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Mitogen-activated protein kinase kinase kinase 1 (EC 2.7.11.25) (MAPK/ERK kinase kinase 1) (MEK kinase 1) (MEKK 1)

 M3K1_HUMAN              Reviewed;        1512 AA.
Q13233;
01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
16-DEC-2008, sequence version 4.
08-MAY-2019, entry version 191.
RecName: Full=Mitogen-activated protein kinase kinase kinase 1;
EC=2.7.11.25;
AltName: Full=MAPK/ERK kinase kinase 1;
Short=MEK kinase 1;
Short=MEKK 1;
Name=MAP3K1; Synonyms=MAPKKK1, MEKK, MEKK1;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=15372022; DOI=10.1038/nature02919;
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T.,
Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
"The DNA sequence and comparative analysis of human chromosome 5.";
Nature 431:268-274(2004).
[2]
NUCLEOTIDE SEQUENCE [MRNA] OF 20-1512, FUNCTION, AND INTERACTION WITH
MAP2K4.
PubMed=9808624; DOI=10.1101/gad.12.21.3369;
Xia Y., Wu Z., Su B., Murray B., Karin M.;
"JNKK1 organizes a MAP kinase module through specific and sequential
interactions with upstream and downstream components mediated by its
amino-terminal extension.";
Genes Dev. 12:3369-3381(1998).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1238-1274.
TISSUE=Leukocyte;
PubMed=8597633; DOI=10.1007/BF00539003;
Vinik B.S., Kay E.S., Fiedorek F.T. Jr.;
"Mapping of the MEK kinase gene (Mekk) to mouse chromosome 13 and
human chromosome 5.";
Mamm. Genome 6:782-783(1995).
[4]
INTERACTION WITH AXIN1.
PubMed=12223491; DOI=10.1074/jbc.M208099200;
Rui H.L., Fan E., Zhou H.M., Xu Z., Zhang Y., Lin S.C.;
"SUMO-1 modification of the C-terminal KVEKVD of Axin is required for
JNK activation but has no effect on Wnt signaling.";
J. Biol. Chem. 277:42981-42986(2002).
[5]
INTERACTION WITH AXIN1.
PubMed=15262978; DOI=10.1074/jbc.M404598200;
Wong C.K., Luo W., Deng Y., Zou H., Ye Z., Lin S.-C.;
"The DIX domain protein coiled-coil-DIX1 inhibits c-Jun N-terminal
kinase activation by Axin and dishevelled through distinct
mechanisms.";
J. Biol. Chem. 279:39366-39373(2004).
[6]
FUNCTION, AND INTERACTION WITH GRIPAP1.
PubMed=17761173; DOI=10.1016/j.febslet.2007.08.008;
Ye B., Yu W.P., Thomas G.M., Huganir R.L.;
"GRASP-1 is a neuronal scaffold protein for the JNK signaling
pathway.";
FEBS Lett. 581:4403-4410(2007).
[7]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-292, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=18220336; DOI=10.1021/pr0705441;
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
Yates J.R. III;
"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
efficient phosphoproteomic analysis.";
J. Proteome Res. 7:1346-1351(2008).
[8]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-154 AND SER-1043, 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).
[9]
INTERACTION WITH STK38.
PubMed=17906693; DOI=10.1038/sj.onc.1210828;
Enomoto A., Kido N., Ito M., Morita A., Matsumoto Y., Takamatsu N.,
Hosoi Y., Miyagawa K.;
"Negative regulation of MEKK1/2 signaling by serine-threonine kinase
38 (STK38).";
Oncogene 27:1930-1938(2008).
[10]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-292; SER-297; SER-300;
SER-507 AND SER-1018, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE
SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=18669648; DOI=10.1073/pnas.0805139105;
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
Elledge S.J., Gygi S.P.;
"A quantitative atlas of mitotic phosphorylation.";
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
[11]
ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS
SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=19413330; DOI=10.1021/ac9004309;
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
Mohammed S.;
"Lys-N and trypsin cover complementary parts of the phosphoproteome in
a refined SCX-based approach.";
Anal. Chem. 81:4493-4501(2009).
[12]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-275 AND SER-292, AND
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).
[13]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21; SER-35; SER-275;
THR-285; SER-292; SER-531; SER-923 AND SER-1018, AND IDENTIFICATION BY
MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma, and Erythroleukemia;
PubMed=23186163; DOI=10.1021/pr300630k;
Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
Mohammed S.;
"Toward a comprehensive characterization of a human cancer cell
phosphoproteome.";
J. Proteome Res. 12:260-271(2013).
[14]
VARIANTS [LARGE SCALE ANALYSIS] ASN-92 AND SER-443.
PubMed=17344846; DOI=10.1038/nature05610;
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
"Patterns of somatic mutation in human cancer genomes.";
Nature 446:153-158(2007).
[15]
VARIANTS SRXY6 PRO-189; ARG-189; ILE-GLN-211 INS AND ARG-616, AND
CHARACTERIZATION OF VARIANTS SRXY6 PRO-189 AND ARG-189.
