371851753 rs1586833258	331	V>M		No	ClinGen Ensembl
CA182764462 rs974748998	332	E>D		No	ClinGen gnomAD
CA371851729 rs1247462781	334	V>G		No	ClinGen gnomAD
rs762767274 COSM270249 CA4821706	335	G>D	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs1393907753 CA371851720	336	T>N		No	ClinGen gnomAD
CA4821703 rs374974168	337	M>I		No	ClinGen ESP ExAC TOPMed gnomAD
CA4821704 rs765265719	337	M>T		No	ClinGen ExAC gnomAD
rs200907713 CA4821701	338	R>Q		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA4821702 rs776913859	338	R>W		No	ClinGen ExAC gnomAD
CA371851705 rs1165415842	339	A>S		No	ClinGen gnomAD
CA4821700 rs747251874	340	T>R		No	ClinGen ExAC gnomAD
rs775790253 CA4821699	341	S>G		No	ClinGen ExAC TOPMed gnomAD
rs202028661 CA4821698	342	T>M		No	ClinGen ExAC gnomAD
CA371851679 rs1456450036	343	M>I		No	ClinGen TOPMed
rs771509402 CA4821695	343	M>T		No	ClinGen ExAC TOPMed gnomAD
rs370561303 CA4821696	343	M>V		No	ClinGen ESP ExAC gnomAD
CA371851640 rs1372946741	349	T>A		No	ClinGen TOPMed gnomAD
rs780693454 CA4821693	349	T>I		No	ClinGen ExAC gnomAD
rs1301013549 CA371851633	350	M>T		No	ClinGen TOPMed
COSM1266933 CA182764461 rs908567268	350	M>V	oesophagus [Cosmic]	No	ClinGen cosmic curated TOPMed
CA4821692 rs377506715	351	I>T		No	ClinGen ESP ExAC TOPMed gnomAD
rs760363706 CA4821690	356	T>M		No	ClinGen ExAC TOPMed gnomAD
CA371851588 rs1430855193	356	T>S		No	ClinGen gnomAD
CA4821688 rs750268928	359	E>D		No	ClinGen ExAC gnomAD
rs1563727806 CA371851567	359	E>K		No	ClinGen Ensembl
CA182764459 rs1037209658	360	S>Y		No	ClinGen TOPMed
rs1408936576 CA371851555	361	D>N		No	ClinGen gnomAD
rs1390002585 CA371851528	365	M>T		No	ClinGen gnomAD
CA4821684 rs753775021	365	M>V		No	ClinGen ExAC gnomAD
rs764276576 CA4821683	366	V>A		No	ClinGen ExAC TOPMed gnomAD
rs1365697292 CA371851494	370	E>K		No	ClinGen gnomAD
CA371851484 rs1250035123	371	D>G		No	ClinGen gnomAD
rs369783350 CA4821682	371	D>N		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA4821681 rs775878140	372	E>K		No	ClinGen ExAC TOPMed gnomAD
CA371851467 rs1586832732	373	E>V		No	ClinGen Ensembl
CA371851461 rs1289794117	374	E>A		No	ClinGen gnomAD
CA371851450 rs759645713	375	E>D		No	ClinGen ExAC TOPMed gnomAD
rs772387341 CA4821680	375	E>K		No	ClinGen ExAC TOPMed gnomAD
CA371851446 rs771142783	376	D>G		No	ClinGen ExAC gnomAD
rs560205328 CA4821678	376	D>N		No	ClinGen 1000Genomes ExAC gnomAD
rs771142783 CA4821677	376	D>V		No	ClinGen ExAC gnomAD
CA371851443 rs1284949342	377	G>R		No	ClinGen gnomAD
CA182764456 rs778211075	378	T>A		No	ClinGen ExAC TOPMed gnomAD
CA4821675 rs778211075	378	T>P		No	ClinGen ExAC TOPMed gnomAD
CA4821676 rs778211075	378	T>S		No	ClinGen ExAC TOPMed gnomAD
CA371851433 rs1330381946	379	M>V		No	ClinGen gnomAD
CA371851423 rs1563727510	380	K>E		No	ClinGen Ensembl
CA371851421 rs1321523112	380	K>R		No	ClinGen gnomAD
rs1327011454 CA371852872	382	N>S		No	ClinGen TOPMed gnomAD
rs759861263 CA4821659	384	T>P		No	ClinGen ExAC gnomAD
CA371852852 rs1563702897	385	S>L		No	ClinGen Ensembl
CA4821658 rs142241647	386	P>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs763253379 CA4821656	387	Q>P		No	ClinGen ExAC TOPMed gnomAD
CA371852843 rs763253379	387	Q>R		No	ClinGen ExAC TOPMed gnomAD
CA371852829 rs1415359087	389	Q>R		No	ClinGen gnomAD
rs1424860490 CA371852825	390	R>G		No	ClinGen gnomAD
rs1176079716 CA371852823	390	R>I		No	ClinGen gnomAD
rs1563702776 CA371852816	391	P>S		No	ClinGen Ensembl
rs773542636 CA371852797	394	M>L		No	ClinGen ExAC TOPMed gnomAD
CA4821655 rs773542636	394	M>V		No	ClinGen ExAC TOPMed gnomAD
rs1187315994 CA371852790	395	D>N		No	ClinGen gnomAD
CA4821653 rs770322622	397	F>V		No	ClinGen ExAC gnomAD
rs372444294 CA182760948	398	D>G		No	ClinGen ESP TOPMed gnomAD
CA371852759 rs1210425693	399	K>E		No	ClinGen TOPMed gnomAD
