AiPD: Autoinhibited Protein Database

Q16644

Gene name	MAPKAPK3
Protein name	MAP kinase-activated protein kinase 3
Names	MAPK-activated protein kinase 3 , MAPKAP kinase 3 , MAPKAP-K3 , MAPKAPK-3 , MK-3 , EC 2.7.11.1 , Chromosome 3p kinase , 3pK
Species	Homo sapiens (Human)
KEGG Pathway	hsa:7867
EC number	2.7.11.1: Protein-serine/threonine kinases
Protein Class

Descriptions

MAPKAPK2 is a stress-activated serine/threonine-protein kinase. MAPKAPK2, contains an 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 MAPKAPK2 prevents exportin binding to NES. Phosphorylation of MAPKAPK2 at threonine 317 induces a conformational change, thus unmasks and increases the activity of NES.

Autoinhibitory domains (AIDs)

311-331 (Autoinhibitory A-helix) SS

Target domain	4-304 (Protein kinase domain)
Relief mechanism	PTM
Assay

AID

311-331 (Autoinhibitory A-helix)

Target domain

4-304 (Protein kinase domain)

Relief mechanism

PTM (Phosphorylation at Thr-317)

Assay

Accessory elements

186-207 (Activation loop from InterPro)

Target domain	43-304 (Protein kinase domain)
Relief mechanism
Assay

186-207 (Activation loop from InterPro)

Target domain	43-304 (Protein kinase domain)
Relief mechanism
Assay

References

Yeon JH et al. (2016) "Systems-wide Identification of cis-Regulatory Elements in Proteins", Cell systems, 2, 89-100

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

6 structures for Q16644

Entry ID	Method	Resolution	Chain	Position	Source
3FHR	X-ray	190 A	A	33-349	PDB
3FXW	X-ray	200 A	A	33-349	PDB
3R1N	X-ray	209 A	A	33-349	PDB
3SHE	X-ray	225 A	A	33-349	PDB
7NRB	X-ray	190 A	A	33-349	PDB
AF-Q16644-F1	Predicted				AlphaFoldDB

