AiPD: Autoinhibited Protein Database

P41279

Gene name	MAP3K8 (COT, ESTF)
Protein name	Mitogen-activated protein kinase kinase kinase 8
Names	Cancer Osaka thyroid oncogene, Proto-oncogene c-Cot, Serine/threonine-protein kinase cot, Tumor progression locus 2, TPL-2
Species	Homo sapiens (Human)
KEGG Pathway	hsa:1326
EC number
Protein Class	MAP KINASE KINASE KINASE SSK2-RELATED-RELATED (PTHR48016)

Descriptions

MAP3K8 is a mitogen-activated protein kinase kinase kinase 8, involved in cellular activation as well as cell proliferation. The C-terminal autoinhibitory domain represses MAP3K8 kinase activity by folding back onto the kinase domain.

Autoinhibitory domains (AIDs)

Target domain	138-388 (Protein kinase domain)
Relief mechanism	PTM, Cleavage
Assay	Deletion assay

AID

425-467 (C-terminal autoinhibitory domain)

Target domain

138-388 (Protein kinase domain)

Relief mechanism

PTM (Phosphorylation at Thr-290 and Ser-400), Cleavage (C-terminal truncation by provirus insertion or degradation via proteasome)

Assay

Deletion assay

Accessory elements

269-292 (Activation loop from InterPro)

Target domain	138-388 (Protein kinase domain)
Relief mechanism
Assay

References

Gándara ML et al. (2003) "The COOH-terminal domain of wild-type Cot regulates its stability and kinase specific activity", Molecular and cellular biology, 23, 7377-90

Kyriakis JM et al. (2012) "Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10-year update", Physiological reviews, 92, 689-737

Ceci JD et al. (1997) "Tpl-2 is an oncogenic kinase that is activated by carboxy-terminal truncation", Genes & development, 11, 688-700

Gantke T et al. (2011) "Regulation and function of TPL-2, an IκB kinase-regulated MAP kinase kinase kinase", Cell research, 21, 131-45

Autoinhibited structure

Activated structure

4 structures for P41279

Entry ID	Method	Resolution	Chain	Position	Source
4Y83	X-ray	289 A	A/B/C	66-395	PDB
4Y85	X-ray	233 A	A/B/C	66-395	PDB
5IU2	X-ray	270 A	A/B	66-395	PDB
AF-P41279-F1	Predicted				AlphaFoldDB