PubMed=21129722; DOI=10.1016/j.ajhg.2010.11.003;
Pearlman A., Loke J., Le Caignec C., White S., Chin L., Friedman A.,
Warr N., Willan J., Brauer D., Farmer C., Brooks E., Oddoux C.,
Riley B., Shajahan S., Camerino G., Homfray T., Crosby A.H.,
Couper J., David A., Greenfield A., Sinclair A., Ostrer H.;
"Mutations in MAP3K1 cause 46,XY disorders of sex development and
implicate a common signal transduction pathway in human testis
determination.";
Am. J. Hum. Genet. 87:898-904(2010).
-!- FUNCTION: Component of a protein kinase signal transduction
cascade (PubMed:9808624). Activates the ERK and JNK kinase
pathways by phosphorylation of MAP2K1 and MAP2K4 (PubMed:9808624).
May phosphorylate the MAPK8/JNK1 kinase (PubMed:17761173).
Activates CHUK and IKBKB, the central protein kinases of the NF-
kappa-B pathway (PubMed:9808624). {ECO:0000269|PubMed:17761173,
ECO:0000269|PubMed:9808624}.
-!- CATALYTIC ACTIVITY:
Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999,
ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216;
EC=2.7.11.25;
-!- CATALYTIC ACTIVITY:
Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
EC=2.7.11.25;
-!- COFACTOR:
Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
-!- ACTIVITY REGULATION: Activated by autophosphorylation on Thr-1400
and Thr-1412 following oligomerization.
-!- SUBUNIT: Binds both upstream activators and downstream substrates
in multimolecular complexes through its N-terminus
(PubMed:9808624). Oligomerizes after binding MAP2K4 or TRAF2
(PubMed:9808624). Interacts with AXIN1 (PubMed:12223491,
PubMed:15262978). Interacts (via the kinase catalytic domain) with
STK38 (PubMed:17906693). Interacts with GRIPAP1 (PubMed:17761173).
{ECO:0000269|PubMed:12223491, ECO:0000269|PubMed:15262978,
ECO:0000269|PubMed:17761173, ECO:0000269|PubMed:17906693,
ECO:0000269|PubMed:9808624}.
-!- INTERACTION:
P32121:ARRB2; NbExp=2; IntAct=EBI-49776, EBI-714559;
P15056:BRAF; NbExp=2; IntAct=EBI-49776, EBI-365980;
P61962:DCAF7; NbExp=7; IntAct=EBI-49776, EBI-359808;
O75369:FLNB; NbExp=2; IntAct=EBI-49776, EBI-352089;
P45985:MAP2K4; NbExp=3; IntAct=EBI-49776, EBI-447868;
Q12851:MAP4K2; NbExp=2; IntAct=EBI-49776, EBI-49783;
Q12933:TRAF2; NbExp=2; IntAct=EBI-49776, EBI-355744;
-!- PTM: Autophosphorylated. {ECO:0000250}.
-!- DISEASE: 46,XY sex reversal 6 (SRXY6) [MIM:613762]: A disorder of
sex development. Affected individuals have a 46,XY karyotype but
present as phenotypically normal females.
{ECO:0000269|PubMed:21129722}. 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 kinase subfamily.
{ECO:0000305}.
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EMBL; AC008937; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AF042838; AAC97073.1; -; mRNA.
EMBL; U29671; AAB05828.1; -; Genomic_DNA.
CCDS; CCDS43318.1; -.
PIR; G01887; G01887.
RefSeq; NP_005912.1; NM_005921.1.
SMR; Q13233; -.
BioGrid; 110378; 139.
DIP; DIP-27520N; -.
ELM; Q13233; -.
IntAct; Q13233; 41.
MINT; Q13233; -.
STRING; 9606.ENSP00000382423; -.
BindingDB; Q13233; -.
ChEMBL; CHEMBL3956; -.
DrugBank; DB06061; AZD-8330.
GuidetoPHARMACOLOGY; 2069; -.
iPTMnet; Q13233; -.
PhosphoSitePlus; Q13233; -.
BioMuta; MAP3K1; -.
DMDM; 218512139; -.
SWISS-2DPAGE; Q13233; -.
EPD; Q13233; -.
jPOST; Q13233; -.
MaxQB; Q13233; -.
PaxDb; Q13233; -.
PeptideAtlas; Q13233; -.
PRIDE; Q13233; -.
ProteomicsDB; 59240; -.
DNASU; 4214; -.
Ensembl; ENST00000399503; ENSP00000382423; ENSG00000095015.
GeneID; 4214; -.
KEGG; hsa:4214; -.
UCSC; uc003jqw.5; human.
CTD; 4214; -.
DisGeNET; 4214; -.
GeneCards; MAP3K1; -.
GeneReviews; MAP3K1; -.
H-InvDB; HIX0024789; -.
HGNC; HGNC:6848; MAP3K1.
HPA; CAB004500; -.
HPA; HPA046509; -.
MalaCards; MAP3K1; -.
MIM; 600982; gene.
MIM; 613762; phenotype.
neXtProt; NX_Q13233; -.
