AiPD: Autoinhibited Protein Database

O14733

Gene name	MAP2K7 (JNKK2, MEK7, MKK7, PRKMK7, SKK4)
Protein name	Dual specificity mitogen-activated protein kinase kinase 7
Names	MAP kinase kinase 7, MAPKK 7, JNK-activating kinase 2, MAPK/ERK kinase 7, MEK 7, Stress-activated protein kinase kinase 4, SAPK kinase 4, SAPKK-4, SAPKK4, c-Jun N-terminal kinase kinase 2, JNK kinase 2, JNKK 2
Species	Homo sapiens (Human)
KEGG Pathway	hsa:5609
EC number	2.7.12.2: Dual-specificity kinases (those acting on Ser/Thr and Tyr residues)
Protein Class

Descriptions

The autoinhibited protein was predicted that may have potential autoinhibitory elements via cis-regPred.

Autoinhibitory domains (AIDs)

1-144 (Predicted disordered autoinhibitory region) PR

Target domain
Relief mechanism
Assay	cis-regPred

AID

1-144 (Predicted disordered autoinhibitory region)

Target domain

Relief mechanism

Assay

cis-regPred

Accessory elements

260-282 (Activation loop from InterPro)

Target domain	120-380 (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

Autoinhibited structure

Activated structure

37 structures for O14733

Entry ID	Method	Resolution	Chain	Position	Source
2DYL	X-ray	245 A	A	101-405	PDB
3WZU	X-ray	301 A	A	103-419	PDB
4UX9	X-ray	234 A	F/G/H/I	37-48	PDB
5B2K	X-ray	275 A	A	103-419	PDB
5B2L	X-ray	210 A	A	103-419	PDB
5B2M	X-ray	306 A	A	103-419	PDB
5Y8U	X-ray	292 A	A	103-419	PDB
5Y90	X-ray	130 A	A	103-419	PDB
5Z1D	X-ray	228 A	A	102-419	PDB
5Z1E	X-ray	230 A	A	102-419	PDB
6IB0	X-ray	260 A	A	101-408	PDB
6IB2	X-ray	210 A	A	101-408	PDB
6QFL	X-ray	220 A	A	101-408	PDB
6QFR	X-ray	230 A	A	101-408	PDB
6QFT	X-ray	270 A	A	101-408	PDB
6QG4	X-ray	230 A	A	111-408	PDB
6QG7	X-ray	210 A	A	101-408	PDB
6QHO	X-ray	270 A	A	111-408	PDB
6QHR	X-ray	252 A	A	111-408	PDB
6YFZ	X-ray	190 A	A	100-405	PDB
6YG0	X-ray	200 A	A	100-405	PDB
6YG1	X-ray	222 A	A/B/C	60-405	PDB
6YG2	X-ray	200 A	A	100-405	PDB
6YG3	X-ray	205 A	A	100-405	PDB
6YG4	X-ray	230 A	A	100-405	PDB
6YG5	X-ray	240 A	A	100-405	PDB
6YG6	X-ray	215 A	A/B	100-405	PDB
6YG7	X-ray	220 A	A/B	100-405	PDB
6YZ4	X-ray	170 A	A	100-405	PDB
7CBX	X-ray	206 A	A	103-419	PDB
7OVI	X-ray	195 A	A	101-408	PDB
7OVJ	X-ray	235 A	A	101-408	PDB
7OVK	X-ray	205 A	A	101-408	PDB
7OVL	X-ray	290 A	A	101-408	PDB
7OVM	X-ray	290 A	A	101-408	PDB
7OVN	X-ray	290 A	A	101-408	PDB
AF-O14733-F1	Predicted				AlphaFoldDB

