KEGG   ENZYME: 2.7.11.25Help
Entry
EC 2.7.11.25                Enzyme                                 
Name
mitogen-activated protein kinase kinase kinase;
cMos;
cRaf;
MAPKKK;
MAP3K;
MAP kinase kinase kinase;
MEKK;
MEKK1;
MEKK2;
MEKK3;
MEK kinase;
Mil/Raf;
MLK-like mitogen-activated protein triple kinase;
MLTK;
MLTKa;
MLTKb;
REKS;
STK28
Class
Transferases;
Transferring phosphorus-containing groups;
Protein-serine/threonine kinases
BRITE hierarchy
Sysname
ATP:protein phosphotransferase (MAPKKKK-activated)
Reaction(IUBMB)
ATP + a protein = ADP + a phosphoprotein [RN:R00162]
Reaction(KEGG)
Substrate
ATP [CPD:C00002];
protein [CPD:C00017]
Product
ADP [CPD:C00008];
phosphoprotein [CPD:C00562]
Comment
This enzyme phosphorylates and activates its downstream protein kinase, EC 2.7.12.2, mitogen-activated protein kinase kinase (MAPKK) but requires MAPKKKK for activation. Some members of this family can be activated by p21-activated kinases (PAK/STE20) or Ras. While c-Raf and c-Mos activate the classical MAPK/ERK pathway, MEKK1 and MEKK2 preferentially activate the c-Jun N-terminal protein kinase(JNK)/stress-activated protein kinase (SAPK) pathway [2]. Mitogen-activated protein kinase (MAPK) signal transduction pathways are among the most widespread mechanisms of cellular regulation. Mammalian MAPK pathways can be recruited by a wide variety of stimuli including hormones (e.g. insulin and growth hormone), mitogens (e.g. epidermal growth factor and platelet-derived growth factor), vasoactive peptides (e.g. angiotensin-II and endothelin), inflammatory cytokines of the tumour necrosis factor (TNF) family and environmental stresses such as osmotic shock, ionizing radiation and ischaemic injury.
Orthology
K04415  
mitogen-activated protein kinase kinase kinase 8
K04416  
mitogen-activated protein kinase kinase kinase 1
K04417  
mitogen-activated protein kinase kinase kinase 9
K04418  
mitogen-activated protein kinase kinase kinase 10
K04419  
mitogen-activated protein kinase kinase kinase 11
K04420  
mitogen-activated protein kinase kinase kinase 2
K04421  
mitogen-activated protein kinase kinase kinase 3
K04422  
mitogen-activated protein kinase kinase kinase 13
K04423  
mitogen-activated protein kinase kinase kinase 12
K04424  
sterile alpha motif and leucine zipper containing kinase AZK
K04425  
mitogen-activated protein kinase kinase kinase 6
K04426  
mitogen-activated protein kinase kinase kinase 5
K04427  
mitogen-activated protein kinase kinase kinase 7
K04428  
mitogen-activated protein kinase kinase kinase 4
K04466  
mitogen-activated protein kinase kinase kinase 14
K11230  
mitogen-activated protein kinase kinase kinase
K13414  
mitogen-activated protein kinase kinase kinase 1, plant
K13986  
