AiPD: Autoinhibited Protein Database

Q8IW41

Gene name	MAPKAPK5 (PRAK)
Protein name	MAP kinase-activated protein kinase 5
Names	MAPK-activated protein kinase 5, MAPKAP kinase 5, MAPKAP-K5, MAPKAPK-5, MK-5, MK5, p38-regulated/activated protein kinase, PRAK
Species	Homo sapiens (Human)
KEGG Pathway	hsa:8550
EC number	2.7.11.1: Protein-serine/threonine kinases
Protein Class

Descriptions

MAPKAPK5 is a MAP kinase-activated protein kinase 5, activated by stress-related extracellular stimuli, and is able to shuttle between the nucleus (unstimulated cells) and the cytoplasm (stimulated cells). The proposed autoinhibitory region is within the C-terminal domain of MAPKAPK5, contains autoinhibitory α-helix overlapping with a leucine-rich nuclear export signal (NES), and also lies close to the nuclear localization signal (NLS). The closed conformation of MAPKAPK5 prevents exportin binding to NES. Phosphorylation of MAPKAPK5 at threonine 182 by p38 MAPK induces a conformational change, thus unmasks and increases the activity of NES.

Autoinhibitory domains (AIDs)

308-350 (Putative autoinhibitory α-helix) SS

Target domain	22-304 (Protein kinase domain)
Relief mechanism	PTM
Assay

AID

308-350 (Putative autoinhibitory α-helix)

Target domain

22-304 (Protein kinase domain)

Relief mechanism

PTM (Phosphorylation at Thr-182 by p38 MAPK)

Assay

Accessory elements

168-188 (Activation loop from InterPro)

Target domain	22-304 (Protein kinase domain)
Relief mechanism
Assay

References

Seternes OM et al. (2002) "Both binding and activation of p38 mitogen-activated protein kinase (MAPK) play essential roles in regulation of the nucleocytoplasmic distribution of MAPK-activated protein kinase 5 by cellular stress", Molecular and cellular biology, 22, 6931-45

Engel K et al. (1998) "Leptomycin B-sensitive nuclear export of MAPKAP kinase 2 is regulated by phosphorylation", The EMBO journal, 17, 3363-71

Autoinhibited structure

Activated structure

1 structures for Q8IW41

Entry ID	Method	Resolution	Chain	Position	Source
AF-Q8IW41-F1	Predicted				AlphaFoldDB