297 variants for O14733

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
RCV000505552 CA403679635 rs1555701191	251	L>P	Neuroblastoma [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
CA9148223 rs763754700	2	A>T		No	ClinGen ExAC gnomAD
rs1443440676 CA403677842	6	L>V		No	ClinGen gnomAD
COSM1397681 rs1301547539 CA403677856	8	Q>*	Variant assessed as Somatic; 0.0 impact. large_intestine [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated NCI-TCGA gnomAD
CA403677886 rs1433064449	12	R>L		No	ClinGen TOPMed
CA9148229 rs766283924	22	R>Q		No	ClinGen ExAC gnomAD
CA9148228 rs750181141	22	R>W		No	ClinGen ExAC gnomAD
rs751559509 CA9148230	25	R>W		No	ClinGen ExAC gnomAD
rs1403159799 CA403677981	27	R>M		No	ClinGen gnomAD
CA403678016 rs1169050667	32	L>P		No	ClinGen gnomAD
CA403678014 rs1453514771	32	L>V		No	ClinGen gnomAD
rs749341799 CA9148233	33	D>E		No	ClinGen ExAC gnomAD
TCGA novel	33	D>H	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA9148234 rs757454138	34	I>M		No	ClinGen ExAC TOPMed gnomAD
rs1460437314 CA403678026	34	I>V		No	ClinGen TOPMed gnomAD
rs1391474983 CA403678044	36	P>L		No	ClinGen gnomAD
rs1370547916 CA403678055	38	R>Q		No	ClinGen gnomAD
CA403678054 rs1324055434	38	R>W		No	ClinGen gnomAD
CA9148235 rs779037374	40	R>G		No	ClinGen ExAC gnomAD
rs533132248 CA304961967	42	T>A		No	ClinGen 1000Genomes TOPMed
CA304967969 rs1024708183	44	Q>R		No	ClinGen TOPMed
CA304967970 rs967433524	46	P>L		No	ClinGen TOPMed gnomAD
rs967433524 CA403678224	46	P>R		No	ClinGen TOPMed gnomAD
rs778375800 CA9148308	50	D>N		No	ClinGen ExAC TOPMed gnomAD
rs957493807 CA304967979	51	G>A		No	ClinGen TOPMed
CA403678251 rs1284071014	51	G>R		No	ClinGen gnomAD
CA403678253 rs1284071014	51	G>W		No	ClinGen gnomAD
rs748767169 CA9148309	52	G>A		No	ClinGen ExAC gnomAD
rs1484368982 CA403678262	53	S>G		No	ClinGen gnomAD
CA403678264 rs1186294216	53	S>N		No	ClinGen gnomAD
CA9148310 rs756811414	54	R>C		No	ClinGen ExAC TOPMed gnomAD
rs533357050 CA9148311	54	R>H		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs745585391 CA9148312	55	S>L		No	ClinGen ExAC TOPMed gnomAD
CA304967997 rs976387571	57	S>F		No	ClinGen TOPMed
rs1435136254 CA403678294	58	S>L		No	ClinGen gnomAD
rs1175363004 CA403678316	61	S>F		No	ClinGen gnomAD
rs775089795 CA9148314	62	P>L		No	ClinGen ExAC gnomAD
CA403678319 rs1373620825	62	P>S		No	ClinGen gnomAD
rs1337733940 CA403678326	63	Q>R		No	ClinGen gnomAD
CA403678334 rs1252128134	64	H>R		No	ClinGen TOPMed
rs1440233859 CA403678343	65	P>L		No	ClinGen gnomAD
rs1213372895 CA403678339	65	P>S		No	ClinGen TOPMed
rs746839170 CA9148315	66	T>M		No	ClinGen ExAC TOPMed gnomAD
rs1308848837 CA403678344	66	T>P		No	ClinGen gnomAD
rs1044083059 CA304968056	67	P>R		No	ClinGen gnomAD
CA304968032 rs948274560	67	P>S		No	ClinGen Ensembl
CA403678355 rs1347873574	68	P>S		No	ClinGen gnomAD
TCGA novel	69	A>R	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1316384071 CA403678364	69	A>V		No	ClinGen TOPMed
CA403678367 rs1439065076	70	R>P		No	ClinGen gnomAD
CA403678368 rs1439065076	70	R>Q		No	ClinGen gnomAD
rs768434615 CA9148316	70	R>W		No	ClinGen ExAC gnomAD
CA403678376 rs1237190214	72	R>C		No	ClinGen TOPMed gnomAD
rs758493704 CA9148317 COSM3693225	72	R>H	Variant assessed as Somatic; 0.0 impact. large_intestine [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated ExAC NCI-TCGA TOPMed gnomAD
CA403678396 rs1195341922	74	M>I		No	ClinGen gnomAD
CA304968081 rs138677713	75	L>M		No	ClinGen Ensembl
rs1393160324 CA403678406	76	G>E		No	ClinGen gnomAD
TCGA novel	76	G>W	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1168449280 CA403678409	77	L>F		No	ClinGen TOPMed gnomAD
CA403678424 rs1408284809	79	S>L		No	ClinGen gnomAD
CA403678441 rs1372070521	82	F>C		No	ClinGen gnomAD
CA403678442 rs1452479193	82	F>L		No	ClinGen TOPMed
CA403678444 rs763099575	83	T>A		No	ClinGen ExAC TOPMed
CA9148318 rs763099575	83	T>P		No	ClinGen ExAC TOPMed
CA403678454 rs1599625307	84	P>R		No	ClinGen Ensembl