mitogen-activated protein kinase kinase kinase 15
Genes
HSA: 
10746(MAP3K2) 1326(MAP3K8) 389840(MAP3K15) 4214(MAP3K1) 4215(MAP3K3) 4216(MAP3K4) 4217(MAP3K5) 4293(MAP3K9) 4294(MAP3K10) 4296(MAP3K11) 51776(ZAK) 6885(MAP3K7) 7786(MAP3K12) 9020(MAP3K14) 9064(MAP3K6) 9175(MAP3K13)
PTR: 
450384(MAP3K8) 451326(MAP3K11) 451940(MAP3K12) 454750(MAP3K14) 456674(MAP3K6) 459745 462888(MAP3K7) 463023(MAP3K5) 463119(MAP3K4) 465526(MAP3K15) 467498(MAP3K9) 468286(MAP3K3) 468880(MAP3K10) 471543(MAP3K1) 736244(MAP3K2) 737524(MAP3K13)
PPS: 
100969705(MAP3K3) 100973371(MAP3K2) 100974026(MAP3K7) 100975785(MAP3K15) 100977883(MAP3K10) 100978161(MAP3K8) 100981441(MAP3K4) 100983287(MAP3K12) 100984930(MAP3K14) 100985472(MAP3K13) 100985853(MAP3K11) 100990426(MAP3K9) 100991014(MAP3K5) 100992712(MAP3K6) 100994192 100994796(MAP3K1)
GGO: 
101128207(MAP3K13) 101129821(MAP3K15) 101133328(MAP3K8) 101135149(MAP3K9) 101136722(MAP3K1) 101137766(MAP3K6) 101144707(MAP3K7) 101147354(MAP3K5) 101147819(MAP3K14) 101148044(MAP3K3) 101148067(MAP3K10) 101148964(MAP3K11) 101149805(MAP3K2) 101151387(MAP3K12) 101152649(MAP3K4) 101154523
PON: 
100171454(MAP3K7) 100172208(MAP3K12) 100172983(MAP3K13) 100433831(MAP3K9) 100434157 100436201(MAP3K14) 100440278 100442172(MAP3K4) 100444678(MAP3K3) 100445147(MAP3K6) 100450054(MAP3K2) 100450681(MAP3K10) 100452447(MAP3K15) 100453309(MAP3K1) 100456749(MAP3K11) 100458776(MAP3K5)
MCC: 
100424131(MAP3K2) 693835(MAP3K9) 695958 696936 698274(ZAK) 700477(MAP3K10) 701085 703059(MAP3K12) 703101(MAP3K7) 710360(MAP3K4) 710979(MAP3K1) 711382(MAP3K5) 715911(MAP3K6) 716038(MAP3K11) 716258(MAP3K14) 717866(MAP3K3)
MMU: 
26401(Map3k1) 26403(Map3k11) 26404(Map3k12) 26405(Map3k2) 26406(Map3k3) 26407(Map3k4) 26408(Map3k5) 26409(Map3k7) 26410(Map3k8) 269881(Map3k10) 270672(Map3k15) 338372(Map3k9) 53608(Map3k6) 53859(Map3k14) 65964(B230120H23Rik) 71751(Map3k13)
RNO: 
100910771 116596(Map3k8) 116667(Map3k1) 171492(Map3k2) 25579(Map3k12) 303604(Map3k3) 303823(Map3k13) 308106(Map3k4) 308463(Map3k10) 309168(Map3k11) 311743(Zak) 313022(Map3k6) 313121(Map3k7) 360640(Map3k14) 500690(Map3k9) 501558(Map3k15)
CFA: 
100685499(MAP3K13) 476215(MAP3K5) 476262(MAP3K4) 478061(MAP3K1) 478802(ZAK) 480481(MAP3K3) 483732(MAP3K11) 484504(MAP3K10) 487085(MAP3K8) 487345(MAP3K6) 490765(MAP3K9) 490926(MAP3K14) 491765(MAP3K15) 607170(MAP3K12) 612902(MAP3K2)
AML: 
FCA: 
101081315(MAP3K6) 101082912(MAP3K5) 101083468(MAP3K14) 101083633(MAP3K3) 101084717(MAP3K9) 101087164(MAP3K12) 101089731(MAP3K10) 101089836(MAP3K15) 101090328(MAP3K1) 101090624(MAP3K8) 101093205(MAP3K13) 101094038 101095899(MAP3K7) 101096406(MAP3K2) 101097977(MAP3K4) 101098654(MAP3K11)
BTA: 