282 variants for Q8IW41

Variant ID(s)	Position	Change	Diseaes Association	Provenance
rs1290239848 CA386740186	2	S>L	No	ClinGen TOPMed
CA6793293 rs146929382	3	E>V	No	ClinGen 1000Genomes ExAC gnomAD
CA386740197 rs1224456515	4	E>A	No	ClinGen TOPMed
CA386740222 rs1314260040	7	M>T	No	ClinGen TOPMed
rs768360343 CA6793295	7	M>V	No	ClinGen ExAC gnomAD
CA386740232 rs1451884069	8	D>E	No	ClinGen gnomAD
CA6793296 rs773408629	8	D>G	No	ClinGen ExAC gnomAD
rs535440906 CA6793298	10	A>S	No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs535440906 CA6793297	10	A>T	No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs377746987 CA6793299	11	I>V	No	ClinGen ESP ExAC TOPMed gnomAD
CA6793321 rs775396958	14	T>I	No	ClinGen ExAC gnomAD
CA243670637 rs868595422	15	S>Y	No	ClinGen Ensembl
CA386744315 rs1424431370	18	E>G	No	ClinGen TOPMed gnomAD
CA243670645 rs1025180882	23	N>S	No	ClinGen gnomAD
CA243670648 rs902715144	30	A>T	No	ClinGen Ensembl
CA386744479 rs1371492489	30	A>V	No	ClinGen gnomAD
CA386744522 rs1171089014	34	G>S	No	ClinGen gnomAD
rs970954826 CA243671616	40	V>G	No	ClinGen TOPMed gnomAD
rs1239020379 CA386744916	40	V>I	No	ClinGen gnomAD
CA243671628 rs995235966	42	K>N	No	ClinGen Ensembl
rs897851325 CA243671626	42	K>Q	No	ClinGen TOPMed
CA386744947 rs768779519	45	Q>E	No	ClinGen ExAC gnomAD
rs768779519 CA6793344	45	Q>K	No	ClinGen ExAC gnomAD
CA386744950 rs1283595466	45	Q>R	No	ClinGen TOPMed
rs762069860 CA6793346	47	R>Q	No	ClinGen ExAC TOPMed gnomAD
rs201672082 CA6793345	47	R>W	No	ClinGen ESP ExAC TOPMed gnomAD
rs765561015 CA243671659	49	A>G	No	ClinGen ExAC gnomAD
CA6793347 rs765561015	49	A>V	No	ClinGen ExAC gnomAD
rs765989660 CA243671709	54	L>H	No	ClinGen ExAC
rs765989660 CA243671710	54	L>P	No	ClinGen ExAC
rs765989660 CA6793349	54	L>R	No	ClinGen ExAC
rs766126807 CA6793350	56	R>C	No	ClinGen ExAC gnomAD
rs371560016 CA6793351	56	R>H	No	ClinGen ESP ExAC TOPMed gnomAD
rs754925992 CA6793352	60	R>K	No	ClinGen ExAC gnomAD
rs1012038247 CA243671747	61	N>S	No	ClinGen Ensembl
rs1566245083 CA386745068	62	E>G	No	ClinGen Ensembl
rs1387837173 CA386745063	62	E>Q	No	ClinGen TOPMed
rs763331862 CA6793368	64	R>C	No	ClinGen ExAC TOPMed gnomAD
rs770743097 CA6793369	64	R>H	No	ClinGen ExAC TOPMed gnomAD
rs34132040 VAR_040758 CA6793370	67	M>I	No	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA386745234 rs1329807131	67	M>T	No	ClinGen gnomAD
rs1461751279 CA386745229	67	M>V	No	ClinGen gnomAD
rs572623319 CA6793371	70	A>G	No	ClinGen 1000Genomes ExAC gnomAD
rs915371429 CA243673051	70	A>S	No	ClinGen TOPMed
rs1377000480 CA386745288	71	T>A	No	ClinGen gnomAD
rs752157478 CA6793373	72	H>Q	No	ClinGen ExAC gnomAD
