KEGG   ENZYME: 2.7.12.2Help
Entry
EC 2.7.12.2                 Enzyme                                 
Name
mitogen-activated protein kinase kinase;
MAP kinase kinase;
MAP kinase kinase 4;
MAP kinase kinase 7;
MAP kinase or ERK kinase;
MAP2K;
MAPKK;
MAPKK1;
MEK;
MEK1;
MEK2;
MKK;
MKK2;
MKK4;
MKK6;
MKK7;
STK27
Class
Transferases;
Transferring phosphorus-containing groups;
Dual-specificity kinases (those acting on Ser/Thr and Tyr residues)
BRITE hierarchy
Sysname
ATP:protein phosphotransferase (MAPKKK-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 is a dual-specific protein kinase and requires mitogen-activated protein kinase kinase kinase (MAPKKK) for activation. It is required for activation of EC 2.7.11.24, mitogen-activated protein kinase. Phosphorylation of MEK1 by Raf involves phosphorylation of two serine residues [5]. 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
K04368  
mitogen-activated protein kinase kinase 1
K04369  
mitogen-activated protein kinase kinase 2
K04430  
mitogen-activated protein kinase kinase 4
K04431  
mitogen-activated protein kinase kinase 7
K04432  
mitogen-activated protein kinase kinase 3
K04433  
mitogen-activated protein kinase kinase 6
K04463  
mitogen-activated protein kinase kinase 5
K08294  
mitogen-activated protein kinase kinase
K08865  
PDZ-binding kinase
K11226  
mitogen-activated protein kinase kinase
K11227  
mitogen-activated protein kinase kinase
K13413  
mitogen-activated protein kinase kinase 4/5, plant
K14511  
mitogen-activated protein kinase kinase SIMKK
Genes
HSA: 
55872(PBK) 5604(MAP2K1) 5605(MAP2K2) 5606(MAP2K3) 5607(MAP2K5) 5608(MAP2K6) 5609(MAP2K7) 6416(MAP2K4)
PTR: 
100611792 450188(MAP2K1) 453532(MAP2K5) 454515(MAP2K3) 455065(MAP2K4) 456390(MAP2K2) 464496(PBK) 468310(MAP2K6) 743199(MAP2K7) 746715
PPS: 
100972424(MAP2K6) 100975020(MAP2K3) 100977025(MAP2K2) 100988422(MAP2K1) 100988437 100989445(PBK) 100989537(MAP2K7) 100991495(MAP2K4) 100994910(MAP2K5)
GGO: 
101124339(MAP2K7) 101126885(MAP2K2) 101132391(MAP2K1) 101137194(MAP2K5) 101140044(PBK) 101142374(MAP2K6) 101145420(MAP2K3) 101148200 101154090
PON: 
100431600(MAP2K7) 100439299 100446021(MAP2K1) 100448382(MAP2K6) 100449213(MAP2K5) 100450988 100453095(PBK) 100457536(MAP2K3)
MCC: 
693914(MAP2K6) 705195(MAP2K3) 710077 710415(MAP2K1) 711672(MAP2K5) 713242(PBK) 718155(MAP2K4) 721821(MAP2K2)
MMU: 
23938(Map2k5) 26395(Map2k1) 26396(Map2k2) 26397(Map2k3) 26398(Map2k4) 26399(Map2k6) 26400(Map2k7) 52033(Pbk)
RNO: 
100911550 114495(Map2k6) 170851(Map2k1) 287398(Map2k4) 290326(Pbk) 29568(Map2k5) 303200(Map2k3) 363855(Map2k7) 58960(Map2k2)