100335458 504592(MAP3K2) 505369(MAP3K13) 505427(MAP3K12) 508367(MAP3K14) 508943(MAP3K3) 511779(MAP3K4) 514210(MAP3K11) 519251(ZAK) 523962(MAP3K1) 529146(MAP3K7) 529335(MAP3K15) 535622(MAP3K8) 537380(MAP3K5) 538340(MAP3K9) 614598(MAP3K6) 781037(MAP3K10)
SSC: 
100135663(MAP3K7) 100152572 100154202(MAP3K4) 100155753(MAP3K9) 100512235(MAP3K6) 100513491(MAP3K3) 100515448 100517714(MAP3K12) 100520402(MAP3K14) 100521453(MAP3K10) 100621234(MAP3K2) 100624078 100627235 100739216(MAP3K15) 396617(MAP3K1)
ECB: 
100050140(MAP3K14) 100050628(MAP3K2) 100053153 100054289(MAP3K9) 100057319 100058153(MAP3K4) 100058434(MAP3K15) 100059237(MAP3K13) 100061688(MAP3K1) 100063602(MAP3K8) 100064002(MAP3K12) 100064751(MAP3K3) 100065841(MAP3K7) 100070933(MAP3K6) 100073186(MAP3K5)
MDO: 
100014185 100014282(MAP3K13) 100017378(MAP3K6) 100017495(MAP3K10) 100018494 100018684(MAP3K8) 100019975(MAP3K7) 100020082(MAP3K9) 100020668(MAP3K14) 100025970(MAP3K3) 100026735(MAP3K2) 100030111(MAP3K11) 100031527(MAP3K5) 100032065(MAP3K1) 100032495(MAP3K4)
SHR: 
100913571(MAP3K1) 100913706(MAP3K12) 100916246(MAP3K9) 100916713(MAP3K2) 100917439(MAP3K5) 100918124(MAP3K14) 100920997(MAP3K7) 100925633(MAP3K8) 100927077(MAP3K6) 100928208(MAP3K4) 100932862(MAP3K15) 100932989(MAP3K11) 100933813 100933837(MAP3K3)
OAA: 
100076215(MAP3K8) 100076229(MAP3K7) 100076612 100076986(MAP3K13) 100081079(MAP3K5) 100081562 100083301 100083521(MAP3K15) 100084257 100085554 100086943 100091166 100091507 100092024(MAP3K3) 100092492 100092507
GGA: 
100858193(MAP3K6) 418609(MAP3K15) 419954(MAP3K3) 419964(MAP3K14) 420419 420479(MAP3K8) 421579(MAP3K4) 421688(MAP3K5) 421808(MAP3K7) 424149(ZAK) 424225(MAP3K2) 424876(MAP3K13) 425792 427144(MAP3K1)
MGP: 
100538760(MAP3K14) 100539749 100541097(MAP3K8) 100542691 100542719 100543830(MAP3K2) 100547994(MAP3K13) 100548383(MAP3K4) 100550623(MAP3K1) 100550956 100551250(MAP3K5)
TGU: 
100217837(MAP3K14) 100219311(MAP3K15) 100219827(MAP3K2) 100221443(MAP3K7) 100223633(MAP3K3) 100224192(MAP3K5) 100225400(MAP3K13) 100225825(MAP3K1) 100226503(MAP3K3) 100228461 100229586(MAP3K9) 100229845(MAP3K4) 100230596(MAP3K8)
ACS: 
100551616(map3k5) 100552553(map3k6) 100553164 100556486 100557698(map3k3) 100558170(map3k2) 100558270(map3k13) 100560027(map3k4) 100560190(map3k14) 100561745(map3k1) 100562159 100562883(map3k8) 100565973 100566960 100568169(map3k15)
XLA: 
100113430(map3k12-a) 100337576(map3k12-b) 100337577(map3k13-b) 100337578(map3k13-a) 379399(MGC53150) 398612(map3k10) 399459(map3k7) 734336(map3k3)
XTR: 
100101764(map3k7) 100488058 100488307 100488360 100488949 100489201 100490021(map3k3) 100490504(map3k1) 100493069 100493570(map3k2) 100493878 100495797 100497217(map3k4) 100497692
DRE: 
100004261 100005496(fa92h04) 100334289 100334486 325488(map3k4) 404626(map3k12) 553788(map3k7) 555703(map3k5) 558321(map3k2) 559247 560211(map3k3) 560639 560932 563727 568412 570051 795766