296 variants for Q16644

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
RCV000240674 rs886037913 CA10586363 VAR_077085	173	L>P	Patterned macular dystrophy 3 MDPT3; decreased localization to the nucleus [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV002562452 RCV001218305 rs2033320923	323	E>K	Inborn genetic diseases [ClinVar]	Yes	ClinVar dbSNP
CA352961285 rs1204460425	2	D>H		No	ClinGen gnomAD
rs368742045 CA2420130	3	G>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA2420131 rs763518219	3	G>V		No	ClinGen ExAC gnomAD
rs766895982 CA2420132	4	E>Q		No	ClinGen ExAC TOPMed gnomAD
rs751937158 CA2420133	5	T>I		No	ClinGen ExAC gnomAD
rs372994175 CA74652787	9	Q>*		No	ClinGen ESP
rs955808780 CA352961332	9	Q>P		No	ClinGen TOPMed
CA74652788 rs955808780	9	Q>R		No	ClinGen TOPMed
CA2420135 rs149349769	10	G>E		No	ClinGen ExAC TOPMed gnomAD
TCGA novel	10	G>L	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1183625080 CA352961338	10	G>W		No	ClinGen gnomAD
CA2420139 rs777789251	11	G>A		No	ClinGen ExAC TOPMed gnomAD
CA2420137 TCGA novel rs147044454 RCV001201570	11	G>C	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA2420138 rs777789251	11	G>D		No	ClinGen ExAC TOPMed gnomAD
rs147044454 CA352961342	11	G>R		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
TCGA novel	12	P>T	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1042257886 CA74652855	15	P>L		No	ClinGen TOPMed
rs778722098 CA2420141	16	P>L		No	ClinGen ExAC TOPMed gnomAD
rs745672353 CA2420143	18	A>E		No	ClinGen ExAC TOPMed gnomAD
rs745672353 CA2420142	18	A>V		No	ClinGen ExAC TOPMed gnomAD
CA352961384 rs1238369685	19	P>H		No	ClinGen gnomAD
CA2420144 rs779772290	19	P>T		No	ClinGen ExAC gnomAD
CA352961389 rs1286539544	20	G>S		No	ClinGen gnomAD
CA352961394 rs768248070	21	G>*		No	ClinGen ExAC gnomAD
CA352961395 rs776254646	21	G>E		No	ClinGen ExAC TOPMed gnomAD
CA2420146 rs768248070	21	G>R		No	ClinGen ExAC gnomAD
CA2420147 rs776254646	21	G>V		No	ClinGen ExAC TOPMed gnomAD
CA352961401 rs1487407777	22	P>L		No	ClinGen gnomAD
TCGA novel	25	G>C	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA352961422 rs1436891964	26	G>S		No	ClinGen gnomAD
rs375412266 CA2420150	28	P>A		No	ClinGen ExAC TOPMed gnomAD
rs759957245 CA2420152	28	P>L		No	ClinGen ExAC TOPMed
CA2420153 rs759957245	28	P>R		No	ClinGen ExAC TOPMed
VAR_040755 COSM3408768 CA352961435 rs375412266	28	P>S	Variant assessed as Somatic; 0.0 impact. central_nervous_system a glioblastoma multiforme sample; somatic mutation [NCI-TCGA, Cosmic, UniProt]	No	ClinGen cosmic curated UniProt ExAC NCI-TCGA TOPMed dbSNP gnomAD
CA352961439 rs764208748	29	G>A		No	ClinGen ExAC TOPMed gnomAD
CA2420156 rs764208748	29	G>E		No	ClinGen ExAC TOPMed gnomAD
rs373642329 CA2420154	29	G>R		No	ClinGen ESP ExAC gnomAD
RCV001206489 rs373642329 CA2420155	29	G>W		No	ClinGen ClinVar ESP ExAC dbSNP gnomAD
CA352961443 rs1027886642	30	G>A		No	ClinGen TOPMed gnomAD
CA74652989 rs1027886642	30	G>E		No	ClinGen TOPMed gnomAD
CA352961451 rs1456669605	32	R>W		No	ClinGen gnomAD
CA2420159 rs368714447	35	K>M		No	ClinGen ESP ExAC TOPMed gnomAD