OpenTargets; ENSG00000095015; -.
Orphanet; 242; 46,XY complete gonadal dysgenesis.
Orphanet; 251510; 46,XY partial gonadal dysgenesis.
PharmGKB; PA30592; -.
eggNOG; KOG4279; Eukaryota.
eggNOG; ENOG410XQGS; LUCA.
GeneTree; ENSGT00940000159154; -.
HOGENOM; HOG000113437; -.
InParanoid; Q13233; -.
KO; K04416; -.
OMA; STTMEQP; -.
OrthoDB; 385042at2759; -.
PhylomeDB; Q13233; -.
TreeFam; TF105112; -.
Reactome; R-HSA-166058; MyD88:MAL(TIRAP) cascade initiated on plasma membrane.
Reactome; R-HSA-2871796; FCERI mediated MAPK activation.
Reactome; R-HSA-933542; TRAF6 mediated NF-kB activation.
Reactome; R-HSA-975138; TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation.
Reactome; R-HSA-975871; MyD88 cascade initiated on plasma membrane.
SignaLink; Q13233; -.
SIGNOR; Q13233; -.
ChiTaRS; MAP3K1; human.
GeneWiki; MAP3K1; -.
GenomeRNAi; 4214; -.
PRO; PR:Q13233; -.
Proteomes; UP000005640; Chromosome 5.
Bgee; ENSG00000095015; Expressed in 213 organ(s), highest expression level in blood.
Genevisible; Q13233; HS.
GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
GO; GO:0005829; C:cytosol; TAS:Reactome.
GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO; GO:0004709; F:MAP kinase kinase kinase activity; NAS:UniProtKB.
GO; GO:0004672; F:protein kinase activity; IDA:MGI.
GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
GO; GO:0004674; F:protein serine/threonine kinase activity; EXP:Reactome.
GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
GO; GO:0032147; P:activation of protein kinase activity; IBA:GO_Central.
GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB.
GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome.
GO; GO:0006468; P:protein phosphorylation; NAS:UniProtKB.
GO; GO:0023014; P:signal transduction by protein phosphorylation; IBA:GO_Central.
GO; GO:0031098; P:stress-activated protein kinase signaling cascade; IBA:GO_Central.
Gene3D; 1.25.10.10; -; 1.
Gene3D; 3.30.40.10; -; 1.
InterPro; IPR011989; ARM-like.
InterPro; IPR016024; ARM-type_fold.
InterPro; IPR011009; Kinase-like_dom_sf.
InterPro; IPR000719; Prot_kinase_dom.
InterPro; IPR017441; Protein_kinase_ATP_BS.
InterPro; IPR008271; Ser/Thr_kinase_AS.
InterPro; IPR001841; Znf_RING.
InterPro; IPR013083; Znf_RING/FYVE/PHD.
InterPro; IPR007527; Znf_SWIM.
Pfam; PF00069; Pkinase; 1.
SMART; SM00220; S_TKc; 1.
SUPFAM; SSF48371; SSF48371; 1.
SUPFAM; SSF56112; SSF56112; 1.
PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PROSITE; PS50089; ZF_RING_2; 1.
PROSITE; PS50966; ZF_SWIM; 1.
1: Evidence at protein level;
Acetylation; ATP-binding; Complete proteome; Kinase; Magnesium;
Metal-binding; Nucleotide-binding; Phosphoprotein; Polymorphism;
Reference proteome; Serine/threonine-protein kinase; Transferase;
Zinc; Zinc-finger.
INIT_MET 1 1 Removed. {ECO:0000244|PubMed:19413330}.
CHAIN 2 1512 Mitogen-activated protein kinase kinase
kinase 1.
/FTId=PRO_0000086240.
DOMAIN 1243 1508 Protein kinase. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
ZN_FING 338 366 SWIM-type. {ECO:0000255|PROSITE-
ProRule:PRU00325}.
ZN_FING 443 492 RING-type. {ECO:0000255|PROSITE-
ProRule:PRU00175}.
NP_BIND 1249 1257 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
COMPBIAS 2 5 Poly-Ala.
COMPBIAS 25 29 Poly-Gly.
COMPBIAS 36 41 Poly-Ala.
COMPBIAS 422 431 Poly-Ser.
COMPBIAS 842 847 Poly-Ser.
COMPBIAS 942 949 Poly-Thr.
COMPBIAS 1182 1187 Poly-Glu.
COMPBIAS 1216 1219 Poly-Ile.
ACT_SITE 1369 1369 Proton acceptor. {ECO:0000255|PROSITE-
ProRule:PRU00159, ECO:0000255|PROSITE-
ProRule:PRU10027}.
BINDING 1272 1272 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
MOD_RES 2 2 N-acetylalanine.
{ECO:0000244|PubMed:19413330}.
MOD_RES 21 21 Phosphoserine.
{ECO:0000244|PubMed:23186163}.
MOD_RES 35 35 Phosphoserine.
{ECO:0000244|PubMed:23186163}.
MOD_RES 137 137 Phosphoserine.