rs760159176 CA6793374	73	P>A	No	ClinGen ExAC gnomAD
rs994196006 CA243673078	74	N>D	No	ClinGen TOPMed gnomAD
CA386745347 rs1333349714	75	I>M	No	ClinGen Ensembl
CA386745353 rs1166566180	76	V>I	No	ClinGen TOPMed
rs1196511949 CA386745376	77	Q>H	No	ClinGen gnomAD
rs1593151863 CA386745392	78	I>M	No	ClinGen Ensembl
CA386745547 rs1458141829	86	V>I	No	ClinGen gnomAD
CA6793377 rs753486641	87	Q>R	No	ClinGen ExAC gnomAD
CA6793378 rs756919484	88	F>L	No	ClinGen ExAC gnomAD
rs1026550110 CA243673150	90	H>R	No	ClinGen TOPMed
CA243673158 rs952340486	93	S>G	No	ClinGen TOPMed
CA6793380 rs543312049	93	S>N	No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA243673167 rs984945842	93	S>R	No	ClinGen gnomAD
CA6793381 rs755471766	94	P>A	No	ClinGen ExAC TOPMed gnomAD
rs781758975 CA6793382	94	P>L	No	ClinGen ExAC gnomAD
rs868642182 CA243673876	101	V>L	No	ClinGen TOPMed gnomAD
CA386745849 rs1423932138	102	M>I	No	ClinGen gnomAD
CA386745870 rs1478313022	104	M>L	No	ClinGen TOPMed gnomAD
rs1172374513 CA386745917	106	E>D	No	ClinGen gnomAD
CA243673877 rs1012399660	107	G>A	No	ClinGen TOPMed gnomAD
CA386745921 rs1206432262	107	G>R	No	ClinGen TOPMed
rs369792889 CA6793394	108	G>V	No	ClinGen ESP ExAC gnomAD
CA386745986 rs1398262420	112	H>R	No	ClinGen gnomAD
CA6793396 rs771954889	113	R>G	No	ClinGen ExAC gnomAD
rs1357302824 CA386746020	115	S>G	No	ClinGen TOPMed
rs1222662740 CA386746041	116	Q>L	No	ClinGen TOPMed gnomAD
rs1272927224 CA386746046	117	H>N	No	ClinGen gnomAD
rs1347003500 CA386746054	117	H>R	No	ClinGen gnomAD
rs532582869 CA6793398	118	R>Q	No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1283501108 CA386746064	118	R>W	No	ClinGen TOPMed gnomAD
CA386746112 rs1218167230	121	T>I	No	ClinGen gnomAD
rs753361806 CA6793400	125	A>G	No	ClinGen ExAC gnomAD
CA386746180 rs1376324572	126	S>T	No	ClinGen gnomAD
rs1173630962 CA386746199	127	Q>H	No	ClinGen gnomAD
rs761463408 CA6793401	127	Q>K	No	ClinGen ExAC gnomAD
rs576655529 CA6793402	128	V>L	No	ClinGen 1000Genomes ExAC gnomAD
CA386746216 rs750138450	129	T>A	No	ClinGen ExAC gnomAD
CA243673959 rs763976548	129	T>I	No	ClinGen Ensembl
CA6793403 rs750138450	129	T>P	No	ClinGen ExAC gnomAD
rs776078907 CA6793420	135	A>V	No	ClinGen ExAC gnomAD
CA6793421 rs761251796	137	R>Q	No	ClinGen ExAC TOPMed gnomAD
CA243675034 rs1047472716	137	R>W	No	ClinGen Ensembl
rs969676659 CA243675042	138	H>D	No	ClinGen TOPMed
rs1393148438 CA386746880	140	H>R	No	ClinGen gnomAD
rs772734420 CA6793423	142	L>S	No	ClinGen ExAC TOPMed gnomAD
CA386746922 rs368919807	143	N>K	No	ClinGen ESP ExAC TOPMed gnomAD
rs199721843 CA6793425	144	I>L	No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA386746936 rs1309324159	144	I>M	No	ClinGen gnomAD