253 variants for P41279

Variant ID(s)	Position	Change	Diseaes Association	Provenance
rs1264548095 CA376435330	4	M>L	No	ClinGen TOPMed
CA376435340 rs1334713360	5	S>G	No	ClinGen Ensembl
CA205307067 rs1016753845	5	S>I	No	ClinGen TOPMed
CA5459567 rs757273381	5	S>R	No	ClinGen ExAC gnomAD
rs780995987 CA5459568	7	G>E	No	ClinGen ExAC TOPMed gnomAD
rs752421142 CA5459569	8	S>N	No	ClinGen ExAC gnomAD
rs777682936 CA376435401	13	E>D	No	ClinGen ExAC gnomAD
CA5459571 rs777682936	13	E>D	No	ClinGen ExAC gnomAD
CA5459573 rs372120772	14	I>M	No	ClinGen ESP ExAC TOPMed gnomAD
CA5459575 rs778965236	22	N>H	No	ClinGen ExAC TOPMed gnomAD
rs776014707 CA5459578	24	S>F	No	ClinGen ExAC TOPMed gnomAD
rs747361922 CA5459579	26	V>I	No	ClinGen ExAC
CA376435501 rs1564363565	28	D>G	No	ClinGen Ensembl
rs150579938 CA5459580	28	D>N	No	ClinGen 1000Genomes ESP ExAC gnomAD
CA5459581 rs777243002	29	I>V	No	ClinGen ExAC TOPMed gnomAD
CA5459582 rs762418488	31	E>G	No	ClinGen ExAC gnomAD
CA5459584 rs139640494	32	N>D	No	ClinGen ESP ExAC TOPMed
CA5459585 rs374430565	33	L>V	No	ClinGen ESP ExAC TOPMed gnomAD
rs767144818 CA5459586	35	A>S	No	ClinGen ExAC gnomAD
CA376435551 rs1392922417	35	A>V	No	ClinGen gnomAD
rs1384970865 CA376435552	36	S>R	No	ClinGen gnomAD
rs1313819971 CA376435566	37	E>D	No	ClinGen gnomAD
CA376435560 rs1246587849	37	E>K	No	ClinGen gnomAD
rs1356621670 CA376435577	39	P>A	No	ClinGen gnomAD
CA205307144 rs539535216	40	A>P	No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA5459589 rs539535216	40	A>T	No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA5459590 rs753839798	42	Y>C	No	ClinGen ExAC gnomAD
rs577031274 CA376435605	43	E>D	No	ClinGen TOPMed gnomAD
rs757105191 CA5459591	43	E>G	No	ClinGen ExAC
rs1462185869 CA376435611	44	P>L	No	ClinGen gnomAD
CA5459593 rs745882056	47	M>I	No	ClinGen ExAC TOPMed gnomAD
rs1424905760 CA376435634	48	T>A	No	ClinGen TOPMed
CA376435637 rs1564363680	48	T>S	No	ClinGen Ensembl
rs1476435489 CA376435642	49	M>K	No	ClinGen TOPMed gnomAD
CA376435644 rs1476435489	49	M>T	No	ClinGen TOPMed gnomAD
rs1196507195 CA376435640	49	M>V	No	ClinGen TOPMed
rs1036237977 CA205307174	54	N>D	No	ClinGen TOPMed gnomAD
CA5459596 rs150001848	57	D>N	No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs117396201 CA5459597	59	R>C	No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs146728212 CA5459598	59	R>H	No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1336012993 CA376435738	62	S>A	No	ClinGen gnomAD
rs916277317 CA205307189	63	L>P	No	ClinGen gnomAD
rs773924433 CA5459601	65	L>V	No	ClinGen ExAC TOPMed gnomAD
rs758966181 CA5459602	66	S>G	No	ClinGen ExAC TOPMed gnomAD
CA5459603 rs767198025	67	G>D	No	ClinGen ExAC TOPMed gnomAD
CA5459604 rs775103410	68	Q>E	No	ClinGen ExAC gnomAD
rs760273502 CA5459605	70	V>I	No	ClinGen ExAC gnomAD
CA376435792 rs1241868987	71	P>R	No	ClinGen gnomAD
CA5459607 rs753513338	72	W>R	No	ClinGen ExAC TOPMed gnomAD
