UniProtKB - Q63932 (MP2K2_MOUSE)
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Protein
Dual specificity mitogen-activated protein kinase kinase 2
Gene
Map2k2
Organism
Mus musculus (Mouse)
Status
Functioni
Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates the ERK1 and ERK2 MAP kinases.1 Publication
Catalytic activityi
ATP + a protein = ADP + a phosphoprotein.1 Publication
Cofactori
Mg2+1 Publication
Enzyme regulationi
Inhibited by serine/threonine phosphatase 2A.
Sites
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Binding sitei | 101 | ATP | 1 | |
| Active sitei | 194 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Nucleotide bindingi | 78 – 86 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- MAP kinase kinase activity Source: MGI
- metal ion binding Source: UniProtKB-KW
- PDZ domain binding Source: MGI
- protein complex scaffold Source: BHF-UCL
- protein serine/threonine/tyrosine kinase activity Source: UniProtKB
- protein serine/threonine kinase activator activity Source: MGI
- protein serine/threonine kinase activity Source: GO_Central
- protein tyrosine kinase activity Source: UniProtKB-KW
- scaffold protein binding Source: MGI
GO - Biological processi
- activation of MAPK activity Source: UniProtKB
- epithelial cell proliferation involved in lung morphogenesis Source: MGI
- ERK1 and ERK2 cascade Source: MGI
- face development Source: MGI
- heart development Source: MGI
- lung morphogenesis Source: MGI
- negative regulation of gene expression Source: MGI
- peptidyl-serine autophosphorylation Source: MGI
- positive regulation of axonogenesis Source: MGI
- positive regulation of cell motility Source: BHF-UCL
- positive regulation of ERK1 and ERK2 cascade Source: MGI
- positive regulation of production of miRNAs involved in gene silencing by miRNA Source: MGI
- positive regulation of protein serine/threonine kinase activity Source: MGI
- positive regulation of transcription, DNA-templated Source: MGI
- regulation of apoptotic process Source: GO_Central
- regulation of axon regeneration Source: MGI
- regulation of early endosome to late endosome transport Source: UniProtKB
- regulation of Golgi inheritance Source: UniProtKB
- regulation of mitotic cell cycle Source: GO_Central
- regulation of protein phosphorylation Source: MGI
- regulation of stress-activated MAPK cascade Source: UniProtKB
- thymus development Source: MGI
- thyroid gland development Source: MGI
- trachea formation Source: MGI
Keywordsi
| Molecular function | Kinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase |
| Ligand | ATP-binding, Magnesium, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
| BRENDAi | 2.7.12.2. 3474. |
| Reactomei | R-MMU-112411. MAPK1 (ERK2) activation. R-MMU-445144. Signal transduction by L1. R-MMU-5673000. RAF activation. R-MMU-5674135. MAP2K and MAPK activation. R-MMU-5674499. Negative feedback regulation of MAPK pathway. |
Names & Taxonomyi
| Protein namesi | Recommended name: Dual specificity mitogen-activated protein kinase kinase 2 (EC:2.7.12.21 Publication)Short name: MAP kinase kinase 2 Short name: MAPKK 2 Alternative name(s): ERK activator kinase 2 MAPK/ERK kinase 2 Short name: MEK 2 |
| Gene namesi | Name:Map2k2 Synonyms:Mek2, Mkk2, Prkmk2 |
| Organismi | Mus musculus (Mouse) |
| Taxonomic identifieri | 10090 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
| Proteomesi |
|
Organism-specific databases
| MGIi | MGI:1346867. Map2k2. |
Subcellular locationi
- Cytoplasm 1 Publication
- Membrane 1 Publication; Peripheral membrane protein 1 Publication
Note: Membrane localization is probably regulated by its interaction with KSR1.1 Publication
GO - Cellular componenti
- cell-cell junction Source: MGI
- cell cortex Source: Ensembl
- cytoplasm Source: MGI
- cytoplasmic side of plasma membrane Source: MGI
- cytosol Source: MGI
- early endosome Source: UniProtKB
- endoplasmic reticulum Source: MGI
- focal adhesion Source: UniProtKB
- Golgi apparatus Source: MGI
- late endosome Source: UniProtKB
- microtubule Source: MGI
- mitochondrion Source: UniProtKB
- nucleus Source: UniProtKB
- perinuclear region of cytoplasm Source: MGI
- peroxisomal membrane Source: MGI
Keywords - Cellular componenti
Cytoplasm, MembranePathology & Biotechi
Mutagenesis
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Mutagenesisi | 101 | K → M: Inactivation. 1 Publication | 1 |
PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| ChainiPRO_0000086373 | 1 – 401 | Dual specificity mitogen-activated protein kinase kinase 2Add BLAST | 401 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Modified residuei | 1 | N-acetylmethionineBy similarity | 1 | |
| Modified residuei | 23 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 222 | Phosphoserine; by RAF1 Publication | 1 | |
| Modified residuei | 226 | Phosphoserine; by RAFBy similarity | 1 | |
| Modified residuei | 293 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 295 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 306 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 395 | PhosphothreonineBy similarity | 1 | |
| Modified residuei | 397 | PhosphothreonineBy similarity | 1 |
Post-translational modificationi
Phosphorylation on Ser/Thr by MAP kinase kinase kinases (RAF or MEKK1) regulates positively the kinase activity. Phosphorylated by MAP2K1/MEK1. Low levels of autophosphorylation have been observed.1 Publication
Sites
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sitei | 10 – 11 | Cleavage; by anthrax lethal factorBy similarity | 2 |
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
| EPDi | Q63932. |
| MaxQBi | Q63932. |
| PaxDbi | Q63932. |
| PeptideAtlasi | Q63932. |
| PRIDEi | Q63932. |
PTM databases
| iPTMneti | Q63932. |
| PhosphoSitePlusi | Q63932. |
Expressioni
Tissue specificityi
Expressed in adult intestine, kidney, liver, lung, pancreas, spleen, thymus, and at high levels in the neonatal brain. Lower expression is found in adult brain and heart.
