AiPD: Autoinhibited Protein Database

P45983

Gene name	MAPK8 (JNK1, PRKM8, SAPK1, SAPK1C)
Protein name	Mitogen-activated protein kinase 8
Names	MAP kinase 8 , MAPK 8 , EC 2.7.11.24 , JNK-46 , Stress-activated protein kinase 1c , SAPK1c , Stress-activated protein kinase JNK1 , c-Jun N-terminal kinase 1
Species	Homo sapiens (Human)
KEGG Pathway	hsa:5599
EC number	2.7.11.24: Protein-serine/threonine kinases
Protein Class	MITOGEN-ACTIVATED PROTEIN KINASE (PTHR24055)

Descriptions

JNK1 is a member of the mitogen-activated protein kinase (MAPK) family, involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. It undergoes autoinhibition through peptide-induced interlobe opening and rotation, moving αC out of the catalytic site and allowing the activation loop to form an inhibitory helix blocking the ATP binding site of JNK1’s kinase domain. Autoinhibition is relieved by phosphorylation of the activation loop.

Autoinhibitory domains (AIDs)

Accessory elements

168-178 (Activation loop from InterPro)

Target domain	26-321 (Protein kinase domain)
Relief mechanism	PTM
Assay	Structural analysis, Mutagenesis experiment

182-190 (Activation loop from InterPro)

Target domain	26-321 (Protein kinase domain)
Relief mechanism	PTM
Assay	Structural analysis, Mutagenesis experiment

References

Laughlin JD et al. (2012) "Structural mechanisms of allostery and autoinhibition in JNK family kinases", Structure (London, England : 1993), 20, 2174-84

Autoinhibited structure

Activated structure

35 structures for P45983

Entry ID	Method	Resolution	Chain	Position	Source
1UKH	X-ray	235 A	A	1-363	PDB
1UKI	X-ray	270 A	A	1-363	PDB
2G01	X-ray	350 A	A/B	1-364	PDB
2GMX	X-ray	350 A	A/B	1-364	PDB
2H96	X-ray	300 A	A/B	1-364	PDB
2NO3	X-ray	320 A	A/B	1-364	PDB
2XRW	X-ray	133 A	A	2-364	PDB
2XS0	X-ray	260 A	A	1-379	PDB
3ELJ	X-ray	180 A	A	1-364	PDB
3O17	X-ray	300 A	A/B	1-364	PDB
3O2M	X-ray	270 A	A/B	1-364	PDB
3PZE	X-ray	200 A	A	7-364	PDB
3V3V	X-ray	270 A	A	1-366	PDB
3VUD	X-ray	350 A	A	1-364	PDB
3VUG	X-ray	324 A	A	1-364	PDB
3VUH	X-ray	270 A	A	1-364	PDB
3VUI	X-ray	280 A	A	1-364	PDB
3VUK	X-ray	295 A	A	1-364	PDB
3VUL	X-ray	281 A	A	1-364	PDB
3VUM	X-ray	269 A	A	1-364	PDB
4AWI	X-ray	191 A	A	1-364	PDB
4E73	X-ray	227 A	A	1-363	PDB
4G1W	X-ray	245 A	A	1-363	PDB
4HYS	X-ray	242 A	A	1-363	PDB
4HYU	X-ray	215 A	A	1-363	PDB
4IZY	X-ray	230 A	A	1-363	PDB
4L7F	X-ray	195 A	A	7-362	PDB
4QTD	X-ray	150 A	A	1-363	PDB
4UX9	X-ray	234 A	A/B/C/D	1-364	PDB
4YR8	X-ray	240 A	A/C/E/F	1-363	PDB
5LW1	X-ray	320 A	B/E/H	2-363	PDB
6F5E	X-ray	270 A	B	2-363	PDB
6ZR5	X-ray	270 A	A/B	1-364	PDB
8X5M	X-ray	200 A	A	2-364	PDB
AF-P45983-F1	Predicted				AlphaFoldDB

