Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures
Basic Information
Protein Name :  Dual specificity mitogen-activated protein kinase kinase 1  

UniProtKB / Swiss-Prot ID :  MP2K1_HUMAN

Gene Name (Synonyms) : 
MAP2K1, MEK1, PRKMK1  

Species :  Homo sapiens (Human). 

Subcellular Localization :  Cytoplasm, cytoskeleton, centrosome. Cytoplasm, cytoskeleton, spindle pole body. Cytoplasm. Nucleus. Note=Localizes at centrosomes during prometaphase, midzone during anaphase and midbody during telophase/cytokinesis. 

Protein 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. 

Protein Sequence MPKKKPTPIQLNPAPDGSAVNGTSSAETNLEALQKKLEELELDEQQRKRLEAFLTQKQKVGELKDDDFEK...
Predicted Secondary Structure CCCCCCCCCCCCCCCCCCCCCCCCCCCCCHHHHHCCCCCCCCCCHHHHCCCCCCCCCCCCCCCCCCCEEE...
Protein Variant
LocationDescription
53F -> S (in CFC syndrome). VAR_035093
130Y -> C (in CFC syndrome). VAR_035094
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Overview of Protein Modification Sites with Functional and Structural Information
Accessible Surface Area (ASA)
Pred. Secondary
Real Secondary
Disorder Prediction
Protein Domain
&
Experimental PTM Sites
Predicted PTM Sites
Protein Variant
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Experimental Post-Translational Modification Sites Download
Locations
Modification
Substrate Sites
&
Secondary Structure
Accessible Surface Area (%)
Resource
Reference
Structural Characterization
Orthologous
Protein Cluster
16Caspase cleavage aspartic acidNPAPDGSAV
CCCCCCCCC
66.83Phosphositeplus
Link-
23Phosphothreonine (MAP2K_group)AVNGTSSAE
CCCCCCCCC
17.82PhosphoELM
Link-
24Phosphoserine (MAP2K_group)VNGTSSAET
CCCCCCCCC
29.02PhosphoELM
Link-
25Phosphoserine (MAP2K_group)NGTSSAETN
CCCCCCCCC
29.93PhosphoELM
Link-
36Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)ALQKKLEEL
HHHCCCCCC
48.44Phosphositeplus
Link-
57Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)FLTQKQKVG
CCCCCCCCC
47.02Phosphositeplus
Link-
64Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)VGELKDDDF
CCCCCCCCE
55.60Phosphositeplus
Link
104Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)HLEIKPAIR
CHHHCCCHH
21.01Phosphositeplus
Link
175Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)IAVIKGLTY
HHHHHHHHH
41.07Phosphositeplus
Link
192Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)HRDVKPSNI
EEECCHHHE
47.20Phosphositeplus
Link
205Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)RGEIKLCDF
CCCEEEEEC
38.47Phosphositeplus
Link
212PhosphoserineDFGVSGQLI
ECEEEEEEC
22.62PhosphoELM
Link
212PhosphoserineDFGVSGQLI
ECEEEEEEC
22.62Phosphositeplus
Link
218PhosphoserineQLIDSMANS
EECCCEEEE
16.89HPRD
Link
218PhosphoserineQLIDSMANS
EECCCEEEE
16.89Phosphositeplus
Link
218Phosphoserine (ARAF)QLIDSMANS
EECCCEEEE
16.89HPRD
Link
218Phosphoserine (BRAF)QLIDSMANS
EECCCEEEE
16.89HPRD
Link
218Phosphoserine (MAP2K_group;MAP3K_group;MAP3K_group;RAF1;MAP3K8)QLIDSMANS
EECCCEEEE
16.89PhosphoELM