rs1474590339 CA376435817	75	S>A	No	ClinGen gnomAD
rs549474 CA5459610	77	R>I	No	ClinGen ExAC gnomAD
CA205307245 rs549474	77	R>K	No	ClinGen ExAC gnomAD
CA376435829 rs549474	77	R>T	No	ClinGen ExAC gnomAD
CA205307247 rs947835153	78	Y>C	No	ClinGen TOPMed gnomAD
CA205307246 rs914933119	78	Y>H	No	ClinGen TOPMed
rs1169193008 CA376435855	81	V>A	No	ClinGen TOPMed
rs1400005181 CA376435856	82	E>K	No	ClinGen gnomAD
rs1325344717 CA376435878	84	L>F	No	ClinGen gnomAD
CA376435914 rs1435286873	90	H>N	No	ClinGen TOPMed
rs1259896555 CA376435927	91	I>M	No	ClinGen gnomAD
rs755208662 CA5459614	93	N>S	No	ClinGen ExAC gnomAD
rs1203600563 CA376435962	97	H>Y	No	ClinGen gnomAD
CA205307282 rs780656361	100	G>R	No	ClinGen Ensembl
CA5459616 rs748402123	101	Q>K	No	ClinGen ExAC gnomAD
rs938853569 CA205307288	102	R>G	No	ClinGen TOPMed gnomAD
rs747304103 CA5459617	102	R>Q	No	ClinGen ExAC TOPMed gnomAD
CA376436002 rs1206231462	103	P>S	No	ClinGen gnomAD
CA376436015 rs1187322311	105	E>Q	No	ClinGen gnomAD
CA376436064 rs1240091650	112	M>V	No	ClinGen TOPMed
rs1243797037 CA376436713	113	V>I	No	ClinGen gnomAD
CA5459648 rs368515552	115	T>A	No	ClinGen ESP ExAC TOPMed gnomAD
rs767829783 CA5459649	118	N>S	No	ClinGen ExAC gnomAD
rs1196207926 CA376436760	120	R>C	No	ClinGen gnomAD
CA376436761 rs1249518228	120	R>H	No	ClinGen gnomAD
rs756322304 CA376436779	122	Q>H	No	ClinGen ExAC TOPMed gnomAD
rs1262650142 CA376436781	123	I>V	No	ClinGen gnomAD
CA5459652 rs764373700	125	S>C	No	ClinGen ExAC gnomAD
CA5459654 rs201540136	126	D>N	No	ClinGen ESP ExAC TOPMed gnomAD
rs1462161246 CA376436814	128	L>V	No	ClinGen gnomAD
CA205312503 rs976900167	129	L>V	No	ClinGen TOPMed
rs754420261 CA5459657	130	I>M	No	ClinGen ExAC gnomAD
rs1398554399 CA376436827	130	I>T	No	ClinGen gnomAD
rs780701286 CA5459658	134	L>M	No	ClinGen ExAC gnomAD
rs868808843 CA205312548	136	Y>*	No	ClinGen Ensembl
CA5459660 rs769419375	137	R>G	No	ClinGen ExAC gnomAD
rs1327286561 CA376436871	137	R>K	No	ClinGen gnomAD
CA376436875 rs1226956889	137	R>S	No	ClinGen gnomAD
rs1564368907 CA376436882	138	N>K	No	ClinGen Ensembl
rs1257248007 CA376436888	139	I>T	No	ClinGen gnomAD
rs201892819 CA5459661	140	G>C	No	ClinGen 1000Genomes ExAC gnomAD
rs749080158 CA5459662	141	S>A	No	ClinGen ExAC gnomAD
rs868635815 CA205312549	141	S>F	No	ClinGen Ensembl
rs771058225 CA5459663	143	F>L	No	ClinGen ExAC gnomAD
CA5459665 rs143041571	146	R>Q	No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs369295837 CA5459664	146	R>W	No	ClinGen ESP ExAC TOPMed gnomAD
CA5459667 rs3751449	148	A>T	No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA5459669 rs368789124	158	I>L	No	ClinGen ESP ExAC gnomAD
rs1406054811 CA376437099	158	I>M	No	ClinGen gnomAD
rs1177540087 CA376437095	158	I>T	No	ClinGen TOPMed gnomAD
CA5459670 rs754271777	160	T>M	No	ClinGen ExAC gnomAD
rs757590491 CA5459671	161	K>N	No	ClinGen ExAC gnomAD
CA5459672 rs765778036	165	A>V	No	ClinGen ExAC TOPMed gnomAD