CA6793426 rs199721843	144	I>V	No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1341844200 CA386746945	145	A>V	No	ClinGen gnomAD
rs1282723240 CA386746991	149	L>F	No	ClinGen TOPMed gnomAD
CA386747043 rs1266786306	153	N>D	No	ClinGen gnomAD
rs1356683282 CA386747058	154	L>V	No	ClinGen TOPMed gnomAD
rs1255056166 CA386747110	158	D>H	No	ClinGen TOPMed
CA386747125 rs1212091890	159	N>D	No	ClinGen TOPMed
CA6793430 rs757256612	160	S>F	No	ClinGen ExAC gnomAD
rs1456809669 CA386747155	161	L>S	No	ClinGen TOPMed gnomAD
CA386747244 rs1464520138	163	A>S	No	ClinGen gnomAD
CA386747275 rs1402235314	165	V>A	No	ClinGen gnomAD
CA6793446 rs762443184	165	V>L	No	ClinGen ExAC gnomAD
rs371243208 CA6793447	167	L>F	No	ClinGen ESP ExAC TOPMed gnomAD
CA386747428 rs1295895550	178	G>D	No	ClinGen gnomAD
rs1469564616 CA386747440	180	L>V	No	ClinGen TOPMed
rs775943469 CA6793448	181	M>K	No	ClinGen ExAC gnomAD
rs1251514051 CA386747462	183	P>S	No	ClinGen TOPMed
rs1213519352 CA386747472	184	Q>H	No	ClinGen TOPMed
rs1593172335 CA386747903	194	V>G	No	ClinGen Ensembl
rs947286159 CA243682472	197	A>V	No	ClinGen TOPMed gnomAD
CA6793470 rs762163257	198	Q>*	No	ClinGen ExAC gnomAD
CA386747934 rs1176204266	199	R>K	No	ClinGen gnomAD
rs372088425 CA6793471	203	K>R	No	ClinGen ESP ExAC TOPMed gnomAD
rs1369989238 CA386747974	204	E>D	No	ClinGen TOPMed
rs1049589744 CA243682505	206	S>Y	No	ClinGen Ensembl
CA386747993 rs1163585299	207	G>A	No	ClinGen gnomAD
CA386748024 rs1273365740	211	T>S	No	ClinGen TOPMed
rs751526420 CA6793474	213	P>L	No	ClinGen ExAC TOPMed gnomAD
CA386748050 rs751526420	213	P>R	No	ClinGen ExAC TOPMed gnomAD
rs1372322864 CA386748066	214	T>M	No	ClinGen gnomAD
rs780782397 CA6793477	217	T>P	No	ClinGen ExAC gnomAD
CA386748134 rs1224409918	219	N>K	No	ClinGen gnomAD
CA386748150 rs1289347797	220	K>N	No	ClinGen gnomAD
CA243682557 rs1019294575	220	K>R	No	ClinGen Ensembl
CA386748391 rs1285147385	224	L>F	No	ClinGen TOPMed
rs1045094325 CA243684692	224	L>V	No	ClinGen TOPMed
CA607604136 rs1235292061	225	W>*	No	ClinGen gnomAD
rs1566269359 CA386748429	230	I>T	No	ClinGen Ensembl
rs1017284090 CA243684745	231	I>S	No	ClinGen Ensembl
CA243684756 rs900180178	232	Y>C	No	ClinGen TOPMed
CA386748441 rs900180178	232	Y>F	No	ClinGen TOPMed
CA386748444 rs1477664534	233	V>M	No	ClinGen gnomAD
CA6793496 rs755904783	234	M>V	No	ClinGen ExAC gnomAD
rs1566269482 CA386748473	237	G>R	No	ClinGen Ensembl
CA6793499 rs757276097	244	K>R	No	ClinGen ExAC TOPMed gnomAD
CA6793501 rs745405567	248	R>Q	No	ClinGen ExAC gnomAD
rs1340138794 CA386748551	248	R>W	No	ClinGen TOPMed gnomAD
rs1402119792 CA386748558	249	T>S	No	ClinGen TOPMed
