AiPD: Autoinhibited Protein Database

P49137

Gene name	MAPKAPK2
Protein name	MAP kinase-activated protein kinase 2
Names	MAPK-activated protein kinase 2 , MAPKAP kinase 2 , MAPKAP-K2 , MAPKAPK-2 , MK-2 , MK2 , EC 2.7.11.1
Species	Homo sapiens (Human)
KEGG Pathway	hsa:9261
EC number	2.7.11.1: Protein-serine/threonine kinases
Protein Class

Descriptions

MAP KAP kinase 2 (MK2), a Ser/Thr kinase, plays a crucial role in the inflammatory process. MK2 contains an autoinhibitory domain within its C-terminal region. This domain regulates the enzyme by acting as a pseudosubstrate, blocking substrate binding and thus inhibiting activity. The autoinhibitory domain affects the catalytic kinase domain of MK2, specifically influencing the binding of peptide substrates and ATP, which are crucial for the enzyme’s activity. Phosphorylation by p38 MAP kinase alleviates autoinhibition. It induces conformational changes in MK2, particularly in the autoinhibitory domain and the activation segment, allowing efficient substrate binding and restoring enzymatic activity.

Autoinhibitory domains (AIDs)

Target domain	5-325 (Protein kinase domain)
Relief mechanism	PTM
Assay	Structural analysis, Deletion assay

AID

365-400 (Autoinhibitory domain)

Target domain

5-325 (Protein kinase domain)

Relief mechanism

PTM (Phosphorylation by p38 MAP kinase)

Assay

Structural analysis, Deletion assay

Accessory elements

206-228 (Activation loop from InterPro)

Target domain	64-325 (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

30 structures for P49137

Entry ID	Method	Resolution	Chain	Position	Source
1KWP	X-ray	280 A	A/B	1-400	PDB
1NXK	X-ray	270 A	A/B/C/D	1-400	PDB
1NY3	X-ray	300 A	A	1-400	PDB
2JBO	X-ray	310 A	A	41-364	PDB
2JBP	X-ray	331 A	A/B/C/D/E/F/G/H/I/J/K/L	41-364	PDB
2OKR	X-ray	200 A	C/F	370-393	PDB
2ONL	X-ray	400 A	C/D	1-400	PDB
2OZA	X-ray	270 A	A	47-400	PDB
2P3G	X-ray	380 A	X	45-371	PDB
2PZY	X-ray	290 A	A/B/C/D	41-364	PDB
3A2C	X-ray	290 A	A/B/C/D/E/F/G/H/I/J/K/L	41-364	PDB
3FPM	X-ray	330 A	A	41-364	PDB
3FYJ	X-ray	380 A	X	45-371	PDB
3FYK	X-ray	350 A	X	45-371	PDB
3GOK	X-ray	320 A	A/B/C/D/E/F/G/H/I/J/K/L	41-364	PDB
3KA0	X-ray	290 A	A	47-366	PDB
3KC3	X-ray	290 A	A/B/C/D/E/F/G/H/I/J/K/L	41-364	PDB
3KGA	X-ray	255 A	A	47-364	PDB
3M2W	X-ray	241 A	A	47-364	PDB
3M42	X-ray	268 A	A	47-364	PDB
3R2B	X-ray	290 A	A/B/C/D/E/F/G/H/I/J/K/L	47-364	PDB
3R2Y	X-ray	300 A	A	46-364	PDB
3R30	X-ray	320 A	A	46-364	PDB
3WI6	X-ray	299 A	A/B/C/D/E/F	41-364	PDB
4TYH	X-ray	300 A	A	51-400	PDB
6T8X	X-ray	281 A	A/B/C/D/E/F	41-338	PDB
6TCA	X-ray	370 A	A/C/E/G	41-400	PDB
7NRY	X-ray	380 A	X	45-371	PDB
8XU4	X-ray	340 A	A/B/C/D/E/F/G/H/I/J/K/L	47-364	PDB
AF-P49137-F1	Predicted				AlphaFoldDB