TCGA novel	35	K>Q	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA2420160 rs368714447	35	K>R		No	ClinGen ESP ExAC TOPMed gnomAD
rs1041696500 CA74653011	36	K>E		No	ClinGen TOPMed
rs1397398299 CA352961489	37	Y>*		No	ClinGen gnomAD
rs1391053347 CA352961492	38	A>P		No	ClinGen gnomAD
rs1391053347 CA352961491	38	A>S		No	ClinGen gnomAD
CA2420162 rs779678577	39	V>E		No	ClinGen ExAC TOPMed gnomAD
CA2420163 rs746700451	40	T>I		No	ClinGen ExAC TOPMed gnomAD
CA2420166 rs372238062	41	D>N		No	ClinGen ESP ExAC gnomAD
CA2420167 rs372238062	41	D>Y		No	ClinGen ESP ExAC gnomAD
rs1338275124 CA352961516	42	D>G		No	ClinGen gnomAD
rs78528472 CA74653090	42	D>N		No	ClinGen gnomAD
rs78528472 CA352961513	42	D>Y		No	ClinGen gnomAD
rs1239435558 CA352961563	48	Q>H		No	ClinGen gnomAD
CA352961559 rs1375464774	48	Q>P		No	ClinGen TOPMed
CA352961578 rs1485734849	51	G>D		No	ClinGen gnomAD
rs759919624 CA2420170	53	G>D		No	ClinGen ExAC gnomAD
CA2420169 rs759919624	53	G>V		No	ClinGen ExAC gnomAD
rs1281857290 CA352961606	56	G>S		No	ClinGen TOPMed
CA352961609 rs1479819710	56	G>V		No	ClinGen gnomAD
TCGA novel	60	E>K	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs764298483 CA2420173	60	E>Q		No	ClinGen ExAC gnomAD
CA2420174 rs753977197	61	C>R		No	ClinGen ExAC gnomAD
CA352961661 rs1446697428	64	R>Q		No	ClinGen TOPMed
rs1377334631 CA352961660	64	R>W		No	ClinGen gnomAD
rs1302364943 CA352961666	65	R>C		No	ClinGen gnomAD
rs35362731 CA2420176	65	R>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
TCGA novel	65	R>S	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA352961669 rs750410127	66	T>A		No	ClinGen ExAC TOPMed gnomAD
CA2420177 rs750410127	66	T>S		No	ClinGen ExAC TOPMed gnomAD
CA352961684 RCV001065640 rs1296010021	68	Q>R		No	ClinGen ClinVar dbSNP gnomAD
rs758222981 CA2420178	69	K>R		No	ClinGen ExAC gnomAD
rs1283225219 CA352925710	75	L>P		No	ClinGen TOPMed
CA352925717 rs1422921375	76	Y>*		No	ClinGen TOPMed gnomAD
CA352925716 rs141282634	76	Y>C		No	ClinGen ESP gnomAD
CA74623782 rs141282634	76	Y>F		No	ClinGen ESP gnomAD
CA352925713 rs1477536792	76	Y>H		No	ClinGen Ensembl
CA2420200 rs752419500	81	A>V		No	ClinGen ExAC gnomAD
rs777383707 CA2420202	82	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs755805527 CA2420201	82	R>W		No	ClinGen ExAC gnomAD
rs1159952352 CA352925772	84	E>D		No	ClinGen gnomAD
TCGA novel	86	D>N	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs2033150698 RCV001238607	86	D>Y		No	ClinVar dbSNP
CA2420203 rs748745169	87	H>L	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
rs748745169 CA352925792	87	H>R		No	ClinGen ExAC gnomAD
CA352925790 rs1387729630	87	H>Y		No	ClinGen TOPMed gnomAD
rs575368406 CA2420204	91	A>T		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
RCV001232934 rs2033151576	93	G>D		No	ClinVar dbSNP
CA352925840 rs1291483185	94	G>A		No	ClinGen gnomAD
RCV001340980 CA2420207 rs143980632	94	G>S		No	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
rs77366433 CA74623870	96	H>P		No	ClinGen Ensembl
CA352925936 rs1375109467	100	I>T		No	ClinGen gnomAD
rs1188918209 CA352926008	104	Y>F		No	ClinGen TOPMed
VAR_040756	105	E>A	an ovarian endometrioid sample; somatic mutation [UniProt]	No	UniProt