CA386748595 rs1218523837	254	M>I	No	ClinGen gnomAD
rs1008088417 CA243684821	255	R>*	No	ClinGen TOPMed
CA386748599 rs1481045832	255	R>Q	No	ClinGen TOPMed
rs1314063555 CA386748618	258	I>V	No	ClinGen gnomAD
rs779735297 CA6793503	259	M>L	No	ClinGen ExAC gnomAD
rs746682798 CA6793504	259	M>T	No	ClinGen ExAC gnomAD
CA243684838 rs74739940	262	S>R	No	ClinGen Ensembl
CA6793505 rs770180691	264	E>A	No	ClinGen ExAC TOPMed
CA386748712 rs1221723068	271	S>R	No	ClinGen TOPMed gnomAD
CA6793507 rs773577595	272	Q>E	No	ClinGen ExAC TOPMed gnomAD
rs963680187 CA243684872	274	S>P	No	ClinGen TOPMed gnomAD
CA243684874 rs745558333	277	A>L	No	ClinGen Ensembl
rs1475960758 CA386748756	277	A>T	No	ClinGen gnomAD
CA6793509 rs749728532	278	K>R	No	ClinGen ExAC gnomAD
rs749728532 CA243684881	278	K>T	No	ClinGen ExAC gnomAD
rs1423694212 CA386748768	279	D>N	No	ClinGen gnomAD
rs1174403051 CA386748784	281	V>L	No	ClinGen gnomAD
rs1398438731 CA386748789	282	R>G	No	ClinGen gnomAD
rs34843470 CA6793511 VAR_040759	282	R>K	No	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs201245512 CA6793512	283	K>R	No	ClinGen ESP ExAC gnomAD
rs1593180524 CA386748837	287	V>G	No	ClinGen Ensembl
rs1338368828 CA386748842	288	K>I	No	ClinGen Ensembl
rs564949554 CA6793523	289	P>L	No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs564949554 CA386748849	289	P>R	No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1028263034 CA243686328	289	P>S	No	ClinGen TOPMed
rs778071951 CA6793525	291	E>D	No	ClinGen ExAC gnomAD
CA243686343 rs1000278909	292	R>I	No	ClinGen TOPMed
rs771330462 CA6793527	296	E>K	No	ClinGen ExAC gnomAD
CA243686370 rs1033553141	297	G>R	No	ClinGen TOPMed
CA386748901 rs1279713733	297	G>V	No	ClinGen gnomAD
rs746425611 CA6793529	301	H>Y	No	ClinGen ExAC gnomAD
CA386748931 rs1209613106	302	P>A	No	ClinGen gnomAD
rs775448365 CA6793531	304	L>H	No	ClinGen ExAC gnomAD
CA6793532 rs373594164	305	N>S	No	ClinGen ESP ExAC TOPMed gnomAD
rs764446347 CA6793533	306	S>F	No	ClinGen ExAC gnomAD
CA6793534 rs776521475	307	T>I	No	ClinGen ExAC TOPMed gnomAD
rs765163892 CA6793536	308	E>K	No	ClinGen ExAC TOPMed gnomAD
CA386749028 rs1161223991	309	A>V	No	ClinGen TOPMed gnomAD
CA6793538 rs758280140	312	N>K	No	ClinGen ExAC TOPMed gnomAD
rs1330517983 CA386749064	312	N>S	No	ClinGen gnomAD
rs765846409 CA6793539	315	P>S	No	ClinGen ExAC gnomAD
CA6793540 rs370054317	320	M>I	No	ClinGen ExAC gnomAD
CA6793541 rs754609169	321	M>T	No	ClinGen ExAC TOPMed gnomAD
rs1285624494 CA386749142	323	K>T	No	ClinGen gnomAD
rs1593184279 CA386749163	324	A>V	No	ClinGen Ensembl
CA386749198 rs1253588411	330	Q>*	No	ClinGen TOPMed
CA243688409 rs367573915	333	H>Y	No	ClinGen ESP TOPMed gnomAD