CFA: 
477371(PBK) 478347(MAP2K1) 480454(MAP2K6) 485004(MAP2K7) 489508(MAP2K4) 489547(MAP2K3) 609559(MAP2K5) 611939(MAP2K2)
AML: 
FCA: 
101080784(PBK) 101081387(MAP2K1) 101082274(MAP2K3) 101086432(MAP2K4) 101089813(MAP2K6) 101095157(MAP2K7) 101100281 101100725(MAP2K5)
BTA: 
100295732(MAP2K5) 286883(MAP2K6) 510434(MAP2K2) 516039(MAP2K3) 526469(MAP2K4) 533199(MAP2K1) 534781(PBK) 787278(MAP2K7)
SSC: 
100141310(PBK) 100233191(MAP2K1) 100520100 100520164 100520418 100525505(MAP2K2) 100625946
ECB: 
100052849(MAP2K5) 100053056(MAP2K6) 100053481(MAP2K3) 100060789 100065996(MAP2K1) 100073094(MAP2K4) 100147230
MDO: 
100014462 100016872 100018044 100018410(MAP2K1) 100019828(MAP2K4) 100025486(MAP2K5) 100026752 100029049(MAP2K6)
SHR: 
100917396(MAP2K2) 100922086(PBK) 100924259(MAP2K5) 100925586 100926110(MAP2K7) 100931587
OAA: 
100077802 100078394 100080362 100080734 100085895(MAP2K5) 100087942
GGA: 
396349(MAP2K2) 415549(MAP2K1) 415557(MAP2K5) 416496(MAP2K3) 417312(MAP2K4) 417445(MAP2K6) 422003(PBK)
MGP: 
100542290 100543421 100544509 100544828 100545287 100550535 100551337
TGU: 
100219724(MAP2K5) 100219801 100226448(MAP2K1) 100229860(MAP2K3)
ACS: 
100556629 100561588 100562970(map2k5) 100565867 100566152 100567176 100567963(map2k6)
XLA: 
379638(map2k6) 379991(map2k1) 394391(map2k7) 414694(map2k5) 496340(pbk)
XTR: 
100135013(map2k4) 448132(map2k6) 493420(map2k1) 496810(pbk) 549042(map2k5) 613115(map2k7)
DRE: 
100002225(map2k2b) 100007679(map2k5) 360218(pbk) 403052(map2k4a) 406728(map2k1) 560913(map2k7) 563181(map2k2a) 568951(map2k4b) 65239(map2k6)
TRU: 
101063584 101064151 101064650 101070236 101072590 101073869 101078396
OLA: 
101161098 101162677 101163933 101164950 101169919 101171635 101173453 101174917
BFO: 
BRAFLDRAFT_124326 BRAFLDRAFT_125171 BRAFLDRAFT_200264 BRAFLDRAFT_217608 BRAFLDRAFT_99237 BRAFLDRAFT_99242
CIN: 
100179846 778672(mapkk4) 778673(mapkk5) 778674(mapkk7) 778902(mapkk3/6) 778923(mapkk1/2)
SPU: 
576066 581169 585817 589763 591137 594211
DME: 
Dmel_CG12244(lic) Dmel_CG15793(Dsor1) Dmel_CG4353(hep) Dmel_CG8173 Dmel_CG9738(Mkk4)
DPO: 
Dpse_GA11504 Dpse_GA13960 Dpse_GA21998 Dpse_GA22607 Dpse_GA22809
DAN: 
Dana_GF16332 Dana_GF19085(Dana_Dsor1) Dana_GF20874 Dana_GF21160 Dana_GF21403
DER: 
Dere_GG17438 Dere_GG17753 Dere_GG18164 Dere_GG18305 Dere_GG19526
DPE: 
Dper_GL16000 Dper_GL16492 Dper_GL16493 Dper_GL16519 Dper_GL24503
DSE: 
Dsec_GM11518 Dsec_GM11599 Dsec_GM13297 Dsec_GM22414 Dsec_GM26332
DSI: 
Dsim_GD15909 Dsim_GD16945(Dsim_Dsor1) Dsim_GD17342 Dsim_GD20857 Dsim_GD24803(Dsim_lic)