CA376437200 rs1171416401	167	K>T	No	ClinGen gnomAD
rs771989921 CA5459686	169	I>V	No	ClinGen ExAC gnomAD
rs151108315 CA5459687	172	D>H	No	ClinGen ESP ExAC TOPMed gnomAD
CA376437760 rs764343724	181	I>M	No	ClinGen ExAC gnomAD
rs776807837 CA5459690	185	F>L	No	ClinGen ExAC gnomAD
CA5459692 rs373057774	186	R>Q	No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs750729733 CA5459693	188	E>K	No	ClinGen ExAC TOPMed gnomAD
rs1408669942 CA376437805	188	E>V	No	ClinGen TOPMed
rs1245706749 CA376437819	190	I>L	No	ClinGen gnomAD
rs1245706749 CA376437818	190	I>V	No	ClinGen gnomAD
CA376437824 rs1179273995	191	A>T	No	ClinGen gnomAD
CA5459699 rs753577719	196	A>T	No	ClinGen ExAC TOPMed gnomAD
rs142650056 CA5459700	196	A>V	No	ClinGen ESP ExAC TOPMed gnomAD
CA5459703 rs771973010	199	W>C	No	ClinGen ExAC TOPMed gnomAD
rs146749791 CA5459702	199	W>R	No	ClinGen ESP ExAC TOPMed gnomAD
rs1481998031 CA376437882	200	G>D	No	ClinGen TOPMed
rs932880053 CA205314242	211	E>K	No	ClinGen TOPMed
CA376437963 rs1396509308	212	G>R	No	ClinGen gnomAD
CA376437977 rs1588782220	214	S>A	No	ClinGen Ensembl
CA205314247 VAR_051638 rs3087944	214	S>F	No	ClinGen UniProt Ensembl dbSNP
CA376437987 rs1245985205	216	L>M	No	ClinGen TOPMed gnomAD
rs773505013 CA5459710	225	M>V	No	ClinGen ExAC gnomAD
rs1218317330 CA376438075	228	F>S	No	ClinGen TOPMed
rs1276050889 CA376438110	233	V>M	No	ClinGen TOPMed
CA376438126 rs1177302035	235	K>R	No	ClinGen gnomAD
rs1162966054 CA376438141	237	V>A	No	ClinGen gnomAD
CA5459712 rs766835566	237	V>I	No	ClinGen ExAC gnomAD
rs1588782360 CA376438167	241	L>P	No	ClinGen Ensembl
CA376438217 rs1354883034	248	K>R	No	ClinGen gnomAD
rs761372768 CA5459735	257	S>G	No	ClinGen ExAC TOPMed gnomAD
CA376438314 rs1191283360	260	V>I	No	ClinGen gnomAD
rs1431157160 CA376438330	262	M>T	No	ClinGen gnomAD
rs954461874 CA205314889	276	Q>E	No	ClinGen TOPMed gnomAD
CA5459738 rs373977741	277	M>I	No	ClinGen ESP ExAC TOPMed gnomAD
rs960674093 CA205314890	277	M>T	No	ClinGen Ensembl
rs139293295 CA205314893	278	T>N	No	ClinGen ESP
rs1564370920 CA376438435	278	T>P	No	ClinGen Ensembl
rs751299982 CA5459740	279	E>K	No	ClinGen ExAC TOPMed gnomAD
CA376438465 rs1397742363	282	Y>C	No	ClinGen gnomAD
rs1305400973 CA376438483	285	K>E	No	ClinGen gnomAD
rs781104573 CA376438505	288	R>*	No	ClinGen ExAC TOPMed gnomAD
rs781104573 CA5459742	288	R>G	No	ClinGen ExAC TOPMed gnomAD
rs779977265 CA205314954	288	R>Q	No	ClinGen TOPMed gnomAD
CA5459759 rs767492585	294	M>I	No	ClinGen ExAC gnomAD
CA376431366 rs1457067245	310	I>V	No	ClinGen gnomAD
CA376431401 rs1274805221	313	L>M	No	ClinGen TOPMed
rs919957360 CA205302969	316	T>A	No	ClinGen TOPMed gnomAD
rs546658132 CA5459764	316	T>M	No	ClinGen 1000Genomes ExAC gnomAD
rs919957360 CA205302982	316	T>S	No	ClinGen TOPMed gnomAD
CA376431505 rs1277948342	321	Q>H	No	ClinGen TOPMed
rs775953433 CA205303003	322	T>A	No	ClinGen ExAC TOPMed gnomAD
