AiPD: Autoinhibited Protein Database

Q13043

Gene name	STK4 (KRS2, MST1)
Protein name	Serine/threonine-protein kinase 4
Names	Mammalian STE20-like protein kinase 1, MST-1, STE20-like kinase MST1, Serine/threonine-protein kinase Krs-2
Species	Homo sapiens (Human)
KEGG Pathway	hsa:6789
EC number	2.7.11.1: Protein-serine/threonine kinases
Protein Class	SERINE/THREONINE-PROTEIN KINASE TAO (PTHR48015)

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)

Target domain	30-281 (Protein kinase domain)
Relief mechanism	Cleavage
Assay	Deletion assay

AID

331-394 (Inhibitory domain)

Target domain

30-281 (Protein kinase domain)

Relief mechanism

Cleavage (Cleavage by caspase3)

Assay

Deletion assay

Accessory elements

166-189 (Activation loop from InterPro)

Target domain	30-281 (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

9 structures for Q13043

Entry ID	Method	Resolution	Chain	Position	Source
2JO8	NMR	-	A/B	432-480	PDB
3COM	X-ray	220 A	A/B	2-311	PDB
4NR2	X-ray	200 A	A/B/C/D/E/F/G/H	432-480	PDB
4OH8	X-ray	228 A	A	432-480	PDB
5TWG	X-ray	230 A	E	343-356	PDB
5TWH	X-ray	250 A	E	358-374	PDB
6YAT	X-ray	258 A	A/B	1-311	PDB
8A5J	X-ray	212 A	A/B	28-309	PDB
AF-Q13043-F1	Predicted				AlphaFoldDB