DWI: 
Dwil_GK14073 Dwil_GK16200 Dwil_GK25111 Dwil_GK25249 Dwil_GK25671
DYA: 
Dyak_GE15575 Dyak_GE16180 Dyak_GE17041 Dyak_GE17784 Dyak_GE24839
DGR: 
Dgri_GH12078 Dgri_GH12793 Dgri_GH22908 Dgri_GH24432 Dgri_GH24549
DMO: 
Dmoj_GI10233 Dmoj_GI11083 Dmoj_GI15238 Dmoj_GI16263 Dmoj_GI16291
DVI: 
Dvir_GJ11038 Dvir_GJ15766 Dvir_GJ16530 Dvir_GJ16904 Dvir_GJ18839
AGA: 
AgaP_AGAP000147 AgaP_AGAP000310 AgaP_AGAP001103 AgaP_AGAP001867 AgaP_AGAP003365
AAG: 
AaeL_AAEL001622 AaeL_AAEL003013 AaeL_AAEL003359 AaeL_AAEL012723 AaeL_AAEL014729
CQU: 
CpipJ_CPIJ003157 CpipJ_CPIJ010611 CpipJ_CPIJ015801
AME: 
409925(Dsor1) 410575(Mkk4) 413389(hem) 551365
NVI: 
100114951(NV11003) 100119456(NV16376) 100120952(NV15520) 100121060(NV11611)
TCA: 
661608 661995 662917
API: 
100159396 100161114 100164531 100165019 100167099
PHU: 
Phum_PHUM001030 Phum_PHUM196800 Phum_PHUM372730 Phum_PHUM413460 Phum_PHUM492330
ISC: 
IscW_ISCW002764 IscW_ISCW005428 IscW_ISCW006910 IscW_ISCW023081
CEL: 
CELE_F42G10.2(mkk-4) CELE_K08A8.1(mek-1) CELE_R03G5.2(sek-1) CELE_Y54E10BL.6(mek-2)
CBR: 
CBG01940(Cbr-mkk-4) CBG04190(Cbr-mek-2) CBG16698(Cbr-mek-1) CBG16802(Cbr-sek-1)
BMY: 
Bm1_10515 Bm1_27865 Bm1_39990 Bm1_48560
TSP: 
Tsp_00085 Tsp_02206 Tsp_10801
SMM: 
Smp_026510 Smp_086690
NVE: 
NEMVE_v1g106419 NEMVE_v1g114199 NEMVE_v1g144733 NEMVE_v1g229025 NEMVE_v1g237148 NEMVE_v1g83596 NEMVE_v1g91949
HMG: 
100200909 100201328 100203621 100207769 100213114
TAD: 
TRIADDRAFT_21026 TRIADDRAFT_21281 TRIADDRAFT_21381
AQU: 
100633628 100638124 100640493
ATH: 
AT1G51660(MKK4) AT3G21220(MKK5) AT4G26070(MEK1) AT4G29810(MKK2) AT5G56580(MKK6)
ALY: 
ARALYDRAFT_329070 ARALYDRAFT_474280 ARALYDRAFT_479642 ARALYDRAFT_491777 ARALYDRAFT_495747
GMX: 
100786284 100786390 100789734 100792457 100818488 547701(MAPKK2)
MTR: 
MTR_4g005830 MTR_6g090470
CSV: 
101204545 101218848 101219669
RCU: 
RCOM_0727440 RCOM_1046440 RCOM_1049070
POP: 
POPTR_563479 POPTR_577971 POPTR_745168
VVI: 
100247508 100252603 100258699
OSA: 
4324023 4330957 4340126
DOSA: 
Os01t0510100-01(Os01g0510100) Os02t0787300-01(Os02g0787300) Os06t0147800-01(Os06g0147800)
BDI: 
100823700 100826178(MKK6.1) 100843567
SBI: 
SORBI_03g033190(SORBIDRAFT_03g033190) SORBI_04g035370(SORBIDRAFT_04g035370)
ZMA: 
100281486 100857056 542356(mek1)
SMO: 
SELMODRAFT_272204(NQK-2) SELMODRAFT_450110(NQK-1)
PPP: 
PHYPADRAFT_181532 PHYPADRAFT_206232
CRE: 
CHLREDRAFT_187846
VCN: 
VOLCADRAFT_73333
OLU: 
OSTLU_4731
OTA: 
Ot04g04050
SCE: 
YDL159W(STE7) YJL128C(PBS2) YOR231W(MKK1) YPL140C(MKK2)
AGO: 
AGOS_ACR117W AGOS_ACR196C AGOS_AFL217C