225 variants for P49137

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
RCV001262851 rs1673811124	149	R>*	Neurodevelopmental disorder [ClinVar]	Yes	ClinVar dbSNP
CA344484263 rs1553425290	3	S>P		No	ClinGen Ensembl
rs1245550536 CA344484308	5	S>C		No	ClinGen TOPMed gnomAD
rs1245550536 CA344484302	5	S>F	Variant assessed as Somatic; impact. [NCI-TCGA]	No	ClinGen NCI-TCGA TOPMed gnomAD
rs1284284124 CA344484353	7	G>D		No	ClinGen TOPMed gnomAD
rs1553425301 CA344484368	8	Q>R		No	ClinGen Ensembl
CA344484410 rs1206536591	10	P>L		No	ClinGen TOPMed gnomAD
CA344484407 rs1206536591	10	P>Q		No	ClinGen TOPMed gnomAD
CA344484435 rs1308290172	12	V>M		No	ClinGen TOPMed
rs1246509011 CA344484460	13	P>L		No	ClinGen TOPMed
rs1246509011 CA344484457	13	P>Q		No	ClinGen TOPMed
CA344484458 rs1246509011	13	P>R		No	ClinGen TOPMed
TCGA novel	14	F>L	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA344484483 rs1319019572	15	P>R		No	ClinGen TOPMed
CA344484479 rs1553425319	15	P>S		No	ClinGen gnomAD
CA344484489 rs1553425321	16	A>P		No	ClinGen Ensembl
CA344484494 rs1553425322	16	A>V		No	ClinGen gnomAD
CA344484521 rs1553425325	18	A>V		No	ClinGen gnomAD
TCGA novel	19	P>L	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1553425339 CA344484547	21	P>S		No	ClinGen gnomAD
CA344484560 rs1425759842	22	Q>L		No	ClinGen TOPMed gnomAD
CA344484562 rs1425759842	22	Q>P		No	ClinGen TOPMed gnomAD
rs782036969 CA1363301	23	P>S		No	ClinGen ExAC TOPMed gnomAD
CA1363302 rs782186251	24	P>L		No	ClinGen ExAC TOPMed gnomAD
CA1363305 rs181345810	25	T>A		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
TCGA novel	25	T>H	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs181345810 CA1363306	25	T>P		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA344484606 rs1558569683	26	P>H		No	ClinGen Ensembl
rs1553425349 CA344484613	27	A>P		No	ClinGen gnomAD
CA344484628 rs1553425354	28	L>P		No	ClinGen gnomAD
rs782139014 CA1363309	30	H>P		No	ClinGen ExAC
CA344484653 rs782797008 CA1363310	30	H>Q		No	ClinGen ExAC TOPMed gnomAD
CA1363312 rs782064315	32	P>A		No	ClinGen ExAC TOPMed gnomAD
rs1338511158 CA344484664	32	P>L		No	ClinGen TOPMed gnomAD
CA344484662 rs1338511158	32	P>Q		No	ClinGen TOPMed gnomAD
CA344484668 rs573218643	33	A>E		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA1363313 rs573218643	33	A>G		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA344484666 rs1553425370	33	A>P		No	ClinGen gnomAD
CA344484672 rs1553425374	34	Q>E		No	ClinGen gnomAD
CA344484680 rs1572470610	35	P>S		No	ClinGen Ensembl
CA1363319 rs782504552	37	P>L		No	ClinGen ExAC TOPMed gnomAD
rs1553425392 CA344484699	38	P>L		No	ClinGen gnomAD
CA1363320 rs782674769	38	P>S		No	ClinGen ExAC TOPMed gnomAD
rs1553425396 CA344484700	39	P>S		No	ClinGen gnomAD
CA344484707 rs1572470680	40	P>A		No	ClinGen Ensembl
CA1363322 rs782451973	40	P>L		No	ClinGen ExAC TOPMed gnomAD
rs782451973 CA344484710	40	P>R		No	ClinGen ExAC TOPMed gnomAD
CA344484714 rs1553425404	41	Q>L		No	ClinGen gnomAD
rs782578871 CA1363323	43	F>L		No	ClinGen ExAC TOPMed gnomAD
rs1244786492 CA344484757	44	P>L		No	ClinGen TOPMed gnomAD
CA344484753 rs1244786492	44	P>Q		No	ClinGen TOPMed gnomAD
CA344484755 rs1244786492	44	P>R		No	ClinGen TOPMed gnomAD
CA344484801 rs782364714	47	H>Q		No	ClinGen ExAC TOPMed gnomAD
rs1275111539 CA344484847	51	G>C		No	ClinGen TOPMed
rs146073998 COSM4143283 COSM4143282 CA1363327	51	G>V	thyroid [Cosmic]	No	ClinGen cosmic curated 1000Genomes ESP ExAC TOPMed gnomAD
rs370656530 CA1363328	53	Q>R		No	ClinGen ESP ExAC TOPMed gnomAD
rs1553425419 CA344484879	54	I>V		No	ClinGen gnomAD