{ECO:0000250|UniProtKB:P53349}.
MOD_RES 154 154 Phosphoserine.
{ECO:0000244|PubMed:18691976}.
MOD_RES 275 275 Phosphoserine.
{ECO:0000244|PubMed:19369195,
ECO:0000244|PubMed:23186163}.
MOD_RES 285 285 Phosphothreonine.
{ECO:0000244|PubMed:23186163}.
MOD_RES 292 292 Phosphoserine.
{ECO:0000244|PubMed:18220336,
ECO:0000244|PubMed:18669648,
ECO:0000244|PubMed:19369195,
ECO:0000244|PubMed:23186163}.
MOD_RES 297 297 Phosphoserine.
{ECO:0000244|PubMed:18669648}.
MOD_RES 300 300 Phosphoserine.
{ECO:0000244|PubMed:18669648}.
MOD_RES 507 507 Phosphoserine.
{ECO:0000244|PubMed:18669648}.
MOD_RES 531 531 Phosphoserine.
{ECO:0000244|PubMed:23186163}.
MOD_RES 923 923 Phosphoserine.
{ECO:0000244|PubMed:23186163}.
MOD_RES 1018 1018 Phosphoserine.
{ECO:0000244|PubMed:18669648,
ECO:0000244|PubMed:23186163}.
MOD_RES 1043 1043 Phosphoserine.
{ECO:0000244|PubMed:18691976}.
MOD_RES 1400 1400 Phosphothreonine; by autocatalysis.
{ECO:0000250|UniProtKB:P53349}.
MOD_RES 1412 1412 Phosphothreonine; by autocatalysis.
{ECO:0000250|UniProtKB:P53349}.
VARIANT 92 92 S -> N. {ECO:0000269|PubMed:17344846}.
/FTId=VAR_040680.
VARIANT 189 189 L -> P (in SRXY6; increases
phosphorylation of the downstream target
MAPK3/MAPK1 compared to wild-type and
enhances binding of RHOA to the mutant
MAP3K1 complex; dbSNP:rs387906788).
{ECO:0000269|PubMed:21129722}.
/FTId=VAR_065504.
VARIANT 189 189 L -> R (in SRXY6; increases
phosphorylation of the downstream targets
MAPK14 and MAPK3/MAPK1 compared to wild-
type and enhances binding of RHOA to the
mutant MAP3K1 complex;
dbSNP:rs387906788).
{ECO:0000269|PubMed:21129722}.
/FTId=VAR_065505.
VARIANT 211 211 V -> VIQ (in SRXY6).
/FTId=VAR_065506.
VARIANT 443 443 C -> S. {ECO:0000269|PubMed:17344846}.
/FTId=VAR_040681.
VARIANT 616 616 G -> R (in SRXY6; dbSNP:rs143853590).
{ECO:0000269|PubMed:21129722}.
/FTId=VAR_065507.
VARIANT 806 806 D -> N (in dbSNP:rs702689).
/FTId=VAR_051636.
VARIANT 906 906 V -> I (in dbSNP:rs832582).
/FTId=VAR_051637.
CONFLICT 20 20 T -> P (in Ref. 2; AAC97073).
{ECO:0000305}.
CONFLICT 37 37 P -> R (in Ref. 2; AAC97073).
{ECO:0000305}.
CONFLICT 120 120 G -> R (in Ref. 2; AAC97073).
{ECO:0000305}.
CONFLICT 351 351 R -> H (in Ref. 2; AAC97073).
{ECO:0000305}.
CONFLICT 845 845 S -> SV (in Ref. 2; AAC97073).
{ECO:0000305}.
CONFLICT 859 859 I -> Y (in Ref. 2; AAC97073).
{ECO:0000305}.
CONFLICT 878 902 DGQQDSFLQASVPNNYLETTENSSP -> QRQQHNSFCRHL
FPTTIWKPQRTVPL (in Ref. 2; AAC97073).
{ECO:0000305}.
CONFLICT 933 933 S -> R (in Ref. 2; AAC97073).
{ECO:0000305}.
CONFLICT 1097 1097 C -> L (in Ref. 2; AAC97073).
{ECO:0000305}.
CONFLICT 1104 1107 AVIP -> CCYT (in Ref. 2; AAC97073).
{ECO:0000305}.
CONFLICT 1200 1200 D -> V (in Ref. 2; AAC97073).
{ECO:0000305}.