rs867974734 CA352926076 CA74623896	107	M>I		No	ClinGen TOPMed gnomAD
CA352926065 rs1559488884	107	M>R		No	ClinGen Ensembl
rs769899324 CA2420210	107	M>V		No	ClinGen ExAC TOPMed gnomAD
CA2420211 rs773395153	109	H>Y		No	ClinGen ExAC gnomAD
rs762952384 CA2420212	110	G>D		No	ClinGen ExAC TOPMed gnomAD
rs1245151932 CA352926153	111	K>R		No	ClinGen gnomAD
rs200955406 CA2420214	112	R>C		No	ClinGen ExAC gnomAD
CA2420215 rs759497061	112	R>H	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
rs1471567769 CA352926248	116	I>M		No	ClinGen gnomAD
CA352926232 rs1260815780	116	I>V		No	ClinGen TOPMed
CA74623925 rs1032039030 RCV001346405	117	I>T		No	ClinGen ClinVar Ensembl dbSNP
rs1411074539 CA352926284	118	M>V		No	ClinGen TOPMed gnomAD
CA74623952 rs1029588764	120	C>G		No	ClinGen TOPMed gnomAD
rs1559488925 CA352926350	120	C>Y		No	ClinGen Ensembl
rs1576012847 CA352926619	121	M>I		No	ClinGen Ensembl
CA352926637 rs1258094000	122	E>A		No	ClinGen gnomAD
rs1234361182 CA352926631	122	E>K		No	ClinGen TOPMed
rs1323850753 CA352926660	123	G>S		No	ClinGen TOPMed
rs770936440 CA2420230	126	L>V		No	ClinGen ExAC gnomAD
COSM584380 rs199541398 CA2420233	129	R>S	lung [Cosmic]	No	ClinGen cosmic curated 1000Genomes ESP ExAC TOPMed gnomAD
rs775483656 CA2420234	132	E>K		No	ClinGen ExAC gnomAD
CA2420235 rs760401804	133	R>C		No	ClinGen ExAC gnomAD
rs763883941 CA2420236	133	R>H		No	ClinGen ExAC gnomAD
TCGA novel	134	G>D	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs761480203 CA2420238	135	D>N	Variant assessed as Somatic; 0.0001386 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
rs761480203 CA352927051	135	D>Y		No	ClinGen ExAC TOPMed gnomAD
rs1282787052 CA352927287	142	E>*		No	ClinGen gnomAD
rs754225374 CA2420266	148	R>Q	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
CA2420265 rs765824190 COSM236156	148	R>W	lung autonomic_ganglia [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs935316501 CA74625195	149	D>G		No	ClinGen TOPMed gnomAD
CA352927710 rs935316501	149	D>V		No	ClinGen TOPMed gnomAD
RCV001040833 rs757611175 CA2420267	150	I>T		No	ClinGen ClinVar ExAC dbSNP gnomAD
CA2420268 rs370373095	152	T>A		No	ClinGen ESP ExAC TOPMed gnomAD
CA352927838 rs1410718421	153	A>T		No	ClinGen gnomAD
rs746022177 CA2420269	157	L>R		No	ClinGen ExAC gnomAD
CA542863216 rs1458245905	158	H>F		No	ClinGen gnomAD
CA2420271 rs77859836	158	H>P		No	ClinGen ExAC gnomAD
rs1386988451 CA352928024	158	H>Y		No	ClinGen gnomAD
rs1324508879 CA352928058	159	S>G		No	ClinGen gnomAD
CA2420272 rs746971211	160	H>Y		No	ClinGen ExAC TOPMed gnomAD
CA352928197 rs1227782579	162	I>T		No	ClinGen gnomAD
CA2420274 rs776361214	162	I>V		No	ClinGen ExAC gnomAD
CA352928217 rs1265975887	163	A>D		No	ClinGen TOPMed gnomAD
CA2420275 rs747984036	164	H>Y		No	ClinGen ExAC gnomAD
CA74625237 rs757882175	165	R>*		No	ClinGen gnomAD
CA352928273 rs1266182170	165	R>Q	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
CA352928324 rs1363506925	167	V>I		No	ClinGen TOPMed gnomAD
rs769508657 CA2420276	168	K>Q		No	ClinGen ExAC gnomAD
CA352929807 rs1185560872	169	P>A		No	ClinGen TOPMed
CA2420297 rs773801086	173	L>F		No	ClinGen ExAC TOPMed gnomAD
CA2420299 rs372421280	181	A>S		No	ClinGen ESP ExAC TOPMed gnomAD