Gene expression databases
| Bgeei | ENSMUSG00000035027. |
| CleanExi | MM_MAP2K2. |
| ExpressionAtlasi | Q63932. baseline and differential. |
| Genevisiblei | Q63932. MM. |
Interactioni
Subunit structurei
Interacts with MORG1 (PubMed:15118098). Interacts with SGK1 (By similarity). Interacts KSR1 (PubMed:10409742).By similarity2 Publications
Binary interactionsi
GO - Molecular functioni
- PDZ domain binding Source: MGI
- protein complex scaffold Source: BHF-UCL
- scaffold protein binding Source: MGI
Protein-protein interaction databases
| BioGridi | 204950. 5 interactors. |
| DIPi | DIP-454N. |
| IntActi | Q63932. 9 interactors. |
| MINTi | MINT-1518275. |
| STRINGi | 10090.ENSMUSP00000121111. |
Structurei
3D structure databases
| Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
| 1JKY | X-ray | 3.90 | B | 1-16 | [»] | |
| ProteinModelPortali | Q63932. | |||||
| SMRi | Q63932. | |||||
| ModBasei | Search... | |||||
| MobiDBi | Search... | |||||
Family & Domainsi
Domains and Repeats
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Domaini | 72 – 370 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 299 |
Compositional bias
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Compositional biasi | 266 – 316 | Pro-richAdd BLAST | 51 |
Sequence similaritiesi
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.Curated
Phylogenomic databases
| eggNOGi | KOG0581. Eukaryota. ENOG410XQ5A. LUCA. |
| GeneTreei | ENSGT00760000119199. |
| HOGENOMi | HOG000234206. |
| HOVERGENi | HBG108518. |
| InParanoidi | Q63932. |
| KOi | K04369. |
| OMAi | IAGWVCK. |
| OrthoDBi | EOG091G0DEC. |
| TreeFami | TF105137. |
Family and domain databases
| InterProi | View protein in InterPro IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_dom. IPR017441. Protein_kinase_ATP_BS. IPR008271. Ser/Thr_kinase_AS. |
| Pfami | View protein in Pfam PF00069. Pkinase. 1 hit. |
| SMARTi | View protein in SMART SM00220. S_TKc. 1 hit. |
| SUPFAMi | SSF56112. SSF56112. 1 hit. |
| PROSITEi | View protein in PROSITE PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. |
Sequencei
Sequence statusi: Complete.
Q63932-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MLARRKPVLP ALTINPTIAE GPSPTSEGAS EANLVDLQKK LEELDLDEQQ
60 70 80 90 100
RKRLEAFLTQ KAKVGELKDD DFERISELGA GNGGVVTKAR HRPSGLIMAR
110 120 130 140 150
KLIHLEIKPA VRNQIIRELQ VLHECNSPYI VGFYGAFYSD GEISICMEHM
160 170 180 190 200
DGGSLDQVLK EAKRIPEDIL GKVSIAVLRG LAYLREKHQI MHRDVKPSNI
210 220 230 240 250
LVNSRGEIKL CDFGVSGQLI DSMANSFVGT RSYMSPERLQ GTHYSVQSDI
260 270 280 290 300
WSMGLSLVEL AIGRYPIPPP DAKELEASFG RPVVDGADGE PHSVSPRPRP
310 320 330 340 350
PGRPISVGHG MDSRPAMAIF ELLDYIVNEP PPKLPSGVFS SDFQEFVNKC
360 370 380 390 400
LIKNPAERAD LKLLMNHAFI KRSEGEEVDF AGWLCRTLRL KQPSTPTRTA
V
Experimental Info
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sequence conflicti | 96 | L → F in AAC60678 (PubMed:8297798).Curated | 1 |
Sequence databases
| Select the link destinations: EMBLi GenBanki DDBJi Links Updated | S68267 mRNA. Translation: AAC60678.1. AK009392 mRNA. Translation: BAB26261.1. AK080574 mRNA. Translation: BAC37945.1. CH466553 Genomic DNA. Translation: EDL31456.1. |
| CCDSi | CCDS24044.1. |
| RefSeqi | NP_075627.2. NM_023138.5. |
| UniGenei | Mm.275436. |
Genome annotation databases
| Ensembli | ENSMUST00000143517; ENSMUSP00000121111; ENSMUSG00000035027. |
| GeneIDi | 26396. |
| KEGGi | mmu:26396. |
| UCSCi | uc007gfx.2. mouse. |
Similar proteinsi
Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:| 100% | UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry. |
| 90% | UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence). |
| 50% | UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster. |
Entry informationi
| Entry namei | MP2K2_MOUSE | |
| Accessioni | Q63932Primary (citable) accession number: Q63932 Secondary accession number(s): Q9D7B0 | |
| Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
| Last sequence update: | July 27, 2011 | |
| Last modified: | July 5, 2017 | |
| This is version 151 of the entry and version 2 of the sequence. See complete history. | ||
| Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
| Annotation program | Chordata Protein Annotation Program | |
Miscellaneousi
Keywords - Technical termi
3D-structure, Complete proteome, Direct protein sequencing, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - Human and mouse protein kinases
Human and mouse protein kinases: classification and index - SIMILARITY comments
Index of protein domains and families
