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Dual specificity mitogen-activated protein kinase kinase 1 (MAP kinase kinase 1) (MAPKK 1) (MKK1) (EC 2.7.12.2) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK 1)

 MP2K1_HUMAN             Reviewed;         393 AA.
Q02750;
01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
23-JAN-2007, sequence version 2.
27-SEP-2017, entry version 196.
RecName: Full=Dual specificity mitogen-activated protein kinase kinase 1;
Short=MAP kinase kinase 1;
Short=MAPKK 1;
Short=MKK1;
EC=2.7.12.2;
AltName: Full=ERK activator kinase 1;
AltName: Full=MAPK/ERK kinase 1;
Short=MEK 1;
Name=MAP2K1; Synonyms=MEK1, PRKMK1;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PARTIAL PROTEIN
SEQUENCE, AND TISSUE SPECIFICITY.
TISSUE=T-cell;
PubMed=1281467;
Seger R., Seger D., Lozeman F.J., Ahn N.G., Graves L.M.,
Campbell J.S., Ericsson L., Harrylock M., Jensen A.M., Krebs E.G.;
"Human T-cell mitogen-activated protein kinase kinases are related to
yeast signal transduction kinases.";
J. Biol. Chem. 267:25628-25631(1992).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
PubMed=8388392;
Zheng C.-F., Guan K.-L.;
"Cloning and characterization of two distinct human extracellular
signal-regulated kinase activator kinases, MEK1 and MEK2.";
J. Biol. Chem. 268:11435-11439(1993).
[3]
PROTEIN SEQUENCE OF 35-45; 48-57; 175-183 AND 344-353, INTERACTION
WITH KSR1, SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT SER-218.
PubMed=10409742; DOI=10.1128/MCB.19.8.5523;
Stewart S., Sundaram M., Zhang Y., Lee J., Han M., Guan K.L.;
"Kinase suppressor of Ras forms a multiprotein signaling complex and
modulates MEK localization.";
Mol. Cell. Biol. 19:5523-5534(1999).
[4]
PHOSPHORYLATION AT SER-218 AND SER-222, AND MUTAGENESIS OF LYS-97;
SER-150; SER-212; SER-218 AND SER-222.
PubMed=8131746;
Zheng C.-F., Guan K.-L.;
"Activation of MEK family kinases requires phosphorylation of two
conserved Ser/Thr residues.";
EMBO J. 13:1123-1131(1994).
[5]
CLEAVAGE BY ANTHRAX LETHAL FACTOR, AND PROTEIN SEQUENCE OF 9-17.
PubMed=9563949; DOI=10.1126/science.280.5364.734;
Duesbery N.S., Webb C.P., Leppla S.H., Gordon V.M., Klimpel K.R.,
Copeland T.D., Ahn N.G., Oskarsson M.K., Fukasawa K., Paull K.D.,
Vande Woude G.F.;
"Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal
factor.";
Science 280:734-737(1998).
[6]
CLEAVAGE BY ANTHRAX LETHAL FACTOR.
PubMed=11104681; DOI=10.1042/bj3520739;
Vitale G., Bernardi L., Napolitani G., Mock M., Montecucco C.;
"Susceptibility of mitogen-activated protein kinase kinase family
members to proteolysis by anthrax lethal factor.";
Biochem. J. 352:739-745(2000).
[7]
SUBCELLULAR LOCATION, AND FUNCTION.
PubMed=14737111; DOI=10.1038/sj.onc.1207188;
Liu X., Yan S., Zhou T., Terada Y., Erikson R.L.;
"The MAP kinase pathway is required for entry into mitosis and cell
survival.";
Oncogene 23:763-776(2004).
[8]
PHOSPHORYLATION AT SER-298.
PubMed=16129686; DOI=10.1074/jbc.M502306200;
Beeser A., Jaffer Z.M., Hofmann C., Chernoff J.;
"Role of group A p21-activated kinases in activation of extracellular-
regulated kinase by growth factors.";
J. Biol. Chem. 280:36609-36615(2005).
[9]
INTERACTION WITH YOPJ, AND ACETYLATION.
PubMed=16728640; DOI=10.1126/science.1126867;
Mukherjee S., Keitany G., Li Y., Wang Y., Ball H.L., Goldsmith E.J.,
Orth K.;
"Yersinia YopJ acetylates and inhibits kinase activation by blocking
phosphorylation.";
Science 312:1211-1214(2006).
[10]
FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PPARG.
PubMed=17101779; DOI=10.1128/MCB.00601-06;
Burgermeister E., Chuderland D., Hanoch T., Meyer M., Liscovitch M.,
Seger R.;
"Interaction with MEK causes nuclear export and downregulation of
peroxisome proliferator-activated receptor gamma.";
Mol. Cell. Biol. 27:803-817(2007).
[11]
INTERACTION WITH BIRC6/BRUCE.
PubMed=18329369; DOI=10.1016/j.cell.2008.01.012;
Pohl C., Jentsch S.;
"Final stages of cytokinesis and midbody ring formation are controlled
by BRUCE.";
Cell 132:832-845(2008).
[12]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-286, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
Greff Z., Keri G., Stemmann O., Mann M.;
"Kinase-selective enrichment enables quantitative phosphoproteomics of
the kinome across the cell cycle.";
Mol. Cell 31:438-448(2008).
[13]
INTERACTION WITH SGK1.
PubMed=19447520; DOI=10.1016/j.jhep.2009.02.027;
Won M., Park K.A., Byun H.S., Kim Y.R., Choi B.L., Hong J.H., Park J.,
Seok J.H., Lee Y.H., Cho C.H., Song I.S., Kim Y.K., Shen H.M.,
Hur G.M.;
"Protein kinase SGK1 enhances MEK/ERK complex formation through the
phosphorylation of ERK2: implication for the positive regulatory role
of SGK1 on the ERK function during liver regeneration.";
J. Hepatol. 51:67-76(2009).
[14]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
Mann M., Daub H.;
"Large-scale proteomics analysis of the human kinome.";
Mol. Cell. Proteomics 8:1751-1764(2009).
[15]
INTERACTION WITH VRK2.
PubMed=20679487; DOI=10.1128/MCB.01581-09;
Fernandez I.F., Blanco S., Lozano J., Lazo P.A.;
"VRK2 inhibits mitogen-activated protein kinase signaling and
inversely correlates with ErbB2 in human breast cancer.";
Mol. Cell. Biol. 30:4687-4697(2010).