290 variants for P45983

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
rs770396528	2	S>N		No	ExAC gnomAD
rs2042165911	3	R>G		No	Ensembl
rs2042166036	4	S>C		No	Ensembl
rs2042166193	4	S>R		No	Ensembl
COSM5074514 COSM170014 rs773780784	6	R>C	Variant assessed as Somatic; MODERATE impact. large_intestine [NCI-TCGA, Cosmic]	No	cosmic curated NCI-TCGA Cosmic ExAC NCI-TCGA TOPMed gnomAD
COSM4014379 COSM4014380 rs759178320 COSM4014381	6	R>H	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic ExAC NCI-TCGA TOPMed gnomAD
rs773780784	6	R>S		No	ExAC TOPMed gnomAD
rs2042166874	7	D>G		No	TOPMed
rs771655862	8	N>S		No	ExAC gnomAD
rs1467885822	9	N>D		No	gnomAD
rs150753150	9	N>K		No	ESP ExAC TOPMed gnomAD
rs1047240487	9	N>S		No	TOPMed gnomAD
rs1406003607	10	F>I		No	TOPMed gnomAD
rs1299206807	11	Y>C		No	gnomAD
rs760960935	11	Y>H		No	ExAC gnomAD
rs754396010	14	E>G		No	ExAC TOPMed gnomAD
rs764612003	14	E>K		No	ExAC gnomAD
rs2042169022	17	D>E		No	Ensembl
rs1233570131	17	D>V		No	TOPMed gnomAD
rs765388602	19	T>A		No	ExAC gnomAD
rs370411166	22	V>I		No	ESP ExAC TOPMed gnomAD
rs2132977018	23	L>M		No	Ensembl
rs780150000	24	K>T		No	ExAC TOPMed gnomAD
COSM427595 rs2042170101 COSM5196829 COSM427596	25	R>*	Variant assessed as Somatic; HIGH impact. breast [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated gnomAD
COSM5349138 COSM5349139 COSM216920 rs755894470	25	R>Q	liver Variant assessed as Somatic; MODERATE impact. [Cosmic, NCI-TCGA]	No	NCI-TCGA Cosmic cosmic curated ExAC NCI-TCGA TOPMed gnomAD
rs1318665915	26	Y>*		No	TOPMed gnomAD
rs2042170781	28	N>K		No	Ensembl
COSM918463 COSM918462 rs1417658483	31	P>L	Variant assessed as Somatic; MODERATE impact. endometrium [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated NCI-TCGA gnomAD
rs2132977453	32	I>T		No	Ensembl
rs1481506037	32	I>V		No	TOPMed gnomAD
COSM1347947 COSM1347948 COSM5135354	38	G>R	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1664423061	39	I>T		No	TOPMed gnomAD
rs1323103105	39	I>V		No	gnomAD
COSM918464 COSM918465 rs778730942 COSM5165497	41	C>=	Variant assessed as Somatic; LOW impact. [NCI-TCGA]	No	NCI-TCGA Cosmic NCI-TCGA
rs770874861	41	C>Y		No	ExAC TOPMed gnomAD
rs200350498	42	A>S		No	ExAC TOPMed gnomAD
rs200350498 COSM1347950 COSM1347949 COSM4602711	42	A>T	Variant assessed as Somatic; MODERATE impact. large_intestine [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated ExAC NCI-TCGA TOPMed gnomAD
rs1361641151	43	A>G		No	gnomAD
rs1589210960	43	A>T		No	Ensembl
rs2042377460	44	Y>F		No	Ensembl
rs1467645843	44	Y>H		No	gnomAD
rs143875999	46	A>T		No	ESP ExAC TOPMed gnomAD
rs779657933	46	A>V		No	ExAC TOPMed gnomAD
rs2042377938	47	I>V		No	Ensembl
rs746642373	48	L>P		No	ExAC gnomAD
rs1233762287	49	E>G		No	gnomAD
rs2042378605	51	N>H		No	Ensembl
rs2042378763	51	N>S		No	TOPMed
rs2042379221	53	A>G		No	gnomAD
rs2042379049	53	A>T		No	TOPMed
rs2133024036	54	I>V		No	Ensembl
rs1157307365	58	S>G		No	gnomAD
rs554758335	59	R>*		No	1000Genomes ExAC gnomAD
rs573076590	59	R>Q		No	1000Genomes ExAC TOPMed gnomAD
rs1363332287	68	K>N		No	gnomAD
rs1411261165	69	R>Q		No	gnomAD
COSM918467 COSM918466	73	E>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1739252749	76	L>F		No	gnomAD
COSM1347954 COSM5171750 COSM1347953	77	M>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1334928589	77	M>T		No	gnomAD
rs2042381603	79	C>S		No	gnomAD
rs2133024708	80	V>A		No	Ensembl
rs1439986144	80	V>I		No	gnomAD
rs2042381911	83	K>N		No	gnomAD
TCGA novel	84	N>K	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs1029787979	85	I>V		No	TOPMed
rs780976087	90	N>H		No	ExAC gnomAD