TRU: 
101061432 101061953 101062891 101063413 101063524 101064896 101067596 101068242 101068369 101069247 101069629 101069746 101071039 101072543 101076353 101076799 101078679 101079141
OLA: 
101156127 101159779 101160297 101160549 101160858 101161665 101162759 101164271 101166009 101167985 101169290 101169326 101170310 101174595 101174856 101175702
BFO: 
BRAFLDRAFT_125878 BRAFLDRAFT_219597 BRAFLDRAFT_221293 BRAFLDRAFT_66872 BRAFLDRAFT_70437 BRAFLDRAFT_76434
CIN: 
100174992 100177364 100186217 100186887 778771(tak1/mapkkk7) 778975(mapkkk4) 778976(mltk)
SPU: 
577291 582769 590385 590478 590951 592507(MAP3K5) 592876
DME: 
Dmel_CG18492(Tak1) Dmel_CG4720(Pk92B) Dmel_CG8789(wnd)
DPO: 
Dpse_GA14958 Dpse_GA18383(Dpse_Pk92B) Dpse_GA18443 Dpse_GA21324
DAN: 
Dana_GF10720 Dana_GF15984 Dana_GF17624 Dana_GF18291
DER: 
Dere_GG13387 Dere_GG17579 Dere_GG23570(Dere_Pk92B)
DPE: 
Dper_GL12207 Dper_GL15931 Dper_GL20878 Dper_GL23779
DSE: 
Dsec_GM17139 Dsec_GM22666 Dsec_GM26871
DSI: 
Dsim_GD12264 Dsim_GD15532(Dsim_Tak1) Dsim_GD19320
DWI: 
Dwil_GK20056 Dwil_GK22362(Dwil_Pk92B) Dwil_GK25814
DYA: 
Dyak_GE15342(Dyak_Tak1) Dyak_GE22480 Dyak_GE25632
DGR: 
Dgri_GH14621 Dgri_GH16508 Dgri_GH17735
DMO: 
Dmoj_GI13508 Dmoj_GI15482 Dmoj_GI22433
DVI: 
Dvir_GJ10996 Dvir_GJ11870 Dvir_GJ19194
AGA: 
AgaP_AGAP000747 AgaP_AGAP006461
AAG: 
AaeL_AAEL007035 AaeL_AAEL008306 AaeL_AAEL008311 AaeL_AAEL010466 AaeL_AAEL010835
CQU: 
CpipJ_CPIJ006370 CpipJ_CPIJ008487
AME: 
408533 410119 411566(MAPKKK9) 413809(Tak1)
NVI: 
100118641(NV17884) 100119561(NV17160) 100120628(NV14593) 100123601(NV13729)
TCA: 
656961(Tak1) 661249 661365 663503 664510
API: 
100159713 100161755 100165908 100166541 100168328
PHU: 
Phum_PHUM125410 Phum_PHUM582410 Phum_PHUM596320
ISC: 
IscW_ISCW002017 IscW_ISCW002207 IscW_ISCW010233 IscW_ISCW023496
CEL: 
CELE_B0414.7(mtk-1) CELE_R13F6.6(zak-1)
CBR: 
CBG02299(Cbr-nsy-1) CBG04061(Cbr-mtk-1) CBG08707(Cbr-dlk-1) CBG16544(Cbr-zak-1)
BMY: 
Bm1_11350 Bm1_16860 Bm1_26085 Bm1_48405 Bm1_52175
TSP: 
Tsp_00404 Tsp_07016 Tsp_09483
SMM: 
Smp_050380 Smp_162800.1
NVE: 
NEMVE_v1g104385 NEMVE_v1g116420 NEMVE_v1g120549 NEMVE_v1g87118
HMG: 
100199949 100202032 100206143 100206765
TAD: 
TRIADDRAFT_10277 TRIADDRAFT_22456 TRIADDRAFT_24805 TRIADDRAFT_25066 TRIADDRAFT_26486 TRIADDRAFT_28738
AQU: 
100631731(Map3k15) 100632568 100634854 100635655
ATH: 
AT4G08500(MEKK1) AT5G11850
ALY: 
ARALYDRAFT_489755 ARALYDRAFT_909157
GMX: 
100819177
MTR: 
MTR_5g060350
CSV: 
101218538
RCU: 
RCOM_1032850
POP: 
POPTR_1071643 POPTR_1078383
VVI: 
100241228 100264291
OSA: 
4332325 4333845
DOSA: 
Os03t0262200-00(Os03g0262200)
BDI: 
100825446
SBI: 
SORBI_01g010800(SORBIDRAFT_01g010800) SORBI_01g040360(SORBIDRAFT_01g040360)