rs766635456 CA9148319	85	R>C		No	ClinGen ExAC TOPMed gnomAD
rs1301746163 CA403678457	85	R>H	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA TOPMed gnomAD
rs766635456 CA403678455	85	R>S		No	ClinGen ExAC TOPMed gnomAD
rs1469619336 CA403678461	86	S>G		No	ClinGen TOPMed
rs1331007401 CA403678463	86	S>N		No	ClinGen gnomAD
rs774579720 CA9148320	87	M>V		No	ClinGen ExAC gnomAD
rs1476247422 CA403678569	98	E>D		No	ClinGen gnomAD
rs1177582341 CA403678579	100	M>V		No	ClinGen gnomAD
COSM3773231 CA9148337 rs769867905	103	T>M	Variant assessed as Somatic; 0.0 impact. pancreas urinary_tract [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated ExAC NCI-TCGA TOPMed gnomAD
rs759693800 CA9148339	104	G>D		No	ClinGen ExAC gnomAD
rs1383410204 CA403678624	106	L>P	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
TCGA novel	107	T>A	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA403678630 rs1256880340	107	T>S		No	ClinGen TOPMed
CA403678633 rs1314051512	108	I>V		No	ClinGen gnomAD
CA9148342 rs760936521 CA304968429	109	G>R		No	ClinGen ExAC TOPMed gnomAD
CA9148343 rs557240660	110	G>D		No	ClinGen 1000Genomes ExAC gnomAD
CA403678643 rs1310113723	110	G>S		No	ClinGen gnomAD
TCGA novel	112	R>C	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA403678671 rs1191058688	112	R>H		No	ClinGen TOPMed gnomAD
CA403678676 rs1428581952	113	Y>H		No	ClinGen gnomAD
TCGA novel	114	Q>*	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1323652275 CA403678694	115	A>G		No	ClinGen TOPMed
CA304968685 rs28395770	116	E>K		No	ClinGen Ensembl
rs979747164 CA304968687	118	N>D		No	ClinGen Ensembl
CA9148389 rs56316660 VAR_040825	118	N>S		No	ClinGen UniProt ESP ExAC TOPMed dbSNP gnomAD
rs1326208752 CA403678722	119	D>E		No	ClinGen gnomAD
rs1464734841 CA403678716	119	D>N		No	ClinGen gnomAD
CA9148392 rs753585786	123	L>F		No	ClinGen ExAC gnomAD
rs372177955 CA9148391	123	L>M		No	ClinGen ESP ExAC TOPMed gnomAD
rs1292855446 CA403678752	124	G>C		No	ClinGen gnomAD
TCGA novel	125	E>*	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
COSM568986 CA403678790 rs1276435407	129	G>D	lung Variant assessed as Somatic; 0.0 impact. [Cosmic, NCI-TCGA]	No	ClinGen cosmic curated NCI-TCGA gnomAD
CA9148396 rs755099146	132	G>S	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
TCGA novel	134	V>A	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
TCGA novel	135	W>*	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA9148397 rs56106612 VAR_040826	138	R>C		No	ClinGen UniProt 1000Genomes ExAC TOPMed dbSNP gnomAD
rs748434331 CA9148398	138	R>H		No	ClinGen ExAC TOPMed gnomAD
CA403678854 rs748434331	138	R>L		No	ClinGen ExAC TOPMed gnomAD
CA9148400 rs773578983	139	F>L		No	ClinGen ExAC gnomAD
rs771439651 CA9148402	140	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs749648216 CA9148401	140	R>W		No	ClinGen ExAC TOPMed gnomAD
rs763308668 CA304968795	141	K>E		No	ClinGen TOPMed gnomAD
rs376991761 CA9148403	141	K>T		No	ClinGen ESP ExAC TOPMed gnomAD
rs1205135126 CA403678876	142	T>I		No	ClinGen TOPMed
CA9148405 rs771779482	143	G>S		No	ClinGen ExAC TOPMed gnomAD
TCGA novel	144	H>Q	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA403678885 rs1233328050	144	H>Y		No	ClinGen TOPMed
CA403678894 rs1401718147	145	V>G		No	ClinGen gnomAD
CA304968823 rs1049003237	145	V>I		No	ClinGen TOPMed gnomAD
rs200200323 CA9148407	146	I>V		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs761549769 CA9148410	148	V>I		No	ClinGen ExAC TOPMed gnomAD
rs1045580606 CA304968973	152	R>Q		No	ClinGen TOPMed gnomAD
rs761655517 CA9148427 COSM3693227	152	R>W	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA403678956 COSM1680582 rs1441304667	153	R>H	Variant assessed as Somatic; 0.0 impact. large_intestine [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated NCI-TCGA gnomAD
CA403678968 rs1568278051	155	G>E		No	ClinGen Ensembl
rs1384098610 CA403678980	157	K>E		No	ClinGen gnomAD
CA9148429 rs367833467	157	K>R		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