336 variants for Q13043

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
rs780774353 RCV001046943 CA9873717	36	L>P	Combined immunodeficiency due to STK4 deficiency [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
RCV001027635 rs387907316 RCV000030863 CA130168	117	R>*	Combined immunodeficiency due to STK4 deficiency Inherited Immunodeficiency Diseases [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
COSM1027149 RCV000706508 CA9873777 COSM1027148 rs368513990	120	T>M	Combined immunodeficiency due to STK4 deficiency endometrium [ClinVar, Cosmic]	Yes	ClinGen cosmic curated ClinVar ESP ExAC TOPMed dbSNP gnomAD
RCV000650576 CA9873798 rs371332575	129	I>M	Combined immunodeficiency due to STK4 deficiency [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
CA9873808 RCV000685113 rs774250826	158	N>S	Combined immunodeficiency due to STK4 deficiency [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
rs371236375 RCV000650577 CA9873867	241	P>S	Combined immunodeficiency due to STK4 deficiency [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA9873871 rs748660310 RCV001036103	245	R>*	Combined immunodeficiency due to STK4 deficiency [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
CA409125157 rs1601230245 RCV000030865	250	W>*	Combined immunodeficiency due to STK4 deficiency [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs35447878 RCV000546884 CA9873927 VAR_041124	310	R>Q	Combined immunodeficiency due to STK4 deficiency [ClinVar]	Yes	ClinGen ClinVar UniProt ESP ExAC TOPMed dbSNP gnomAD
rs776978911 RCV000553868 CA409126640	344	A>V	Combined immunodeficiency due to STK4 deficiency [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
RCV000698230 rs930004106 CA315491311	349	D>N	Combined immunodeficiency due to STK4 deficiency [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP
CA9873971 rs35944046 RCV000650578 VAR_041125	355	I>T	Combined immunodeficiency due to STK4 deficiency [ClinVar]	Yes	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
RCV000030864 rs1601240010	368	M>missing	Combined immunodeficiency due to STK4 deficiency [ClinVar]	Yes	ClinVar dbSNP
rs1568709093 CA409127002 RCV000698834	372	A>P	Combined immunodeficiency due to STK4 deficiency [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
VAR_041126 RCV000650580 CA9874019 rs33963346	416	P>L	Combined immunodeficiency due to STK4 deficiency [ClinVar]	Yes	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs1431659437 CA409146305	2	E>K		No	ClinGen gnomAD
rs1291531683 CA409146314	3	T>A		No	ClinGen TOPMed
rs927162591 CA315500585	5	Q>L		No	ClinGen TOPMed
rs927162591 CA409146329	5	Q>R		No	ClinGen TOPMed
CA409146336 rs1380933102	6	L>P		No	ClinGen TOPMed
rs958687601 CA315500588	8	N>S		No	ClinGen TOPMed
CA409146356 rs1159526308	9	P>L		No	ClinGen TOPMed
rs1203443460 CA409146362	10	P>L		No	ClinGen TOPMed gnomAD
rs1164496396 CA409146368	11	R>H		No	ClinGen TOPMed
CA409146371 rs1473059279	12	R>Q		No	ClinGen TOPMed
CA9873705 rs751316400	13	Q>H		No	ClinGen ExAC gnomAD
CA409147174 rs1365819917	13	Q>P		No	ClinGen gnomAD
rs142594802 CA9873707	16	K>R		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA409147228 rs1487847206	18	D>Y		No	ClinGen TOPMed
rs1285494085 CA409147240	19	E>K		No	ClinGen TOPMed
CA409147261 rs1223830795	20	D>G		No	ClinGen gnomAD
rs1601173350 CA409147281	21	S>R		No	ClinGen Ensembl
rs150984577 CA9873709	23	T>I		No	ClinGen ESP ExAC TOPMed gnomAD
rs777881846 CA9873710	26	P>L		No	ClinGen ExAC gnomAD
CA409147367 rs1204758943	28	E>D		No	ClinGen gnomAD
rs757796995 CA9873712	28	E>K		No	ClinGen ExAC TOPMed gnomAD