CA4821652 rs368988843	404	N>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs1276226100 CA371852709	405	K>R		No	ClinGen gnomAD
CA4821650 rs552761087	407	H>Q		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA371852684 rs1249444212	408	E>D		No	ClinGen TOPMed
rs1190611897 CA371852687	408	E>G		No	ClinGen TOPMed
COSM3835206 rs545643657 CA4821648	408	E>K	breast [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
CA371852670 rs1449689641	410	C>Y		No	ClinGen TOPMed
CA4821647 rs376001012	411	N>S		No	ClinGen ESP ExAC gnomAD
CA4821646 rs749145486	412	Q>K		No	ClinGen ExAC TOPMed gnomAD
CA4821645 rs577057842	413	N>I		No	ClinGen 1000Genomes ExAC gnomAD
rs371715105 CA371852647	413	N>K		No	ClinGen ESP ExAC TOPMed
CA4821642 rs369763923	414	M>I		No	ClinGen ESP ExAC TOPMed gnomAD
CA4821643 rs752670614	414	M>T		No	ClinGen ExAC gnomAD
CA4821640 rs754970839	417	P>R		No	ClinGen ExAC TOPMed gnomAD
VAR_051670 rs36047674 CA4821639	418	F>C		No	ClinGen UniProt ESP ExAC TOPMed dbSNP gnomAD
rs536624746 CA4821637	420	M>I		No	ClinGen 1000Genomes ExAC gnomAD
rs200371466 CA4821638	420	M>V		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA182760945 rs907796486	422	K>R		No	ClinGen TOPMed gnomAD
rs765569770 CA4821635	424	V>I		No	ClinGen ExAC gnomAD
rs776939644 CA4821633	427	D>E		No	ClinGen ExAC TOPMed gnomAD
CA4821634 rs762318051	427	D>H		No	ClinGen ExAC gnomAD
CA371852550 rs1273771278	428	N>Y		No	ClinGen gnomAD
rs199671137 CA4821632	429	W>*		No	ClinGen ESP ExAC TOPMed gnomAD
CA4821631 rs745324819	430	K>T		No	ClinGen ExAC gnomAD
rs773893604 CA4821630	433	Q>*		No	ClinGen ExAC gnomAD
CA4821629 rs554676158	433	Q>R		No	ClinGen 1000Genomes ExAC gnomAD
rs775921874 CA182760943	434	D>G		No	ClinGen gnomAD
rs748944234 CA4821628	435	G>R		No	ClinGen ExAC gnomAD
rs1371596952 CA371852493	436	D>E		No	ClinGen gnomAD
rs913664536 CA182744183	441	K>E		No	ClinGen TOPMed
rs1481303387 CA371852215	444	S>N		No	ClinGen TOPMed gnomAD
rs1165890095 CA371852186	447	E>*		No	ClinGen TOPMed
CA4821610 rs770553429	451	R>L		No	ClinGen ExAC TOPMed gnomAD
CA4821611 rs770553429	451	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA4821612 rs761214264	451	R>W		No	ClinGen ExAC TOPMed gnomAD
rs772958070 CA4821608	453	K>E		No	ClinGen ExAC gnomAD
rs1586601579 CA371852129	454	A>S		No	ClinGen Ensembl
rs747942047 CA4821606	456	D>N		No	ClinGen ExAC gnomAD
CA371852111 rs1586601543	457	P>S		No	ClinGen Ensembl
CA371852105 rs1386682197	458	M>K		No	ClinGen gnomAD
rs781008057 CA4821605	458	M>V		No	ClinGen ExAC TOPMed gnomAD
rs746947660 CA4821603 COSM1102913	461	R>Q	endometrium [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA4821604 rs200670480	461	R>W		No	ClinGen ESP ExAC TOPMed gnomAD
rs1028037134 CA182744166	465	E>Q		No	ClinGen TOPMed gnomAD
CA4821602 rs780118311	466	L>V		No	ClinGen ExAC TOPMed gnomAD
CA182744162 rs750630819	467	R>C		No	ClinGen TOPMed gnomAD
rs758402378 CA4821601	467	R>H		No	ClinGen ExAC TOPMed gnomAD
CA182744160 rs758402378	467	R>L		No	ClinGen ExAC TOPMed gnomAD
CA182744157 rs981667264	469	R>K		No	ClinGen Ensembl
rs750678047 CA4821600	470	Y>*		No	ClinGen ExAC gnomAD
rs779061311 CA4821599	471	T>A		No	ClinGen ExAC TOPMed gnomAD
CA4821598 rs757483119	472	A>T		No	ClinGen ExAC gnomAD
rs1421649694 CA371852011 COSM1458839	472	A>V	large_intestine [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
CA371851980 rs1465415994	477	I>V		No	ClinGen gnomAD
rs1207020028 CA371851964	479	D>V		No	ClinGen gnomAD
rs1484388193 CA371851960	480	A>T		No	ClinGen gnomAD
CA4821595 COSM1102911 rs761145064	480	A>V	endometrium [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA182744145 rs370627525	481	M>T		No	ClinGen ESP
CA371851931 rs1408718916	484	K>R		No	ClinGen gnomAD
CA371851930 rs1408718916	484	K>T		No	ClinGen gnomAD
CA918324422 rs1586601195	492	F>E		No	ClinGen Ensembl
CA371851868 rs1300464561	492	F>S		No	ClinGen gnomAD