rs200881923	94	P>R		No	1000Genomes
TCGA novel	95	Q>L	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs773674759	97	S>C		No	ExAC TOPMed gnomAD
COSM3438211 COSM1702325 rs773674759 COSM1702324	97	S>F	Variant assessed as Somatic; MODERATE impact. skin [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated ExAC NCI-TCGA TOPMed gnomAD
rs2042660731	98	L>P		No	TOPMed
COSM918469 rs2042661088 COSM918470	101	F>L	Variant assessed as Somatic; MODERATE impact. endometrium [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated Ensembl
COSM190535 COSM918468	101	F>S	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs771498910	102	Q>R		No	ExAC gnomAD
TCGA novel	103	D>Y	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1444972184	105	Y>*		No	gnomAD
rs750668630	106	I>M		No	Ensembl
rs2042667596	106	I>V		No	gnomAD
rs752372488	110	L>R		No	ExAC gnomAD
rs2042668485	112	D>G		No	Ensembl
rs755812386	113	A>G		No	ExAC gnomAD
rs2042668649	113	A>T		No	TOPMed gnomAD
COSM5560673 COSM5560674 COSM5560675	114	N>H	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
COSM257372 COSM918471	115	L>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
COSM3438213 COSM3438212 COSM3438214	121	M>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1173910920	121	M>V		No	gnomAD
rs1418848027	122	E>A		No	TOPMed gnomAD
rs1418848027	122	E>V		No	TOPMed gnomAD
COSM3967075 COSM3967076 COSM3967077	125	H>R	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1181281990	128	M>I		No	TOPMed gnomAD
rs2042670235	131	L>R		No	TOPMed
rs1196726534	135	M>L		No	TOPMed gnomAD
rs1196726534	135	M>V		No	TOPMed gnomAD
rs1215027038	143	H>N		No	TOPMed gnomAD
rs779380684	145	A>V		No	ExAC gnomAD
rs1398431451	146	G>V		No	gnomAD
rs2042672007	148	I>V		No	gnomAD
COSM684193 COSM684192	149	H>Y	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs755655560	155	S>N		No	ExAC TOPMed gnomAD
rs2043275782	155	S>R		No	Ensembl
rs1451383737	157	I>M		No	TOPMed
rs368198154	157	I>V		No	ESP ExAC TOPMed gnomAD
rs1220824711	163	C>F		No	TOPMed gnomAD
TCGA novel	166	K>M	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
VAR_042258	171	G>S	a renal clear cell carcinoma sample; somatic mutation [UniProt]	No	UniProt
rs2043277231	172	L>P		No	Ensembl
rs868234992	173	A>V		No	Ensembl
rs372126348	176	A>S		No	ESP ExAC TOPMed gnomAD
COSM13337 rs2043278229 VAR_042259	177	G>R	central_nervous_system a glioblastoma multiforme sample; somatic mutation [Cosmic, UniProt]	No	cosmic curated gnomAD UniProt
COSM4827338 COSM4827337 rs1162940624 COSM4827336	178	T>M	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic NCI-TCGA gnomAD
rs1356700893	182	M>V		No	gnomAD
COSM918472 COSM918473	183	T>M	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs2043279063	186	V>E		No	TOPMed
TCGA novel	188	T>A	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
COSM684190 rs202013888 COSM684191	189	R>C	lung Variant assessed as Somatic; MODERATE impact. [Cosmic, NCI-TCGA]	No	NCI-TCGA Cosmic cosmic curated 1000Genomes ExAC NCI-TCGA gnomAD
COSM918474 COSM918475	189	R>H	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
COSM684186 COSM684187	189	R>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1589253309	194	P>S		No	Ensembl
rs868332724	198	L>P		No	Ensembl
rs1037196002	205	N>=	Variant assessed as Somatic; LOW impact. [NCI-TCGA]	No	NCI-TCGA
TCGA novel	206	V>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs2043526046	209	W>G		No	TOPMed gnomAD
rs1199564380	211	V>L		No	TOPMed
rs747531271	214	I>S		No	ExAC gnomAD
rs2043527558	215	M>V		No	Ensembl
rs1262446655	216	G>E		No	gnomAD