rs558706666 CA9873715	30	F>S		No	ClinGen 1000Genomes ExAC gnomAD
rs1461522494 CA409147492	39	G>W		No	ClinGen gnomAD
rs1356974803 CA409148304	40	S>C		No	ClinGen gnomAD
CA315508915 rs140854695	41	Y>C		No	ClinGen ESP TOPMed gnomAD
rs140854695 CA409148315	41	Y>F		No	ClinGen ESP TOPMed gnomAD
CA315508928 rs147806598	44	V>I		No	ClinGen ESP gnomAD
CA409148359 rs1271653511	45	Y>F		No	ClinGen gnomAD
CA409148381 rs1362380823	47	A>T		No	ClinGen gnomAD
CA409148390 rs1215444331	47	A>V		No	ClinGen gnomAD
rs747776044 CA9873738	48	I>V		No	ClinGen ExAC gnomAD
rs755753311 CA9873739	49	H>L		No	ClinGen ExAC gnomAD
rs1355232511 CA409148433	51	E>Q		No	ClinGen Ensembl
CA409148456 rs770860898	53	G>C		No	ClinGen gnomAD
CA315508933 rs770860898	53	G>S		No	ClinGen gnomAD
rs374689115 CA9873741	56	V>A		No	ClinGen ESP ExAC TOPMed gnomAD
CA409148512 rs1244262418	58	I>V		No	ClinGen gnomAD
rs545381981 CA9873743	60	Q>E		No	ClinGen 1000Genomes ExAC gnomAD
CA409148560 rs1190323794	62	P>T		No	ClinGen gnomAD
rs1422563116 CA409148585	64	E>Q		No	ClinGen gnomAD
rs1297320177 CA409148627	67	L>P		No	ClinGen TOPMed
CA409148677 rs1481152044	71	I>M		No	ClinGen gnomAD
rs1218691869 CA409148708	76	I>V		No	ClinGen TOPMed
rs1209193935 CA409148727	78	Q>R		No	ClinGen gnomAD
CA409148757 rs1301214486	82	S>C		No	ClinGen TOPMed
CA9873761 rs756803470	83	P>L		No	ClinGen ExAC TOPMed gnomAD
rs1408559557 CA409148804	85	V>A		No	ClinGen gnomAD
rs993507146 CA315511936	85	V>I		No	ClinGen TOPMed gnomAD
CA315511937 rs1026387287	86	V>I		No	ClinGen Ensembl
rs778374900 CA9873762	87	K>R		No	ClinGen ExAC gnomAD
rs75329306 CA9873764	91	S>R		No	ClinGen ExAC gnomAD
rs775157618 CA9873765	96	T>A		No	ClinGen ExAC TOPMed gnomAD
rs141098686 CA9873766	96	T>I		No	ClinGen ESP ExAC TOPMed gnomAD
rs768328182 CA9873767	97	D>E		No	ClinGen ExAC TOPMed gnomAD
CA409148982 rs1172195088	99	W>*		No	ClinGen TOPMed
CA9873770 rs371926152	99	W>*		No	ClinGen ESP ExAC TOPMed gnomAD
CA9873769 rs371926152	99	W>C		No	ClinGen ESP ExAC TOPMed gnomAD
rs763376298 CA9873772	101	V>A		No	ClinGen ExAC gnomAD
CA9873771 rs375543946	101	V>I		No	ClinGen ESP ExAC TOPMed gnomAD
rs1435589794 CA409149019	102	M>T		No	ClinGen TOPMed gnomAD
rs1250583882 CA409149014	102	M>V		No	ClinGen gnomAD
rs1183297955 CA409149035	103	E>G		No	ClinGen gnomAD
CA409149046 rs1601195313	104	Y>D		No	ClinGen Ensembl
CA409149064 rs1568687080	105	C>Y		No	ClinGen Ensembl
CA409149077 rs1601195329	106	G>E		No	ClinGen Ensembl
CA409149082 rs1416861097	107	A>T		No	ClinGen TOPMed
rs1233390216 CA409149122	110	V>A		No	ClinGen gnomAD
CA409149157 rs1161387048	113	I>T		No	ClinGen gnomAD
rs766853466 CA9873773	113	I>V		No	ClinGen ExAC gnomAD
CA9873774 rs751997042	115	R>*		No	ClinGen ExAC TOPMed gnomAD
rs1425040490 COSM1027147 COSM1027146 CA409149176	115	R>Q	endometrium [Cosmic]	No	ClinGen cosmic curated gnomAD
rs202040819 CA9873775	117	R>Q		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA9873776 rs767840614	119	K>E		No	ClinGen ExAC gnomAD
CA409124143 rs1402035924	123	E>D		No	ClinGen TOPMed
CA9873792 rs759942089	124	D>N		No	ClinGen ExAC TOPMed gnomAD
rs767893628 CA9873793	124	D>V		No	ClinGen ExAC gnomAD
rs761464846 CA9873795	126	I>T		No	ClinGen ExAC gnomAD
rs764924378 CA9873796	128	T>P		No	ClinGen ExAC gnomAD
CA9873797 rs750035253	129	I>V		No	ClinGen ExAC gnomAD
CA409124192 rs1422212937	131	Q>E		No	ClinGen TOPMed
CA409124195 rs1568692148	131	Q>R		No	ClinGen Ensembl
CA9873800 rs751537507	132	S>A		No	ClinGen ExAC TOPMed gnomAD
rs781137671 CA9873802	133	T>A		No	ClinGen ExAC TOPMed gnomAD
rs1193928841 CA409124237	138	E>A		No	ClinGen gnomAD