rs747527547 CA5459769	322	T>M	No	ClinGen ExAC gnomAD
CA5459768 rs775953433	322	T>S	No	ClinGen ExAC TOPMed gnomAD
CA376431519 rs1588795912	324	T>P	No	ClinGen Ensembl
rs1431523218 CA376431534	325	P>S	No	ClinGen TOPMed
CA376431544 rs1171221778	326	P>A	No	ClinGen gnomAD
CA376431567 rs548193504	328	V>L	No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs548193504 CA5459772	328	V>M	No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs759141078 CA5459776	330	R>L	No	ClinGen ExAC gnomAD
rs759141078 CA5459775	330	R>P	No	ClinGen ExAC gnomAD
rs1327705787 CA376431628	333	R>C	No	ClinGen gnomAD
rs1170356333 CA376431630	333	R>H	No	ClinGen gnomAD
rs1398803716 CA376431668	337	P>S	No	ClinGen gnomAD
rs1220675583 CA376431905	346	Q>R	No	ClinGen gnomAD
rs1301937436 CA376431938	349	P>Q	No	ClinGen gnomAD
CA5459854 rs771751474	354	A>S	No	ClinGen ExAC gnomAD
CA5459853 rs771751474	354	A>T	No	ClinGen ExAC gnomAD
CA5459855 rs746620830	355	D>E	No	ClinGen ExAC TOPMed gnomAD
rs1588797689 CA376432020	356	D>N	No	ClinGen Ensembl
rs768363204 CA5459856	358	S>N	No	ClinGen ExAC gnomAD
rs1004276395 CA205304115	358	S>R	No	ClinGen gnomAD
rs776417442 CA5459857	360	G>V	No	ClinGen ExAC TOPMed gnomAD
rs1267327326 CA376432102	361	M>I	No	ClinGen gnomAD
rs765256009 CA5459859	363	E>*	No	ClinGen ExAC gnomAD
rs773495911 CA5459860	364	L>V	No	ClinGen ExAC gnomAD
rs751754929 CA5459863	374	N>D	No	ClinGen ExAC TOPMed gnomAD
rs755188415 CA5459864	374	N>S	No	ClinGen ExAC TOPMed gnomAD
CA205304187 rs143874924	377	P>S	No	ClinGen ESP TOPMed
CA376432272 rs1321200473	378	R>K	No	ClinGen TOPMed
rs368578451 CA5459866	380	A>T	No	ClinGen ESP ExAC TOPMed gnomAD
rs1310891021 CA376432308	381	D>G	No	ClinGen gnomAD
rs1283465231 CA376432363	385	H>L	No	ClinGen gnomAD
rs1283465231 CA376432362	385	H>R	No	ClinGen gnomAD
CA5459868 rs77316331	385	H>Y	No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1031875220 CA205304222	386	E>K	No	ClinGen Ensembl
CA376432391 rs1323121748	387	A>D	No	ClinGen gnomAD
CA5459869 rs745430402	388	L>V	No	ClinGen ExAC gnomAD
rs138733925 CA5459871	390	P>L	No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1439199393 CA376432424	391	P>S	No	ClinGen gnomAD
CA5459874 rs371438608	392	R>K	No	ClinGen ESP ExAC TOPMed gnomAD
rs1406142857 CA376432490	396	P>L	No	ClinGen gnomAD
rs769894329 CA5459876	397	R>C	No	ClinGen ExAC TOPMed gnomAD
CA5459877 rs773263158	398	C>S	No	ClinGen ExAC TOPMed gnomAD
CA376432522 rs1377486358	399	Q>H	No	ClinGen gnomAD
rs374373740 CA5459878	399	Q>L	No	ClinGen ESP ExAC TOPMed gnomAD
CA205304314 rs374373740	399	Q>R	No	ClinGen ESP ExAC TOPMed gnomAD
CA376432588 rs1306417003	405	L>P	No	ClinGen gnomAD
rs200350013 CA376432617	408	R>G	No	ClinGen 1000Genomes gnomAD
rs774423439 CA5459880	408	R>H	No	ClinGen ExAC TOPMed gnomAD
rs200350013 CA205304332	408	R>S	No	ClinGen 1000Genomes gnomAD
CA376432624 rs1320296400	409	K>Q	No	ClinGen gnomAD