COSM3696170 rs372421280 CA74626740	181	A>T	large_intestine [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
rs944547158 CA74626755	181	A>V		No	ClinGen Ensembl
rs375549664 CA2420301	184	K>R		No	ClinGen ESP ExAC gnomAD
CA2420302 rs765735423	185	L>F		No	ClinGen ExAC gnomAD
CA352930441 rs1255878697	186	T>A		No	ClinGen TOPMed gnomAD
CA2420304 rs763321551	193	E>D		No	ClinGen ExAC gnomAD
CA2420306 rs751679355	196	Q>*		No	ClinGen ExAC gnomAD
rs1039317010 CA74626809	197	N>K		No	ClinGen Ensembl
rs2033243949 RCV001236207	198	A>V		No	ClinVar dbSNP
rs755111080 CA74626815	202	P>L		No	ClinGen ExAC TOPMed gnomAD
CA2420307 rs755111080	202	P>R		No	ClinGen ExAC TOPMed gnomAD
CA74626817 rs766928449	207	Y>D		No	ClinGen Ensembl
rs1387018762	210	A>=	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
TCGA novel	210	A>P	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1302247089 CA352931108	210	A>T		No	ClinGen gnomAD
rs757096737 CA2420331	216	P>L		No	ClinGen ExAC gnomAD
rs1328969736 CA352933166	222	S>*		No	ClinGen gnomAD
rs1207253573 CA352933243	224	D>G		No	ClinGen gnomAD
TCGA novel	226	W>R	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1488933589 CA352933532	229	G>V		No	ClinGen gnomAD
rs778530686 CA2420332	230	V>I		No	ClinGen ExAC TOPMed gnomAD
TCGA novel	231	I>missing	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA2420333 rs375875691	232	M>R		No	ClinGen ESP ExAC gnomAD
CA2420334 rs375875691	232	M>T		No	ClinGen ESP ExAC gnomAD
rs779765556 CA2420335	233	Y>C		No	ClinGen ExAC TOPMed gnomAD
TCGA novel	233	Y>H	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA352933709 rs1411178007	235	L>P		No	ClinGen gnomAD
rs753802960 CA2420348	238	G>V		No	ClinGen ExAC TOPMed gnomAD
CA2420352 rs758133512	243	Y>*		No	ClinGen ExAC gnomAD
rs372815253 CA352934052	243	Y>C		No	ClinGen ESP ExAC TOPMed gnomAD
CA2420351 rs372815253	243	Y>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs779853542 CA2420353	244	S>C		No	ClinGen ExAC gnomAD
CA352934099 rs1469284266	245	N>S		No	ClinGen TOPMed
rs1429867795 CA352934114	246	T>A		No	ClinGen TOPMed
rs746597729 RCV001243263 CA2420354	246	T>M		No	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
CA74628047 rs780822673	247	G>A		No	ClinGen ExAC TOPMed gnomAD
rs754571545 CA2420355	247	G>S		No	ClinGen ExAC gnomAD
CA2420356 rs780822673	247	G>V		No	ClinGen ExAC TOPMed gnomAD
rs1241745111 CA352934210	250	I>V		No	ClinGen TOPMed
CA74628092 rs975963806	252	P>L		No	ClinGen TOPMed gnomAD
rs975963806 CA352934272	252	P>Q		No	ClinGen TOPMed gnomAD
CA352934256 rs1212198874	252	P>S		No	ClinGen gnomAD
rs1179935029 CA352934286	253	G>E		No	ClinGen gnomAD
rs1168548018 CA352934368	255	K>M		No	ClinGen TOPMed
rs1168548018 CA352934364	255	K>R		No	ClinGen TOPMed
CA74628118 rs746224997	257	R>K		No	ClinGen ExAC gnomAD
rs746224997 CA2420360	257	R>M		No	ClinGen ExAC gnomAD
RCV001223745 rs199901611 CA2420361	259	R>C		No	ClinGen ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
CA2420362 RCV001349223 rs775712762	259	R>H		No	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
rs775712762 CA352934496	259	R>L		No	ClinGen ExAC TOPMed gnomAD