CA9873805 rs778208531	146	I>M		No	ClinGen ExAC gnomAD
CA9873806 COSM1027150 rs749441226 COSM1027151	148	R>*	endometrium [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs374685235 CA9873807	148	R>Q		No	ClinGen ESP ExAC gnomAD
rs1408957049 CA409124374	157	L>P		No	ClinGen gnomAD
rs772504626 CA9873810	160	E>K		No	ClinGen ExAC gnomAD
CA9873811 rs55850759 VAR_041123	162	H>N		No	ClinGen UniProt ExAC TOPMed dbSNP gnomAD
CA409124415 rs1318602836	164	K>E		No	ClinGen gnomAD
CA409124428 rs1330083709	166	A>T		No	ClinGen gnomAD
rs772963142 CA9873814	171	A>V		No	ClinGen ExAC gnomAD
CA409124515 rs1259481890	177	T>A		No	ClinGen TOPMed
CA315489128 rs778662421	180	K>E		No	ClinGen Ensembl
rs202070040 CA315489130 COSM1027153 COSM1027152	181	R>Q	endometrium [Cosmic]	No	ClinGen cosmic curated 1000Genomes TOPMed gnomAD
CA409124570 rs1261102030	185	I>T		No	ClinGen TOPMed
rs1225128691 CA409124582	187	T>I		No	ClinGen TOPMed
CA409124587 rs1601225538	188	P>S		No	ClinGen Ensembl
rs1490543634 CA409124596	189	F>C		No	ClinGen gnomAD
rs1312616952 CA409124644	196	I>V		No	ClinGen TOPMed
CA9873834 rs765887990	198	E>Q		No	ClinGen ExAC gnomAD
rs774041672 CA9873835	199	I>M		No	ClinGen ExAC gnomAD
CA409124683 rs1376471950	201	Y>*		No	ClinGen gnomAD
rs767104688 CA9873837	204	V>I		No	ClinGen ExAC gnomAD
rs201578965 CA409124723	207	I>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA9873839 rs201578965	207	I>T		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs377733474 CA9873838	207	I>V		No	ClinGen ESP ExAC TOPMed gnomAD
rs867168175 CA315489155	209	S>F		No	ClinGen Ensembl
CA315489159 rs76539764	211	G>E		No	ClinGen Ensembl
CA315489162 rs912491141	215	I>V		No	ClinGen TOPMed
rs552199529 CA315489165	217	M>V		No	ClinGen gnomAD
CA409124792 rs1295887166	218	A>S		No	ClinGen gnomAD
CA9873840 rs1406011532	221	K>N		No	ClinGen TOPMed
CA409124848 rs1311891170	226	D>G		No	ClinGen gnomAD
CA409124855 rs1468029746	227	I>T		No	ClinGen TOPMed
CA9873844 rs757517757	230	M>V		No	ClinGen ExAC gnomAD
rs761550159 CA409124973	233	I>F		No	ClinGen ExAC gnomAD
rs761550159 CA9873863	233	I>V		No	ClinGen ExAC gnomAD
CA9873864 rs370157810	235	M>T		No	ClinGen ESP ExAC gnomAD
rs750661803 CA9873865	238	T>R		No	ClinGen ExAC TOPMed gnomAD
COSM1027155 CA409125026 COSM1027154 rs1254975766	239	N>H	endometrium [Cosmic]	No	ClinGen cosmic curated gnomAD
rs758578817 CA9873866	239	N>S		No	ClinGen ExAC gnomAD
CA315489867 rs1042693898	240	P>L		No	ClinGen Ensembl
rs1206107298 CA409125041	240	P>T		No	ClinGen TOPMed gnomAD
CA409125063 rs1279829809	241	P>L		No	ClinGen TOPMed
rs751578463 CA9873868	242	P>L		No	ClinGen ExAC gnomAD
rs770104834 CA9873872	245	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs368707737 CA315489888	247	P>S		No	ClinGen ESP TOPMed gnomAD
CA9873873 rs778235129	249	L>P		No	ClinGen ExAC gnomAD
CA409125146 rs1293024363	249	L>V		No	ClinGen TOPMed
rs149432644 CA9873874	253	N>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA9873876 rs775155977	255	T>I		No	ClinGen ExAC gnomAD
CA409125226 rs1568703034	256	D>G		No	ClinGen Ensembl
CA9873877 rs760323489	256	D>N		No	ClinGen ExAC gnomAD
CA9873878 rs768176881	257	F>C		No	ClinGen ExAC gnomAD
rs761758117 CA9873880	258	V>A		No	ClinGen ExAC TOPMed gnomAD
CA9873879 rs372125666	258	V>M		No	ClinGen ESP ExAC TOPMed gnomAD
rs544097245 CA9873881	259	K>E		No	ClinGen 1000Genomes ExAC gnomAD
CA409125268 rs1327245783	260	Q>E		No	ClinGen TOPMed
rs750149771 CA9873882	262	L>P		No	ClinGen ExAC gnomAD
CA315489915 rs1039341969	263	V>A		No	ClinGen TOPMed gnomAD
CA409125302 rs1225933872	263	V>I		No	ClinGen TOPMed gnomAD