TCGA novel	159	E>K	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA403679014 rs1174269918	161	K>R		No	ClinGen TOPMed gnomAD
VAR_040827	162	R>C	a colorectal adenocarcinoma sample; somatic mutation [UniProt]	No	UniProt
VAR_040828	162	R>H	a colorectal adenocarcinoma sample; somatic mutation [UniProt]	No	UniProt
rs528497143 CA9148430	164	L>F		No	ClinGen 1000Genomes ExAC gnomAD
rs1413990204 CA403679045	166	D>N		No	ClinGen gnomAD
CA9148433 rs756198072	169	V>L		No	ClinGen ExAC gnomAD
rs1372204318 CA403679100	174	H>Y		No	ClinGen gnomAD
CA403679112 rs370478429	175	D>E		No	ClinGen ESP ExAC gnomAD
rs754078664 CA9148435	175	D>N		No	ClinGen ExAC gnomAD
CA9148438 rs746254265	177	P>L		No	ClinGen ExAC gnomAD
rs779365415 CA9148437	177	P>S		No	ClinGen ExAC gnomAD
rs975881933 CA304969056	178	Y>C		No	ClinGen Ensembl
TCGA novel	178	Y>T	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1196504228 CA403679133	179	I>V		No	ClinGen gnomAD
COSM1680583 rs746502176 CA9148441	180	V>M	pancreas Variant assessed as Somatic; impact. haematopoietic_and_lymphoid_tissue [Cosmic, NCI-TCGA]	No	ClinGen cosmic curated ExAC NCI-TCGA gnomAD
CA403679164 rs1375915089	183	F>S		No	ClinGen gnomAD
rs776342808 CA9148443	185	T>M		No	ClinGen ExAC gnomAD
CA403679178 rs776342808	185	T>R		No	ClinGen ExAC gnomAD
rs769499056 CA9148445	188	T>N		No	ClinGen ExAC gnomAD
CA304969089 rs887570441	189	N>D		No	ClinGen gnomAD
CA9148446 rs199553372	189	N>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA9148488 COSM1397683 rs377648179	190	T>M	Variant assessed as Somatic; 0.0 impact. large_intestine [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated ESP ExAC NCI-TCGA TOPMed gnomAD
CA403679224 rs1160351321	191	D>N		No	ClinGen TOPMed
CA304972245 rs55800262 VAR_040829	195	A>T	Variant assessed as Somatic; impact. [NCI-TCGA]	No	ClinGen UniProt Ensembl NCI-TCGA dbSNP
CA403679263 rs1440693094	196	M>I		No	ClinGen gnomAD
rs775543935 CA9148493	199	M>T		No	ClinGen ExAC gnomAD
CA403679302 rs1433998983	202	C>Y		No	ClinGen TOPMed
rs1174847870 CA403679307	203	A>T	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
CA403679313 rs1467142899	204	E>K		No	ClinGen gnomAD
rs773428876 CA9148496	205	K>N		No	ClinGen ExAC gnomAD
rs1401142748 CA403679330	206	L>F		No	ClinGen gnomAD
CA403679341 rs1568278464	207	K>N		No	ClinGen Ensembl
CA9148497 rs763209807	208	K>M		No	ClinGen ExAC TOPMed gnomAD
CA9148499 rs751828868	209	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA9148498 rs552080947	209	R>W		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA9148500 rs759996040	210	M>I		No	ClinGen ExAC gnomAD
CA403679354 rs1301903022	210	M>L		No	ClinGen gnomAD
rs753313895 CA9148502	211	Q>H		No	ClinGen ExAC TOPMed gnomAD
CA9148501 rs767899243	211	Q>R		No	ClinGen ExAC gnomAD
rs756619690 CA9148503	212	G>D		No	ClinGen ExAC TOPMed gnomAD
TCGA novel	214	I>N	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA403679384 rs1192222025	215	P>T		No	ClinGen gnomAD
TCGA novel	216	E>V	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs745624779 CA9148508	217	R>C		No	ClinGen ExAC gnomAD
rs868265912 CA304972375	217	R>H	Variant assessed as Somatic; 4.813e-05 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
CA403679401 rs868265912	217	R>L		No	ClinGen gnomAD
rs771955180 CA9148509	218	I>F		No	ClinGen ExAC gnomAD
rs372316207 CA304972405	221	K>R		No	ClinGen TOPMed
rs373789571 CA304972409	224	V>E		No	ClinGen ESP TOPMed
rs746875567 CA9148517	225	A>V	Variant assessed as Somatic; 9.758e-05 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
rs1421560106 CA403679470	227	V>M		No	ClinGen gnomAD
rs765979119 CA9148557	228	K>N		No	ClinGen ExAC gnomAD
rs1383490584 CA403679485	229	A>S		No	ClinGen TOPMed
CA403679487 rs1325957309	229	A>V		No	ClinGen gnomAD
rs1377356152 CA403679498	231	Y>C		No	ClinGen gnomAD
CA403679506 rs1310627873	232	Y>C		No	ClinGen gnomAD
CA403679518 rs1356525990	234	K>T		No	ClinGen gnomAD
CA403679537 rs748034368	236	K>N		No	ClinGen ExAC gnomAD