rs1360271800 CA352934523	261	G>R		No	ClinGen gnomAD
CA352934564 rs1447672702	262	Q>R		No	ClinGen gnomAD
CA352934603 rs187648751	263	Y>*		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
TCGA novel	263	Y>C	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs761866056 CA74628151	264	G>D		No	ClinGen ExAC TOPMed gnomAD
rs372960797 CA2420366	264	G>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA2420367 rs761866056	264	G>V		No	ClinGen ExAC TOPMed gnomAD
CA352934731 rs1576016686	267	N>H		No	ClinGen Ensembl
CA352934766 rs1337584009	267	N>S		No	ClinGen gnomAD
rs1576016700 CA352934901	271	S>A		No	ClinGen Ensembl
rs758137071 CA2420370	272	E>G		No	ClinGen ExAC gnomAD
rs750304055 CA2420369	272	E>K		No	ClinGen ExAC TOPMed gnomAD
CA2420371 rs377010404	275	E>G		No	ClinGen ESP ExAC TOPMed gnomAD
rs751301162 CA352935037	276	D>G		No	ClinGen ExAC TOPMed gnomAD
rs751301162 CA2420372	276	D>V		No	ClinGen ExAC TOPMed gnomAD
VAR_040757 rs56107897 CA74628228	276	D>Y		No	ClinGen UniProt Ensembl dbSNP
rs750932578 CA2420396	277	A>G		No	ClinGen ExAC TOPMed gnomAD
rs750932578 CA352935312	277	A>V		No	ClinGen ExAC TOPMed gnomAD
rs1351066812 CA352935350	279	Q>K		No	ClinGen gnomAD
CA2420397 rs79652799 RCV001237182	282	R>C		No	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs747366676 RCV001323969 CA2420399	282	R>H		No	ClinGen ClinVar ExAC dbSNP gnomAD
rs747366676 CA2420400	282	R>L		No	ClinGen ExAC gnomAD
rs79652799 CA2420398	282	R>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs748349748 CA2420402	283	L>R		No	ClinGen ExAC TOPMed
rs1484183504 CA352935621	288	D>G		No	ClinGen TOPMed
CA2420403 rs769809042 RCV001321703	288	D>N		No	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
rs1254507565 CA352935661	289	P>S		No	ClinGen TOPMed gnomAD
rs1254507565 CA352935658	289	P>T		No	ClinGen TOPMed gnomAD
CA2420404 rs373989634	290	T>I		No	ClinGen ESP ExAC gnomAD
TCGA novel	290	T>R	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs774366640 CA2420407	297	Q>*		No	ClinGen ExAC gnomAD
CA74628702 rs759419783 RCV001351422 CA2420408	301	H>Q		No	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
CA2420410 rs752324089	302	P>T		No	ClinGen ExAC gnomAD
rs760343500 CA2420411	303	W>*		No	ClinGen ExAC gnomAD
CA2420412 rs763562128	303	W>*	Variant assessed as Somatic; 4.62e-05 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
rs957985236	305	N>=	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	NCI-TCGA
rs1304557436 CA352936523	305	N>S		No	ClinGen TOPMed gnomAD
rs764674138 CA74628858	307	S>*		No	ClinGen ExAC gnomAD
CA2420432 rs764674138	307	S>L	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
rs1190804603 CA352936779	308	M>T		No	ClinGen gnomAD
rs1391040721 CA352936843	309	V>A		No	ClinGen gnomAD
CA74628868 rs554702337	310	V>M		No	ClinGen Ensembl
CA74628876 rs893709381	312	Q>H		No	ClinGen Ensembl
CA2420436 rs753103323	314	P>R		No	ClinGen ExAC gnomAD
CA2420435 rs376026422	314	P>T		No	ClinGen ESP ExAC TOPMed gnomAD
RCV001300450 CA74628898 rs868590760	315	L>F		No	ClinGen ClinVar dbSNP gnomAD
CA2420439 rs749474530 RCV001206873 COSM3722473	317	T>M	upper_aerodigestive_tract [Cosmic]	No	ClinGen cosmic curated ClinVar ExAC dbSNP gnomAD