[16]
REVIEW ON FUNCTION.
PubMed=9779990; DOI=10.1038/sj.onc.1202251;
Dhanasekaran N., Premkumar Reddy E.;
"Signaling by dual specificity kinases.";
Oncogene 17:1447-1455(1998).
[17]
REVIEW ON ENZYME REGULATION.
PubMed=15520807; DOI=10.1038/nrm1498;
Wellbrock C., Karasarides M., Marais R.;
"The RAF proteins take centre stage.";
Nat. Rev. Mol. Cell Biol. 5:875-885(2004).
[18]
REVIEW ON FUNCTION.
PubMed=19565474; DOI=10.1002/biof.52;
Yao Z., Seger R.;
"The ERK signaling cascade--views from different subcellular
compartments.";
BioFactors 35:407-416(2009).
[19]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=21269460; DOI=10.1186/1752-0509-5-17;
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
"Initial characterization of the human central proteome.";
BMC Syst. Biol. 5:17-17(2011).
[20]
REVIEW ON FUNCTION.
PubMed=21779493; DOI=10.1177/1947601911407328;
Wortzel I., Seger R.;
"The ERK cascade: distinct functions within various subcellular
organelles.";
Genes Cancer 2:195-209(2011).
[21]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Liver;
PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
Wang L., Ye M., Zou H.;
"An enzyme assisted RP-RPLC approach for in-depth analysis of human
liver phosphoproteome.";
J. Proteomics 96:253-262(2014).
[22]
X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 62-392 IN COMPLEX WITH ATP
AND INHIBITOR.
PubMed=15543157; DOI=10.1038/nsmb859;
Ohren J.F., Chen H., Pavlovsky A., Whitehead C., Zhang E., Kuffa P.,
Yan C., McConnell P., Spessard C., Banotai C., Mueller W.T.,
Delaney A., Omer C., Sebolt-Leopold J., Dudley D.T., Leung I.K.,
Flamme C., Warmus J., Kaufman M., Barrett S., Tecle H., Hasemann C.A.;
"Structures of human MAP kinase kinase 1 (MEK1) and MEK2 describe
novel noncompetitive kinase inhibition.";
Nat. Struct. Mol. Biol. 11:1192-1197(2004).
[23]
X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 62-393 IN COMPLEX WITH ATP
AND INHIBITOR.
PubMed=17880056; DOI=10.1021/jm0704548;
Spicer J.A., Rewcastle G.W., Kaufman M.D., Black S.L., Plummer M.S.,
Denny W.A., Quin J. III, Shahripour A.B., Barrett S.D.,
Whitehead C.E., Milbank J.B., Ohren J.F., Gowan R.C., Omer C.,
Camp H.S., Esmaeil N., Moore K., Sebolt-Leopold J.S.,
Pryzbranowski S., Merriman R.L., Ortwine D.F., Warmus J.S.,
Flamme C.M., Pavlovsky A.G., Tecle H.;
"4-anilino-5-carboxamido-2-pyridone derivatives as noncompetitive
inhibitors of mitogen-activated protein kinase kinase.";
J. Med. Chem. 50:5090-5102(2007).
[24]
X-RAY CRYSTALLOGRAPHY (2.62 ANGSTROMS) OF 62-393 IN COMPLEX WITH ATP
AND INHIBITOR.
PubMed=18951019; DOI=10.1016/j.bmcl.2008.10.015;
Warmus J.S., Flamme C., Zhang L.Y., Barrett S., Bridges A., Chen H.,
Gowan R., Kaufman M., Sebolt-Leopold J., Leopold W., Merriman R.,
Ohren J., Pavlovsky A., Przybranowski S., Tecle H., Valik H.,
Whitehead C., Zhang E.;
"2-Alkylamino- and alkoxy-substituted 2-amino-1,3,4-oxadiazoles-O-
Alkyl benzohydroxamate esters replacements retain the desired
inhibition and selectivity against MEK (MAP ERK kinase).";
Bioorg. Med. Chem. Lett. 18:6171-6174(2008).
[25]
X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 35-393 IN COMPLEX WITH ADP
AND INHIBITOR.
PubMed=19161339; DOI=10.1021/bi801898e;
Fischmann T.O., Smith C.K., Mayhood T.W., Myers J.E., Reichert P.,
Mannarino A., Carr D., Zhu H., Wong J., Yang R.S., Le H.V.,
Madison V.S.;
"Crystal structures of MEK1 binary and ternary complexes with
nucleotides and inhibitors.";
Biochemistry 48:2661-2674(2009).
[26]
X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 62-382 IN COMPLEX WITH ATP
AND INHIBITOR.
PubMed=19019675; DOI=10.1016/j.bmcl.2008.10.108;
Tecle H., Shao J., Li Y., Kothe M., Kazmirski S., Penzotti J.,
Ding Y.H., Ohren J., Moshinsky D., Coli R., Jhawar N., Bora E.,
Jacques-O'Hagan S., Wu J.;
"Beyond the MEK-pocket: can current MEK kinase inhibitors be utilized
to synthesize novel type III NCKIs? Does the MEK-pocket exist in
kinases other than MEK?";
Bioorg. Med. Chem. Lett. 19:226-229(2009).
[27]
X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 62-393 IN COMPLEX WITH ATP
AND INHIBITOR.
PubMed=19706763; DOI=10.1158/0008-5472.CAN-09-0679;
Iverson C., Larson G., Lai C., Yeh L.T., Dadson C., Weingarten P.,
Appleby T., Vo T., Maderna A., Vernier J.M., Hamatake R., Miner J.N.,
Quart B.;
"RDEA119/BAY 869766: a potent, selective, allosteric inhibitor of
MEK1/2 for the treatment of cancer.";
Cancer Res. 69:6839-6847(2009).
[28]
X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 62-382 IN COMPLEX WITH ADP
AND INHIBITOR.
PubMed=20621728; DOI=10.1016/j.bmcl.2010.05.058;
Wallace M.B., Adams M.E., Kanouni T., Mol C.D., Dougan D.R.,
Feher V.A., O'Connell S.M., Shi L., Halkowycz P., Dong Q.;
"Structure-based design and synthesis of pyrrole derivatives as MEK
inhibitors.";
Bioorg. Med. Chem. Lett. 20:4156-4158(2010).
[29]
X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 62-382 IN COMPLEX WITH ATP
AND INHIBITOR.