rs906866888 CA304972862	237	H>L		No	ClinGen TOPMed
CA403679544 rs756020181	237	H>Q		No	ClinGen ExAC TOPMed gnomAD
rs1283210992 CA403679541	237	H>Y		No	ClinGen gnomAD
rs1210306090 CA403679546	238	G>S		No	ClinGen gnomAD
TCGA novel	239	V>A	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA403679559 rs1489727215	240	I>V		No	ClinGen gnomAD
CA403679567 rs1277929944	241	H>Y		No	ClinGen TOPMed
rs1156815343 COSM1165620 CA403679580	243	D>N	Variant assessed as Somatic; 0.0 impact. large_intestine [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated NCI-TCGA gnomAD
rs769071544 CA9148568	244	V>I		No	ClinGen ExAC gnomAD
rs769071544 CA403679587	244	V>L		No	ClinGen ExAC gnomAD
rs1338503438 CA403679621	249	I>V		No	ClinGen TOPMed
CA403679627 rs1599627776	250	L>M		No	ClinGen Ensembl
rs1409519936 CA403679632	251	L>M		No	ClinGen gnomAD
CA9148572 rs772735492	252	D>G		No	ClinGen ExAC gnomAD
TCGA novel	252	D>H	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1238524673 CA403679644	253	E>K	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
rs1599627826 CA403679649	253	E>V		No	ClinGen Ensembl
CA304972896 rs913866951	254	R>Q	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA TOPMed gnomAD
CA403679653 rs1279498308	254	R>W	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
CA403679665 rs1302728142	256	Q>L		No	ClinGen gnomAD
CA403679666 rs1302728142	256	Q>R		No	ClinGen gnomAD
CA403679672 rs1332085514	257	I>F		No	ClinGen gnomAD
CA403679673 rs1439010437	257	I>N		No	ClinGen TOPMed gnomAD
rs1439010437 CA403679674	257	I>T		No	ClinGen TOPMed gnomAD
CA403679671 rs1332085514	257	I>V		No	ClinGen gnomAD
rs1053566 CA304972901 VAR_029890	259	L>F		No	ClinGen UniProt Ensembl dbSNP
rs1599627883 CA403679690	260	C>S		No	ClinGen Ensembl
CA9148578 rs752458822	263	G>S		No	ClinGen ExAC gnomAD
rs1474172928 CA403679742	267	R>C		No	ClinGen TOPMed
rs1177861432 CA403679758	270	D>H		No	ClinGen Ensembl
CA403679781 rs1332304138	273	A>S		No	ClinGen gnomAD
CA403679798 rs1445100216	275	T>K		No	ClinGen gnomAD
rs1445100216 CA403679796 COSM302613	275	T>M	ovary Variant assessed as Somatic; 0.0 impact. oesophagus central_nervous_system [Cosmic, NCI-TCGA]	No	ClinGen cosmic curated NCI-TCGA gnomAD
CA403679800 rs1332216223	276	R>W		No	ClinGen gnomAD
CA304972946 rs942074295	282	A>T	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA TOPMed gnomAD
rs757758116	286	P>=	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	NCI-TCGA
rs1190484047 CA403679895	288	R>C		No	ClinGen gnomAD
CA9148678 rs779562628	288	R>H	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
rs1312792372 CA403679918	291	P>L		No	ClinGen gnomAD
rs779379219 CA9148681	294	P>L		No	ClinGen ExAC TOPMed gnomAD
rs746557259 CA9148682	295	T>P		No	ClinGen ExAC gnomAD
rs768160589 CA9148683	296	K>N		No	ClinGen ExAC gnomAD
TCGA novel	296	K>N	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1341085574 CA403679956	298	D>N		No	ClinGen TOPMed
COSM1641275 rs1425924011 CA403679969	299	Y>C	Variant assessed as Somatic; 0.0 impact. stomach [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated NCI-TCGA gnomAD
CA403679979 rs1599628435	300	D>E		No	ClinGen Ensembl
COSM3938384 rs1185925179 CA403679989	302	R>Q	Variant assessed as Somatic; 0.0 impact. oesophagus [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated NCI-TCGA gnomAD
CA9148686 rs769642939	304	D>N	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
rs879150050 CA304973305	305	V>I		No	ClinGen Ensembl
CA304973328 rs1046459698 COSM94662	311	S>L	lung [Cosmic]	No	ClinGen cosmic curated Ensembl
CA403680143 rs1369799132	317	T>I		No	ClinGen gnomAD
TCGA novel	322	Y>R	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs778579797 CA9148731	331	V>I		No	ClinGen ExAC gnomAD
CA403680268 rs1568279607	335	V>I		No	ClinGen Ensembl
CA403680301 rs1417048704	339	E>D		No	ClinGen gnomAD
TCGA novel	341	P>R	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA304973526 rs982599133	342	L>F		No	ClinGen TOPMed gnomAD