Link
218Phosphoserine (RAF1)QLIDSMANS
EECCCEEEE
16.89HPRD
Link
218Phosphoserine; by RAF.QLIDSMANS
EECCCEEEE
16.89UniProtKB
Link
222PhosphoserineSMANSFVGT
CEEEEEEEE
16.27HPRD
Link
222PhosphoserineSMANSFVGT
CEEEEEEEE
16.27Phosphositeplus
Link
222Phosphoserine (ARAF)SMANSFVGT
CEEEEEEEE
16.27HPRD
Link
222Phosphoserine (BRAF)SMANSFVGT
CEEEEEEEE
16.27HPRD
Link
222Phosphoserine (MAP3K_group;MAP3K_group;PDK-1;RAF1;MAP3K8)SMANSFVGT
CEEEEEEEE
16.27PhosphoELM
Link
222Phosphoserine (RAF1)SMANSFVGT
CEEEEEEEE
16.27HPRD
Link
222Phosphoserine; by RAF.SMANSFVGT
CEEEEEEEE
16.27UniProtKB
Link
231PhosphoserineRSYMSPERL
CCCCCHHHH
18.51HPRD
Link
231PhosphoserineRSYMSPERL
CCCCCHHHH
18.51Phosphositeplus
Link
231PhosphoserineRSYMSPERL
CCCCCHHHH
18.51SysPTM
Link
231Phosphoserine.RSYMSPERL
CCCCCHHHH
18.51UniProtKB
Link
282Caspase cleavage aspartic acidQVEGDAAET
HHHCCCCCC
29.15Phosphositeplus
Link-
286PhosphothreonineDAAETPPRP
CCCCCCCCC
33.59Phosphositeplus
Link-
286PhosphothreonineDAAETPPRP
CCCCCCCCC
33.59SysPTM
Link-
286Phosphothreonine (CDK5)DAAETPPRP
CCCCCCCCC
33.59HPRD
Link-
286Phosphothreonine (CDK_group;CDK1)DAAETPPRP
CCCCCCCCC
33.59PhosphoELM
Link-
286Phosphothreonine (RAF1)DAAETPPRP
CCCCCCCCC
33.59HPRD
Link-
286Phosphothreonine.DAAETPPRP
CCCCCCCCC
33.59UniProtKB
Link-
292PhosphothreoninePRPRTPGRP
CCCCCCCCH
32.55Phosphositeplus
Link-
292Phosphothreonine (MAPK1)PRPRTPGRP
CCCCCCCCH
32.55HPRD
Link-
292Phosphothreonine (MAPK1)PRPRTPGRP
CCCCCCCCH
32.55PhosphoELM
Link-
292Phosphothreonine (RAF1)PRPRTPGRP
CCCCCCCCH
32.55HPRD
Link-
298PhosphoserineGRPLSSYGM
CCHHHHHCC
24.97Phosphositeplus
Link-
298Phosphoserine (MAP2K_group;PAK1;PAK1;PAK1;PAK1)GRPLSSYGM
CCHHHHHCC
24.97PhosphoELM
Link-
298Phosphoserine (PAK1)GRPLSSYGM
CCHHHHHCC
24.97HPRD
Link-
304Phosphoserine (MAP2K1)YGMDSRPPM
HCCCCCCCH
37.48HPRD
Link
353Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)RADLKQLMV
CCCHHHHHC
41.77Phosphositeplus
Link
385PhosphoserineLNQPSTPTH
CCCCCCCCC
36.94HPRD
Link-
385PhosphoserineLNQPSTPTH
CCCCCCCCC
36.94Phosphositeplus
Link-
385Phosphoserine.LNQPSTPTH
CCCCCCCCC
36.94UniProtKB
Link-
386PhosphothreonineNQPSTPTHA
CCCCCCCCC
38.60Phosphositeplus
Link-
386PhosphothreonineNQPSTPTHA
CCCCCCCCC
38.60SysPTM
Link-
386Phosphothreonine (MAPK1)NQPSTPTHA
CCCCCCCCC
38.60PhosphoELM
Link-
386Phosphothreonine (RAF1)NQPSTPTHA
CCCCCCCCC
38.60HPRD
Link-
386Phosphothreonine.NQPSTPTHA
CCCCCCCCC
38.60UniProtKB
Link-
388PhosphothreoninePSTPTHAAG
CCCCCCCCC
25.00Phosphositeplus
Link-
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Protein-Protein Interactions
      Interacting Protein      
Interaction type
Source ID
      Resource      
      Pubmed ID      
Domain-Domain Interactions
IL6RB_HUMANphysical interactionMINT-14915MINT11464862
M3K1_HUMANphysical interactionMINT-3391583MINT17110930
GRB10_HUMANphysical interactionMINT-17333MINT9553107
TRIB1_HUMANphysical interactionEBI-492579
intact15299019
TRIB3_HUMANphysical interactionEBI-492595