COSM3415062	217	E>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
COSM918476	217	E>Q	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs2043527957	218	M>T		No	TOPMed gnomAD
TCGA novel	221	H>T	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs2043528776	226	P>A		No	Ensembl
rs376010774	226	P>L		No	ESP ExAC TOPMed gnomAD
rs774221220	229	D>N		No	ExAC gnomAD
rs1402727389	231	I>L		No	TOPMed gnomAD
rs1402727389 COSM190546	231	I>V	Variant assessed as Somatic; MODERATE impact. large_intestine [NCI-TCGA, Cosmic]	No	cosmic curated NCI-TCGA TOPMed gnomAD
rs748025349	235	N>S		No	ExAC gnomAD
rs2043653013	240	Q>H		No	TOPMed
COSM3790810 COSM3790809	240	Q>R	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
TCGA novel	241	L>F	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
COSM1297286 COSM1297287	246	P>R	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
COSM415015 COSM415014	247	E>Q	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs756073891	249	M>L		No	ExAC TOPMed gnomAD
rs377156368	249	M>T		No	ESP TOPMed gnomAD
rs756073891	249	M>V		No	ExAC TOPMed gnomAD
rs2043654040	251	K>R		No	Ensembl
rs780732703	253	Q>*		No	Ensembl
rs2043654875	256	V>I		No	Ensembl
rs1589269014	258	T>A		No	Ensembl
rs1352216003	260	V>A		No	gnomAD
COSM1347970 COSM1347971	260	V>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1205418935	262	N>S		No	gnomAD
rs770530313	263	R>K		No	ExAC TOPMed gnomAD
rs752183776	264	P>T		No	Ensembl
rs1201342024	266	Y>F		No	gnomAD
COSM3438218 COSM3438219	266	Y>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1269301566	267	A>S		No	TOPMed gnomAD
rs1269301566	267	A>T		No	TOPMed gnomAD
rs2043657678	268	G>R		No	TOPMed
rs2043658283	269	Y>C		No	gnomAD
rs199509878	269	Y>H		No	1000Genomes ExAC gnomAD
rs758356952	270	S>C		No	Ensembl
rs569412118	272	E>A		No	1000Genomes
TCGA novel	275	F>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
COSM4014383 COSM4014384	276	P>S	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
TCGA novel	280	F>P	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
COSM415012 COSM415013	283	D>H	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1290318874	283	D>N		No	TOPMed
rs2043660231	287	N>D		No	Ensembl
rs1430973969	288	K>Q		No	Ensembl
rs2043660607	288	K>R		No	Ensembl
rs1159852187	292	S>G		No	TOPMed gnomAD
rs1448138314	292	S>N		No	gnomAD
rs1454207254	293	Q>R		No	TOPMed gnomAD
rs2043686720	297	L>V		No	TOPMed gnomAD
rs2043686904	299	S>P		No	Ensembl
rs2043687080	301	M>L		No	Ensembl
rs2043687877	304	I>L		No	TOPMed
rs45505100	304	I>M		No	ExAC gnomAD
rs1313003666	306	A>E		No	gnomAD
rs775931291	306	A>S	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA gnomAD
rs1320670600	308	K>E		No	gnomAD
rs1242378993	308	K>R		No	gnomAD
rs747392955	311	S>C		No	ExAC gnomAD
rs540242907	313	D>E		No	1000Genomes ExAC TOPMed gnomAD
rs1237716763	313	D>G		No	TOPMed gnomAD
rs769203778	313	D>N		No	ExAC TOPMed gnomAD
rs769203778	313	D>Y		No	ExAC TOPMed gnomAD
rs1185435366	314	E>K		No	gnomAD
TCGA novel	316	L>F	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
TCGA novel	320	Y>C	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs142342900	322	N>S		No	ESP ExAC TOPMed gnomAD
TCGA novel	325	Y>F	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1454123136	330	A>T		No	gnomAD
rs2043692546	332	A>G		No	Ensembl
rs986626073	334	P>L		No	gnomAD
rs763747268	336	K>R		No	ExAC gnomAD
rs1427342522	337	I>M		No	Ensembl
rs2043731220	338	P>H		No	TOPMed
rs1276026393	338	P>S		No	TOPMed gnomAD
rs1276026393	338	P>T		No	TOPMed gnomAD
rs2043731418	339	D>H		No	TOPMed