SEQUENCE 1512 AA; 164470 MW; 5CB78242295411D9 CRC64;
MAAAAGNRAS SSGFPGARAT SPEAGGGGGA LKASSAPAAA AGLLREAGSG GRERADWRRR
QLRKVRSVEL DQLPEQPLFL AASPPASSTS PSPEPADAAG SGTGFQPVAV PPPHGAASRG
GAHLTESVAA PDSGASSPAA AEPGEKRAPA AEPSPAAAPA GREMENKETL KGLHKMDDRP
EERMIREKLK ATCMPAWKHE WLERRNRRGP VVVKPIPVKG DGSEMNHLAA ESPGEVQASA
ASPASKGRRS PSPGNSPSGR TVKSESPGVR RKRVSPVPFQ SGRITPPRRA PSPDGFSPYS
PEETNRRVNK VMRARLYLLQ QIGPNSFLIG GDSPDNKYRV FIGPQNCSCA RGTFCIHLLF
VMLRVFQLEP SDPMLWRKTL KNFEVESLFQ KYHSRRSSRI KAPSRNTIQK FVSRMSNSHT
LSSSSTSTSS SENSIKDEEE QMCPICLLGM LDEESLTVCE DGCRNKLHHH CMSIWAEECR
RNREPLICPL CRSKWRSHDF YSHELSSPVD SPSSLRAAQQ QTVQQQPLAG SRRNQESNFN
LTHYGTQQIP PAYKDLAEPW IQVFGMELVG CLFSRNWNVR EMALRRLSHD VSGALLLANG
ESTGNSGGSS GSSPSGGATS GSSQTSISGD VVEACCSVLS MVCADPVYKV YVAALKTLRA
MLVYTPCHSL AERIKLQRLL QPVVDTILVK CADANSRTSQ LSISTLLELC KGQAGELAVG
REILKAGSIG IGGVDYVLNC ILGNQTESNN WQELLGRLCL IDRLLLEFPA EFYPHIVSTD
VSQAEPVEIR YKKLLSLLTF ALQSIDNSHS MVGKLSRRIY LSSARMVTTV PHVFSKLLEM
LSVSSSTHFT RMRRRLMAIA DEVEIAEAIQ LGVEDTLDGQ QDSFLQASVP NNYLETTENS
SPECTVHLEK TGKGLCATKL SASSEDISER LASISVGPSS STTTTTTTTE QPKPMVQTKG
RPHSQCLNSS PLSHHSQLMF PALSTPSSST PSVPAGTATD VSKHRLQGFI PCRIPSASPQ
TQRKFSLQFH RNCPENKDSD KLSPVFTQSR PLPSSNIHRP KPSRPTPGNT SKQGDPSKNS
MTLDLNSSSK CDDSFGCSSN SSNAVIPSDE TVFTPVEEKC RLDVNTELNS SIEDLLEASM
PSSDTTVTFK SEVAVLSPEK AENDDTYKDD VNHNQKCKEK MEAEEEEALA IAMAMSASQD
ALPIVPQLQV ENGEDIIIIQ QDTPETLPGH TKAKQPYRED TEWLKGQQIG LGAFSSCYQA
QDVGTGTLMA VKQVTYVRNT SSEQEEVVEA LREEIRMMSH LNHPNIIRML GATCEKSNYN
LFIEWMAGGS VAHLLSKYGA FKESVVINYT EQLLRGLSYL HENQIIHRDV KGANLLIDST
GQRLRIADFG AAARLASKGT GAGEFQGQLL GTIAFMAPEV LRGQQYGRSC DVWSVGCAII
EMACAKPPWN AEKHSNHLAL IFKIASATTA PSIPSHLSPG LRDVALRCLE LQPQDRPPSR
ELLKHPVFRT TW


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Catalog number Product name Quantity
E1358m ELISA kit Apoptosis signal-regulating kinase 1,Ask1,ASK-1,Map3k5,MAPK_ERK kinase kinase 5,MEK kinase 5,MEKK 5,Mekk5,Mitogen-activated protein kinase kinase kinase 5,Mouse,Mus musculus 96T
U1358m CLIA Apoptosis signal-regulating kinase 1,Ask1,ASK-1,Map3k5,MAPK_ERK kinase kinase 5,MEK kinase 5,MEKK 5,Mekk5,Mitogen-activated protein kinase kinase kinase 5,Mouse,Mus musculus 96T
E1358m ELISA Apoptosis signal-regulating kinase 1,Ask1,ASK-1,Map3k5,MAPK_ERK kinase kinase 5,MEK kinase 5,MEKK 5,Mekk5,Mitogen-activated protein kinase kinase kinase 5,Mouse,Mus musculus 96T
E1358h ELISA kit Apoptosis signal-regulating kinase 1,ASK1,ASK-1,Homo sapiens,Human,MAP3K5,MAPK_ERK kinase kinase 5,MAPKKK5,MEK kinase 5,MEKK 5,MEKK5,Mitogen-activated protein kinase kinase kinase 5 96T
U1358h CLIA Apoptosis signal-regulating kinase 1,ASK1,ASK-1,Homo sapiens,Human,MAP3K5,MAPK_ERK kinase kinase 5,MAPKKK5,MEK kinase 5,MEKK 5,MEKK5,Mitogen-activated protein kinase kinase kinase 5 96T
E1358h ELISA Apoptosis signal-regulating kinase 1,ASK1,ASK-1,Homo sapiens,Human,MAP3K5,MAPK_ERK kinase kinase 5,MAPKKK5,MEK kinase 5,MEKK 5,MEKK5,Mitogen-activated protein kinase kinase kinase 5 96T
EIAAB25244 c-Jun N-terminal kinase kinase 2,Dual specificity mitogen-activated protein kinase kinase 7,JNK kinase 2,JNK-activating kinase 2,JNKK 2,MAP kinase kinase 7,Map2k7,MAPK_ERK kinase 7,MAPKK 7,MEK 7,Mkk7,
EIAAB25239 C-JUN N-terminal kinase kinase 1,Dual specificity mitogen-activated protein kinase kinase 4,JNK kinase 1,JNK-activating kinase 1,JNKK 1,Jnkk1,MAP kinase kinase 4,Map2k4,MAPK_ERK kinase 4,MAPKK 4,MEK 4