rs1214007736 CA409125321	264	K>R		No	ClinGen gnomAD
CA409125332 rs766646031	265	S>N		No	ClinGen ExAC TOPMed gnomAD
CA9873884 rs766646031	265	S>T		No	ClinGen ExAC TOPMed gnomAD
rs143845252 CA315489924	266	P>A		No	ClinGen ESP ExAC TOPMed gnomAD
rs143845252 CA9873885	266	P>T		No	ClinGen ESP ExAC TOPMed gnomAD
CA9873886 rs755054432	267	E>D		No	ClinGen ExAC gnomAD
rs781309885 CA9873888	268	Q>E		No	ClinGen ExAC
rs778290237 CA9873890	268	Q>H		No	ClinGen ExAC TOPMed gnomAD
rs781309885 CA9873887	268	Q>K		No	ClinGen ExAC
CA9873889 rs756604776	268	Q>P		No	ClinGen ExAC
CA9873891 rs749609433	269	R>G		No	ClinGen ExAC
CA9873892 rs757686883	270	A>P		No	ClinGen ExAC gnomAD
CA9873893 rs757686883	270	A>S		No	ClinGen ExAC gnomAD
rs757686883 CA409125379	270	A>T		No	ClinGen ExAC gnomAD
rs1014058732 CA315489942	270	A>V		No	ClinGen Ensembl
rs1423957175 CA409125393	271	T>I		No	ClinGen TOPMed
CA9873894 rs80013229	271	T>P		No	ClinGen ExAC gnomAD
CA9873895 rs768070960	272	A>G		No	ClinGen ExAC gnomAD
rs1407114206 CA409125395	272	A>T		No	ClinGen gnomAD
CA315489950 rs374505931	273	T>I		No	ClinGen ESP TOPMed gnomAD
rs1601230790 CA409125421	274	Q>R		No	ClinGen Ensembl
rs373362307 CA9873897	275	L>V		No	ClinGen ExAC TOPMed gnomAD
CA409126115 rs754588774	278	H>Q		No	ClinGen ExAC gnomAD
rs1245644852 CA409126117	279	P>A		No	ClinGen gnomAD
CA315490990 rs1029856335	279	P>R		No	ClinGen Ensembl
CA315490992 rs982427313	280	F>L		No	ClinGen TOPMed
CA315490994 rs6103955	282	R>K		No	ClinGen Ensembl
CA409126144 rs1601237714	283	S>I		No	ClinGen Ensembl
CA409126155 rs1210052606	285	K>E		No	ClinGen gnomAD
CA9873916 rs747750281	287	V>A		No	ClinGen ExAC TOPMed gnomAD
CA409126171 rs747750281	287	V>G		No	ClinGen ExAC TOPMed gnomAD
CA9873915 rs372387562	287	V>M		No	ClinGen ESP ExAC gnomAD
rs769288309 CA9873917	289	I>V		No	ClinGen ExAC TOPMed gnomAD
rs148138374 CA9873918	291	R>*		No	ClinGen ESP ExAC TOPMed gnomAD
CA9873919 rs749201774	291	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs569736817 CA9873920	292	D>G		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1601237853 CA409126192	292	D>N		No	ClinGen Ensembl
rs569736817 CA409126196	292	D>V		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA315491003 rs377009560	293	L>F		No	ClinGen ESP gnomAD
CA409126205 rs1164016163	294	I>L		No	ClinGen gnomAD
rs985745801 CA315491006	295	N>D		No	ClinGen Ensembl
CA409126216 rs1277742961	295	N>S		No	ClinGen TOPMed gnomAD
CA9873921 rs763253365	297	A>V		No	ClinGen ExAC TOPMed gnomAD
CA409126238 rs1366384790	298	M>I		No	ClinGen TOPMed
rs759684081 CA9873922	299	D>G		No	ClinGen ExAC gnomAD
CA9873923 rs201208315	304	R>C		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA9873924 COSM1227899 rs200716827 COSM1227900	304	R>H	large_intestine [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
CA315491020 rs200716827	304	R>L		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs371733260 CA315491022	305	Q>P		No	ClinGen Ensembl
rs760880030 CA9873925	307	S>C		No	ClinGen ExAC gnomAD
rs1601238030 CA409126294	307	S>P		No	ClinGen Ensembl
rs35447878 CA9873928	310	R>P		No	ClinGen ESP ExAC TOPMed gnomAD
rs764241940 CA9873926	310	R>W		No	ClinGen ExAC gnomAD
CA9873929 rs765698660	311	E>K		No	ClinGen ExAC gnomAD
CA315491041 rs765698660	311	E>Q		No	ClinGen ExAC gnomAD
VAR_027040 rs17420378 CA9873930	312	V>M		No	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA9873931 rs758674718	313	D>G		No	ClinGen ExAC TOPMed gnomAD
CA409126350 rs374601797	316	D>H		No	ClinGen ESP ExAC TOPMed gnomAD
CA9873933 rs374601797	316	D>N		No	ClinGen ESP ExAC TOPMed gnomAD