COSM4014386 COSM4014385	339	D>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1475171749	340	K>N		No	TOPMed gnomAD
COSM1347973 COSM1347972	341	Q>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs2043731777	343	D>N		No	TOPMed
rs753698159	345	R>K		No	ExAC gnomAD
rs765234973	346	E>K		No	ExAC gnomAD
rs750388057	347	H>Y		No	ExAC gnomAD
rs757980939	348	T>A		No	ExAC gnomAD
rs1390438534	349	I>T		No	TOPMed gnomAD
rs1488717032	349	I>V		No	TOPMed gnomAD
rs1328803228	350	E>D		No	TOPMed gnomAD
rs944850013	353	K>R		No	TOPMed gnomAD
rs1354748570	355	L>M		No	TOPMed gnomAD
rs2044217039	356	I>M		No	Ensembl
rs754818843	357	Y>C		No	TOPMed gnomAD
rs201417282	357	Y>H		No	1000Genomes ExAC TOPMed gnomAD
rs371493413	361	M>T		No	ESP ExAC TOPMed gnomAD
rs45483593 VAR_050592	365	E>K		No	UniProt Ensembl dbSNP
rs2044219561	366	R>G		No	TOPMed
rs28395809	367	T>A		No	Ensembl
rs751150249	367	T>S		No	ExAC gnomAD
rs1346038846	368	K>E		No	gnomAD
rs767178901	372	I>L		No	ExAC TOPMed gnomAD
rs988262121	372	I>T		No	gnomAD
rs767178901	372	I>V		No	ExAC TOPMed gnomAD
rs756498386	373	R>L		No	ExAC TOPMed gnomAD
rs756498386	373	R>Q		No	ExAC TOPMed gnomAD
rs752334346	373	R>W	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA TOPMed gnomAD
rs151285118	374	G>A		No	ESP ExAC TOPMed gnomAD
rs151285118	374	G>E		No	ESP ExAC TOPMed gnomAD
rs778058488	374	G>R		No	ExAC gnomAD
rs1348073540	376	P>L		No	gnomAD
rs1348073540	376	P>R		No	gnomAD
rs778924369	377	S>A		No	ExAC gnomAD
rs778924369	377	S>P		No	ExAC gnomAD
rs745968638	378	P>R		No	ExAC gnomAD
rs2133327919	378	P>S		No	Ensembl
rs1019024052	380	G>V		No	Ensembl
rs1323743097	382	A>T		No	TOPMed
rs2044726922	384	I>M		No	Ensembl
rs758497860	384	I>N		No	ExAC gnomAD
rs780052742	385	N>S		No	ExAC TOPMed gnomAD
rs780052742	385	N>T		No	ExAC TOPMed gnomAD
rs747193295	387	S>F		No	ExAC gnomAD
rs768761581	389	H>P		No	ExAC TOPMed gnomAD
TCGA novel	389	H>Y	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs749073014	392	S>A		No	ExAC gnomAD
rs1422869920	393	S>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA gnomAD
rs2044729666	394	S>L		No	TOPMed
rs933003988	395	S>C		No	TOPMed gnomAD
TCGA novel	395	S>F	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs759451457	397	N>D		No	ExAC TOPMed gnomAD
rs367599489	397	N>S		No	ESP ExAC TOPMed gnomAD
rs2044731322	398	D>Y		No	TOPMed
rs1353720299	399	V>A		No	TOPMed gnomAD
rs992324943	399	V>M		No	gnomAD
rs763758430	402	M>K		No	ExAC TOPMed gnomAD
rs774869055	402	M>L		No	ExAC TOPMed gnomAD
rs774869055	402	M>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA TOPMed gnomAD
rs1285833471	404	T>A		No	Ensembl
rs1340500693	404	T>I		No	gnomAD
TCGA novel	405	D>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs765655352	406	P>L		No	ExAC TOPMed gnomAD
rs1199331193	408	L>S		No	gnomAD
rs2044734894	409	A>D		No	Ensembl
rs1276075262	410	S>C		No	TOPMed gnomAD
rs1276075262	410	S>F		No	TOPMed gnomAD
rs2044735690	412	T>K		No	Ensembl
rs2044735940	414	S>R		No	TOPMed
rs1489044523	416	L>R		No	gnomAD
rs147673874	418	A>G		No	ESP ExAC TOPMed gnomAD
rs147673874	418	A>V		No	ESP ExAC TOPMed gnomAD
rs972332361	419	A>S		No	TOPMed
rs972332361	419	A>T		No	TOPMed
rs142606131	420	A>D		No	ESP ExAC gnomAD
rs1011736095	420	A>P		No	gnomAD
rs2044738415	421	G>R		No	Ensembl
rs1589341428	423	L>Q		No	Ensembl
rs1589341428	423	L>R		No	Ensembl
rs1325673457	423	L>V		No	gnomAD
rs781538114	424	G>D		No	ExAC gnomAD
rs781538114	424	G>V		No	ExAC gnomAD
rs2044740086	425	C>F		No	Ensembl
rs2044739854	425	C>G		No	Ensembl
rs748451475	427	R>G		No	ExAC gnomAD
rs1478396994	427	R>I		No	gnomAD
rs2044740784	427	R>S		No	Ensembl
rs2044741039	428	R>R		No	TOPMed