EIAAB25245 c-Jun N-terminal kinase kinase 2,Dual specificity mitogen-activated protein kinase kinase 7,JNK kinase 2,JNK-activating kinase 2,JNKK 2,MAP kinase kinase 7,Map2k7,MAPK_ERK kinase 7,MAPKK 7,MEK 7,Rat,R
EIAAB24784 GCK family kinase MiNK,Map4k6,MAPK_ERK kinase kinase kinase 6,MEK kinase kinase 6,MEKKK 6,Mink,Mink1,Misshapen_NIK-related kinase,Misshapen-like kinase 1,Mitogen-activated protein kinase kinase kinase
EIAAB24783 GCK family kinase MiNK,Map4k6,MAPK_ERK kinase kinase kinase 6,MEK kinase kinase 6,MEKKK 6,Mink,Mink1,Misshapen_NIK-related kinase,Misshapen-like kinase 1,Mitogen-activated protein kinase kinase kinase
E1206r ELISA kit Erk2,ERK-2,ERT1,Extracellular signal-regulated kinase 2,MAP kinase 1,MAP kinase 2,MAP kinase isoform p42,Mapk,MAPK 1,MAPK 2,Mapk1,Mitogen-activated protein kinase 1,Mitogen-activated protei 96T
E1206m ELISA kit Erk2,ERK-2,ERT1,Extracellular signal-regulated kinase 2,MAP kinase 1,MAP kinase 2,MAP kinase isoform p42,Mapk,MAPK 1,MAPK 2,Mapk1,Mitogen-activated protein kinase 1,Mitogen-activated protei 96T
E1206h ELISA kit ERK2,ERK-2,ERT1,Extracellular signal-regulated kinase 2,Homo sapiens,Human,MAP kinase 1,MAP kinase 2,MAP kinase isoform p42,MAPK 1,MAPK 2,MAPK1,Mitogen-activated protein kinase 1,Mitogen-ac 96T
E1206h ELISA ERK2,ERK-2,ERT1,Extracellular signal-regulated kinase 2,Homo sapiens,Human,MAP kinase 1,MAP kinase 2,MAP kinase isoform p42,MAPK 1,MAPK 2,MAPK1,Mitogen-activated protein kinase 1,Mitogen-activat 96T
U1206h CLIA ERK2,ERK-2,ERT1,Extracellular signal-regulated kinase 2,Homo sapiens,Human,MAP kinase 1,MAP kinase 2,MAP kinase isoform p42,MAPK 1,MAPK 2,MAPK1,Mitogen-activated protein kinase 1,Mitogen-activate 96T
U1206m CLIA Erk2,ERK-2,ERT1,Extracellular signal-regulated kinase 2,MAP kinase 1,MAP kinase 2,MAP kinase isoform p42,Mapk,MAPK 1,MAPK 2,Mapk1,Mitogen-activated protein kinase 1,Mitogen-activated protein kina 96T
U1206r CLIA Erk2,ERK-2,ERT1,Extracellular signal-regulated kinase 2,MAP kinase 1,MAP kinase 2,MAP kinase isoform p42,Mapk,MAPK 1,MAPK 2,Mapk1,Mitogen-activated protein kinase 1,Mitogen-activated protein kina 96T
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E1206b ELISA Bos taurus,Bovine,ERK2,ERK-2,ERT1,Extracellular signal-regulated kinase 2,MAP kinase 1,MAP kinase 2,MAPK 1,MAPK 2,MAPK1,Mitogen-activated protein kinase 1,Mitogen-activated protein kinase 2,PRKM 96T
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
E1206m ELISA Erk2,ERK-2,ERT1,Extracellular signal-regulated kinase 2,MAP kinase 1,MAP kinase 2,MAP kinase isoform p42,Mapk,MAPK 1,MAPK 2,Mapk1,Mitogen-activated protein kinase 1,Mitogen-activated protein kin 96T
E1206r ELISA Erk2,ERK-2,ERT1,Extracellular signal-regulated kinase 2,MAP kinase 1,MAP kinase 2,MAP kinase isoform p42,Mapk,MAPK 1,MAPK 2,Mapk1,Mitogen-activated protein kinase 1,Mitogen-activated protein kin 96T
E1206b ELISA kit Bos taurus,Bovine,ERK2,ERK-2,ERT1,Extracellular signal-regulated kinase 2,MAP kinase 1,MAP kinase 2,MAPK 1,MAPK 2,MAPK1,Mitogen-activated protein kinase 1,Mitogen-activated protein kinase 2 96T

Kits Elisa; taq POLYMERASE

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Gentaur; yes we can

Pathways :
WP1493: Carbon assimilation C4 pathway
WP1567: Glycolysis and Gluconeogenesis
WP1619: Amino sugar and nucleotide sugar metabolism
WP1653: Galactose metabolism
WP1681: Pantothenate and CoA biosynthesis