PubMed=21310613; DOI=10.1016/j.bmcl.2011.01.071;
Dong Q., Dougan D.R., Gong X., Halkowycz P., Jin B., Kanouni T.,
O'Connell S.M., Scorah N., Shi L., Wallace M.B., Zhou F.;
"Discovery of TAK-733, a potent and selective MEK allosteric site
inhibitor for the treatment of cancer.";
Bioorg. Med. Chem. Lett. 21:1315-1319(2011).
[30]
X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 62-393.
PubMed=21316218; DOI=10.1016/j.bmcl.2011.01.062;
Isshiki Y., Kohchi Y., Iikura H., Matsubara Y., Asoh K., Murata T.,
Kohchi M., Mizuguchi E., Tsujii S., Hattori K., Miura T.,
Yoshimura Y., Aida S., Miwa M., Saitoh R., Murao N., Okabe H.,
Belunis C., Janson C., Lukacs C., Schuck V., Shimma N.;
"Design and synthesis of novel allosteric MEK inhibitor CH4987655 as
an orally available anticancer agent.";
Bioorg. Med. Chem. Lett. 21:1795-1801(2011).
[31]
VARIANTS CFC3 SER-53 AND CYS-130.
PubMed=16439621; DOI=10.1126/science.1124642;
Rodriguez-Viciana P., Tetsu O., Tidyman W.E., Estep A.L., Conger B.A.,
Cruz M.S., McCormick F., Rauen K.A.;
"Germline mutations in genes within the MAPK pathway cause cardio-
facio-cutaneous syndrome.";
Science 311:1287-1290(2006).
[32]
VARIANT CFC3 VAL-128.
PubMed=18042262; DOI=10.1111/j.1399-0004.2007.00931.x;
Schulz A.L., Albrecht B., Arici C., van der Burgt I., Buske A.,
Gillessen-Kaesbach G., Heller R., Horn D., Hubner C.A., Korenke G.C.,
Konig R., Kress W., Kruger G., Meinecke P., Mucke J., Plecko B.,
Rossier E., Schinzel A., Schulze A., Seemanova E., Seidel H.,
Spranger S., Tuysuz B., Uhrig S., Wieczorek D., Kutsche K., Zenker M.;
"Mutation and phenotypic spectrum in patients with cardio-facio-
cutaneous and Costello syndrome.";
Clin. Genet. 73:62-70(2008).
-!- FUNCTION: Dual specificity protein kinase which acts as an
essential component of the MAP kinase signal transduction pathway.
Binding of extracellular ligands such as growth factors, cytokines
and hormones to their cell-surface receptors activates RAS and
this initiates RAF1 activation. RAF1 then further activates the
dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both
MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK
cascade, and catalyze the concomitant phosphorylation of a
threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located
in the extracellular signal-regulated kinases MAPK3/ERK1 and
MAPK1/ERK2, leading to their activation and further transduction
of the signal within the MAPK/ERK cascade. Depending on the
cellular context, this pathway mediates diverse biological
functions such as cell growth, adhesion, survival and
differentiation, predominantly through the regulation of
transcription, metabolism and cytoskeletal rearrangements. One
target of the MAPK/ERK cascade is peroxisome proliferator-
activated receptor gamma (PPARG), a nuclear receptor that promotes
differentiation and apoptosis. MAP2K1/MEK1 has been shown to
export PPARG from the nucleus. The MAPK/ERK cascade is also
involved in the regulation of endosomal dynamics, including
lysosome processing and endosome cycling through the perinuclear
recycling compartment (PNRC), as well as in the fragmentation of
the Golgi apparatus during mitosis. {ECO:0000269|PubMed:14737111,
ECO:0000269|PubMed:17101779}.
-!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
-!- ENZYME REGULATION: Ras proteins such as HRAS mediate the
activation of RAF proteins such as RAF1 or BRAF which in turn
activate extracellular signal-regulated kinases (ERK) through MAPK
(mitogen-activated protein kinases) and ERK kinases MAP2K1/MEK1
and MAP2K2/MEK2. Activation occurs through phosphorylation of Ser-
218 and Ser-222. MAP2K1/MEK1 is also the target of negative feed-
back regulation by its substrate kinases, such as MAPK1/ERK2.
These phosphorylate MAP2K1/MEK1 on Thr-292, thereby facilitating
dephosphorylation of the activating residues Ser-218 and Ser-222.
Inhibited by serine/threonine phosphatase 2A (By similarity). Many
inhibitors have been identified including pyrrole derivatives,
TAK-733 (one of a series of 8-methylpyrido[2,3-d]pyrimidine-
4,7(3H,8H)-dione derivatives), CH4987655 and RDEA119/BAY 869766.
{ECO:0000250}.
-!- SUBUNIT: Found in a complex with at least BRAF, HRAS, MAP2K1,
MAPK3/ERK1 and RGS14. Forms a heterodimer with MAP2K2/MEK2. Forms
heterodimers with KSR2 which further dimerize to form tetramers.
Interacts with ARBB2, LAMTOR3, MAPK1/ERK2, MORG1 and RAF1 (By
similarity). Interacts with PPARG and with isoform 1 of VRK2
(PubMed:20679487, PubMed:17101779). Interacts with Yersinia yopJ
(PubMed:16728640). Interacts with SGK1 (PubMed:19447520).
Interacts with BIRC6/bruce (PubMed:18329369). Interacts with KSR1
(PubMed:10409742). {ECO:0000250|UniProtKB:P29678,
ECO:0000250|UniProtKB:P31938, ECO:0000250|UniProtKB:Q01986,
ECO:0000269|PubMed:10409742, ECO:0000269|PubMed:16728640,
ECO:0000269|PubMed:17101779, ECO:0000269|PubMed:18329369,
ECO:0000269|PubMed:19447520, ECO:0000269|PubMed:20679487}.