rs80319832 CA386749229	334	A>G	No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs770704768 CA6793559	334	A>T	No	ClinGen ExAC gnomAD
rs80319832 CA6793560	334	A>V	No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1198816659 CA386749232	335	E>*	No	ClinGen TOPMed gnomAD
CA386749236 rs1259860566	335	E>D	No	ClinGen gnomAD
rs1198816659 CA386749230	335	E>K	No	ClinGen TOPMed gnomAD
rs755773338 CA386749247	337	L>V	No	ClinGen ExAC gnomAD
rs370196787 CA6793563	339	N>D	No	ClinGen ESP ExAC TOPMed gnomAD
rs374501499 CA6793564	339	N>K	No	ClinGen ESP ExAC TOPMed gnomAD
CA386749265 rs1430116411	340	M>L	No	ClinGen gnomAD
CA386749274 rs1170979391	341	R>G	No	ClinGen TOPMed gnomAD
CA386749303 rs1434860725	344	D>E	No	ClinGen TOPMed
CA6793566 rs372410297	353	H>Q	No	ClinGen ESP ExAC gnomAD
rs944985806 CA243688471	356	N>S	No	ClinGen TOPMed gnomAD
rs1418760231 CA386749395	358	P>L	No	ClinGen gnomAD
rs1343853552 CA386749390	358	P>S	No	ClinGen gnomAD
CA243688492 rs1042083154	360	L>P	No	ClinGen TOPMed
rs747593345 CA6793567	361	R>W	No	ClinGen ExAC TOPMed gnomAD
rs768852344 CA6793568	365	L>I	No	ClinGen ExAC gnomAD
CA6793570 rs376460255	366	L>I	No	ClinGen ESP ExAC TOPMed gnomAD
CA386749443 rs1477039622	366	L>P	No	ClinGen TOPMed
CA386749440 rs376460255	366	L>V	No	ClinGen ESP ExAC TOPMed gnomAD
CA386749463 rs1593184830	368	T>P	No	ClinGen Ensembl
rs781378938 CA6793589	370	P>A	No	ClinGen ExAC TOPMed gnomAD
rs756265404 CA6793590	370	P>R	No	ClinGen ExAC gnomAD
CA6793588 rs781378938	370	P>S	No	ClinGen ExAC TOPMed gnomAD
rs977731207 CA243688604	371	K>T	No	ClinGen TOPMed gnomAD
CA386749496 rs1319023554	373	S>G	No	ClinGen gnomAD
rs1264685541 CA386749514	375	Y>C	No	ClinGen gnomAD
rs770615564 CA6793593	378	D>N	No	ClinGen ExAC TOPMed gnomAD
rs770615564 CA6793594	378	D>Y	No	ClinGen ExAC TOPMed gnomAD
CA6793595 rs373010591	379	H>L	No	ClinGen ESP ExAC TOPMed gnomAD
CA6793597 rs774935495	380	E>G	No	ClinGen ExAC gnomAD
rs375055742 CA6793596	380	E>K	No	ClinGen ESP ExAC gnomAD
CA386749567 rs1368209688	383	A>T	No	ClinGen gnomAD
rs1328444434 CA386749573	384	E>K	No	ClinGen TOPMed gnomAD
rs1566277268 CA386749594	387	N>D	No	ClinGen Ensembl
CA6793600 rs370061191	387	N>S	No	ClinGen ESP ExAC TOPMed gnomAD
rs766595699 CA6793602	388	V>I	No	ClinGen ExAC gnomAD
CA6793603 rs751979756	394	R>*	No	ClinGen ExAC gnomAD
CA386749657 rs1555274813	396	V>A	No	ClinGen Ensembl
rs1312314684 CA386749682	400	C>Y	No	ClinGen gnomAD
CA386749700 rs948859508	403	P>S	No	ClinGen TOPMed gnomAD
CA243688700 rs948859508	403	P>T	No	ClinGen TOPMed gnomAD
rs1234923809 CA386749705	404	Q>K	No	ClinGen gnomAD