WP1701: Starch and sucrose metabolism
WP1703: Streptomycin biosynthesis
WP1844: MAP kinase cascade
WP1946: Cori Cycle
WP2340: Thiamine (vitamin B1) biosynthesis and salvage
WP2341: vitamin B1 (thiamin) biosynthesis and salvage pathway
WP253: Glycolysis
WP32: Translation Factors
WP2292: Chemokine signaling pathway
WP402: ERK1 - ERK2 MAPK cascade
WP1009: MAPK Cascade
WP1032: NLR proteins
WP1037: p38 MAPK Signaling Pathway
WP1038: Vitamin A and carotenoid metabolism
WP1049: G Protein Signaling Pathways
WP1052: Id Signaling Pathway
WP1114: MAPK signaling pathway
WP1128: MAPK Cascade
WP1154: p38 MAPK Signaling Pathway
WP1155: Vitamin A and carotenoid metabolism

Related Genes :
[Map3k1 Mekk Mekk1] Mitogen-activated protein kinase kinase kinase 1 (EC 2.7.11.25) (MAPK/ERK kinase kinase 1) (MEK kinase 1) (MEKK 1)
[MAP3K1 MAPKKK1 MEKK MEKK1] Mitogen-activated protein kinase kinase kinase 1 (EC 2.7.11.25) (MAPK/ERK kinase kinase 1) (MEK kinase 1) (MEKK 1)
[Map3k1 Mekk Mekk1] Mitogen-activated protein kinase kinase kinase 1 (EC 2.7.11.25) (MAPK/ERK kinase kinase 1) (MEK kinase 1) (MEKK 1)
[mkkA DDB_G0283265] Mitogen-activated protein kinase kinase kinase A (EC 2.7.11.25) (MAPK/ERK kinase 1) (MEK kinase 1) (MEKK 1) (MAPK/ERK kinase A) (MEK kinase A) (MEKK A) (MEKKalpha)
[Map3k2 Mekk2] Mitogen-activated protein kinase kinase kinase 2 (EC 2.7.11.25) (MAPK/ERK kinase kinase 2) (MEK kinase 2) (MEKK 2)
[MAP3K5 ASK1 MAPKKK5 MEKK5] Mitogen-activated protein kinase kinase kinase 5 (EC 2.7.11.25) (Apoptosis signal-regulating kinase 1) (ASK-1) (MAPK/ERK kinase kinase 5) (MEK kinase 5) (MEKK 5)
[MAP2K1 MEK1 PRKMK1] 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)
[MAP2K1 MEK1 PRKMK1] Dual specificity mitogen-activated protein kinase kinase 1 (MAP kinase kinase 1) (MAPKK 1) (EC 2.7.12.2) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK 1)
[Map2k1 Mek1 Prkmk1] Dual specificity mitogen-activated protein kinase kinase 1 (MAP kinase kinase 1) (MAPKK 1) (EC 2.7.12.2) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK 1)
[Map3k5 Ask1 Mekk5] Mitogen-activated protein kinase kinase kinase 5 (EC 2.7.11.25) (Apoptosis signal-regulating kinase 1) (ASK-1) (MAPK/ERK kinase kinase 5) (MEK kinase 5) (MEKK 5)
[Map2k1 Mek1 Prkmk1] Dual specificity mitogen-activated protein kinase kinase 1 (MAP kinase kinase 1) (MAPKK 1) (EC 2.7.12.2) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK 1)
[MAP2K1 MEK1 PRKMK1] Dual specificity mitogen-activated protein kinase kinase 1 (MAP kinase kinase 1) (MAPKK 1) (EC 2.7.12.2) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK 1)
[Mapk1 Erk2 Mapk Prkm1] Mitogen-activated protein kinase 1 (MAP kinase 1) (MAPK 1) (EC 2.7.11.24) (ERT1) (Extracellular signal-regulated kinase 2) (ERK-2) (MAP kinase isoform p42) (p42-MAPK) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2)
[MAP2K1 MEK1 PRKMK1] Dual specificity mitogen-activated protein kinase kinase 1 (MAP kinase kinase 1) (MAPKK 1) (EC 2.7.12.2) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK 1)
[mekA MEK1 DDB_G0269152] Dual specificity mitogen-activated protein kinase kinase 1 (MAP kinase kinase 1) (MAPKK 1) (EC 2.7.12.2) (ERK activator kinase 1) (MAPK/ERK kinase 1) (DdMEK1) (MEK1) (MAPK/ERK kinase A) (MEKA)
[MAP4K2 GCK RAB8IP] Mitogen-activated protein kinase kinase kinase kinase 2 (EC 2.7.11.1) (B lymphocyte serine/threonine-protein kinase) (Germinal center kinase) (GC kinase) (MAPK/ERK kinase kinase kinase 2) (MEK kinase kinase 2) (MEKKK 2) (Rab8-interacting protein)