-!- INTERACTION:
Q8N9N5:BANP; NbExp=3; IntAct=EBI-492564, EBI-744695;
Q9NR09:BIRC6; NbExp=2; IntAct=EBI-492564, EBI-1765160;
P15056:BRAF; NbExp=54; IntAct=EBI-492564, EBI-365980;
Q9Y297:BTRC; NbExp=3; IntAct=EBI-492564, EBI-307461;
O15519-1:CFLAR; NbExp=3; IntAct=EBI-492564, EBI-4567563;
Q61097:Ksr1 (xeno); NbExp=2; IntAct=EBI-492564, EBI-1536336;
P28482:MAPK1; NbExp=2; IntAct=EBI-492564, EBI-959949;
P27361:MAPK3; NbExp=2; IntAct=EBI-492564, EBI-73995;
Q9H8W4:PLEKHF2; NbExp=4; IntAct=EBI-492564, EBI-742388;
P04049:RAF1; NbExp=31; IntAct=EBI-492564, EBI-365996;
Q86Y07:VRK2; NbExp=2; IntAct=EBI-492564, EBI-1207615;
Q86Y07-1:VRK2; NbExp=2; IntAct=EBI-492564, EBI-1207633;
P46937:YAP1; NbExp=3; IntAct=EBI-492564, EBI-1044059;
-!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule
organizing center, centrosome {ECO:0000269|PubMed:14737111}.
Cytoplasm, cytoskeleton, microtubule organizing center, spindle
pole body {ECO:0000269|PubMed:14737111}. Cytoplasm
{ECO:0000269|PubMed:10409742, ECO:0000269|PubMed:17101779}.
Nucleus {ECO:0000269|PubMed:17101779}. Membrane
{ECO:0000269|PubMed:10409742}; Peripheral membrane protein
{ECO:0000269|PubMed:10409742}. Note=Localizes at centrosomes
during prometaphase, midzone during anaphase and midbody during
telophase/cytokinesis (PubMed:14737111). Membrane localization is
probably regulated by its interaction with KSR1 (PubMed:10409742).
{ECO:0000269|PubMed:10409742, ECO:0000269|PubMed:14737111}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1; Synonyms=MKK1a;
IsoId=Q02750-1; Sequence=Displayed;
Name=2; Synonyms=MKK1b;
IsoId=Q02750-2; Sequence=VSP_040500;
-!- TISSUE SPECIFICITY: Widely expressed, with extremely low levels in
brain. {ECO:0000269|PubMed:1281467}.
-!- DOMAIN: The proline-rich region localized between residues 270 and
307 is important for binding to RAF1 and activation of
MAP2K1/MEK1. {ECO:0000250}.
-!- PTM: Phosphorylation at Ser-218 and Ser-222 by MAP kinase kinase
kinases (RAF or MEKK1) positively regulates kinase activity. Also
phosphorylated at Thr-292 by MAPK1/ERK2 and at Ser-298 by PAK.
MAPK1/ERK2 phosphorylation of Thr-292 occurs in response to
cellular adhesion and leads to inhibition of Ser-298
phosphorylation by PAK. {ECO:0000269|PubMed:16129686,
ECO:0000269|PubMed:8131746}.
-!- PTM: Acetylation by Yersinia yopJ prevents phosphorylation and
activation, thus blocking the MAPK signaling pathway.
{ECO:0000269|PubMed:16728640}.
-!- DISEASE: Cardiofaciocutaneous syndrome 3 (CFC3) [MIM:615279]: A
form of cardiofaciocutaneous syndrome, a multiple congenital
anomaly disorder characterized by a distinctive facial appearance,
heart defects and mental retardation. Heart defects include
pulmonic stenosis, atrial septal defects and hypertrophic
cardiomyopathy. Some affected individuals present with ectodermal
abnormalities such as sparse, friable hair, hyperkeratotic skin
lesions and a generalized ichthyosis-like condition. Typical
facial features are similar to Noonan syndrome. They include high
forehead with bitemporal constriction, hypoplastic supraorbital
ridges, downslanting palpebral fissures, a depressed nasal bridge,
and posteriorly angulated ears with prominent helices. Distinctive
features of CFC3 include macrostomia and horizontal shape of
palpebral fissures. {ECO:0000269|PubMed:16439621,
ECO:0000269|PubMed:18042262}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
protein kinase family. MAP kinase kinase subfamily. {ECO:0000305}.
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EMBL; L05624; AAA36318.1; -; mRNA.
EMBL; L11284; -; NOT_ANNOTATED_CDS; mRNA.
CCDS; CCDS10216.1; -. [Q02750-1]
PIR; A45100; A45100.
RefSeq; NP_002746.1; NM_002755.3. [Q02750-1]
RefSeq; XP_016877900.1; XM_017022411.1. [Q02750-2]
UniGene; Hs.145442; -.
UniGene; Hs.677223; -.
PDB; 1S9J; X-ray; 2.40 A; A=62-393.
PDB; 2P55; X-ray; 2.80 A; A=62-393.
PDB; 3DV3; X-ray; 2.30 A; A=62-382.
PDB; 3DY7; X-ray; 2.70 A; A=62-393.
PDB; 3E8N; X-ray; 2.50 A; A=62-393.
PDB; 3EQB; X-ray; 2.62 A; A=62-393.
PDB; 3EQC; X-ray; 1.80 A; A=35-393.
PDB; 3EQD; X-ray; 2.10 A; A=35-393.
PDB; 3EQF; X-ray; 2.70 A; A=35-393.
PDB; 3EQG; X-ray; 2.50 A; A=35-393.
PDB; 3EQH; X-ray; 2.00 A; A=35-393.
PDB; 3EQI; X-ray; 1.90 A; A=35-393.
PDB; 3MBL; X-ray; 2.60 A; A=62-382.
PDB; 3ORN; X-ray; 2.80 A; A=62-393.
PDB; 3OS3; X-ray; 2.80 A; A=62-393.
PDB; 3PP1; X-ray; 2.70 A; A=62-382.
PDB; 3SLS; X-ray; 2.30 A; A/B=45-263, A/B=308-383.
PDB; 3V01; X-ray; 2.70 A; A=62-393.
PDB; 3V04; X-ray; 2.70 A; A=62-393.
PDB; 3VVH; X-ray; 2.00 A; A/B/C=62-393.
PDB; 3W8Q; X-ray; 2.20 A; A=39-382.
PDB; 3WIG; X-ray; 2.70 A; A=62-393.
PDB; 3ZLS; X-ray; 2.50 A; A=37-383.
PDB; 3ZLW; X-ray; 2.12 A; A=37-383.
PDB; 3ZLX; X-ray; 2.20 A; A=37-383.
PDB; 3ZLY; X-ray; 2.11 A; A=37-383.
PDB; 3ZM4; X-ray; 2.37 A; A=37-383.
PDB; 4AN2; X-ray; 2.50 A; A=61-392.
PDB; 4AN3; X-ray; 2.10 A; A=61-392.
PDB; 4AN9; X-ray; 2.80 A; A=61-392.
PDB; 4ANB; X-ray; 2.20 A; A=61-392.