CA9873934 rs374601797	316	D>Y		No	ClinGen ESP ExAC TOPMed gnomAD
rs1460859084 CA409126356	317	E>K		No	ClinGen gnomAD
CA9873935 rs777217023	318	E>Q		No	ClinGen ExAC gnomAD
CA9873936 rs749256812	319	N>D		No	ClinGen ExAC gnomAD
CA409126385 rs1601238212	319	N>T		No	ClinGen Ensembl
rs1344343086 CA409126464	323	D>N		No	ClinGen gnomAD
rs1601239548 CA409126484	325	M>T		No	ClinGen Ensembl
rs1402506836 CA409126501	327	S>C		No	ClinGen gnomAD
CA315491281 rs985634108	328	G>A		No	ClinGen TOPMed gnomAD
CA409126521 rs1258818326	330	M>I		No	ClinGen gnomAD
CA409126517 rs1238230164	330	M>K		No	ClinGen gnomAD
COSM188567 rs1331548146 CA409126515 COSM188568	330	M>V	large_intestine [Cosmic]	No	ClinGen cosmic curated gnomAD
rs146085540 CA9873960	332	R>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs146085540 CA9873959	332	R>Q		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs771955007 RCV000332737 CA9873961	335	G>D		No	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
rs779670569 CA9873962	338	M>V		No	ClinGen ExAC gnomAD
CA409126588 rs1427880156	339	G>S		No	ClinGen TOPMed
rs1372989393 CA409126599	340	T>A		No	ClinGen TOPMed
CA9873963 rs201970002	342	R>Q		No	ClinGen ExAC gnomAD
CA9873965 rs776978911	344	A>G		No	ClinGen ExAC gnomAD
rs1465906051 CA409126646	345	S>G		No	ClinGen TOPMed
CA409126673 rs1181681923	347	M>I		No	ClinGen gnomAD
CA315491308 rs918470885	347	M>T		No	ClinGen Ensembl
CA315491305 rs374331006	347	M>V		No	ClinGen ESP TOPMed
CA409126687 rs1362470660	348	T>A		No	ClinGen TOPMed gnomAD
rs1421851448 CA409126720	351	A>P		No	ClinGen gnomAD
CA9873968 rs140089638	353	T>A		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA9873970 rs376301299	354	M>I		No	ClinGen ESP ExAC TOPMed gnomAD
rs763320987 CA9873969	354	M>V		No	ClinGen ExAC TOPMed gnomAD
rs923962859 CA315491323	357	H>R		No	ClinGen TOPMed
rs1304760359 CA409126787	357	H>Y		No	ClinGen gnomAD
CA409126807 rs1308718946	358	D>N		No	ClinGen gnomAD
rs561228188 CA409126829	359	D>E		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1358925572 CA409126853	360	T>M		No	ClinGen TOPMed gnomAD
rs1310270958 CA409126846	360	T>S		No	ClinGen gnomAD
CA315491335 rs893319752	367	T>A		No	ClinGen Ensembl
rs770308320 CA315491338	367	T>I		No	ClinGen Ensembl
CA9873977 rs750401960	368	M>V		No	ClinGen ExAC TOPMed gnomAD
CA315491354 rs747608171	369	V>E		No	ClinGen Ensembl
CA9873978 rs758200174	369	V>M		No	ClinGen ExAC gnomAD
rs1384985474 CA409126981	370	I>M		No	ClinGen TOPMed gnomAD
CA409126990 rs1442472112	371	N>S		No	ClinGen gnomAD
rs1166439547 CA409127013	372	A>V		No	ClinGen gnomAD
rs1470492673 CA409127016	373	E>K		No	ClinGen TOPMed
CA9873980 rs746855384	374	D>V		No	ClinGen ExAC gnomAD
rs1011676864 COSM1751472 CA315491374 COSM1751471	379	G>E	urinary_tract [Cosmic]	No	ClinGen cosmic curated Ensembl
CA9873983 rs781603743	379	G>R		No	ClinGen ExAC gnomAD
CA409127136 rs1335908744	380	T>S		No	ClinGen gnomAD
rs201224293 CA9873984	381	M>T		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1380266799 CA409127147	381	M>V		No	ClinGen TOPMed gnomAD
rs1315046947 CA409127165	382	K>Q		No	ClinGen gnomAD
rs571847724 CA9874003	383	R>I		No	ClinGen 1000Genomes ExAC gnomAD
rs534100971 CA9874004	383	R>S		No	ClinGen 1000Genomes ExAC gnomAD
rs756224873 CA9874005	384	R>K		No	ClinGen ExAC gnomAD
rs1189817024 CA409129800	384	R>S		No	ClinGen TOPMed
CA409129806 rs1197990310	385	D>V		No	ClinGen gnomAD
rs1478828108 CA409129818	387	T>A		No	ClinGen TOPMed
rs749388176 CA9874007	388	M>I		No	ClinGen ExAC TOPMed gnomAD
CA409129832 rs749388176	388	M>I		No	ClinGen ExAC TOPMed gnomAD
CA9874006 rs777923911	388	M>T		No	ClinGen ExAC gnomAD