[MAP2K2 MEK2 MKK2 PRKMK2] Dual specificity mitogen-activated protein kinase kinase 2 (MAP kinase kinase 2) (MAPKK 2) (EC 2.7.12.2) (ERK activator kinase 2) (MAPK/ERK kinase 2) (MEK 2)
[MAPK1 ERK2 PRKM1 PRKM2] Mitogen-activated protein kinase 1 (MAP kinase 1) (MAPK 1) (EC 2.7.11.24) (ERT1) (Extracellular signal-regulated kinase 2) (ERK-2) (MAP kinase isoform p42) (p42-MAPK) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2)
[Mapk1 Erk2 Mapk Prkm1] Mitogen-activated protein kinase 1 (MAP kinase 1) (MAPK 1) (EC 2.7.11.24) (ERT1) (Extracellular signal-regulated kinase 2) (ERK-2) (MAP kinase isoform p42) (p42-MAPK) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2)
[Map2k2 Mek2 Mkk2 Prkmk2] Dual specificity mitogen-activated protein kinase kinase 2 (MAP kinase kinase 2) (MAPKK 2) (EC 2.7.12.2) (ERK activator kinase 2) (MAPK/ERK kinase 2) (MEK 2)
[MAPK3 ERK1 PRKM3] Mitogen-activated protein kinase 3 (MAP kinase 3) (MAPK 3) (EC 2.7.11.24) (ERT2) (Extracellular signal-regulated kinase 1) (ERK-1) (Insulin-stimulated MAP2 kinase) (MAP kinase isoform p44) (p44-MAPK) (Microtubule-associated protein 2 kinase) (p44-ERK1)
[MAPK1 ERK2 PRKM1] Mitogen-activated protein kinase 1 (MAP kinase 1) (MAPK 1) (EC 2.7.11.24) (ERT1) (Extracellular signal-regulated kinase 2) (ERK-2) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2)
[Map2k2 Mek2 Mkk2 Prkmk2] Dual specificity mitogen-activated protein kinase kinase 2 (MAP kinase kinase 2) (MAPKK 2) (EC 2.7.12.2) (ERK activator kinase 2) (MAPK/ERK kinase 2) (MEK 2)
[MAP2K6 MEK6 MKK6 PRKMK6 SKK3] Dual specificity mitogen-activated protein kinase kinase 6 (MAP kinase kinase 6) (MAPKK 6) (EC 2.7.12.2) (MAPK/ERK kinase 6) (MEK 6) (Stress-activated protein kinase kinase 3) (SAPK kinase 3) (SAPKK-3) (SAPKK3)
[Mapk3 Erk1 Prkm3] Mitogen-activated protein kinase 3 (MAP kinase 3) (MAPK 3) (EC 2.7.11.24) (ERT2) (Extracellular signal-regulated kinase 1) (ERK-1) (Insulin-stimulated MAP2 kinase) (MAP kinase isoform p44) (p44-MAPK) (MNK1) (Microtubule-associated protein 2 kinase) (p44-ERK1)
[Mapk3 Erk1 Prkm3] Mitogen-activated protein kinase 3 (MAP kinase 3) (MAPK 3) (EC 2.7.11.24) (ERT2) (Extracellular signal-regulated kinase 1) (ERK-1) (Insulin-stimulated MAP2 kinase) (MAP kinase isoform p44) (p44-MAPK) (MNK1) (Microtubule-associated protein 2 kinase) (p44-ERK1)
[MAP2K2 MEK2] Dual specificity mitogen-activated protein kinase kinase 2 (MAP kinase kinase 2) (MAPKK 2) (EC 2.7.12.2) (ERK activator kinase 2) (MAPK/ERK kinase 2) (MEK 2)
[Map4k2 Rab8ip] Mitogen-activated protein kinase kinase kinase kinase 2 (EC 2.7.11.1) (Germinal center kinase) (GCK) (MAPK/ERK kinase kinase kinase 2) (MEK kinase kinase 2) (MEKKK 2) (Rab8-interacting protein)
[MAPK7 BMK1 ERK5 PRKM7] Mitogen-activated protein kinase 7 (MAP kinase 7) (MAPK 7) (EC 2.7.11.24) (Big MAP kinase 1) (BMK-1) (Extracellular signal-regulated kinase 5) (ERK-5)
[Mapk7 Bmk1 Erk5] Mitogen-activated protein kinase 7 (MAP kinase 7) (MAPK 7) (EC 2.7.11.24) (Big MAP kinase 1) (BMK-1) (Extracellular signal-regulated kinase 5) (ERK-5)

Bibliography :
[7878028] Tumor necrosis factor alpha rapidly activates the mitogen-activated protein kinase (MAPK) cascade in a MAPK kinase kinase-dependent, c-Raf-1-independent fashion in mouse macrophages.