PDB; 4ARK; X-ray; 2.60 A; A=62-393.
PDB; 4LMN; X-ray; 2.80 A; A=62-393.
PDB; 4MNE; X-ray; 2.85 A; A/D/E/H=62-393.
PDB; 4U7Z; X-ray; 2.80 A; A=62-393.
PDB; 4U80; X-ray; 2.80 A; A=62-393.
PDB; 4U81; X-ray; 2.70 A; A=62-393.
PDB; 5BX0; X-ray; 2.93 A; A=37-383.
PDB; 5EYM; X-ray; 2.70 A; A/B=35-393.
PDB; 5HZE; X-ray; 2.40 A; A=37-383.
PDBsum; 1S9J; -.
PDBsum; 2P55; -.
PDBsum; 3DV3; -.
PDBsum; 3DY7; -.
PDBsum; 3E8N; -.
PDBsum; 3EQB; -.
PDBsum; 3EQC; -.
PDBsum; 3EQD; -.
PDBsum; 3EQF; -.
PDBsum; 3EQG; -.
PDBsum; 3EQH; -.
PDBsum; 3EQI; -.
PDBsum; 3MBL; -.
PDBsum; 3ORN; -.
PDBsum; 3OS3; -.
PDBsum; 3PP1; -.
PDBsum; 3SLS; -.
PDBsum; 3V01; -.
PDBsum; 3V04; -.
PDBsum; 3VVH; -.
PDBsum; 3W8Q; -.
PDBsum; 3WIG; -.
PDBsum; 3ZLS; -.
PDBsum; 3ZLW; -.
PDBsum; 3ZLX; -.
PDBsum; 3ZLY; -.
PDBsum; 3ZM4; -.
PDBsum; 4AN2; -.
PDBsum; 4AN3; -.
PDBsum; 4AN9; -.
PDBsum; 4ANB; -.
PDBsum; 4ARK; -.
PDBsum; 4LMN; -.
PDBsum; 4MNE; -.
PDBsum; 4U7Z; -.
PDBsum; 4U80; -.
PDBsum; 4U81; -.
PDBsum; 5BX0; -.
PDBsum; 5EYM; -.
PDBsum; 5HZE; -.
ProteinModelPortal; Q02750; -.
SMR; Q02750; -.
BioGrid; 111590; 71.
CORUM; Q02750; -.
DIP; DIP-201N; -.
ELM; Q02750; -.
IntAct; Q02750; 67.
MINT; MINT-99632; -.
STRING; 9606.ENSP00000302486; -.
BindingDB; Q02750; -.
ChEMBL; CHEMBL3587; -.
DrugBank; DB06616; Bosutinib.
DrugBank; DB05239; Cobimetinib.
DrugBank; DB02152; K-252a.
DrugBank; DB08911; Trametinib.
GuidetoPHARMACOLOGY; 2062; -.
iPTMnet; Q02750; -.
PhosphoSitePlus; Q02750; -.
BioMuta; MAP2K1; -.
DMDM; 400274; -.
EPD; Q02750; -.
MaxQB; Q02750; -.
PaxDb; Q02750; -.
PeptideAtlas; Q02750; -.
PRIDE; Q02750; -.
DNASU; 5604; -.
Ensembl; ENST00000307102; ENSP00000302486; ENSG00000169032. [Q02750-1]
GeneID; 5604; -.
KEGG; hsa:5604; -.
UCSC; uc010bhq.4; human. [Q02750-1]
CTD; 5604; -.
DisGeNET; 5604; -.
EuPathDB; HostDB:ENSG00000169032.9; -.
GeneCards; MAP2K1; -.
GeneReviews; MAP2K1; -.
HGNC; HGNC:6840; MAP2K1.
HPA; CAB003834; -.
HPA; HPA026430; -.
MalaCards; MAP2K1; -.
MIM; 176872; gene.
MIM; 615279; phenotype.
neXtProt; NX_Q02750; -.
OpenTargets; ENSG00000169032; -.
Orphanet; 1340; Cardiofaciocutaneous syndrome.
PharmGKB; PA30584; -.
eggNOG; KOG0581; Eukaryota.
eggNOG; ENOG410XQ5A; LUCA.
GeneTree; ENSGT00760000119199; -.
HOGENOM; HOG000234206; -.
HOVERGEN; HBG108518; -.
InParanoid; Q02750; -.
KO; K04368; -.
OMA; ELMFGCP; -.
OrthoDB; EOG091G0DEC; -.
PhylomeDB; Q02750; -.
TreeFam; TF105137; -.
BRENDA; 2.7.12.2; 2681.
Reactome; R-HSA-110056; MAPK3 (ERK1) activation.
Reactome; R-HSA-445144; Signal transduction by L1.
Reactome; R-HSA-5210891; Uptake and function of anthrax toxins.
Reactome; R-HSA-5673000; RAF activation.
Reactome; R-HSA-5674135; MAP2K and MAPK activation.
Reactome; R-HSA-5674499; Negative feedback regulation of MAPK pathway.
Reactome; R-HSA-5684264; MAP3K8 (TPL2)-dependent MAPK1/3 activation.
Reactome; R-HSA-6802946; Signaling by moderate kinase activity BRAF mutants.
Reactome; R-HSA-6802948; Signaling by high-kinase activity BRAF mutants.
Reactome; R-HSA-6802949; Signaling by RAS mutants.
Reactome; R-HSA-6802952; Signaling by BRAF and RAF fusions.
Reactome; R-HSA-6802955; Paradoxical activation of RAF signaling by kinase inactive BRAF.
SignaLink; Q02750; -.
SIGNOR; Q02750; -.
ChiTaRS; MAP2K1; human.
EvolutionaryTrace; Q02750; -.
GeneWiki; MAP2K1; -.
GenomeRNAi; 5604; -.
PMAP-CutDB; Q02750; -.
PRO; PR:Q02750; -.
Proteomes; UP000005640; Chromosome 15.
Bgee; ENSG00000169032; -.
CleanEx; HS_MAP2K1; -.
ExpressionAtlas; Q02750; baseline and differential.
Genevisible; Q02750; HS.
GO; GO:0005829; C:cytosol; IDA:HPA.
GO; GO:0005769; C:early endosome; TAS:UniProtKB.
GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
GO; GO:0005925; C:focal adhesion; TAS:UniProtKB.
GO; GO:0005794; C:Golgi apparatus; TAS:UniProtKB.