TCGA novel	343	L>R	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA403680326 rs1302574218	344	P>S		No	ClinGen gnomAD
CA304973544 rs752181956	345	G>A		No	ClinGen ExAC TOPMed gnomAD
CA9148743 rs752181956	345	G>E		No	ClinGen ExAC TOPMed gnomAD
CA9148742 rs200517538 COSM1003407	345	G>R	endometrium [Cosmic]	No	ClinGen cosmic curated 1000Genomes ESP ExAC TOPMed gnomAD
CA304973546 rs915467733	346	H>Y		No	ClinGen TOPMed
CA403680366 rs1351336395	350	S>L		No	ClinGen TOPMed
CA9148746 rs753467019	351	G>R		No	ClinGen ExAC TOPMed gnomAD
CA304973568 rs918854402	354	Q>H		No	ClinGen gnomAD
CA403680394 rs1222436068	354	Q>R		No	ClinGen TOPMed gnomAD
CA9148748 rs778725144	355	S>C		No	ClinGen ExAC TOPMed gnomAD
CA9148750 rs758376970	357	V>I	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
rs1182280031 CA403680432	360	C>R		No	ClinGen gnomAD
CA403680502 rs1334645480	367	K>N		No	ClinGen gnomAD
TCGA novel	368	R>T	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1330906396 CA403680512	369	P>S	Variant assessed as Somatic; impact. [NCI-TCGA]	No	ClinGen NCI-TCGA TOPMed
CA403680526 rs1405096609	371	Y>D		No	ClinGen gnomAD
TCGA novel	373	K>missing	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA403680543 rs1284773326	373	K>T		No	ClinGen TOPMed gnomAD
rs1432947387 CA403680555	375	L>F		No	ClinGen gnomAD
CA304974473 rs923590375	378	S>N		No	ClinGen TOPMed
CA403680591 rs923590375	378	S>T		No	ClinGen TOPMed
rs1312906351 CA403680604	380	I>F		No	ClinGen gnomAD
CA9148821 rs772810212	380	I>N		No	ClinGen ExAC gnomAD
rs774212941 CA9148824	382	R>C	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
CA9148825 rs759229847	382	R>H	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
CA9148826 rs372974513	384	E>K		No	ClinGen ESP ExAC TOPMed gnomAD
CA403680640 rs1431888473	385	T>M		No	ClinGen TOPMed
rs764054804 CA403680641	386	L>M		No	ClinGen ExAC TOPMed gnomAD
rs1331773120 CA403680643	386	L>P		No	ClinGen TOPMed
TCGA novel	386	L>R	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA403680646 rs1267005014	387	E>K		No	ClinGen gnomAD
CA403680664 rs1159130971	389	D>G		No	ClinGen gnomAD
rs1451089097 CA403680669	390	V>L		No	ClinGen gnomAD
CA403680679 rs1406524174	391	A>V		No	ClinGen gnomAD
CA403680703 rs1464023661	395	K>E		No	ClinGen TOPMed
rs1334570087 CA403680707	395	K>R		No	ClinGen gnomAD
rs1391918745 CA403680729	398	M>T		No	ClinGen gnomAD
rs201368825 CA9148834 COSM1397688	399	A>V	large_intestine [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
CA9148836 rs202245509	404	P>L	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ESP ExAC NCI-TCGA TOPMed gnomAD
rs556127943 CA9148840	405	R>Q		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs778482297 CA9148839	405	R>W		No	ClinGen ExAC TOPMed gnomAD
rs1599630114 CA403680778	406	T>I		No	ClinGen Ensembl
CA9148841 rs377699571	406	T>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA403680790 rs1161324664	408	G>D		No	ClinGen gnomAD
rs745460007 CA9148843	408	G>S		No	ClinGen ExAC TOPMed gnomAD
CA403680796 rs1173924867	409	V>A		No	ClinGen gnomAD
CA9148845 rs775112625 COSM1397689	409	V>I	Variant assessed as Somatic; 0.0 impact. large_intestine [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated ExAC NCI-TCGA TOPMed gnomAD
TCGA novel	410	L>P	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA9148846 rs760564022	411	S>I		No	ClinGen ExAC TOPMed gnomAD
CA403680816 rs1458046756	412	Q>H		No	ClinGen TOPMed gnomAD
rs764009958 CA9148847	413	P>L		No	ClinGen ExAC TOPMed gnomAD
CA304974649 rs533495400	413	P>T		No	ClinGen Ensembl
CA403680828 rs761745379	414	H>Q		No	ClinGen ExAC gnomAD
CA9148848 rs776620038	414	H>Y	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
COSM1527476 rs1599630216 CA403680839	416	P>L	lung [Cosmic]	No	ClinGen cosmic curated Ensembl
CA403680844 rs1221943389	417	F>S		No	ClinGen gnomAD
CA403680849 rs1359556850	418	F>L		No	ClinGen gnomAD
rs1055882048 CA304974670	419	R>G		No	ClinGen TOPMed