CA352937167 rs1364047785	318	A>V		No	ClinGen gnomAD
rs1466112278 CA352937180	319	R>*		No	ClinGen TOPMed
rs779105845 CA352937187	319	R>L		No	ClinGen ExAC TOPMed gnomAD
RCV001245148 rs779105845 CA2420441	319	R>Q		No	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
CA352937370 rs745848601	323	E>D		No	ClinGen ExAC TOPMed gnomAD
rs1477373625 CA352937423	324	D>G		No	ClinGen TOPMed
CA2420443 rs368455680	325	K>E		No	ClinGen ESP ExAC TOPMed gnomAD
CA352937615 rs1262884842	327	H>D		No	ClinGen gnomAD
RCV001352258 rs2033321555	328	W>*		No	ClinVar dbSNP
rs1211001436 CA352937726	329	D>H		No	ClinGen gnomAD
rs768275251 CA352937764	330	E>*		No	ClinGen ExAC TOPMed gnomAD
CA74628934 rs776286044 CA352937805	330	E>D		No	ClinGen ExAC TOPMed gnomAD
rs768275251 CA2420446	330	E>K	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
rs1433672274 CA352937839	332	K>Q		No	ClinGen gnomAD
CA352939571 rs1166410053	335	M>T		No	ClinGen gnomAD
rs1350141172 CA352939599	336	T>A		No	ClinGen TOPMed gnomAD
rs779191741 CA2420462	337	S>G		No	ClinGen ExAC gnomAD
TCGA novel	337	S>R	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA352939658 rs1364236066 RCV001236870	338	A>T		No	ClinGen ClinVar dbSNP gnomAD
RCV001241566 rs750526292 CA2420463	338	A>V		No	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
CA2420466 rs539746424	340	A>V		No	ClinGen 1000Genomes ExAC gnomAD
CA2420467 rs768522300	341	T>S		No	ClinGen ExAC gnomAD
CA352939942 rs1221769570	343	R>Q		No	ClinGen TOPMed gnomAD
CA2420468 rs557756970	343	R>W		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1576018619 CA352939946	344	V>I		No	ClinGen Ensembl
TCGA novel	345	D>T	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs199560575 CA2420470	346	Y>*		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA2420469 rs201584585	346	Y>H		No	ClinGen ExAC gnomAD
rs2033344630 RCV001240927	346	Y>Q		No	ClinVar dbSNP
CA352940111 rs1205843411	347	D>N		No	ClinGen TOPMed gnomAD
rs1205843411 CA352940128	347	D>Y		No	ClinGen TOPMed gnomAD
rs1232255502 CA352940180	348	Q>K		No	ClinGen gnomAD
rs762542270 CA2420472	349	V>M		No	ClinGen ExAC gnomAD
CA352940306 rs1338453711	350	K>N		No	ClinGen TOPMed
CA2420473 rs770298926	352	K>*		No	ClinGen ExAC gnomAD
rs1443688749 CA352940479	354	L>V		No	ClinGen gnomAD
rs761057460 CA2420476	355	K>N		No	ClinGen ExAC gnomAD
rs1559491747 CA352940541	356	T>I		No	ClinGen Ensembl
rs1432149629 CA352940531	356	T>S		No	ClinGen gnomAD
rs2033345821 RCV001214009	357	S>C		No	ClinVar dbSNP
CA74629390 rs368591672	360	R>Q		No	ClinGen TOPMed gnomAD
RCV001063369 CA2420478 rs762190469	360	R>W		No	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
rs141897508 CA2420479	363	N>S		No	ClinGen ESP ExAC gnomAD
rs924312729 CA74629401	365	R>K		No	ClinGen TOPMed
CA2420481 rs758524278	367	K>R		No	ClinGen ExAC TOPMed gnomAD
rs779952844 CA2420482	369	Q>*		No	ClinGen ExAC TOPMed gnomAD
rs1272121660 CA352941091	371	G>D	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
rs1237906944 CA352941362	380	N>K		No	ClinGen gnomAD
rs1576018745 CA352941352	380	N>T		No	ClinGen Ensembl
rs754885308 CA2420484	382	Q>*		No	ClinGen ExAC TOPMed gnomAD