GO; GO:0005770; C:late endosome; TAS:UniProtKB.
GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
GO; GO:0005739; C:mitochondrion; TAS:UniProtKB.
GO; GO:0005634; C:nucleus; TAS:UniProtKB.
GO; GO:0005886; C:plasma membrane; IDA:HPA.
GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO; GO:0004708; F:MAP kinase kinase activity; IDA:UniProtKB.
GO; GO:0008022; F:protein C-terminus binding; IDA:MGI.
GO; GO:0004672; F:protein kinase activity; TAS:ProtInc.
GO; GO:0047485; F:protein N-terminus binding; IDA:MGI.
GO; GO:0043539; F:protein serine/threonine kinase activator activity; IDA:UniProtKB.
GO; GO:0004674; F:protein serine/threonine kinase activity; TAS:Reactome.
GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; TAS:UniProtKB.
GO; GO:0004713; F:protein tyrosine kinase activity; IEA:UniProtKB-KW.
GO; GO:0004728; F:signal transducer, downstream of receptor, with protein tyrosine phosphatase activity; IEA:Ensembl.
GO; GO:0000187; P:activation of MAPK activity; IDA:AgBase.
GO; GO:0060020; P:Bergmann glial cell differentiation; IEA:Ensembl.
GO; GO:0007050; P:cell cycle arrest; IMP:BHF-UCL.
GO; GO:0048870; P:cell motility; IEA:Ensembl.
GO; GO:0090398; P:cellular senescence; IMP:BHF-UCL.
GO; GO:0021697; P:cerebellar cortex formation; IEA:Ensembl.
GO; GO:0006935; P:chemotaxis; TAS:ProtInc.
GO; GO:0060502; P:epithelial cell proliferation involved in lung morphogenesis; IEA:Ensembl.
GO; GO:0070371; P:ERK1 and ERK2 cascade; IEA:Ensembl.
GO; GO:0060324; P:face development; IEA:Ensembl.
GO; GO:0007507; P:heart development; IEA:Ensembl.
GO; GO:0030216; P:keratinocyte differentiation; IEA:Ensembl.
GO; GO:0060711; P:labyrinthine layer development; IEA:Ensembl.
GO; GO:0000165; P:MAPK cascade; TAS:Reactome.
GO; GO:0006928; P:movement of cell or subcellular component; TAS:ProtInc.
GO; GO:0008285; P:negative regulation of cell proliferation; IDA:BHF-UCL.
GO; GO:0010629; P:negative regulation of gene expression; IGI:UniProtKB.
GO; GO:0030182; P:neuron differentiation; IEA:Ensembl.
GO; GO:0060674; P:placenta blood vessel development; IEA:Ensembl.
GO; GO:0050772; P:positive regulation of axonogenesis; IEA:Ensembl.
GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:BHF-UCL.
GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
GO; GO:1903800; P:positive regulation of production of miRNAs involved in gene silencing by miRNA; IMP:BHF-UCL.
GO; GO:0071902; P:positive regulation of protein serine/threonine kinase activity; IDA:UniProtKB.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:BHF-UCL.
GO; GO:0035897; P:proteolysis in other organism; TAS:Reactome.
GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central.
GO; GO:0048679; P:regulation of axon regeneration; IEA:Ensembl.
GO; GO:2000641; P:regulation of early endosome to late endosome transport; TAS:UniProtKB.
GO; GO:0090170; P:regulation of Golgi inheritance; TAS:UniProtKB.
GO; GO:0007346; P:regulation of mitotic cell cycle; IBA:GO_Central.
GO; GO:0032872; P:regulation of stress-activated MAPK cascade; TAS:UniProtKB.
GO; GO:0007165; P:signal transduction; TAS:ProtInc.
GO; GO:0048538; P:thymus development; IEA:Ensembl.
GO; GO:0030878; P:thyroid gland development; IEA:Ensembl.
GO; GO:0060440; P:trachea formation; IEA:Ensembl.
InterPro; IPR011009; Kinase-like_dom.
InterPro; IPR000719; Prot_kinase_dom.
InterPro; IPR017441; Protein_kinase_ATP_BS.
InterPro; IPR008271; Ser/Thr_kinase_AS.
Pfam; PF00069; Pkinase; 1.
SMART; SM00220; S_TKc; 1.
SUPFAM; SSF56112; SSF56112; 1.
PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
1: Evidence at protein level;
3D-structure; Acetylation; Alternative splicing; ATP-binding;
Cardiomyopathy; Complete proteome; Cytoplasm; Cytoskeleton;
Direct protein sequencing; Disease mutation; Ectodermal dysplasia;
Kinase; Membrane; Mental retardation; Nucleotide-binding; Nucleus;
Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
Transferase; Tyrosine-protein kinase.
CHAIN 1 393 Dual specificity mitogen-activated
protein kinase kinase 1.
/FTId=PRO_0000086365.
DOMAIN 68 361 Protein kinase. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
NP_BIND 74 82 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159,
ECO:0000269|PubMed:15543157,
ECO:0000269|PubMed:17880056,
ECO:0000269|PubMed:18951019,
ECO:0000269|PubMed:19019675,
ECO:0000269|PubMed:19706763,
ECO:0000269|PubMed:21310613}.
NP_BIND 143 146 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159,
ECO:0000269|PubMed:15543157,
ECO:0000269|PubMed:17880056,
ECO:0000269|PubMed:18951019,
ECO:0000269|PubMed:19019675,
ECO:0000269|PubMed:19706763,
ECO:0000269|PubMed:21310613}.
NP_BIND 150 153 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159,
ECO:0000269|PubMed:15543157,
ECO:0000269|PubMed:17880056,
ECO:0000269|PubMed:18951019,
ECO:0000269|PubMed:19019675,
ECO:0000269|PubMed:19706763,
ECO:0000269|PubMed:21310613}.
NP_BIND 192 195 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159,
ECO:0000269|PubMed:15543157,
ECO:0000269|PubMed:17880056,
ECO:0000269|PubMed:18951019,
ECO:0000269|PubMed:19019675,
ECO:0000269|PubMed:19706763,
ECO:0000269|PubMed:21310613}.
REGION 77 78 Inhibitor binding.
REGION 144 146 Inhibitor binding.
REGION 208 212 Inhibitor binding.
REGION 270 307 RAF1-binding. {ECO:0000250}.
COMPBIAS 262 307 Pro-rich.