No associated diseases with P45983

3 regional properties for P45983

Type	Name	Position	InterPro Accession
domain	Protein kinase domain	26 - 321	IPR000719
conserved_site	Mitogen-activated protein (MAP) kinase, conserved site	61 - 163	IPR003527
active_site	Serine/threonine-protein kinase, active site	147 - 159	IPR008271

Functions

		Description
EC Number	2.7.11.24	Protein-serine/threonine kinases
Subcellular Localization	Cytoplasm Nucleus Synapse	In the cortical neurons, predominantly cytoplasmic and associated with the Golgi apparatus and endosomal fraction Increased neuronal activity increases phosphorylated form at synapses (By similarity) Colocalizes with POU5F1 in the nucleus
PANTHER Family	PTHR24055	MITOGEN-ACTIVATED PROTEIN KINASE
PANTHER Subfamily	PTHR24055:SF222	MITOGEN-ACTIVATED PROTEIN KINASE 8
PANTHER Protein Class	non-receptor serine/threonine protein kinase protein modifying enzyme
PANTHER Pathway Category	Integrin signalling pathway Jnk TGF-beta signaling pathway JNK PDGF signaling pathway ERK Angiogenesis JNK1 Interferon-gamma signaling pathway Serine kinase EGF receptor signaling pathway JNK1-3 CCKR signaling map MAPK8-10 FGF signaling pathway JNK1-3 FAS signaling pathway JNK Oxidative stress response JNK1/2 Ras Pathway JNK Alzheimer disease-amyloid secretase pathway MAPK Apoptosis signaling pathway JNK Toll receptor signaling pathway JNK B cell activation Jnk Parkinson disease SAPK Gonadotropin-releasing hormone receptor pathway JNK1/2 T cell activation Jnk

7 GO annotations of cellular component

Name	Definition
axon	The long process of a neuron that conducts nerve impulses, usually away from the cell body to the terminals and varicosities, which are sites of storage and release of neurotransmitter.
basal dendrite	A dendrite that emerges near the basal pole of a neuron. In bipolar neurons, basal dendrites are either on the same side of the soma as the axon, or project toward the axon.
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.
synapse	The junction between an axon of one neuron and a dendrite of another neuron, a muscle fiber or a glial cell. As the axon approaches the synapse it enlarges into a specialized structure, the presynaptic terminal bouton, which contains mitochondria and synaptic vesicles. At the tip of the terminal bouton is the presynaptic membrane; facing it, and separated from it by a minute cleft (the synaptic cleft) is a specialized area of membrane on the receiving cell, known as the postsynaptic membrane. In response to the arrival of nerve impulses, the presynaptic terminal bouton secretes molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane.

9 GO annotations of molecular function

Name	Definition
ATP binding	Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
enzyme binding	Binding to an enzyme, a protein with catalytic activity.
histone deacetylase binding	Binding to histone deacetylase.
histone deacetylase regulator activity	Binds to and modulates the activity of histone deacetylase.
JUN kinase activity	Catalysis of the reaction
protein phosphatase binding	Binding to a protein phosphatase.
protein serine kinase activity	Catalysis of the reactions
protein serine/threonine kinase activity	Catalysis of the reactions
protein serine/threonine kinase binding	Binding to a protein serine/threonine kinase.