No associated diseases with Q16644

4 regional properties for Q16644

Type	Name	Position	InterPro Accession
domain	Death domain	14 - 106	IPR000488
domain	Protein kinase domain	178 - 463	IPR000719
domain	Interleukin-1 receptor-associated kinase 3, pseudokinase domain	184 - 459	IPR042698
domain	IRAK3, death domain	16 - 102	IPR042747

Functions

		Description
EC Number	2.7.11.1	Protein-serine/threonine kinases
Subcellular Localization	Nucleus Cytoplasm	Predominantly located in the nucleus, when activated it translocates to the cytoplasm
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.

8 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
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
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.
protein serine kinase activity	Catalysis of the reactions
protein serine/threonine kinase activity	Catalysis of the reactions

8 GO annotations of biological process

Name	Definition
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.
macropinocytosis	An endocytosis process that results in the uptake of liquid material by cells from their external environment by the 'ruffling' of the cell membrane to form heterogeneously sized intracellular vesicles called macropinosomes, which can be up to 5 micrometers in size.
peptidyl-serine phosphorylation	The phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine.
response to cytokine	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cytokine stimulus.
response to lipopolysaccharide	Any process that results in a change in state or activity of an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipopolysaccharide stimulus; lipopolysaccharide is a major component of the cell wall of gram-negative bacteria.
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.
toll-like receptor signaling pathway	The series of molecular signals initiated by a ligand binding to a toll-like receptor of a target cell. Toll-like receptors directly bind pattern motifs from a variety of microbial sources to initiate an innate immune response.
vascular endothelial growth factor receptor signaling pathway	The series of molecular signals initiated by a ligand binding to a vascular endothelial growth factor receptor (VEGFR) on the surface of the target cell, and ending with the regulation of a downstream cellular process, e.g. transcription.

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
Q8IW41	MAPKAPK5	MAP kinase-activated protein kinase 5	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
O54992	Mapkapk5	MAP kinase-activated protein kinase 5	Mus musculus (Mouse)	EV
P49138	Mapkapk2	MAP kinase-activated protein kinase 2	Mus musculus (Mouse)	EV
Q3UMW7	Mapkapk3	MAP kinase-activated protein kinase 3	Mus musculus (Mouse)	SS
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
MDGETAEEQG	GPVPPPVAPG	GPGLGGAPGG	RREPKKYAVT	DDYQLSKQVL	GLGVNGKVLE
70	80	90	100	110	120
CFHRRTGQKC	ALKLLYDSPK	ARQEVDHHWQ	ASGGPHIVCI	LDVYENMHHG	KRCLLIIMEC
130	140	150	160	170	180
MEGGELFSRI	QERGDQAFTE	REAAEIMRDI	GTAIQFLHSH	NIAHRDVKPE	NLLYTSKEKD
190	200	210	220	230	240
AVLKLTDFGF	AKETTQNALQ	TPCYTPYYVA	PEVLGPEKYD	KSCDMWSLGV	IMYILLCGFP
250	260	270	280	290	300
PFYSNTGQAI	SPGMKRRIRL	GQYGFPNPEW	SEVSEDAKQL	IRLLLKTDPT	ERLTITQFMN
310	320	330	340	350	360
HPWINQSMVV	PQTPLHTARV	LQEDKDHWDE	VKEEMTSALA	TMRVDYDQVK	IKDLKTSNNR
370	380
LLNKRRKKQA	GSSSASQGCN	NQ

Descriptions

Annotation based on sequence homology with P49138

Autoinhibitory domains (AIDs)

Accessory elements

186-207 (Activation loop from InterPro)

186-207 (Activation loop from InterPro)

References

Autoinhibited structure

Activated structure

6 structures for Q16644

296 variants for Q16644

No associated diseases with Q16644

4 regional properties for Q16644

Functions

4 GO annotations of cellular component

8 GO annotations of molecular function

8 GO annotations of biological process

10 homologous proteins in AiPD