No associated diseases with Q13188

No regional properties for Q13188

Type	Name	Position	InterPro Accession
No domain, repeats, and functional sites for Q13188

Functions

		Description
EC Number	2.7.11.1	Protein-serine/threonine kinases
Subcellular Localization	Cytoplasm Nucleus Cytoplasm, cytoskeleton, microtubule organizing center, centrosome	The caspase-cleaved form cycles between nucleus and cytoplasm (PubMed:19525978, PubMed:11278283) Phosphorylation at Thr-117 leads to inhibition of nuclear translocation (PubMed:19525978)
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

4 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.
nucleus	A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
protein-containing complex	A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together.

8 GO annotations of molecular function

Name	Definition
ATP binding	Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
identical protein binding	Binding to an identical protein or proteins.
magnesium ion binding	Binding to a magnesium (Mg) ion.
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 serine kinase activity	Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate.
protein serine/threonine kinase activator activity	Binds to and increases the activity of a protein serine/threonine kinase.
protein serine/threonine kinase activity	Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate.
protein serine/threonine/tyrosine kinase activity	Catalysis of the reactions: ATP + a protein serine = ADP + protein serine phosphate; ATP + a protein threonine = ADP + protein threonine phosphate; and ATP + a protein tyrosine = ADP + protein tyrosine phosphate.

