CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-006026
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Dual specificity mitogen-activated protein kinase kinase 1 
Protein Synonyms/Alias
 MAP kinase kinase 1; MAPKK 1; ERK activator kinase 1; MAPK/ERK kinase 1; MEK 1 
Gene Name
 Map2k1 
Gene Synonyms/Alias
 Mek1; Prkmk1 
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
104KLIHLEIKPAIRNQIubiquitination[1]
168IPEQILGKVSIAVIKubiquitination[1]
175KVSIAVIKGLTYLREubiquitination[1]
192KIMHRDVKPSNILVNubiquitination[1]
353PAERADLKQLMVHAFubiquitination[1]
Reference
 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023] 
Functional Description
 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. 
Sequence Annotation
 DOMAIN 68 361 Protein kinase.
 NP_BIND 74 82 ATP (By similarity).
 REGION 270 307 RAF1-binding (By similarity).
 ACT_SITE 190 190 Proton acceptor (By similarity).
 BINDING 97 97 ATP (By similarity).
 MOD_RES 218 218 Phosphoserine; by RAF (By similarity).
 MOD_RES 222 222 Phosphoserine; by RAF (By similarity).
 MOD_RES 286 286 Phosphothreonine (By similarity).
 MOD_RES 292 292 Phosphothreonine; by MAPK1 (By
 MOD_RES 298 298 Phosphoserine; by PAK (By similarity).  
Keyword
 ATP-binding; Complete proteome; Cytoplasm; Cytoskeleton; Direct protein sequencing; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Transferase; Tyrosine-protein kinase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 393 AA 
Protein Sequence
MPKKKPTPIQ LNPAPDGSAV NGTSSAETNL EALQKKLEEL ELDEQQRKRL EAFLTQKQKV 60
GELKDDDFEK ISELGAGNGG VVFKVSHKPS GLVMARKLIH LEIKPAIRNQ IIRELQVLHE 120
CNSPYIVGFY GAFYSDGEIS ICMEHMDGGS LDQVLKKAGR IPEQILGKVS IAVIKGLTYL 180
REKHKIMHRD VKPSNILVNS RGEIKLCDFG VSGQLIDSMA NSFVGTRSYM SPERLQGTHY 240
SVQSDIWSMG LSLVEMAVGR YPIPPPDAKE LELLFGCHVE GDAAETPPRP RTPGRPLSSY 300
GMDSRPPMAI FELLDYIVNE PPPKLPSGVF SLEFQDFVNK CLIKNPAERA DLKQLMVHAF 360
IKRSDAEEVD FAGWLCSTIG LNQPSTPTHA ASI 393 
Gene Ontology
 GO:0005938; C:cell cortex; IEA:Compara.
 GO:0005829; C:cytosol; TAS:UniProtKB.
 GO:0032839; C:dendrite cytoplasm; IEA:Compara.
 GO:0005769; C:early endosome; TAS:UniProtKB.
 GO:0005925; C:focal adhesion; TAS:UniProtKB.
 GO:0005794; C:Golgi apparatus; TAS:UniProtKB.
 GO:0005770; C:late endosome; TAS:UniProtKB.
 GO:0005739; C:mitochondrion; TAS:UniProtKB.
 GO:0005634; C:nucleus; TAS:UniProtKB.
 GO:0043204; C:perikaryon; IEA:Compara.
 GO:0048471; C:perinuclear region of cytoplasm; IEA:Compara.
 GO:0005886; C:plasma membrane; IEA:Compara.
 GO:0005816; C:spindle pole body; IEA:UniProtKB-SubCell.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004708; F:MAP kinase kinase activity; IMP:MGI.
 GO:0043539; F:protein serine/threonine kinase activator activity; IEA:Compara.
 GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
 GO:0004713; F:protein tyrosine kinase activity; IEA:UniProtKB-KW.
 GO:0004728; F:receptor signaling protein tyrosine phosphatase activity; IMP:MGI.
 GO:0007050; P:cell cycle arrest; IEA:Compara.
 GO:0048870; P:cell motility; IMP:MGI.
 GO:0008283; P:cell proliferation; IEA:Compara.
 GO:0090398; P:cellular senescence; IEA:Compara.
 GO:0048313; P:Golgi inheritance; IEA:Compara.
 GO:0030216; P:keratinocyte differentiation; IMP:MGI.
 GO:0060711; P:labyrinthine layer development; IMP:MGI.
 GO:0032402; P:melanosome transport; IEA:Compara.
 GO:0007067; P:mitosis; IEA:Compara.
 GO:0008285; P:negative regulation of cell proliferation; IEA:Compara.
 GO:0034111; P:negative regulation of homotypic cell-cell adhesion; IEA:Compara.
 GO:0030182; P:neuron differentiation; IMP:MGI.
 GO:0048812; P:neuron projection morphogenesis; IEA:Compara.
 GO:0060674; P:placenta blood vessel development; IMP:MGI.
 GO:0045597; P:positive regulation of cell differentiation; IDA:MGI.
 GO:0030335; P:positive regulation of cell migration; IEA:Compara.
 GO:0032320; P:positive regulation of Ras GTPase activity; IEA:Compara.
 GO:0046579; P:positive regulation of Ras protein signal transduction; ISO:MGI.
 GO:0032968; P:positive regulation of transcription elongation from RNA polymerase II promoter; IEA:Compara.
 GO:0051291; P:protein heterooligomerization; IEA:Compara.
 GO:2000641; P:regulation of early endosome to late endosome transport; TAS:UniProtKB.
 GO:0090170; P:regulation of Golgi inheritance; TAS:UniProtKB.
 GO:0032872; P:regulation of stress-activated MAPK cascade; TAS:UniProtKB.
 GO:0003056; P:regulation of vascular smooth muscle contraction; IEA:Compara.
 GO:0048678; P:response to axon injury; IEA:Compara.
 GO:0051384; P:response to glucocorticoid stimulus; IEA:Compara.
 GO:0006979; P:response to oxidative stress; IEA:Compara.
 GO:0047496; P:vesicle transport along microtubule; IEA:Compara. 
Interpro
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS. 
Pfam
 PF00069; Pkinase 
SMART
 SM00220; S_TKc 
PROSITE
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 
PRINTS