No associated diseases with O14733

2 regional properties for O14733

Type	Name	Position	InterPro Accession
domain	Protein kinase domain	120 - 380	IPR000719
active_site	Serine/threonine-protein kinase, active site	239 - 251	IPR008271

Functions

		Description
EC Number	2.7.12.2	Dual-specificity kinases (those acting on Ser/Thr and Tyr residues)
Subcellular Localization	Nucleus Cytoplasm
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

3 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.
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.

13 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.
JUN kinase kinase activity	Catalysis of the phosphorylation of tyrosine and threonine residues in a c-Jun NH2-terminal kinase (JNK), a member of a subgroup of mitogen-activated protein kinases (MAPKs), which signal in response to cytokines and exposure to environmental stress. JUN kinase kinase (JNKK) is a dual-specificity protein kinase kinase and requires activation by a serine/threonine kinase JUN kinase kinase kinase.
magnesium ion binding	Binding to a magnesium (Mg) ion.
MAP kinase activity	Catalysis of the reaction: protein + ATP = protein phosphate + ADP. This reaction is the phosphorylation of proteins. Mitogen-activated protein kinase; a family of protein kinases that perform a crucial step in relaying signals from the plasma membrane to the nucleus. They are activated by a wide range of proliferation- or differentiation-inducing signals; activation is strong with agonists such as polypeptide growth factors and tumor-promoting phorbol esters, but weak (in most cell backgrounds) by stress stimuli.
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 kinase kinase binding	Binding to a mitogen-activated protein kinase kinase kinase, a protein that can phosphorylate a MAP kinase kinase.
molecular function activator activity	A molecular function regulator that activates or increases the activity of its target via non-covalent binding that does not result in covalent modification to the target.
protein C-terminus binding	Binding to a protein C-terminus, the end of a peptide chain at which the 1-carboxyl function of a constituent amino acid is not attached in peptide linkage to another amino-acid residue.
protein kinase binding	Binding to a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate.
protein phosphatase binding	Binding to a protein phosphatase.
protein serine kinase activity	Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate.
protein tyrosine kinase activity	Catalysis of the reaction: ATP + a protein tyrosine = ADP + protein tyrosine phosphate.