rs537267303 CA6793605	404	Q>R	No	ClinGen ExAC TOPMed gnomAD
rs1457317996 CA386749718	406	G>S	No	ClinGen gnomAD
rs542016883 CA6793606	408	G>*	No	ClinGen 1000Genomes ExAC gnomAD
rs761306955 CA6793620	410	N>S	No	ClinGen ExAC gnomAD
rs1475308475 CA386749773	411	E>D	No	ClinGen gnomAD
rs769507267 CA6793621	414	K>E	No	ClinGen ExAC gnomAD
rs1410594700 CA386749800	415	L>Q	No	ClinGen gnomAD
CA6793622 rs377263347	416	N>S	No	ClinGen ESP ExAC TOPMed gnomAD
rs1313740058 CA386749831	419	M>I	No	ClinGen gnomAD
CA6793623 rs759947497	419	M>V	No	ClinGen ExAC gnomAD
rs1339556329 CA386749869	424	K>N	No	ClinGen gnomAD
CA243689233 rs768789428	425	Y>H	No	ClinGen Ensembl
CA6793625 rs753238884	427	R>W	No	ClinGen ExAC gnomAD
CA386749909 rs1218097652	430	K>T	No	ClinGen gnomAD
CA6793628 rs376033235	434	D>E	No	ClinGen ESP ExAC TOPMed gnomAD
rs757374281 CA6793629	435	T>A	No	ClinGen ExAC gnomAD
rs1284870764 CA386749941	435	T>N	No	ClinGen gnomAD
rs1284870764 CA386749942	435	T>S	No	ClinGen gnomAD
CA386749945 rs1446721817	436	L>M	No	ClinGen gnomAD
CA386749990 rs1229038285	442	N>H	No	ClinGen TOPMed
rs1244333538 CA386749995	442	N>S	No	ClinGen gnomAD
CA243648696 rs199636436	444	R>C	No	ClinGen 1000Genomes TOPMed gnomAD
rs199636436 CA386750016	444	R>G	No	ClinGen 1000Genomes TOPMed gnomAD
rs150495619 CA6793639	444	R>H	No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs199636436 CA243648694	444	R>S	No	ClinGen 1000Genomes TOPMed gnomAD
rs1468841679 CA386750022	445	G>E	No	ClinGen gnomAD
CA386750024 rs1468841679	445	G>V	No	ClinGen gnomAD
rs1566282993 CA386750035	447	T>S	No	ClinGen Ensembl
CA386750046 rs1228074468	448	D>E	No	ClinGen TOPMed
rs1160536703 CA386750048	449	K>E	No	ClinGen gnomAD
rs1460729373 CA386750059	450	V>A	No	ClinGen TOPMed gnomAD
CA243648698 rs890366982	451	D>H	No	ClinGen Ensembl
rs1010565030 CA386750068	452	R>*	No	ClinGen TOPMed gnomAD
rs1010565030 CA243648702	452	R>G	No	ClinGen TOPMed gnomAD
rs1396670521 CA386750069	452	R>Q	No	ClinGen gnomAD
rs867595256 CA243648703	456	A>T	No	ClinGen Ensembl
CA386750120 rs1441002422	460	K>R	No	ClinGen TOPMed gnomAD
rs1333602215 CA386750140	463	I>L	No	ClinGen TOPMed gnomAD
rs1279804064 CA386750156	465	E>A	No	ClinGen gnomAD
rs1240686676 CA386750153	465	E>K	No	ClinGen gnomAD
CA386750174 rs1231966751	467	T>I	No	ClinGen gnomAD
rs775998589 CA6793644	468	T>M	No	ClinGen ExAC gnomAD
rs754354622 CA6793647	469	S>C	No	ClinGen ExAC gnomAD
rs202021541 CA243648740	471	E>D	No	ClinGen Ensembl
rs773696015 CA243648737	471	E>K	No	ClinGen TOPMed gnomAD
CA386750201 rs1566283323	472	S>A	No	ClinGen Ensembl
rs1593191613 CA386750208	473	Q>P	No	ClinGen Ensembl
rs1456426607 CA386750214	474	Q>Q	No	ClinGen TOPMed