30 GO annotations of biological process

Name	Definition
cellular response to amino acid starvation	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 deprivation of amino acids.
cellular response to cadmium ion	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 cadmium (Cd) ion stimulus.
cellular response to lipopolysaccharide	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 lipopolysaccharide stimulus; lipopolysaccharide is a major component of the cell wall of gram-negative bacteria.
cellular response to mechanical 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 mechanical stimulus.
cellular response to oxidative stress	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 oxidative stress, a state often resulting from exposure to high levels of reactive oxygen species, e.g. superoxide anions, hydrogen peroxide (H2O2), and hydroxyl radicals.
cellular response to reactive oxygen species	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 reactive oxygen species stimulus. Reactive oxygen species include singlet oxygen, superoxide, and oxygen free radicals.
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.
Fc-epsilon receptor signaling pathway	The series of molecular signals initiated by the binding of the Fc portion of immunoglobulin E (IgE) to an Fc-epsilon receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. The Fc portion of an immunoglobulin is its C-terminal constant region.
JNK cascade	An intracellular protein kinase cascade containing at least a JNK (a MAPK), a JNKK (a MAPKK) and a JUN3K (a MAP3K). The cascade can also contain an additional tier
JUN phosphorylation	The process of introducing a phosphate group into a JUN protein.
negative regulation of apoptotic process	Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process.
negative regulation of protein binding	Any process that stops, prevents, or reduces the frequency, rate or extent of protein binding.
peptidyl-serine phosphorylation	The phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine.
peptidyl-threonine phosphorylation	The phosphorylation of peptidyl-threonine to form peptidyl-O-phospho-L-threonine.
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 cell killing	Any process that activates or increases the frequency, rate or extent of cell killing.
positive regulation of cyclase activity	Any process that activates or increases the activity of a cyclase.
positive regulation of gene expression	Any process that increases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
positive regulation of NLRP3 inflammasome complex assembly	Any process that activates or increases the frequency, rate or extent of NLRP3 inflammasome complex assembly.
positive regulation of protein metabolic process	Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways involving a protein.
protein phosphorylation	The process of introducing a phosphate group on to a protein.
regulation of circadian rhythm	Any process that modulates the frequency, rate or extent of a circadian rhythm. A circadian rhythm is a biological process in an organism that recurs with a regularity of approximately 24 hours.
regulation of DNA replication origin binding	Any process that modulates the frequency, rate or extent of DNA replication origin binding.
regulation of macroautophagy	Any process that modulates the frequency, rate or extent of macroautophagy.
regulation of protein localization	Any process that modulates the frequency, rate or extent of any process in which a protein is transported to, or maintained in, a specific location.
response to mechanical stimulus	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 mechanical stimulus.
response to oxidative stress	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 oxidative stress, a state often resulting from exposure to high levels of reactive oxygen species, e.g. superoxide anions, hydrogen peroxide (H2O2), and hydroxyl radicals.
response to UV	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 an ultraviolet radiation (UV light) stimulus. Ultraviolet radiation is electromagnetic radiation with a wavelength in the range of 10 to 380 nanometers.
rhythmic process	Any process pertinent to the generation and maintenance of rhythms in the physiology of an organism.
stress-activated MAPK cascade	The series of molecular signals in which a stress-activated MAP kinase cascade relays a signal; MAP kinase cascades involve at least three protein kinase activities and culminate in the phosphorylation and activation of a MAP kinase.