ERC: 
Ecym_4647 Ecym_5209 Ecym_8337
KLA: 
KLLA0C16577g KLLA0D07304g KLLA0E15313g
LTH: 
KLTH0D10670g KLTH0F05918g KLTH0H01584g
PPA: 
PAS_chr1-1_0105 PAS_chr1-4_0008 PAS_chr1-4_0271
VPO: 
Kpol_1031p32 Kpol_1072p31 Kpol_448p13 Kpol_530p41
ZRO: 
ZYRO0D03344g ZYRO0F06798g ZYRO0F11418g
CGR: 
CAGL0I03498g CAGL0J03828g CAGL0L05632g
NCS: 
NCAS_0A09750(NCAS0A09750) NCAS_0A14050(NCAS0A14050) NCAS_0B01450(NCAS0B01450)
NDI: 
NDAI_0A01970(NDAI0A01970) NDAI_0E01310(NDAI0E01310) NDAI_0G06150(NDAI0G06150)
TPF: 
TPHA_0B01150(TPHA0B01150) TPHA_0F02870(TPHA0F02870) TPHA_0G01730(TPHA0G01730)
TBL: 
TBLA_0D05640(TBLA0D05640) TBLA_0F02350(TBLA0F02350)
TDL: 
TDEL_0A05980(TDEL0A05980) TDEL_0C02110(TDEL0C02110) TDEL_0H01070(TDEL0H01070)
KAF: 
KAFR_0A03710(KAFR0A03710) KAFR_0B00920(KAFR0B00920) KAFR_0G01810(KAFR0G01810)
DHA: 
DEHA2C08536g DEHA2C15972g DEHA2F14498g
PIC: 
PICST_33851(STE7) PICST_35816 PICST_40600
PGU: 
PGUG_00992 PGUG_03840 PGUG_04163
LEL: 
LELG_01013 LELG_02820 LELG_03373
CAL: 
CaO19.469(HST7) CaO19.6889(MKK2) CaO19.7388(PBS2) CaO19.8100(HST7)
CTP: 
CTRG_00710 CTRG_01530 CTRG_02256
CDU: 
CD36_20220 CD36_29180(STE7) CD36_86000
COT: 
CORT_0A08790 CORT_0C02430 CORT_0D02490
YLI: 
YALI0B13178g YALI0B15906g
CLU: 
CLUG_01074 CLUG_03729 CLUG_05551
NCR: 
NCU00587 NCU04612 NCU06419
SMP: 
SMAC_01279(os5) SMAC_02183(mek1) SMAC_06526(mek2)
PAN: 
PODANSg4003 PODANSg5429 PODANSg7868
TTT: 
THITE_2106250 THITE_2119959 THITE_2170037
MTM: 
MYCTH_2133010 MYCTH_2297347 MYCTH_81343
MGR: 
MGG_00800 MGG_06482
FGR: 
FG07295.1 FG08691.1 FG09903.1
NHE: 
NECHADRAFT_36390 NECHADRAFT_61076 NECHADRAFT_68573
VAL: 
VDBG_00333 VDBG_02315 VDBG_02628
SSL: 
SS1G_00059 SS1G_10792 SS1G_14143
BFU: 
BC1G_03809 BC1G_07633 BC1G_11713
ANI: 
AN0931.2 AN3422.2 AN4189.2
NFI: 
NFIA_009350 NFIA_018920 NFIA_071330
AFM: 
AFUA_1G05800 AFUA_1G15950 AFUA_3G05900
AOR: 
AOR_1_106084(AO090020000060) AOR_1_1906174(AO090005001093) AOR_1_570184(AO090009000347)
ANG: 
ANI_1_1390094(An11g10690)
AFV: 
AFLA_051240 AFLA_083380 AFLA_103480
ACT: 
ACLA_019390 ACLA_028730 ACLA_033870
PCS: 
Pc16g11400 Pc16g13300 Pc20g08070
CIM: 
CIMG_00541 CIMG_03086 CIMG_03875
CPW: 
CPC735_004680 CPC735_010580 CPC735_056940
PBL: 
PAAG_01808 PAAG_05293 PAAG_06020
URE: 
UREG_00564 UREG_02065 UREG_02872
ABE: 
ARB_02105 ARB_05664 ARB_07210
TVE: 
TRV_01194 TRV_01503 TRV_06933
AJE: 
HCAG_00181 HCAG_02220 HCAG_03461
PNO: 
SNOG_02007 SNOG_05651 SNOG_11919
PTE: 
PTT_12414 PTT_13132 PTT_18338
ZTR: 
MYCGRDRAFT_52389(MgSte7) MYCGRDRAFT_71299(MgMkk1) MYCGRDRAFT_76249(MgPbs2)
TML: 