rs1277577091 CA344484889	55	K>Q		No	ClinGen TOPMed
CA344484931 rs1553425427	58	A>T		No	ClinGen gnomAD
rs1553425429 CA344484941	58	A>V		No	ClinGen gnomAD
rs782041388 CA1363330	60	I>V		No	ClinGen ExAC gnomAD
CA1363335 rs781888295	68	Q>R		No	ClinGen ExAC gnomAD
CA344485199 rs1436257745	72	L>P		No	ClinGen TOPMed
rs1331532151 CA344485279	75	N>S		No	ClinGen TOPMed
rs1553425445 CA344485435	83	N>S		No	ClinGen gnomAD
rs1572470877 CA344485454	84	K>R		No	ClinGen Ensembl
TCGA novel	84	K>T	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
TCGA novel	85	R>M	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1422330364 CA344485474	85	R>S		No	ClinGen TOPMed
TCGA novel	87	Q>H	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1553425447 CA344485497	87	Q>P		No	ClinGen gnomAD
rs781807175 CA1363338	91	A>T		No	ClinGen ExAC gnomAD
CA344485581 rs782468736	92	L>F		No	ClinGen ExAC gnomAD
rs782468736 CA1363339	92	L>V		No	ClinGen ExAC gnomAD
rs1553432180 CA344476243	94	M>I		No	ClinGen gnomAD
CA344476348 rs1553432187	101	A>S		No	ClinGen gnomAD
TCGA novel	102	R>C	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
COSM2156166 rs151079567 COSM2156165 CA1363361	102	R>H	central_nervous_system [Cosmic]	No	ClinGen cosmic curated 1000Genomes ESP ExAC TOPMed gnomAD
rs151079567 CA1363362	102	R>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA344476452 rs1553432196	108	H>Q		No	ClinGen gnomAD
CA344476463 rs1166739803	109	W>L		No	ClinGen TOPMed
rs782527754 CA1363366	110	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA1363365 rs375800332	110	R>W		No	ClinGen ESP ExAC TOPMed gnomAD
rs782185154 CA1363368	111	A>G		No	ClinGen ExAC gnomAD
CA1363370 rs374754928	113	Q>H		No	ClinGen ESP ExAC gnomAD
CA344476516 rs868968219	113	Q>P		No	ClinGen gnomAD
CA1363371 rs782231165	115	P>L	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
rs1553432206 CA344476558	116	H>R		No	ClinGen gnomAD
rs782152248 CA1363375	118	V>I	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
rs141946496 CA1363376	119	R>Q		No	ClinGen ESP ExAC TOPMed gnomAD
CA344476599 rs1553432209	119	R>W		No	ClinGen gnomAD
CA344476610 rs1553432211	120	I>V		No	ClinGen gnomAD
rs781915750 CA1363377	121	V>M		No	ClinGen ExAC TOPMed gnomAD
CA344476645 rs1572515040	122	D>G		No	ClinGen Ensembl
rs1553432214 CA344476652	123	V>M		No	ClinGen gnomAD
rs534203474 CA36555664	127	L>V		No	ClinGen Ensembl
COSM902999 COSM1583988 CA344476742 rs1363430228	129	A>T	Variant assessed as Somatic; impact. endometrium [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated NCI-TCGA TOPMed
rs781887326 CA1363383	130	G>R		No	ClinGen ExAC gnomAD
TCGA novel	131	R>missing	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs782432987 CA1363384	131	R>K		No	ClinGen ExAC gnomAD
rs886806296 CA36555740	133	C>Y		No	ClinGen Ensembl
rs1553432226 CA344476887	140	C>S		No	ClinGen gnomAD
rs1347942859 CA344476953	141	L>M		No	ClinGen TOPMed
rs782082445 CA1363404	141	L>S		No	ClinGen ExAC gnomAD
rs1311181554 CA344476992	143	G>D		No	ClinGen TOPMed
CA344476982 rs1230603507	143	G>S		No	ClinGen TOPMed
TCGA novel	145	E>*	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA1363406 rs781851372	148	S>G		No	ClinGen ExAC TOPMed
CA344477051 rs1348592671	148	S>N		No	ClinGen TOPMed
rs782516721 CA1363407	149	R>Q		No	ClinGen ExAC TOPMed gnomAD
TCGA novel	151	Q>H	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA344477101 rs1376132455	152	D>A		No	ClinGen TOPMed
CA36555958 rs938576272	153	R>G		No	ClinGen Ensembl
rs1175840148 CA344477138	155	D>E		No	ClinGen TOPMed
CA1363409 rs527268461	156	Q>K		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