26 GO annotations of biological process

Name	Definition
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.
cell differentiation involved in embryonic placenta development	The process in which a relatively unspecialized cell acquires specialized features of the embryonic placenta.
central nervous system development	The process whose specific outcome is the progression of the central nervous system over time, from its formation to the mature structure. The central nervous system is the core nervous system that serves an integrating and coordinating function. In vertebrates it consists of the brain and spinal cord. In those invertebrates with a central nervous system it typically consists of a brain, cerebral ganglia and a nerve cord.
endocardium development	The process whose specific outcome is the progression of the endocardium over time, from its formation to the mature structure. The endocardium is an anatomical structure comprised of an endothelium and an extracellular matrix that forms the innermost layer of tissue of the heart, and lines the heart chambers.
hepatocyte apoptotic process	Any apoptotic process in a hepatocyte, the main structural component of the liver.
hippo signaling	The series of molecular signals mediated by the serine/threonine kinase Hippo or one of its orthologs. In Drosophila, Hippo in complex with the scaffold protein Salvador (Sav), phosphorylates and activates Warts (Wts), which in turn phosphorylates and inactivates the Yorkie (Yki) transcriptional activator. The core fly components hippo, sav, wts and mats are conserved in mammals as STK4/3 (MST1/2), SAV1/WW45, LATS1/2 and MOB1.
intracellular signal transduction	The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell.
negative regulation of canonical Wnt signaling pathway	Any process that decreases the rate, frequency, or extent of the Wnt signaling pathway through beta-catenin, the series of molecular signals initiated by binding of a Wnt protein to a frizzled family receptor on the surface of the target cell, followed by propagation of the signal via beta-catenin, and ending with a change in transcription of target genes.
negative regulation of cell population proliferation	Any process that stops, prevents or reduces the rate or extent of cell proliferation.
negative regulation of organ growth	Any process that stops, prevents, or reduces the frequency, rate or extent of growth of an organ of an organism.
neural tube formation	The formation of a tube from the flat layer of ectodermal cells known as the neural plate. This will give rise to the central nervous system.
positive regulation of apoptotic process	Any process that activates or increases the frequency, rate or extent of cell death by apoptotic process.
positive regulation of DNA-binding transcription factor activity	Any process that activates or increases the frequency, rate or extent of activity of a transcription factor, any factor involved in the initiation or regulation of transcription.
positive regulation of extrinsic apoptotic signaling pathway via death domain receptors	Any process that activates or increases the frequency, rate or extent of extrinsic apoptotic signaling pathway via death domain receptors.
positive regulation of fat cell differentiation	Any process that activates or increases the frequency, rate or extent of adipocyte differentiation.
positive regulation of JNK cascade	Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the JNK cascade.
positive regulation of protein binding	Any process that activates or increases the frequency, rate or extent of protein binding.
positive regulation of protein kinase B signaling	Any process that activates or increases the frequency, rate or extent of protein kinase B signaling, a series of reactions mediated by the intracellular serine/threonine kinase protein kinase B.
primitive hemopoiesis	A first transient wave of blood cell production that, in vertebrates, gives rise to erythrocytes (red blood cells) and myeloid cells.
protein import into nucleus	The directed movement of a protein from the cytoplasm to the nucleus.
protein phosphorylation	The process of introducing a phosphate group on to a protein.
protein stabilization	Any process involved in maintaining the structure and integrity of a protein and preventing it from degradation or aggregation.
protein tetramerization	The formation of a protein tetramer, a macromolecular structure consisting of four noncovalently associated identical or nonidentical subunits.
regulation of cell differentiation involved in embryonic placenta development	Any process that modulates the rate, frequency or extent of cell differentiation that contributes to the progression of the placenta over time, from its initial condition to its mature state.
regulation of MAPK cascade	Any process that modulates the frequency, rate or extent of signal transduction mediated by the MAP kinase (MAPK) cascade.
signal transduction	The cellular process in which a signal is conveyed to trigger a change in the activity or state of a cell. Signal transduction begins with reception of a signal (e.g. a ligand binding to a receptor or receptor activation by a stimulus such as light), or for signal transduction in the absence of ligand, signal-withdrawal or the activity of a constitutively active receptor. Signal transduction ends with regulation of a downstream cellular process, e.g. regulation of transcription or regulation of a metabolic process. Signal transduction covers signaling from receptors located on the surface of the cell and signaling via molecules located within the cell. For signaling between cells, signal transduction is restricted to events at and within the receiving cell.