No associated diseases with Q8IW41

3 regional properties for Q8IW41

Type	Name	Position	InterPro Accession
domain	Protein kinase domain	20 - 281	IPR000719
active_site	Serine/threonine-protein kinase, active site	138 - 150	IPR008271
binding_site	Protein kinase, ATP binding site	26 - 49	IPR017441

Functions

		Description
EC Number	2.7.11.1	Protein-serine/threonine kinases
Subcellular Localization	Cytoplasm Nucleus	Translocates to the cytoplasm following phosphorylation and activation Interaction with ERK3/MAPK6 or ERK4/MAPK4 and phosphorylation at Thr-182, activates the protein kinase activity, followed by translocation to the cytoplasm Phosphorylation by PKA/PRKACA at Ser-115 also induces nuclear export
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.
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.

9 GO annotations of molecular function

Name	Definition
ATP binding	Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
calcium-dependent protein serine/threonine kinase activity	Calcium-dependent catalysis of the reactions: ATP + a protein serine = ADP + protein serine phosphate; and ATP + a protein threonine = ADP + protein threonine phosphate.
calmodulin binding	Binding to calmodulin, a calcium-binding protein with many roles, both in the calcium-bound and calcium-free states.
calmodulin-dependent protein kinase activity	Calmodulin-dependent catalysis of the reactions: ATP + a protein serine = ADP + protein serine phosphate; and ATP + a protein threonine = ADP + protein threonine phosphate.
MAP kinase kinase activity	Catalysis of the concomitant phosphorylation of threonine (T) and tyrosine (Y) residues in a Thr-Glu-Tyr (TEY) thiolester sequence in a MAP kinase (MAPK) substrate.
mitogen-activated protein kinase binding	Binding to a mitogen-activated protein kinase.
p53 binding	Binding to one of the p53 family of proteins.
protein serine kinase activity	Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate.
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
cellular senescence	A cell aging process stimulated in response to cellular stress, whereby normal cells lose the ability to divide through irreversible cell cycle arrest.
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 TOR signaling	Any process that stops, prevents, or reduces the frequency, rate or extent of TOR signaling.
peptidyl-serine phosphorylation	The phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine.
positive regulation of telomerase activity	Any process that activates or increases the frequency, rate or extent of telomerase activity, the catalysis of the reaction: deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).
positive regulation of telomere capping	Any process that activates or increases the frequency, rate or extent of telomere capping.
positive regulation of telomere maintenance via telomerase	Any process that activates or increases the frequency, rate or extent of the addition of telomeric repeats by telomerase.
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).
Ras protein signal transduction	The series of molecular signals within the cell that are mediated by a member of the Ras superfamily of proteins switching to a GTP-bound active state.
regulation of signal transduction by p53 class mediator	Any process that modulates the frequency, rate or extent of signal transduction by p53 class mediator.
regulation of translation	Any process that modulates the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of proteins by the translation of mRNA or circRNA.
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.
stress-induced premature senescence	A cellular senescence process associated with the dismantling of a cell as a response to environmental factors such as hydrogen peroxide or X-rays.

10 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q3SYZ2	MAPKAPK3	MAP kinase-activated protein kinase 3	Bos taurus (Bovine)	SS
P49071	MAPk-Ak2	MAP kinase-activated protein kinase 2	Drosophila melanogaster (Fruit fly)	SS
Q16644	MAPKAPK3	MAP kinase-activated protein kinase 3	Homo sapiens (Human)	SS
P49137	MAPKAPK2	MAP kinase-activated protein kinase 2	Homo sapiens (Human)	EV
Q16566	CAMK4	Calcium/calmodulin-dependent protein kinase type IV	Homo sapiens (Human)	SS
P49138	Mapkapk2	MAP kinase-activated protein kinase 2	Mus musculus (Mouse)	EV
Q3UMW7	Mapkapk3	MAP kinase-activated protein kinase 3	Mus musculus (Mouse)	SS
O54992	Mapkapk5	MAP kinase-activated protein kinase 5	Mus musculus (Mouse)	EV
Q66H84	Mapkapk3	MAP kinase-activated protein kinase 3	Rattus norvegicus (Rat)	SS
Q965G5	mak-2	MAP kinase-activated protein kinase mak-2	Caenorhabditis elegans	SS

10	20	30	40	50	60
MSEESDMDKA	IKETSILEEY	SINWTQKLGA	GISGPVRVCV	KKSTQERFAL	KILLDRPKAR
70	80	90	100	110	120
NEVRLHMMCA	THPNIVQIIE	VFANSVQFPH	ESSPRARLLI	VMEMMEGGEL	FHRISQHRHF
130	140	150	160	170	180
TEKQASQVTK	QIALALRHCH	LLNIAHRDLK	PENLLFKDNS	LDAPVKLCDF	GFAKIDQGDL
190	200	210	220	230	240
MTPQFTPYYV	APQVLEAQRR	HQKEKSGIIP	TSPTPYTYNK	SCDLWSLGVI	IYVMLCGYPP
250	260	270	280	290	300
FYSKHHSRTI	PKDMRRKIMT	GSFEFPEEEW	SQISEMAKDV	VRKLLKVKPE	ERLTIEGVLD
310	320	330	340	350	360
HPWLNSTEAL	DNVLPSAQLM	MDKAVVAGIQ	QAHAEQLANM	RIQDLKVSLK	PLHSVNNPIL
370	380	390	400	410	420
RKRKLLGTKP	KDSVYIHDHE	NGAEDSNVAL	EKLRDVIAQC	ILPQAGKGEN	EDEKLNEVMQ
430	440	450	460	470
EAWKYNRECK	LLRDTLQSFS	WNGRGFTDKV	DRLKLAEIVK	QVIEEQTTSH	ESQ