33 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
P32485	HOG1	Mitogen-activated protein kinase HOG1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)	PR
P79996	MAPK9	Mitogen-activated protein kinase 9	Gallus gallus (Chicken)	PR
P20794	MAK	Serine/threonine-protein kinase MAK	Homo sapiens (Human)	PR
Q9UQ07	MOK	MAPK/MAK/MRK overlapping kinase	Homo sapiens (Human)	PR
Q8TD08	MAPK15	Mitogen-activated protein kinase 15	Homo sapiens (Human)	SS
P45984	MAPK9	Mitogen-activated protein kinase 9	Homo sapiens (Human)	SS
P53779	MAPK10	Mitogen-activated protein kinase 10	Homo sapiens (Human)	EV
Q9UBE8	NLK	Serine/threonine-protein kinase NLK	Homo sapiens (Human)	SS
P27361	MAPK3	Mitogen-activated protein kinase 3	Homo sapiens (Human)	SS
P28482	MAPK1	Mitogen-activated protein kinase 1	Homo sapiens (Human)	EV
P31152	MAPK4	Mitogen-activated protein kinase 4	Homo sapiens (Human)	SS
Q16659	MAPK6	Mitogen-activated protein kinase 6	Homo sapiens (Human)	SS
Q13164	MAPK7	Mitogen-activated protein kinase 7	Homo sapiens (Human)	SS
P53778	MAPK12	Mitogen-activated protein kinase 12	Homo sapiens (Human)	SS
O15264	MAPK13	Mitogen-activated protein kinase 13	Homo sapiens (Human)	SS
Q15759	MAPK11	Mitogen-activated protein kinase 11	Homo sapiens (Human)	SS
Q16539	MAPK14	Mitogen-activated protein kinase 14	Homo sapiens (Human)	SS
Q9WTU6	Mapk9	Mitogen-activated protein kinase 9	Mus musculus (Mouse)	PR
Q91Y86	Mapk8	Mitogen-activated protein kinase 8	Mus musculus (Mouse)	PR
P49186	Mapk9	Mitogen-activated protein kinase 9	Rattus norvegicus (Rat)	PR
Q336X9	MPK6	Mitogen-activated protein kinase 6	Oryza sativa subsp. japonica (Rice)	SS
Q5J4W4	MPK2	Mitogen-activated protein kinase 2	Oryza sativa subsp. japonica (Rice)	SS
Q84UI5	MPK1	Mitogen-activated protein kinase 1	Oryza sativa subsp. japonica (Rice)	SS
Q10N20	MPK5	Mitogen-activated protein kinase 5	Oryza sativa subsp. japonica (Rice)	SS
O44408	kgb-1	GLH-binding kinase 1	Caenorhabditis elegans	PR
Q39023	MPK3	Mitogen-activated protein kinase 3	Arabidopsis thaliana (Mouse-ear cress)	SS
Q39026	MPK6	Mitogen-activated protein kinase 6	Arabidopsis thaliana (Mouse-ear cress)	SS
Q39025	MPK5	Mitogen-activated protein kinase 5	Arabidopsis thaliana (Mouse-ear cress)	SS
Q39024	MPK4	Mitogen-activated protein kinase 4	Arabidopsis thaliana (Mouse-ear cress)	SS
Q9M1Z5	MPK10	Mitogen-activated protein kinase 10	Arabidopsis thaliana (Mouse-ear cress)	SS
Q8GYQ5	MPK12	Mitogen-activated protein kinase 12	Arabidopsis thaliana (Mouse-ear cress)	SS
Q9LMM5	MPK11	Mitogen-activated protein kinase 11	Arabidopsis thaliana (Mouse-ear cress)	SS
Q9LQQ9	MPK13	Mitogen-activated protein kinase 13	Arabidopsis thaliana (Mouse-ear cress)	SS

10	20	30	40	50	60
MSRSKRDNNF	YSVEIGDSTF	TVLKRYQNLK	PIGSGAQGIV	CAAYDAILER	NVAIKKLSRP
70	80	90	100	110	120
FQNQTHAKRA	YRELVLMKCV	NHKNIIGLLN	VFTPQKSLEE	FQDVYIVMEL	MDANLCQVIQ
130	140	150	160	170	180
MELDHERMSY	LLYQMLCGIK	HLHSAGIIHR	DLKPSNIVVK	SDCTLKILDF	GLARTAGTSF
190	200	210	220	230	240
MMTPYVVTRY	YRAPEVILGM	GYKENVDLWS	VGCIMGEMVC	HKILFPGRDY	IDQWNKVIEQ
250	260	270	280	290	300
LGTPCPEFMK	KLQPTVRTYV	ENRPKYAGYS	FEKLFPDVLF	PADSEHNKLK	ASQARDLLSK
310	320	330	340	350	360
MLVIDASKRI	SVDEALQHPY	INVWYDPSEA	EAPPPKIPDK	QLDEREHTIE	EWKELIYKEV
370	380	390	400	410	420
MDLEERTKNG	VIRGQPSPLG	AAVINGSQHP	SSSSSVNDVS	SMSTDPTLAS	DTDSSLEAAA

GPLGCCR