ACT_SITE 190 190 Proton acceptor. {ECO:0000255|PROSITE-
ProRule:PRU00159, ECO:0000255|PROSITE-
ProRule:PRU10027}.
BINDING 77 77 Inhibitor; via carbonyl oxygen.
{ECO:0000269|PubMed:15543157,
ECO:0000269|PubMed:17880056,
ECO:0000269|PubMed:18951019,
ECO:0000269|PubMed:19019675,
ECO:0000269|PubMed:19161339,
ECO:0000269|PubMed:19706763,
ECO:0000269|PubMed:20621728,
ECO:0000269|PubMed:21310613}.
BINDING 78 78 Inhibitor; via amide nitrogen and
carbonyl oxygen.
{ECO:0000269|PubMed:15543157,
ECO:0000269|PubMed:17880056,
ECO:0000269|PubMed:18951019,
ECO:0000269|PubMed:19019675,
ECO:0000269|PubMed:19161339,
ECO:0000269|PubMed:19706763,
ECO:0000269|PubMed:20621728,
ECO:0000269|PubMed:21310613}.
BINDING 97 97 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159,
ECO:0000269|PubMed:15543157,
ECO:0000269|PubMed:17880056,
ECO:0000269|PubMed:18951019,
ECO:0000269|PubMed:19019675,
ECO:0000269|PubMed:19706763,
ECO:0000269|PubMed:21310613}.
BINDING 97 97 Inhibitor. {ECO:0000269|PubMed:15543157,
ECO:0000269|PubMed:17880056,
ECO:0000269|PubMed:18951019,
ECO:0000269|PubMed:19019675,
ECO:0000269|PubMed:19161339,
ECO:0000269|PubMed:19706763,
ECO:0000269|PubMed:20621728,
ECO:0000269|PubMed:21310613}.
BINDING 190 190 Inhibitor. {ECO:0000269|PubMed:15543157,
ECO:0000269|PubMed:17880056,
ECO:0000269|PubMed:18951019,
ECO:0000269|PubMed:19019675,
ECO:0000269|PubMed:19161339,
ECO:0000269|PubMed:19706763,
ECO:0000269|PubMed:20621728,
ECO:0000269|PubMed:21310613}.
BINDING 194 194 Inhibitor; via carbonyl oxygen.
{ECO:0000269|PubMed:15543157,
ECO:0000269|PubMed:17880056,
ECO:0000269|PubMed:18951019,
ECO:0000269|PubMed:19019675,
ECO:0000269|PubMed:19161339,
ECO:0000269|PubMed:19706763,
ECO:0000269|PubMed:20621728,
ECO:0000269|PubMed:21310613}.
BINDING 208 208 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159,
ECO:0000269|PubMed:15543157,
ECO:0000269|PubMed:17880056,
ECO:0000269|PubMed:18951019,
ECO:0000269|PubMed:19019675,
ECO:0000269|PubMed:19706763,
ECO:0000269|PubMed:21310613}.
BINDING 208 208 Inhibitor. {ECO:0000269|PubMed:15543157,
ECO:0000269|PubMed:17880056,
ECO:0000269|PubMed:18951019,
ECO:0000269|PubMed:19019675,
ECO:0000269|PubMed:19161339,
ECO:0000269|PubMed:19706763,
ECO:0000269|PubMed:20621728,
ECO:0000269|PubMed:21310613}.
BINDING 212 212 Inhibitor; via amide nitrogen.
{ECO:0000269|PubMed:15543157,
ECO:0000269|PubMed:17880056,
ECO:0000269|PubMed:18951019,
ECO:0000269|PubMed:19019675,
ECO:0000269|PubMed:19161339,
ECO:0000269|PubMed:19706763,
ECO:0000269|PubMed:20621728,
ECO:0000269|PubMed:21310613}.
SITE 8 9 Cleavage; by anthrax lethal factor.
MOD_RES 218 218 Phosphoserine; by RAF.
{ECO:0000269|PubMed:10409742,
ECO:0000269|PubMed:8131746}.
MOD_RES 222 222 Phosphoserine; by RAF.
{ECO:0000269|PubMed:8131746}.
MOD_RES 286 286 Phosphothreonine.
{ECO:0000244|PubMed:18691976}.
MOD_RES 292 292 Phosphothreonine; by MAPK1.
{ECO:0000250|UniProtKB:Q01986}.
MOD_RES 298 298 Phosphoserine; by PAK.
{ECO:0000269|PubMed:16129686}.
VAR_SEQ 147 172 Missing (in isoform 2).
{ECO:0000303|PubMed:1281467}.
/FTId=VSP_040500.
VARIANT 53 53 F -> S (in CFC3; dbSNP:rs121908594).
{ECO:0000269|PubMed:16439621}.
/FTId=VAR_035093.
VARIANT 128 128 G -> V (in CFC3; dbSNP:rs730880508).
{ECO:0000269|PubMed:18042262}.
/FTId=VAR_069780.
VARIANT 130 130 Y -> C (in CFC3; dbSNP:rs121908595).
{ECO:0000269|PubMed:16439621}.
/FTId=VAR_035094.
MUTAGEN 97 97 K->R: Inactivation.
{ECO:0000269|PubMed:8131746}.
MUTAGEN 150 150 S->A: No loss of activity.
{ECO:0000269|PubMed:8131746}.
MUTAGEN 212 212 S->A: No loss of activity.
{ECO:0000269|PubMed:8131746}.
MUTAGEN 218 218 S->A: Inactivation.
{ECO:0000269|PubMed:8131746}.
MUTAGEN 222 222 S->A: Inactivation.
{ECO:0000269|PubMed:8131746}.
CONFLICT 52 52 A -> R (in Ref. 3; AA sequence).
{ECO:0000305}.
CONFLICT 180 180 Missing (in Ref. 3; AA sequence).
{ECO:0000305}.
HELIX 44 58 {ECO:0000244|PDB:3EQC}.
HELIX 65 67 {ECO:0000244|PDB:3EQC}.
STRAND 68 76 {ECO:0000244|PDB:3EQC}.
STRAND 81 87 {ECO:0000244|PDB:3EQC}.
TURN 88 90 {ECO:0000244|PDB:3EQC}.
STRAND 93 100 {ECO:0000244|PDB:3EQC}.
HELIX 105 115 {ECO:0000244|PDB:3EQC}.
HELIX 116 120 {ECO:0000244|PDB:3EQC}.
STRAND 129 135 {ECO:0000244|PDB:3EQC}.