COSM1927707 CA36556348 COSM275991 rs772956044	165	E>K	Variant assessed as Somatic; 0.0 impact. large_intestine [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated NCI-TCGA TOPMed gnomAD
CA344477842 rs1405298202	167	M>V		No	ClinGen TOPMed
CA344477886 rs1397768555	170	I>V		No	ClinGen TOPMed
CA344477896 rs1553432317	171	G>S		No	ClinGen gnomAD
VAR_040753 rs35671930 CA1363436	173	A>G		No	ClinGen UniProt ESP ExAC TOPMed dbSNP gnomAD
rs1173858137 CA344477950	175	Q>*		No	ClinGen TOPMed
rs1553432321 CA344477968	176	Y>C		No	ClinGen gnomAD
TCGA novel	180	I>M	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA344478008 rs1478924734	180	I>V		No	ClinGen TOPMed
CA1363440 rs149638565	182	I>V		No	ClinGen ESP ExAC gnomAD
rs1043183855 CA36556389	185	R>Q		No	ClinGen gnomAD
CA36556737 rs561595271	194	Y>C		No	ClinGen Ensembl
CA1363462 rs531894220	195	T>A		No	ClinGen 1000Genomes ExAC gnomAD
CA344478256 rs531894220	195	T>P		No	ClinGen 1000Genomes ExAC gnomAD
CA1363464 rs782384462	197	K>R		No	ClinGen ExAC
CA344478328 rs375671223	200	N>K		No	ClinGen ESP ExAC TOPMed gnomAD
CA344478322 rs1553432393	200	N>S		No	ClinGen gnomAD
CA1363466 rs782149296	201	A>T	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
rs140901506 CA1363467	202	I>T		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA344478344 rs1484281453	202	I>V		No	ClinGen TOPMed gnomAD
rs368050217 CA1363469	206	T>A		No	ClinGen ExAC TOPMed gnomAD
rs782803587 CA1363475	212	K>Q		No	ClinGen ExAC
CA1363476 rs74538056	213	E>K		No	ClinGen ExAC gnomAD
rs782769109 CA36556910	214	T>I		No	ClinGen gnomAD
CA1363477 rs571837891	214	T>P		No	ClinGen 1000Genomes ExAC gnomAD
CA1363478 rs200028198	215	T>P		No	ClinGen 1000Genomes ExAC gnomAD
rs1257277521 CA344478523	216	S>T		No	ClinGen TOPMed
CA344478535 rs1230915063	217	H>R		No	ClinGen TOPMed
CA1363479 rs781830804	218	N>D		No	ClinGen ExAC
TCGA novel	229	Y>*	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA344478938 rs1261797849	243	S>C		No	ClinGen TOPMed gnomAD
TCGA novel	244	C>Y	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs782414991 CA1363508	246	M>I		No	ClinGen ExAC gnomAD
TCGA novel	249	L>P	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA344479040 rs1203635358	251	V>I		No	ClinGen TOPMed
rs375137265 CA1363510	252	I>V		No	ClinGen ESP ExAC TOPMed gnomAD
rs1572517856 CA344479205	260	Y>D		No	ClinGen Ensembl
TCGA novel	263	F>I	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1553432591	263	F>S	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	NCI-TCGA
CA1363529 rs782375243	266	N>H		No	ClinGen ExAC TOPMed gnomAD
CA1363530 rs782008886	266	N>S		No	ClinGen ExAC TOPMed gnomAD
CA344479287 rs782008886	266	N>T		No	ClinGen ExAC TOPMed gnomAD
rs781923393 CA1363533	271	I>V		No	ClinGen ExAC gnomAD
TCGA novel	272	S>F	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1553432605 CA344479434	278	R>G		No	ClinGen gnomAD
COSM1286098 COSM1286099 rs1553432606 CA344479439	278	R>H	Variant assessed as Somatic; 0.0 impact. autonomic_ganglia [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated NCI-TCGA gnomAD
rs1247727262 CA344479456	280	R>G		No	ClinGen TOPMed
rs782072138 CA1363534 COSM3771605 COSM3771606	280	R>Q	pancreas [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA344479474 rs1483324985	281	M>K		No	ClinGen TOPMed
CA1363536 rs781968571	283	Q>H		No	ClinGen ExAC gnomAD
rs782729938 CA1363535	283	Q>L		No	ClinGen ExAC gnomAD
CA1363538 rs142063401	288	N>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs1553432613 CA344479613	291	W>C		No	ClinGen gnomAD