24 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q5E9L6	STK4	Serine/threonine-protein kinase 4	Bos taurus (Bovine)	SS
Q3SWY6	STK25	Serine/threonine-protein kinase 25	Bos taurus (Bovine)	PR
Q5ZJK4	STK4	Serine/threonine-protein kinase 4	Gallus gallus (Chicken)	SS
Q13043	STK4	Serine/threonine-protein kinase 4	Homo sapiens (Human)	EV
Q9NQU5	PAK6	Serine/threonine-protein kinase PAK 6	Homo sapiens (Human)	EV
Q9P286	PAK5	Serine/threonine-protein kinase PAK 5	Homo sapiens (Human)	EV
O96013	PAK4	Serine/threonine-protein kinase PAK 4	Homo sapiens (Human)	EV
Q13177	PAK2	Serine/threonine-protein kinase PAK 2	Homo sapiens (Human)	EV
O75914	PAK3	Serine/threonine-protein kinase PAK 3	Homo sapiens (Human)	SS
Q13153	PAK1	Serine/threonine-protein kinase PAK 1	Homo sapiens (Human)	EV
O95819	MAP4K4	Mitogen-activated protein kinase kinase kinase kinase 4	Homo sapiens (Human)	PR
Q9Y6E0	STK24	Serine/threonine-protein kinase 24	Homo sapiens (Human)	PR
O00506	STK25	Serine/threonine-protein kinase 25	Homo sapiens (Human)	PR
Q9JI11	Stk4	Serine/threonine-protein kinase 4	Mus musculus (Mouse)	PR
Q9JI10	Stk3	Serine/threonine-protein kinase 3	Mus musculus (Mouse)	SS
Q9Z2W1	Stk25	Serine/threonine-protein kinase 25	Mus musculus (Mouse)	PR
Q99JT2	Stk26	Serine/threonine-protein kinase 26	Mus musculus (Mouse)	PR
Q99KH8	Stk24	Serine/threonine-protein kinase 24	Mus musculus (Mouse)	PR
O54748	Stk3	Serine/threonine-protein kinase 3	Rattus norvegicus (Rat)	SS
A4K2T0	STK4	Serine/threonine-protein kinase 4	Macaca mulatta (Rhesus macaque)	PR
H2L099	gck-1	Germinal center kinase 1	Caenorhabditis elegans	PR
Q9NB31	cst-1	Serine/threonine-protein kinase cst-1	Caenorhabditis elegans	PR
Q6P3Q4	stk4	Serine/threonine-protein kinase 4	Xenopus tropicalis (Western clawed frog) (Silurana tropicalis)	SS
Q7ZUQ3	stk3	Serine/threonine-protein kinase 3	Danio rerio (Zebrafish) (Brachydanio rerio)	SS

10	20	30	40	50	60
MEQPPAPKSK	LKKLSEDSLT	KQPEEVFDVL	EKLGEGSYGS	VFKAIHKESG	QVVAIKQVPV
70	80	90	100	110	120
ESDLQEIIKE	ISIMQQCDSP	YVVKYYGSYF	KNTDLWIVME	YCGAGSVSDI	IRLRNKTLIE
130	140	150	160	170	180
DEIATILKST	LKGLEYLHFM	RKIHRDIKAG	NILLNTEGHA	KLADFGVAGQ	LTDTMAKRNT
190	200	210	220	230	240
VIGTPFWMAP	EVIQEIGYNC	VADIWSLGIT	SIEMAEGKPP	YADIHPMRAI	FMIPTNPPPT
250	260	270	280	290	300
FRKPELWSDD	FTDFVKKCLV	KNPEQRATAT	QLLQHPFIKN	AKPVSILRDL	ITEAMEIKAK
310	320	330	340	350	360
RHEEQQRELE	EEEENSDEDE	LDSHTMVKTS	VESVGTMRAT	STMSEGAQTM	IEHNSTMLES
370	380	390	400	410	420
DLGTMVINSE	DEEEEDGTMK	RNATSPQVQR	PSFMDYFDKQ	DFKNKSHENC	NQNMHEPFPM
430	440	450	460	470	480
SKNVFPDNWK	VPQDGDFDFL	KNLSLEELQM	RLKALDPMME	REIEELRQRY	TAKRQPILDA
490
MDAKKRRQQN	F