CA9874008 rs771041343	389	Q>R		No	ClinGen ExAC gnomAD
CA9874010 rs371924549	391	A>E		No	ClinGen ESP ExAC TOPMed gnomAD
CA9874009 rs371924549	391	A>V		No	ClinGen ESP ExAC TOPMed gnomAD
rs1157119510 CA409129892	394	S>F		No	ClinGen gnomAD
CA315499413 rs1048275236	399	F>L		No	ClinGen Ensembl
CA409129952 rs1362623843	400	E>Q		No	ClinGen gnomAD
rs1293316589 CA409129960	400	E>V		No	ClinGen gnomAD
CA9874013 rs376797397	401	Q>E		No	ClinGen ESP ExAC TOPMed gnomAD
CA409129994 rs1336347884	403	E>K		No	ClinGen gnomAD
rs554264474 CA9874016	407	Q>H		No	ClinGen 1000Genomes ExAC gnomAD
CA315499423 rs971258385	407	Q>R		No	ClinGen TOPMed
rs980823829 CA315499434	408	I>T		No	ClinGen TOPMed
rs762408402 CA9874017	409	N>Y		No	ClinGen ExAC gnomAD
CA315499440 rs867552820	411	F>C		No	ClinGen Ensembl
CA409130107 rs1238345014	413	K>Q		No	ClinGen gnomAD
rs765963968 CA9874018	415	V>I		No	ClinGen ExAC gnomAD
CA409130156 rs1220711062	417	G>A		No	ClinGen TOPMed
rs1207145613 CA409130169	418	P>L		No	ClinGen gnomAD
rs1287175707 CA409130163	418	P>S		No	ClinGen TOPMed gnomAD
rs1409364990 CA409130206	422	S>A		No	ClinGen TOPMed
CA409130232 rs146304786	424	D>G		No	ClinGen ESP TOPMed
CA315499447 rs146304786	424	D>V		No	ClinGen ESP TOPMed
rs1004031378 CA315499448	426	K>E		No	ClinGen Ensembl
CA409130267 rs1222249798	427	I>T		No	ClinGen gnomAD
rs868818419 CA315499449	428	P>S		No	ClinGen Ensembl
rs1468417114 CA409130288	429	Q>R		No	ClinGen TOPMed gnomAD
rs1600495712 CA409130303	430	D>V		No	ClinGen Ensembl
rs755925460 CA409130336	433	Y>*		No	ClinGen ExAC TOPMed gnomAD
rs777926811 CA9874024	434	E>K		No	ClinGen ExAC TOPMed gnomAD
rs1163139493 CA409130361	435	F>L		No	ClinGen gnomAD
CA9874067 rs776425570	436	L>F		No	ClinGen ExAC gnomAD
CA9874066 rs776425570	436	L>V		No	ClinGen ExAC gnomAD
CA9874070 rs758520609	441	V>E		No	ClinGen ExAC gnomAD
CA9874069 rs750610796	441	V>M		No	ClinGen ExAC gnomAD
CA409129500 rs1478534203	447	R>K		No	ClinGen TOPMed gnomAD
CA409129502 rs1478534203	447	R>M		No	ClinGen TOPMed gnomAD
rs766432397 CA9874071	448	L>P		No	ClinGen ExAC gnomAD
rs1281632528 CA409129519	450	A>T		No	ClinGen TOPMed
CA9874075 rs748582253	456	E>K		No	ClinGen ExAC gnomAD
rs376065907 RCV001092540	457	Q>*		No	ClinVar dbSNP
CA9874076 rs376065907	457	Q>K		No	ClinGen ESP ExAC gnomAD
rs559407748 CA9874077	458	E>K		No	ClinGen 1000Genomes ExAC gnomAD
CA409129586 rs1237976406	459	I>S		No	ClinGen gnomAD
COSM577639 rs771492682 CA9874079	461	E>D	lung [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
COSM1412010 rs746946767 CA409129612	463	R>L	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
COSM72838 rs746946767 CA9874081	463	R>Q	ovary [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
COSM1565766 CA9874080 rs774995364	463	R>W	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA409129637 rs1216666438	467	Q>E		No	ClinGen gnomAD
rs528126240 CA409129644	467	Q>H		No	ClinGen 1000Genomes TOPMed gnomAD
CA409129641 rs1488185624	467	Q>R		No	ClinGen gnomAD
CA9874083 rs200190272	470	R>Q		No	ClinGen ExAC gnomAD
COSM443882 rs768691855 CA9874082	470	R>W	breast [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA409129672 rs1600584353	472	P>A		No	ClinGen Ensembl
rs761665678 CA9874084	472	P>H		No	ClinGen ExAC gnomAD
rs201001614 CA9874086	477	I>T		No	ClinGen ExAC gnomAD
CA9874087 rs368897909	479	A>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs766401074 CA9874088	481	K>R		No	ClinGen ExAC gnomAD
rs1295227094 CA409129737	482	R>K		No	ClinGen gnomAD
CA9874090 rs201951179	483	R>W		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD

1 associated diseases with Q13043

[MIM: 614868]: T-cell immunodeficiency, recurrent infections, and autoimmunity with or without cardiac malformations (TIIAC)

A primary T-cell immunodeficiency syndrome characterized by progressive loss of naive T-cells, recurrent bacterial, viral, and fungal infections, warts, and abscesses, autoimmune manifestations, and cardiac malformations, including atrial septal defect. {ECO:0000269|PubMed:22294732}. Note=The disease is caused by variants affecting the gene represented in this entry.

Without disease ID

A primary T-cell immunodeficiency syndrome characterized by progressive loss of naive T-cells, recurrent bacterial, viral, and fungal infections, warts, and abscesses, autoimmune manifestations, and cardiac malformations, including atrial septal defect. {ECO:0000269|PubMed:22294732}. Note=The disease is caused by variants affecting the gene represented in this entry.

2 regional properties for Q13043

Type	Name	Position	InterPro Accession
domain	Zinc finger, A20-type	796 - 831	IPR002653
domain	OTU domain	183 - 365	IPR003323

Functions

		Description
EC Number	2.7.11.1	Protein-serine/threonine kinases
Subcellular Localization	Cytoplasm Nucleus	The caspase-cleaved form cycles between the nucleus and cytoplasm
PANTHER Family	PTHR48015	SERINE/THREONINE-PROTEIN KINASE TAO
PANTHER Subfamily	PTHR48015:SF32	SERINE_THREONINE-PROTEIN KINASE 4
PANTHER Protein Class	non-receptor serine/threonine protein kinase protein modifying enzyme
PANTHER Pathway Category	No pathway information available

6 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 body	Extra-nucleolar nuclear domains usually visualized by confocal microscopy and fluorescent antibodies to specific proteins.
nucleoplasm	That part of the nuclear content other than the chromosomes or the nucleolus.
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.

10 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 homodimerization activity	Binding to an identical protein to form a homodimer.
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.
RNA polymerase II-specific DNA-binding transcription factor binding	Binding to a sequence-specific DNA binding RNA polymerase II transcription factor, any of the factors that interact selectively and non-covalently with a specific DNA sequence in order to modulate transcription.

31 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.
branching involved in blood vessel morphogenesis	The process of coordinated growth and sprouting of blood vessels giving rise to the organized vascular system.
cell differentiation involved in embryonic placenta development	The process in which a relatively unspecialized cell acquires specialized features of the embryonic placenta.
cell morphogenesis	The developmental process in which the size or shape of a cell is generated and organized.
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.
keratinocyte differentiation	The process in which a relatively unspecialized cell acquires specialized features of a keratinocyte.
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.
peptidyl-serine phosphorylation	The phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine.
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 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 peptidyl-serine phosphorylation	Any process that activates or increases the frequency, rate or extent of the phosphorylation of peptidyl-serine.
positive regulation of protein binding	Any process that activates or increases the frequency, rate or extent of protein binding.
positive regulation of protein phosphorylation	Any process that activates or increases the frequency, rate or extent of addition of phosphate groups to amino acids within a protein.
positive regulation of substrate-dependent cell migration, cell attachment to substrate	Any process that activates or increases the frequency, rate or extent of substrate-dependent cell migration, cell attachment to substrate.
primitive hemopoiesis	A first transient wave of blood cell production that, in vertebrates, gives rise to erythrocytes (red blood cells) and myeloid cells.
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 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
Q13188	STK3	Serine/threonine-protein kinase 3	Homo sapiens (Human)	SS
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
Q9JI10	Stk3	Serine/threonine-protein kinase 3	Mus musculus (Mouse)	SS
Q9JI11	Stk4	Serine/threonine-protein kinase 4	Mus musculus (Mouse)	PR
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
METVQLRNPP	RRQLKKLDED	SLTKQPEEVF	DVLEKLGEGS	YGSVYKAIHK	ETGQIVAIKQ
70	80	90	100	110	120
VPVESDLQEI	IKEISIMQQC	DSPHVVKYYG	SYFKNTDLWI	VMEYCGAGSV	SDIIRLRNKT
130	140	150	160	170	180
LTEDEIATIL	QSTLKGLEYL	HFMRKIHRDI	KAGNILLNTE	GHAKLADFGV	AGQLTDTMAK
190	200	210	220	230	240
RNTVIGTPFW	MAPEVIQEIG	YNCVADIWSL	GITAIEMAEG	KPPYADIHPM	RAIFMIPTNP
250	260	270	280	290	300
PPTFRKPELW	SDNFTDFVKQ	CLVKSPEQRA	TATQLLQHPF	VRSAKGVSIL	RDLINEAMDV
310	320	330	340	350	360
KLKRQESQQR	EVDQDDEENS	EEDEMDSGTM	VRAVGDEMGT	VRVASTMTDG	ANTMIEHDDT
370	380	390	400	410	420
LPSQLGTMVI	NAEDEEEEGT	MKRRDETMQP	AKPSFLEYFE	QKEKENQINS	FGKSVPGPLK
430	440	450	460	470	480
NSSDWKIPQD	GDYEFLKSWT	VEDLQKRLLA	LDPMMEQEIE	EIRQKYQSKR	QPILDAIEAK

KRRQQNF