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Protein

Dual specificity mitogen-activated protein kinase kinase 2

Gene

Map2k2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei101ATP1
Active sitei194Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi78 – 86ATPPROSITE-ProRule annotation9

GO - Molecular functioni

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 axon regeneration Source: MGI
  • regulation of early endosome to late endosome transport Source: UniProtKB
  • regulation of Golgi inheritance Source: UniProtKB
  • 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
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.12.2. 3474.
ReactomeiR-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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1346867. Map2k2.

Subcellular locationi

GO - Cellular componenti

  • cell-cell junction Source: MGI
  • cell cortex Source: Ensembl
  • cytoplasm Source: MGI
  • cytoplasmic side of plasma membrane Source: MGI
  • cytosol Source: UniProtKB
  • early endosome Source: UniProtKB
  • endoplasmic reticulum Source: MGI
  • focal adhesion Source: UniProtKB
  • Golgi apparatus Source: UniProtKB
  • late endosome Source: UniProtKB
  • microtubule Source: MGI
  • mitochondrion Source: UniProtKB
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: MGI
  • peroxisomal membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi101K → M: Inactivation. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000863731 – 401Dual specificity mitogen-activated protein kinase kinase 2Add BLAST401

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei23PhosphoserineBy similarity1
Modified residuei222Phosphoserine; by RAF1 Publication1
Modified residuei226Phosphoserine; by RAFBy similarity1
Modified residuei293PhosphoserineBy similarity1
Modified residuei295PhosphoserineBy similarity1
Modified residuei306PhosphoserineBy similarity1
Modified residuei395PhosphothreonineBy similarity1
Modified residuei397PhosphothreonineBy similarity1

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 keyPosition(s)DescriptionActionsGraphical viewLength
Sitei10 – 11Cleavage; by anthrax lethal factorBy similarity2

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ63932.
MaxQBiQ63932.
PaxDbiQ63932.
PeptideAtlasiQ63932.
PRIDEiQ63932.

PTM databases

iPTMnetiQ63932.
PhosphoSitePlusiQ63932.

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

BgeeiENSMUSG00000035027.
CleanExiMM_MAP2K2.
ExpressionAtlasiQ63932. baseline and differential.
GenevisibleiQ63932. MM.

Interactioni

Subunit structurei

Interacts with MORG1 (PubMed:15118098). Interacts with SGK1 (By similarity). Interacts KSR1 (PubMed:10409742).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ARHGAP8P85298-45EBI-397724,EBI-9523517From a different organism.
PIN1Q1352612EBI-397724,EBI-714158From a different organism.
Rgs12Q8CGE93EBI-397724,EBI-7340552

GO - Molecular functioni

  • PDZ domain binding Source: MGI
  • protein complex scaffold Source: BHF-UCL
  • scaffold protein binding Source: MGI

Protein-protein interaction databases

BioGridi204950. 5 interactors.
DIPiDIP-454N.
IntActiQ63932. 9 interactors.
MINTiMINT-1518275.
STRINGi10090.ENSMUSP00000121111.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1JKYX-ray3.90B1-16[»]
ProteinModelPortaliQ63932.
SMRiQ63932.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini72 – 370Protein kinasePROSITE-ProRule annotationAdd BLAST299

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi266 – 316Pro-richAdd BLAST51

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0581. Eukaryota.
ENOG410XQ5A. LUCA.
GeneTreeiENSGT00760000119199.
HOGENOMiHOG000234206.
HOVERGENiHBG108518.
InParanoidiQ63932.
KOiK04369.
OMAiEGASEAH.
OrthoDBiEOG091G0DEC.
TreeFamiTF105137.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q63932-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:401
Mass (Da):44,402
Last modified:July 27, 2011 - v2
Checksum:iF00CD807E86F5B26
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti96L → F in AAC60678 (PubMed:8297798).Curated1

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.
CCDSiCCDS24044.1.
RefSeqiNP_075627.2. NM_023138.4.
UniGeneiMm.275436.

Genome annotation databases

EnsembliENSMUST00000143517; ENSMUSP00000121111; ENSMUSG00000035027.
GeneIDi26396.
KEGGimmu:26396.
UCSCiuc007gfx.2. mouse.

Cross-referencesi

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.
CCDSiCCDS24044.1.
RefSeqiNP_075627.2. NM_023138.4.
UniGeneiMm.275436.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1JKYX-ray3.90B1-16[»]
ProteinModelPortaliQ63932.
SMRiQ63932.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204950. 5 interactors.
DIPiDIP-454N.
IntActiQ63932. 9 interactors.
MINTiMINT-1518275.
STRINGi10090.ENSMUSP00000121111.

PTM databases

iPTMnetiQ63932.
PhosphoSitePlusiQ63932.

Proteomic databases

EPDiQ63932.
MaxQBiQ63932.
PaxDbiQ63932.
PeptideAtlasiQ63932.
PRIDEiQ63932.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000143517; ENSMUSP00000121111; ENSMUSG00000035027.
GeneIDi26396.
KEGGimmu:26396.
UCSCiuc007gfx.2. mouse.

Organism-specific databases

CTDi5605.
MGIiMGI:1346867. Map2k2.

Phylogenomic databases

eggNOGiKOG0581. Eukaryota.
ENOG410XQ5A. LUCA.
GeneTreeiENSGT00760000119199.
HOGENOMiHOG000234206.
HOVERGENiHBG108518.
InParanoidiQ63932.
KOiK04369.
OMAiEGASEAH.
OrthoDBiEOG091G0DEC.
TreeFamiTF105137.

Enzyme and pathway databases

BRENDAi2.7.12.2. 3474.
ReactomeiR-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.

Miscellaneous databases

ChiTaRSiMap2k2. mouse.
PROiQ63932.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000035027.
CleanExiMM_MAP2K2.
ExpressionAtlasiQ63932. baseline and differential.
GenevisibleiQ63932. MM.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMP2K2_MOUSE
AccessioniPrimary (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: November 2, 2016
This is version 146 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  4. SIMILARITY comments
    Index of protein domains and families

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.