TCGA novel	292	S>L	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1261683933 CA344480344	300	M>L		No	ClinGen TOPMed
CA344480343 rs1261683933	300	M>V		No	ClinGen TOPMed
CA1363572 rs545600073	303	R>Q		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1280991127 CA344480384	303	R>W		No	ClinGen TOPMed
CA344480399 rs1334705583	304	N>S		No	ClinGen TOPMed
rs1558589974 CA344480474	311	T>A		No	ClinGen Ensembl
CA1363574 rs782597489	311	T>N		No	ClinGen ExAC TOPMed gnomAD
CA1363573 rs782597489	311	T>S		No	ClinGen ExAC TOPMed gnomAD
CA344480537 rs1454535420	316	I>V		No	ClinGen TOPMed
rs868917636 CA344480560	318	E>K	Variant assessed as Somatic; impact. [NCI-TCGA]	No	ClinGen Ensembl NCI-TCGA
rs1553432730 CA344480567	318	E>V		No	ClinGen gnomAD
rs782279440 CA1363577	320	M>L		No	ClinGen ExAC TOPMed gnomAD
rs782279440 CA344480609	320	M>V		No	ClinGen ExAC TOPMed gnomAD
TCGA novel	322	H>Y	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
TCGA novel	324	W>L	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1553432736 CA344480695	326	M>T		No	ClinGen gnomAD
rs782425128 CA1363601	327	Q>K		No	ClinGen ExAC gnomAD
rs1292139600 CA344480749	327	Q>R		No	ClinGen TOPMed
rs782072519 CA1363603	328	S>T		No	ClinGen ExAC gnomAD
CA1363604 rs782340351	329	T>A		No	ClinGen ExAC gnomAD
CA36558283 rs970977724	330	K>M		No	ClinGen TOPMed
rs868952591 CA344480807	332	P>T		No	ClinGen Ensembl
rs1363748424 CA344480817	333	Q>E		No	ClinGen TOPMed gnomAD
TCGA novel	339	S>N	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs941786201 CA344480907	340	R>L		No	ClinGen TOPMed gnomAD
rs941786201 CA36558301	340	R>Q		No	ClinGen TOPMed gnomAD
rs142025224 CA1363609	340	R>W		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1553432760 CA344480951	344	E>Q	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
CA344481004 rs782749899	348	R>L		No	ClinGen ExAC gnomAD
CA1363613 rs782749899	348	R>Q	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
rs1553432763 CA344481002	348	R>W		No	ClinGen gnomAD
rs140988938 CA1363614	353	K>R		No	ClinGen ESP ExAC TOPMed gnomAD
rs1572519960 CA344481230	360	L>S		No	ClinGen Ensembl
VAR_040754 CA1363667 rs55894011	361	A>S		No	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs782118884 CA1363668	362	T>A		No	ClinGen ExAC gnomAD
CA344481253 rs1553432908	364	R>C		No	ClinGen gnomAD
rs782022011 COSM903001 CA1363670	365	V>I	Variant assessed as Somatic; 0.0 impact. endometrium [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated ExAC NCI-TCGA gnomAD
rs782704000 CA1363672	368	E>K		No	ClinGen ExAC gnomAD
CA344481326 rs1553432914	374	K>E		No	ClinGen gnomAD
CA36559009 rs892611562	374	K>M		No	ClinGen TOPMed
rs1553432912	374	K>R	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1337144318 CA344481336	375	I>T		No	ClinGen TOPMed
rs781818804 CA1363673	377	D>V		No	ClinGen ExAC
CA344481370 rs1553432918	380	N>S		No	ClinGen gnomAD
TCGA novel	386	R>K	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1572520041 CA344481412	387	R>Q		No	ClinGen Ensembl
CA1363678 rs782678368	390	A>T		No	ClinGen ExAC gnomAD
rs191175287 CA1363679	391	R>Q		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA344481437 rs1553432921	391	R>W		No	ClinGen gnomAD
rs1558590699 CA344481443 COSM4143286	392	A>D	thyroid [Cosmic]	No	ClinGen cosmic curated Ensembl
CA1363681 rs782600274	394	E>K		No	ClinGen ExAC gnomAD
CA1363682 rs782232686	396	A>V		No	ClinGen ExAC gnomAD
CA1363684 rs782652551	397	A>G		No	ClinGen ExAC TOPMed gnomAD
TCGA novel	397	A>V	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs782282911 CA1363685	398	L>V		No	ClinGen ExAC TOPMed gnomAD
rs781933066 CA1363687	400	H>Q		No	ClinGen ExAC gnomAD