intact15299019
EP300_HUMANin vitro
in vivo
HPRD:01469HPRD11278389
MP2K1_HUMANin vitro
in vivo
HPRD:01469HPRD9733512
12697810
8226933
CASP9_HUMANin vitro
in vivo
HPRD:01469HPRD12792650
KS6A4_HUMANin vitro
in vivo
HPRD:01469HPRD10806207
PARVA_HUMANin vivoHPRD:01469HPRD15353548
KPCZ_HUMANin vitroHPRD:01469HPRD11535599
KPCI_HUMANin vitroHPRD:01469HPRD10848576
ELK1_HUMANin vitroHPRD:01469HPRD10716983
10997882
MK14_HUMANin vitro
in vivo
HPRD:01469HPRD12697810
TRAF6_HUMANin vitroHPRD:01469HPRD16313339
MK01_HUMANENSP00000302486STRING
MK1I1_HUMANENSP00000302486STRING
MK14_HUMANENSP00000302486STRING
CREB1_HUMANENSP00000302486STRING
EGR1_HUMANENSP00000302486STRING
CDN1A_HUMANENSP00000302486STRING
MKKS_HUMANENSP00000302486STRING
MYOD1_HUMANENSP00000302486STRING
RAF1_HUMANENSP00000302486STRING
JUND_HUMANENSP00000302486STRING
MP2K2_HUMANENSP00000302486STRING
MK03_HUMANENSP00000302486STRING
M3K8_HUMANENSP00000302486STRING
EGFR_HUMANENSP00000302486STRING
BRAF1_HUMANENSP00000302486STRING
FCN2_HUMANENSP00000302486STRING
FCN2_HUMANENSP00000302486STRING
CDC2_HUMANENSP00000302486STRING
FOS_HUMANENSP00000302486STRING
BAD_HUMANENSP00000302486STRING
RASH_HUMANENSP00000302486STRING
VEGFA_HUMANENSP00000302486STRING
CASP9_HUMANENSP00000302486STRING
TRAF3_HUMANENSP00000302486STRING
GATA4_HUMANENSP00000302486STRING
GLI2_HUMANENSP00000302486STRING
NCOR2_HUMANENSP00000302486STRING
MK08_HUMANENSP00000302486STRING
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Disease Reference
Kegg disease
OMIM disease
615279Cardiofaciocutaneous syndrome 3 (CFC3)
Drug Reference
DrugBank
DB06616Bosutinib
DB08911Trametinib
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Related Literatures of Post-Translational Modification
Phosphorylation
ReferencePubMed
"Kinase-selective enrichment enables quantitative phosphoproteomics ofthe kinome across the cell cycle.";
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,Greff Z., Keri G., Stemmann O., Mann M.;
Mol. Cell 31:438-448(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-231; THR-286 ANDTHR-386, AND MASS SPECTROMETRY.
"Large-scale proteomics analysis of the human kinome.";
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.;
Mol. Cell. Proteomics 8:1751-1764(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-385, AND MASSSPECTROMETRY.
"Activation of MEK family kinases requires phosphorylation of twoconserved Ser/Thr residues.";
Zheng C.-F., Guan K.-L.;
EMBO J. 13:1123-1131(1994).
Cited for: PHOSPHORYLATION AT SER-218 AND SER-222, AND MUTAGENESIS.
"Proteomics analysis of protein kinases by target class-selectiveprefractionation and tandem mass spectrometry.";
Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R.,Keri G., Wehland J., Daub H.;
Mol. Cell. Proteomics 6:537-547(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-222, AND MASSSPECTROMETRY.
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Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures