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)
MCF: 
101925060 102116823(MAP2K3) 102118759(MAP2K5) 102125035(MAP2K4) 102126975(MAP2K7) 102136923(PBK) 102140855(MAP2K2) 102141214(MAP2K1)
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)
CGE: 
HGL: 
101703028(Map2k6) 101705822(Map2k4) 101707562(Map2k2) 101710666(Map2k7) 101711080(Map2k5) 101715628(Map2k1) 101718318(Map2k3) 101720410(Pbk)
TUP: 
102469877(MAP2K5) 102476496(MAP2K1) 102478180(PBK) 102482054(MAP2K6) 102483700(MAP2K2) 102493856(MAP2K4) 102499419(MAP2K3) 102500732(MAP2K7)
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)
BOM: 
102267773(MAP2K3) 102271353(PBK) 102271710(MAP2K2) 102272638(MAP2K7) 102272962(MAP2K6) 102280670(MAP2K1) 102283668(MAP2K5) 102287278(MAP2K4)
PHD: 
102315849(MAP2K3) 102317867(MAP2K6) 102325860(MAP2K2) 102327200(MAP2K7) 102331780(MAP2K5) 102332128(PBK) 102333652(MAP2K4)
CHX: 
102169516(MAP2K6) 102170427(MAP2K5) 102173178(MAP2K7) 102173967(MAP2K3) 102175285(MAP2K2) 102175799(MAP2K4) 102181210(PBK) 102190520(MAP2K1)
SSC: 
100141310(PBK) 100233191(MAP2K1) 100520100(MAP2K4) 100520164(MAP2K5) 100520418(MAP2K7) 100525505(MAP2K2) 100625946(MAP2K6)
CFR: 
102506459(MAP2K7) 102511209(MAP2K2) 102513578(MAP2K4) 102515937(MAP2K1) 102517293(MAP2K5) 102518252(PBK) 102523780(MAP2K3)
ECB: 
100052849(MAP2K5) 100053056(MAP2K6) 100053481(MAP2K3) 100060789(PBK) 100063190(MAP2K2) 100065996(MAP2K1) 100073094(MAP2K4) 100147230(MAP2K7)
MYB: 
102240696(MAP2K1) 102244251(MAP2K4) 102245571(MAP2K2) 102246913(MAP2K6) 102247950(MAP2K7) 102253993(PBK) 102259712(MAP2K3) 102260280(MAP2K5)
MDO: 
SHR: 
OAA: 
GGA: 
396349(MAP2K2) 415549(MAP2K1) 415557(MAP2K5) 416496(MAP2K3) 417312(MAP2K4) 417445(MAP2K6) 422003(PBK)
MGP: 
TGU: 
100219724(MAP2K5) 100219801 100226448(MAP2K1) 100229860(MAP2K3)
FAB: 
101809415(MAP2K3) 101812216 101815546(MAP2K5) 101816905(MAP2K1) 101819388(MAP2K6) 101820507(MAP2K2) 101822010(MAP2K4) 101822092(PBK)
PHI: 
102100701(MAP2K7) 102102285(MAP2K2) 102102585 102105268(MAP2K6) 102106364(MAP2K5) 102109535(MAP2K3) 102110075(MAP2K1) 102114327(PBK)
APLA: 
101791037(MAP2K1) 101793398(MAP2K2) 101794019 101798109(PBK) 101799389(MAP2K6) 101801808(MAP2K5) 101803371(MAP2K3) 101805315(MAP2K4)
FPG: 
101913671(MAP2K6) 101918161 101919170(MAP2K3) 101922949(PBK) 101924219 101924296(MAP2K2) 101924559(MAP2K5) 101924998(MAP2K1)
FCH: 
102047307 102048212(PBK) 102049695(MAP2K2) 102052703(MAP2K3) 102053088(MAP2K6) 102053397(MAP2K1) 102053857(MAP2K5)
CLV: 
102084805(PBK) 102085143(MAP2K3) 102085780 102086996(MAP2K6) 102088655 102095101(MAP2K5) 102096091(MAP2K1) 102097053(MAP2K2)
ASN: 
102372350 102373782(MAP2K6) 102373880(MAP2K1) 102375508(MAP2K2) 102378558(PBK) 102379245 102380357(MAP2K5) 102383945(MAP2K3)
PSS: 
102443595(MAP2K1) 102451373(MAP2K5) 102452927 102453281(PBK) 102454019(MAP2K3) 102457075(MAP2K2) 102461243(MAP2K6) 102463924(MAP2K7)
ACS: 
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: 
MZE: 
OLA: 
XMA: 
LCM: 
102350370(MAP2K2) 102351267(MAP2K3) 102352547(MAP2K4) 102353461(PBK) 102357895(MAP2K5) 102358560(MAP2K1) 102365163
BFO: 
CIN: 
100179846 778672(mapkk4) 778673(mapkk5) 778674(mapkk7) 778902(mapkk3/6) 778923(mapkk1/2)
SPU: 
DME: 
DPO: 
DAN: 
DER: 
DPE: 
DSE: 
DSI: 
DWI: 
DYA: 
DGR: 
DMO: 
DVI: 
AGA: 
AAG: 
CQU: 
AME: 
409925(Dsor1) 410575(Mkk4) 413389(hem) 551365(GB13701)
NVI: 
TCA: 
BMOR: 
API: 
PHU: 
ISC: 
CEL: 
CBR: 
CBG01940(Cbr-mkk-4) CBG04190(Cbr-mek-2) CBG16698(Cbr-mek-1) CBG16802(Cbr-sek-1)
BMY: 
LOA: 
TSP: 
SMM: 
NVE: 
HMG: 
TAD: 
AQU: 
ATH: 
AT1G51660(MKK4) AT3G21220(MKK5) AT4G26070(MEK1) AT4G29810(MKK2) AT5G56580(MKK6)
ALY: 
CRB: 
EUS: 
CIT: 
CIC: 
GMX: 
MTR: 
CAM: 
FVE: 
CSV: 
RCU: 
POP: 
POPTR_0008s01030g(POPTRDRAFT_563479) POPTR_0010s25570g(POPTRDRAFT_228518) POPTR_0018s05420g(POPTRDRAFT_577971) POPTR_745168
VVI: 
SLY: 
101260328 543720(mek1) 543946(MKK2) 543947(MKK3)
SOT: 
OSA: 
DOSA: 
Os01t0510100-01(Os01g0510100) Os02t0787300-01(Os02g0787300) Os06t0147800-01(Os06g0147800) Os06t0191300-01(Os06g0191300)
BDI: 
SBI: 
SORBI_03g033190(SORBIDRAFT_03g033190) SORBI_04g035370(SORBIDRAFT_04g035370)
ZMA: 
SITA: 
SMO: 
PPP: 
CRE: 
VCN: 
OLU: 
OTA: 
MIS: 
MPP: 
CCP: 
SCE: 
YDL159W(STE7) YJL128C(PBS2) YOR231W(MKK1) YPL140C(MKK2)
AGO: 
ERC: 
KLA: 
LTH: 
PPA: 
VPO: 
ZRO: 
CGR: 
NCS: 
NCAS_0A09750(NCAS0A09750) NCAS_0B01450(NCAS0B01450)
NDI: 
NDAI_0E01310(NDAI0E01310) NDAI_0G06150(NDAI0G06150)
TPF: 
TPHA_0B01150(TPHA0B01150) TPHA_0G01730(TPHA0G01730)
TBL: 
TBLA_0D05640(TBLA0D05640)
TDL: 
TDEL_0A05980(TDEL0A05980) TDEL_0H01070(TDEL0H01070)
KAF: 
KAFR_0A03710(KAFR0A03710) KAFR_0G01810(KAFR0G01810)
DHA: 
PIC: 
PGU: 
LEL: 
CAL: 
CaO19.469(HST7) CaO19.6889(MKK2) CaO19.7388(PBS2) CaO19.8100(HST7)
CTP: 
CDU: 
COT: 
YLI: 
CLU: 
NCR: 
SMP: 
PAN: 
TTT: 
MTM: 
MGR: 
FGR: 
NHE: 
VAL: 
SSL: 
BFU: 
ANI: 
NFI: 
AFM: 
AOR: 
AOR_1_106084(AO090020000060) AOR_1_1906174(AO090005001093) AOR_1_570184(AO090009000347)
ANG: 
ANI_1_1390094(An11g10690) ANI_1_3024014(An01g11080) ANI_1_476164(An18g03740)
AFV: 
ACT: 
PCS: 
CIM: 
CPW: 
PBL: 
URE: 
ABE: 
TVE: 
AJE: 
PNO: 
PTE: 
ZTR: 
TML: 
SPO: 
CNE: 
CNB: 
CGI: 
PPL: 
LBC: 
MPR: 
CCI: 
SCM: 
UMA: 
MGL: 
PGR: 
MBR: 
DDI: 
DPP: 
DFA: 
DFA_10137(mekA)
ACAN: 
CHO: 
TET: 
PTM: 
PIF: 
EHX: 
GTT: 
TBR: 
Tb927.8.5950(Tb08.11J15.920)
TCR: 
LBZ: 
NGR: 
TVA: 
GLA: 
 » 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]
  Sequence
[hsa:5604 5605]
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]
  Sequence
[rno:58960]
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
  Sequence
[up:P29678]
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]
  Sequence
[hsa:5608]
Other DBs
ExplorEnz - The Enzyme Database: 
IUBMB Enzyme Nomenclature: 
ExPASy - ENZYME nomenclature database: 
BRENDA, the Enzyme Database: 

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