No associated diseases with P49137

3 regional properties for P49137

Type	Name	Position	InterPro Accession
domain	Protein kinase domain	64 - 325	IPR000719
active_site	Serine/threonine-protein kinase, active site	182 - 194	IPR008271
binding_site	Protein kinase, ATP binding site	70 - 93	IPR017441

Functions

		Description
EC Number	2.7.11.1	Protein-serine/threonine kinases
Subcellular Localization	Cytoplasm Nucleus	Phosphorylation and subsequent activation releases the autoinhibitory helix, resulting in the export from the nucleus into the cytoplasm
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

6 GO annotations of cellular component

Name	Definition
centrosome	A structure comprised of a core structure (in most organisms, a pair of centrioles) and peripheral material from which a microtubule-based structure, such as a spindle apparatus, is organized. Centrosomes occur close to the nucleus during interphase in many eukaryotic cells, though in animal cells it changes continually during the cell-division cycle.
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.
extracellular exosome	A vesicle that is released into the extracellular region by fusion of the limiting endosomal membrane of a multivesicular body with the plasma membrane. Extracellular exosomes, also simply called exosomes, have a diameter of about 40-100 nm.
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
mitogen-activated protein kinase binding	Binding to a mitogen-activated protein kinase.
protein kinase activity	Catalysis of the phosphorylation of an amino acid residue in a protein, usually according to the reaction
protein serine kinase activity	Catalysis of the reactions
protein serine/threonine kinase activity	Catalysis of the reactions