ZMA: 
100272734(cl17799_1) 100279294 100304418(pco069828(336))
CRE: 
CHLREDRAFT_182152
OLU: 
OSTLU_42011 OSTLU_6189
SCE: 
YCR073C(SSK22) YNR031C(SSK2)
AGO: 
AGOS_AER264C
ERC: 
Ecym_2499
KLA: 
KLLA0C08525g
LTH: 
KLTH0A06776g
PPA: 
PAS_chr1-4_0279
VPO: 
Kpol_1028p40
ZRO: 
ZYRO0D08184g
NCS: 
NCAS_0A05370(NCAS0A05370) NCAS_0D04600(NCAS0D04600)
NDI: 
NDAI_0I00340(NDAI0I00340)
TPF: 
TPHA_0M01840(TPHA0M01840)
TBL: 
TBLA_0I02400(TBLA0I02400)
TDL: 
TDEL_0A07560(TDEL0A07560)
KAF: 
KAFR_0F04340(KAFR0F04340)
DHA: 
DEHA2C08910g
PIC: 
PICST_28119(SSK2)
PGU: 
PGUG_03774
LEL: 
LELG_04453
CAL: 
CaO19.11257(SSK2)
CTP: 
CTRG_02206
CDU: 
CD36_44660
COT: 
CORT_0E03090
YLI: 
YALI0A05247g
CLU: 
CLUG_02562
NCR: 
NCU03071
SMP: 
SMAC_02801(os4)
PAN: 
PODANSg5912
TTT: 
THITE_2113432
MTM: 
MYCTH_2296333
MGR: 
MGG_00183
FGR: 
FG00408.1
NHE: 
NECHADRAFT_90174
VAL: 
VDBG_04429
SSL: 
SS1G_06598
BFU: 
BC1G_04606
ANI: 
AN1180.2
NFI: 
NFIA_014690
AFM: 
AFUA_1G10940
AOR: 
AOR_1_520074(AO090038000313)
ANG: 
ANI_1_450074(An08g03240)
AFV: 
AFLA_068590
ACT: 
ACLA_024570
PCS: 
Pc13g13500
CIM: 
CIMG_06932
CPW: 
CPC735_033180
PBL: 
PAAG_03029
URE: 
UREG_05917
ABE: 
ARB_02855
TVE: 
TRV_05548
AJE: 
HCAG_01783
PNO: 
SNOG_07196
PTE: 
PTT_19769
ZTR: 
MYCGRDRAFT_67344(MgSsk2)
TML: 
GSTUM_00002374001
SPO: 
SPAC9G1.02(wis4)
CNE: 
CNL05560
CNB: 
CNBI1260
CGI: 
CGB_D1460C
PPL: 
POSPLDRAFT_50885
LBC: 
LACBIDRAFT_141037
CCI: 
CC1G_13687
SCM: 
SCHCODRAFT_255608
UMA: 
UM01544.1
MGL: 
MGL_3138
PGR: 
PGTG_03102
MBR: 
MONBRDRAFT_1800 MONBRDRAFT_25232
DDI: 
DDB_G0281557(drkD)
TET: 
TTHERM_00193390
 » show all
Taxonomy
Reference
1  [PMID:8940179]
  Authors
Wang XS, Diener K, Jannuzzi D, Trollinger D, Tan TH, Lichenstein H, Zukowski M, Yao Z.
  Title
Molecular cloning and characterization of a novel protein kinase with a catalytic domain homologous to mitogen-activated protein kinase kinase kinase.
  Journal
J. Biol. Chem. 271 (1996) 31607-11.
  Organism
Mus musculus [GN:mmu], Drosophila melanogaster [GN:dme], Saccharomyces cerevisiae [GN:sce], Schizosaccharomyces pombe [GN:spo]
Reference
2  [PMID:11042189]
  Authors
Gotoh I, Adachi M, Nishida E.
  Title
Identification and characterization of a novel MAP kinase kinase kinase, MLTK.
  Journal
J. Biol. Chem. 276 (2001) 4276-86.
  Organism
Homo sapiens [GN:hsa]
Reference
3  [PMID:8334704]
  Authors
Vojtek AB, Hollenberg SM, Cooper JA.
  Title
Mammalian Ras interacts directly with the serine/threonine kinase Raf.
  Journal
Cell. 74 (1993) 205-14.
  Organism
Mus musculus [GN:mmu]
Other DBs
ExplorEnz - The Enzyme Database: 
IUBMB Enzyme Nomenclature: 
ExPASy - ENZYME nomenclature database: 
BRENDA, the Enzyme Database: 
CAS: 
146702-84-3
DBGET integrated database retrieval system