GSTUM_00003004001 GSTUM_00005681001 GSTUM_00011865001
SPO: 
SPBC409.07c(wis1) SPBC543.07(pek1)
CNE: 
CNA07470 CNC02350 CNE01930
CNB: 
CNBA7290 CNBC4890 CNBE1890
CGI: 
CGB_A8570W CGB_C3420C CGB_E2440W
PPL: 
POSPLDRAFT_113052 POSPLDRAFT_113082
LBC: 
LACBIDRAFT_324122
MPR: 
MPER_01563
CCI: 
CC1G_01983 CC1G_02205 CC1G_14241
SCM: 
SCHCODRAFT_57501 SCHCODRAFT_77536
UMA: 
UM01514.1 UM04864.1 UM06342.1
MGL: 
MGL_1536 MGL_3129 MGL_3979
PGR: 
PGTG_01624 PGTG_20747 PGTG_22636
MBR: 
MONBRDRAFT_16866 MONBRDRAFT_18821 MONBRDRAFT_26845
NGR: 
NAEGRDRAFT_55909 NAEGRDRAFT_58346
DDI: 
DDB_G0269152(mekA)
DPP: 
DICPUDRAFT_98833
PTM: 
GSPATT00011700001 GSPATT00026784001 GSPATT00039140001
GLA: 
GL50803_22165
TVA: 
TVAG_495060
PIF: 
PITG_00124
 » show all
Taxonomy
Reference
1  [PMID:8004006]
  Authors
Mordret G.
  Title
MAP kinase kinase: a node connecting multiple pathways.
  Journal
Biol. Cell. 79 (1993) 193-207.
  Organism
Homo sapiens [GN:hsa], Rattus norvegicus [GN:rno], Schizosaccharomyces pombe [GN:spo], Mus musculus [GN:mmu], Oryctolagus cuniculus, Xenopus laevis [GN:xla], Saccharomyces cerevisiae [GN:sce], Drosophila melanogaster [GN:dme]
Reference
2  [PMID:8388392]
  Authors
Zheng CF, Guan KL.
  Title
Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2.
  Journal
J. Biol. Chem. 268 (1993) 11435-9.
  Organism
Homo sapiens [GN:hsa]
Reference
3  [PMID:8393135]
  Authors
Wu J, Harrison JK, Dent P, Lynch KR, Weber MJ, Sturgill TW.
  Title
Identification and characterization of a new mammalian mitogen-activated protein kinase kinase, MKK2.
  Journal
Mol. Cell. Biol. 13 (1993) 4539-48.
  Organism
Rattus norvegicus [GN:rno]
Reference
4  [PMID:8157000]
  Authors
Alessi DR, Saito Y, Campbell DG, Cohen P, Sithanandam G, Rapp U, Ashworth A, Marshall CJ, Cowley S.
  Title
Identification of the sites in MAP kinase kinase-1 phosphorylated by p74raf-1.
  Journal
EMBO. J. 13 (1994) 1610-9.
  Organism
Oryctolagus cuniculus
Reference
5  [PMID:7731726]
  Authors
Pham CD, Arlinghaus RB, Zheng CF, Guan KL, Singh B.
  Title
Characterization of MEK1 phosphorylation by the v-Mos protein.
  Journal
Oncogene. 10 (1995) 1683-8.
Reference
6  [PMID:8621675]
  Authors
Han J, Lee JD, Jiang Y, Li Z, Feng L, Ulevitch RJ.
  Title
Characterization of the structure and function of a novel MAP kinase kinase (MKK6).
  Journal
J. Biol. Chem. 271 (1996) 2886-91.
  Organism
Homo sapiens [GN:hsa]
Other DBs
ExplorEnz - The Enzyme Database: 
IUBMB Enzyme Nomenclature: 
ExPASy - ENZYME nomenclature database: 
BRENDA, the Enzyme Database: 
DBGET integrated database retrieval system