23 GO annotations of biological process

Name	Definition
3'-UTR-mediated mRNA stabilization	An mRNA stabilization process in which one or more RNA-binding proteins associate with the 3'-untranslated region (UTR) of an mRNA.
cellular response to vascular endothelial growth factor stimulus	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a vascular endothelial growth factor stimulus.
DNA damage response	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating damage to its DNA from environmental insults or errors during metabolism.
inflammatory response	The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages.
inner ear development	The process whose specific outcome is the progression of the inner ear over time, from its formation to the mature structure.
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.
leukotriene metabolic process	The chemical reactions and pathways involving leukotriene, a pharmacologically active substance derived from a polyunsaturated fatty acid, such as arachidonic acid.
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.
MAPK cascade	An intracellular protein kinase cascade containing at least a MAPK, a MAPKK and a MAP3K. The cascade can also contain an additional tiers
p38MAPK cascade	An intracellular protein kinase cascade containing at least a p38 MAPK, a MAPKK and a MAP3K. The cascade can also contain an additional tier
peptidyl-serine phosphorylation	The phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine.
positive regulation of macrophage cytokine production	Any process that increases the rate, frequency or extent of macrophage cytokine production. Macrophage cytokine production is the appearance of a chemokine due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels.
positive regulation of tumor necrosis factor production	Any process that activates or increases the frequency, rate or extent of tumor necrosis factor production.
protein phosphorylation	The process of introducing a phosphate group on to a protein.
regulation of cellular response to heat	Any process that modulates the frequency, rate or extent of cellular response to heat.
regulation of interleukin-6 production	Any process that modulates the frequency, rate, or extent of interleukin-6 production.
regulation of mRNA stability	Any process that modulates the propensity of mRNA molecules to degradation. Includes processes that both stabilize and destabilize mRNAs.
regulation of tumor necrosis factor production	Any process that modulates the frequency, rate or extent of tumor necrosis factor production.
regulation of tumor necrosis factor-mediated signaling pathway	Any process that modulates the rate or extent of the tumor necrosis factor-mediated signaling pathway. The tumor necrosis factor-mediated signaling pathway is the series of molecular signals generated as a consequence of tumor necrosis factor binding to a cell surface receptor.
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.
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
Q16644	MAPKAPK3	MAP kinase-activated protein kinase 3	Homo sapiens (Human)	SS
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
Q3UMW7	Mapkapk3	MAP kinase-activated protein kinase 3	Mus musculus (Mouse)	SS
P49138	Mapkapk2	MAP kinase-activated protein kinase 2	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
MLSNSQGQSP	PVPFPAPAPP	PQPPTPALPH	PPAQPPPPPP	QQFPQFHVKS	GLQIKKNAII
70	80	90	100	110	120
DDYKVTSQVL	GLGINGKVLQ	IFNKRTQEKF	ALKMLQDCPK	ARREVELHWR	ASQCPHIVRI
130	140	150	160	170	180
VDVYENLYAG	RKCLLIVMEC	LDGGELFSRI	QDRGDQAFTE	REASEIMKSI	GEAIQYLHSI
190	200	210	220	230	240
NIAHRDVKPE	NLLYTSKRPN	AILKLTDFGF	AKETTSHNSL	TTPCYTPYYV	APEVLGPEKY
250	260	270	280	290	300
DKSCDMWSLG	VIMYILLCGY	PPFYSNHGLA	ISPGMKTRIR	MGQYEFPNPE	WSEVSEEVKM
310	320	330	340	350	360
LIRNLLKTEP	TQRMTITEFM	NHPWIMQSTK	VPQTPLHTSR	VLKEDKERWE	DVKEEMTSAL
370	380	390
ATMRVDYEQI	KIKKIEDASN	PLLLKRRKKA	RALEAAALAH