24 GO annotations of biological process

Name	Definition
apoptotic process	A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died.
cellular response to interleukin-1	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 an interleukin-1 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 sorbitol	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 sorbitol stimulus.
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: the upstream MAP4K. The kinases in each tier phosphorylate and activate the kinases in the downstream tier to transmit a signal within a cell.
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: the upstream MAP4K. The kinases in each tier phosphorylate and activate the kinase in the downstream tier to transmit a signal within a cell.
positive regulation of DNA-templated transcription	Any process that activates or increases the frequency, rate or extent of cellular DNA-templated transcription.
positive regulation of ERK1 and ERK2 cascade	Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade.
positive regulation of JNK cascade	Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the JNK cascade.
positive regulation of JUN kinase activity	Any process that activates or increases the frequency, rate or extent of JUN kinase activity.
positive regulation of neuron apoptotic process	Any process that activates or increases the frequency, rate or extent of cell death of neurons by apoptotic process.
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.
regulation of motor neuron apoptotic process	Any process that modulates the frequency, rate or extent of motor neuron apoptotic process.
response to heat	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 heat stimulus, a temperature stimulus above the optimal temperature for that organism.
response to osmotic 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 a stimulus indicating an increase or decrease in the concentration of solutes outside the organism or cell.
response to tumor necrosis factor	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 tumor necrosis factor stimulus.
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.
response to wounding	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 stimulus indicating damage to the organism.
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-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.

16 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q5E9X2	MAP2K6	Dual specificity mitogen-activated protein kinase kinase 6	Bos taurus (Bovine)	EV
P52564	MAP2K6	Dual specificity mitogen-activated protein kinase kinase 6	Homo sapiens (Human)	EV
P46734	MAP2K3	Dual specificity mitogen-activated protein kinase kinase 3	Homo sapiens (Human)	SS
P45985	MAP2K4	Dual specificity mitogen-activated protein kinase kinase 4	Homo sapiens (Human)	EV
Q13163	MAP2K5	Dual specificity mitogen-activated protein kinase kinase 5	Homo sapiens (Human)	PR
P36507	MAP2K2	Dual specificity mitogen-activated protein kinase kinase 2	Homo sapiens (Human)	EV
Q02750	MAP2K1	Dual specificity mitogen-activated protein kinase kinase 1	Homo sapiens (Human)	EV
Q8CE90	Map2k7	Dual specificity mitogen-activated protein kinase kinase 7	Mus musculus (Mouse)	PR
P70236	Map2k6	Dual specificity mitogen-activated protein kinase kinase 6	Mus musculus (Mouse)	EV
P47809	Map2k4	Dual specificity mitogen-activated protein kinase kinase 4	Mus musculus (Mouse)	EV
O09110	Map2k3	Dual specificity mitogen-activated protein kinase kinase 3	Mus musculus (Mouse)	PR
Q4KSH7	Map2k7	Dual specificity mitogen-activated protein kinase kinase 7	Rattus norvegicus (Rat)	PR
G5EDT6	jkk-1	Dual specificity mitogen-activated protein kinase kinase jkk-1	Caenorhabditis elegans	PR
G5EDF7	sek-1	Dual specificity mitogen-activated protein kinase kinase sek-1	Caenorhabditis elegans	PR
Q21307	mek-1	Dual specificity mitogen-activated protein kinase kinase mek-1	Caenorhabditis elegans	PR
Q9DGE0	map2k6	Dual specificity mitogen-activated protein kinase kinase 6	Danio rerio (Zebrafish) (Brachydanio rerio)	PR

10	20	30	40	50	60
MAASSLEQKL	SRLEAKLKQE	NREARRRIDL	NLDISPQRPR	PTLQLPLAND	GGSRSPSSES
70	80	90	100	110	120
SPQHPTPPAR	PRHMLGLPST	LFTPRSMESI	EIDQKLQEIM	KQTGYLTIGG	QRYQAEINDL
130	140	150	160	170	180
ENLGEMGSGT	CGQVWKMRFR	KTGHVIAVKQ	MRRSGNKEEN	KRILMDLDVV	LKSHDCPYIV
190	200	210	220	230	240
QCFGTFITNT	DVFIAMELMG	TCAEKLKKRM	QGPIPERILG	KMTVAIVKAL	YYLKEKHGVI
250	260	270	280	290	300
HRDVKPSNIL	LDERGQIKLC	DFGISGRLVD	SKAKTRSAGC	AAYMAPERID	PPDPTKPDYD
310	320	330	340	350	360
IRADVWSLGI	SLVELATGQF	PYKNCKTDFE	VLTKVLQEEP	PLLPGHMGFS	GDFQSFVKDC
370	380	390	400	410
LTKDHRKRPK	YNKLLEHSFI	KRYETLEVDV	ASWFKDVMAK	TESPRTSGVL	SQPHLPFFR