STRAND 138 143 {ECO:0000244|PDB:3EQC}.
HELIX 151 158 {ECO:0000244|PDB:3EQC}.
HELIX 163 184 {ECO:0000244|PDB:3EQC}.
HELIX 193 195 {ECO:0000244|PDB:3EQC}.
STRAND 196 198 {ECO:0000244|PDB:3EQC}.
TURN 200 202 {ECO:0000244|PDB:3DY7}.
STRAND 204 206 {ECO:0000244|PDB:3EQC}.
HELIX 213 218 {ECO:0000244|PDB:3EQC}.
HELIX 221 223 {ECO:0000244|PDB:3VVH}.
HELIX 227 229 {ECO:0000244|PDB:4AN3}.
HELIX 232 235 {ECO:0000244|PDB:3EQC}.
HELIX 242 258 {ECO:0000244|PDB:3EQC}.
HELIX 268 275 {ECO:0000244|PDB:3EQC}.
HELIX 310 319 {ECO:0000244|PDB:3EQC}.
TURN 327 329 {ECO:0000244|PDB:3EQC}.
HELIX 332 342 {ECO:0000244|PDB:3EQC}.
TURN 346 348 {ECO:0000244|PDB:3EQC}.
HELIX 352 356 {ECO:0000244|PDB:3EQC}.
HELIX 359 366 {ECO:0000244|PDB:3EQC}.
HELIX 371 379 {ECO:0000244|PDB:3EQC}.
SEQUENCE 393 AA; 43439 MW; 0344118FFC842D51 CRC64;
MPKKKPTPIQ LNPAPDGSAV NGTSSAETNL EALQKKLEEL ELDEQQRKRL EAFLTQKQKV
GELKDDDFEK ISELGAGNGG VVFKVSHKPS GLVMARKLIH LEIKPAIRNQ IIRELQVLHE
CNSPYIVGFY GAFYSDGEIS ICMEHMDGGS LDQVLKKAGR IPEQILGKVS IAVIKGLTYL
REKHKIMHRD VKPSNILVNS RGEIKLCDFG VSGQLIDSMA NSFVGTRSYM SPERLQGTHY
SVQSDIWSMG LSLVEMAVGR YPIPPPDAKE LELMFGCQVE GDAAETPPRP RTPGRPLSSY
GMDSRPPMAI FELLDYIVNE PPPKLPSGVF SLEFQDFVNK CLIKNPAERA DLKQLMVHAF
IKRSDAEEVD FAGWLCSTIG LNQPSTPTHA AGV


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10-782-55048 Dual specificity mitogen-activated protein kinase kinase 1 - EC 2.7.12.2; MAP kinase kinase 1; MAPKK 1; ERK activator kinase 1; MAPK_ERK kinase 1; MEK1 N_A 0.05 mg
10-782-55047 Dual specificity mitogen-activated protein kinase kinase 1 - EC 2.7.12.2; MAP kinase kinase 1; MAPKK 1; ERK activator kinase 1; MAPK_ERK kinase 1; MEK1 N_A 0.02 mg
EIAAB25228 Dual specificity mitogen-activated protein kinase kinase 1,ERK activator kinase 1,MAP kinase kinase 1,Map2k1,MAPK_ERK kinase 1,MAPKK 1,MEK 1,Mek1,Prkmk1,Rat,Rattus norvegicus
EIAAB25230 Dual specificity mitogen-activated protein kinase kinase 1,ERK activator kinase 1,MAP kinase kinase 1,Map2k1,MAPK_ERK kinase 1,MAPKK 1,MEK 1,Mek1,Mouse,Mus musculus,Prkmk1
EIAAB25234 Dual specificity mitogen-activated protein kinase kinase 2,ERK activator kinase 2,MAP kinase kinase 2,Map2k2,MAPK_ERK kinase 2,MAPKK 2,MEK 2,Mek2,Mkk2,Prkmk2,Rat,Rattus norvegicus
EIAAB25236 Dual specificity mitogen-activated protein kinase kinase 2,ERK activator kinase 2,MAP kinase kinase 2,Map2k2,MAPK_ERK kinase 2,MAPKK 2,MEK 2,Mek2,Mkk2,Mouse,Mus musculus,Prkmk2
EIAAB25229 Dual specificity mitogen-activated protein kinase kinase 1,ERK activator kinase 1,MAP kinase kinase 1,MAP2K1,MAPK_ERK kinase 1,MAPKK 1,MEK 1,MEK1,Oryctolagus cuniculus,PRKMK1,Rabbit
EIAAB25235 Dual specificity mitogen-activated protein kinase kinase 2,ERK activator kinase 2,Homo sapiens,Human,MAP kinase kinase 2,MAP2K2,MAPK_ERK kinase 2,MAPKK 2,MEK 2,MEK2,MKK2,PRKMK2
EIAAB25240 c-Jun N-terminal kinase kinase 1,Dual specificity mitogen-activated protein kinase kinase 4,Homo sapiens,Human,JNK-activating kinase 1,JNKK,JNKK1,MAP kinase kinase 4,MAP2K4,MAPK_ERK kinase 4,MAPKK 4,M
EIAAB25232 Chicken,Dual specificity mitogen-activated protein kinase kinase 2,ERK activator kinase 2,Gallus gallus,MAP kinase kinase 2,MAP2K2,MAPK_ERK kinase 2,MAPKK 2,MEK2,MEK2,MKK2,PRKMK2
EIAAB25233 Canis familiaris,Canis lupus familiaris,Dog,Dual specificity mitogen-activated protein kinase kinase 2,ERK activator kinase 2,MAP kinase kinase 2,MAP2K2,MAPK_ERK kinase 2,MAPKK 2,MEK 2,MEK2
U1721b CLIA Bos taurus,Bovine,Dual specificity mitogen-activated protein kinase kinase 6,MAP kinase kinase 6,MAP2K6,MAPK_ERK kinase 6,MAPKK 6,MEK 6 96T
E1721b ELISA kit Bos taurus,Bovine,Dual specificity mitogen-activated protein kinase kinase 6,MAP kinase kinase 6,MAP2K6,MAPK_ERK kinase 6,MAPKK 6,MEK 6 96T
E1721b ELISA Bos taurus,Bovine,Dual specificity mitogen-activated protein kinase kinase 6,MAP kinase kinase 6,MAP2K6,MAPK_ERK kinase 6,MAPKK 6,MEK 6 96T


 

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