CA376432637 rs1188267731	410	R>G	No	ClinGen TOPMed
CA205304339 rs967742174	410	R>K	No	ClinGen TOPMed
CA376432659 rs1414235756	412	L>M	No	ClinGen gnomAD
rs767775264 CA5459882	413	S>G	No	ClinGen ExAC TOPMed gnomAD
CA376432675 rs1208299196	413	S>R	No	ClinGen TOPMed
CA376432709 rs1196878465	416	E>D	No	ClinGen gnomAD
rs756446367 CA5459884	418	E>K	No	ClinGen ExAC
CA205304395 rs764390598	420	P>S	No	ClinGen ExAC gnomAD
rs764390598 CA5459885	420	P>T	No	ClinGen ExAC gnomAD
rs757690396 CA5459887	423	I>T	No	ClinGen ExAC
CA376433144 rs1194945390	426	S>Y	No	ClinGen TOPMed
CA5459912 rs143676953	427	S>L	No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1340312546 CA376433176	428	C>F	No	ClinGen gnomAD
CA5459915 rs561785057	428	C>G	No	ClinGen 1000Genomes ExAC gnomAD
rs374109727 CA205305788	429	T>A	No	ClinGen ExAC TOPMed gnomAD
rs374109727 CA5459916	429	T>P	No	ClinGen ExAC TOPMed gnomAD
CA5459918 rs375251313	432	T>S	No	ClinGen ESP ExAC TOPMed gnomAD
rs145710720 CA5459921	433	E>K	No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1392269960 CA376433241	434	E>K	No	ClinGen TOPMed
rs1356191245 CA376433271	435	S>F	No	ClinGen gnomAD
rs1399156551 CA376433259	435	S>P	No	ClinGen TOPMed
rs1334930263 CA376433298	437	M>I	No	ClinGen TOPMed
rs190610498 CA5459922	438	L>I	No	ClinGen 1000Genomes ExAC gnomAD
CA5459923 rs530346284	442	R>C	No	ClinGen ExAC gnomAD
rs532844555 CA5459924	442	R>H	No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs551035154 CA205305846	446	I>V	No	ClinGen 1000Genomes TOPMed
CA5459927 rs139316352	447	D>N	No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1158880021 CA376433421	449	G>S	No	ClinGen gnomAD
CA5459930 rs757096437	450	A>S	No	ClinGen ExAC gnomAD
CA376433433 rs757096437	450	A>T	No	ClinGen ExAC gnomAD
CA376433440 rs1564376035	450	A>V	No	ClinGen Ensembl
CA5459932 rs372679892	453	G>A	No	ClinGen ESP ExAC TOPMed gnomAD
CA5459933 rs549654679	454	Y>C	No	ClinGen 1000Genomes ExAC gnomAD
rs1460565096 CA376433490	455	F>Y	No	ClinGen TOPMed
CA5459934 rs780161279	456	N>D	No	ClinGen ExAC gnomAD
rs376945200 CA5459935	456	N>S	No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs748271376 CA5459938	459	R>Q	No	ClinGen ExAC TOPMed gnomAD
rs776816093 CA5459937	459	R>W	No	ClinGen ExAC
rs770229633 CA5459939	460	G>V	No	ClinGen ExAC gnomAD
rs1020784662 CA205305989	461	P>Q	No	ClinGen Ensembl
rs773384142 CA5459940	462	P>Q	No	ClinGen ExAC gnomAD
rs763529234 CA5459941	463	T>A	No	ClinGen ExAC gnomAD
CA5459942 rs766981801	463	T>M	No	ClinGen ExAC TOPMed gnomAD
CA205306004 rs971537792	464	L>I	No	ClinGen Ensembl
rs760237944 CA5459944	465	E>A	No	ClinGen ExAC TOPMed gnomAD
rs753558022 CA5459946	466	Y>C	No	ClinGen ExAC TOPMed gnomAD
rs763646666 CA5459945	466	Y>H	No	ClinGen ExAC gnomAD
CA376433626 rs1383714844	467	G>S	No	ClinGen TOPMed
rs756790446 CA5459947	468	G>R	No	ClinGen ExAC TOPMed gnomAD
CA5459949 rs750169451	468	G>W	No	ClinGen ExAC gnomAD

No associated diseases with P41279

4 regional properties for P41279

Type	Name	Position	InterPro Accession
domain	Ras-like guanine nucleotide exchange factor, N-terminal	49 - 175	IPR000651
domain	Ras guanine-nucleotide exchange factors catalytic domain	197 - 433	IPR001895
domain	EF-hand domain	466 - 501	IPR002048
domain	Protein kinase C-like, phorbol ester/diacylglycerol-binding domain	540 - 597	IPR002219

Functions

		Description
EC Number
Subcellular Localization	Cytoplasm
PANTHER Family	PTHR48016	MAP KINASE KINASE KINASE SSK2-RELATED-RELATED
PANTHER Subfamily	PTHR48016:SF31	MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE 8
PANTHER Protein Class	non-receptor serine/threonine protein kinase protein modifying enzyme
PANTHER Pathway Category	Toll receptor signaling pathway TPL2 Gonadotropin-releasing hormone receptor pathway MAP3Ks

1 GO annotations of cellular component

Name	Definition
cytosol	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.

6 GO annotations of molecular function

Name	Definition
ATP binding	Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
magnesium ion binding	Binding to a magnesium (Mg) ion.
MAP kinase kinase kinase activity	Catalysis of the phosphorylation and activation of a MAP kinase kinase; each MAP kinase kinase can be phosphorylated by any of several MAP kinase kinase kinases.
protein serine kinase activity	Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate.
protein serine/threonine kinase activity	Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate.
protein serine/threonine/tyrosine kinase activity	Catalysis of the reactions: ATP + a protein serine = ADP + protein serine phosphate; ATP + a protein threonine = ADP + protein threonine phosphate; and ATP + a protein tyrosine = ADP + protein tyrosine phosphate.

3 GO annotations of biological process

Name	Definition
cell cycle	The progression of biochemical and morphological phases and events that occur in a cell during successive cell replication or nuclear replication events. Canonically, the cell cycle comprises the replication and segregation of genetic material followed by the division of the cell, but in endocycles or syncytial cells nuclear replication or nuclear division may not be followed by cell division.
protein phosphorylation	The process of introducing a phosphate group on to a protein.
T cell costimulation	The process of providing, via surface-bound receptor-ligand pairs, a second, antigen-independent, signal in addition to that provided by the T cell receptor to augment T cell activation.

13 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
P25390	SSK22	Serine/threonine-protein kinase SSK22	Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)	PR
Q3SWY6	STK25	Serine/threonine-protein kinase 25	Bos taurus (Bovine)	PR
O00506	STK25	Serine/threonine-protein kinase 25	Homo sapiens (Human)	PR
Q9Y6E0	STK24	Serine/threonine-protein kinase 24	Homo sapiens (Human)	PR
Q9P289	STK26	Serine/threonine-protein kinase 26	Homo sapiens (Human)	PR
Q9Y6R4	MAP3K4	Mitogen-activated protein kinase kinase kinase 4	Homo sapiens (Human)	EV
Q9Z2W1	Stk25	Serine/threonine-protein kinase 25	Mus musculus (Mouse)	PR
Q99JT2	Stk26	Serine/threonine-protein kinase 26	Mus musculus (Mouse)	PR
Q99KH8	Stk24	Serine/threonine-protein kinase 24	Mus musculus (Mouse)	PR
Q07174	Map3k8	Mitogen-activated protein kinase kinase kinase 8	Mus musculus (Mouse)	SS
B0LT89	Stk24	Serine/threonine-protein kinase 24	Rattus norvegicus (Rat)	PR
Q63562	Map3k8	Mitogen-activated protein kinase kinase kinase 8	Rattus norvegicus (Rat)	SS
H2L099	gck-1	Germinal center kinase 1	Caenorhabditis elegans	PR

10	20	30	40	50	60
MEYMSTGSDN	KEEIDLLIKH	LNVSDVIDIM	ENLYASEEPA	VYEPSLMTMC	QDSNQNDERS
70	80	90	100	110	120
KSLLLSGQEV	PWLSSVRYGT	VEDLLAFANH	ISNTAKHFYG	QRPQESGILL	NMVITPQNGR
130	140	150	160	170	180
YQIDSDVLLI	PWKLTYRNIG	SDFIPRGAFG	KVYLAQDIKT	KKRMACKLIP	VDQFKPSDVE
190	200	210	220	230	240
IQACFRHENI	AELYGAVLWG	ETVHLFMEAG	EGGSVLEKLE	SCGPMREFEI	IWVTKHVLKG
250	260	270	280	290	300
LDFLHSKKVI	HHDIKPSNIV	FMSTKAVLVD	FGLSVQMTED	VYFPKDLRGT	EIYMSPEVIL
310	320	330	340	350	360
CRGHSTKADI	YSLGATLIHM	QTGTPPWVKR	YPRSAYPSYL	YIIHKQAPPL	EDIADDCSPG
370	380	390	400	410	420
MRELIEASLE	RNPNHRPRAA	DLLKHEALNP	PREDQPRCQS	LDSALLERKR	LLSRKELELP
430	440	450	460
ENIADSSCTG	STEESEMLKR	QRSLYIDLGA	LAGYFNLVRG	PPTLEYG