UniProtKB - P36507 (MP2K2_HUMAN)
Protein
Dual specificity mitogen-activated protein kinase kinase 2
Gene
MAP2K2
Organism
Homo sapiens (Human)
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 (By similarity). Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation (PubMed:29433126).By similarity1 Publication
Catalytic activityi
Cofactori
Mg2+1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 101 | ATPPROSITE-ProRule annotation | 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: UniProtKB
- MAP-kinase scaffold activity Source: UniProtKB
- metal ion binding Source: UniProtKB-KW
- PDZ domain binding Source: UniProtKB
- protein serine/threonine/tyrosine kinase activity Source: UniProtKB
- protein serine/threonine kinase activator activity Source: UniProtKB
- protein serine/threonine kinase activity Source: Reactome
- protein tyrosine kinase activity Source: UniProtKB-KW
- scaffold protein binding Source: UniProtKB
GO - Biological processi
- activation of MAPK activity Source: GO_Central
- ERK1 and ERK2 cascade Source: BHF-UCL
- MAPK cascade Source: Reactome
- negative regulation of gene expression Source: UniProtKB
- peptidyl-serine autophosphorylation Source: UniProtKB
- positive regulation of production of miRNAs involved in gene silencing by miRNA Source: BHF-UCL
- positive regulation of protein serine/threonine kinase activity Source: UniProtKB
- positive regulation of transcription, DNA-templated Source: BHF-UCL
- regulation of early endosome to late endosome transport Source: UniProtKB
- regulation of Golgi inheritance Source: UniProtKB
- regulation of stress-activated MAPK cascade Source: UniProtKB
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, 2681 |
PathwayCommonsi | P36507 |
Reactomei | R-HSA-112411, MAPK1 (ERK2) activation R-HSA-170968, Frs2-mediated activation R-HSA-445144, Signal transduction by L1 R-HSA-5210891, Uptake and function of anthrax toxins R-HSA-5673000, RAF activation R-HSA-5674135, MAP2K and MAPK activation R-HSA-5674499, Negative feedback regulation of MAPK pathway R-HSA-6802946, Signaling by moderate kinase activity BRAF mutants R-HSA-6802948, Signaling by high-kinase activity BRAF mutants R-HSA-6802952, Signaling by BRAF and RAF fusions R-HSA-6802955, Paradoxical activation of RAF signaling by kinase inactive BRAF R-HSA-9649948, Signaling downstream of RAS mutants R-HSA-9652169, Signaling by MAP2K mutants R-HSA-9656223, Signaling by RAF1 mutants |
SignaLinki | P36507 |
SIGNORi | P36507 |
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 | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000126934.13 |
HGNCi | HGNC:6842, MAP2K2 |
MIMi | 601263, gene |
neXtProti | NX_P36507 |
Subcellular locationi
Other locations
- Cytoplasm 1 Publication
- Membrane 1 Publication; Peripheral membrane protein 1 Publication
Note: Membrane localization is probably regulated by its interaction with KSR1.1 Publication
Cytoskeleton
- microtubule Source: UniProtKB
Cytosol
- cytosol Source: UniProtKB
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB
Endosome
- early endosome Source: UniProtKB
- late endosome Source: UniProtKB
Extracellular region or secreted
- extracellular region Source: UniProtKB
Golgi apparatus
- Golgi apparatus Source: UniProtKB
Mitochondrion
- mitochondrion Source: UniProtKB
Nucleus
- nucleus Source: UniProtKB
Peroxisome
- peroxisomal membrane Source: UniProtKB
Plasma Membrane
- cytoplasmic side of plasma membrane Source: UniProtKB
Other locations
- cell-cell junction Source: UniProtKB
- focal adhesion Source: UniProtKB
- perinuclear region of cytoplasm Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, MembranePathology & Biotechi
Involvement in diseasei
Cardiofaciocutaneous syndrome 4 (CFC4)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of cardiofaciocutaneous syndrome, a multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_035095 | 57 | F → C in CFC4. 1 PublicationCorresponds to variant dbSNP:rs121434497EnsemblClinVar. | 1 | |
Natural variantiVAR_069781 | 57 | F → V in CFC4. 1 PublicationCorresponds to variant dbSNP:rs121434498EnsemblClinVar. | 1 | |
Natural variantiVAR_069782 | 128 | P → Q in CFC4; results in increased kinase activity. 1 PublicationCorresponds to variant dbSNP:rs267607230EnsemblClinVar. | 1 | |
Natural variantiVAR_069783 | 134 | Y → H in CFC4. 1 PublicationCorresponds to variant dbSNP:rs121434499EnsemblClinVar. | 1 |
Keywords - Diseasei
Cardiomyopathy, Disease mutation, Ectodermal dysplasia, Mental retardationOrganism-specific databases
DisGeNETi | 5605 |
GeneReviewsi | MAP2K2 |
MalaCardsi | MAP2K2 |
MIMi | 615280, phenotype |
OpenTargetsi | ENSG00000126934 |
Orphaneti | 1340, Cardiofaciocutaneous syndrome 638, Neurofibromatosis-Noonan syndrome |
PharmGKBi | PA30587 |
Miscellaneous databases
Pharosi | P36507, Tclin |
Chemistry databases
ChEMBLi | CHEMBL2964 |
DrugBanki | DB11967, Binimetinib DB06616, Bosutinib DB12010, Fostamatinib DB11689, Selumetinib DB08911, Trametinib |
DrugCentrali | P36507 |
GuidetoPHARMACOLOGYi | 2063 |
Polymorphism and mutation databases
BioMutai | MAP2K2 |
DMDMi | 547915 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086372 | 1 – 400 | Dual specificity mitogen-activated protein kinase kinase 2Add BLAST | 400 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1 | N-acetylmethionineCombined sources | 1 | |
Modified residuei | 23 | PhosphoserineCombined sources | 1 | |
Modified residuei | 222 | (Microbial infection) O-acetylserine; by Yersinia YopJ; alternate1 Publication | 1 | |
Modified residuei | 222 | Phosphoserine; by RAF; alternate2 Publications | 1 | |
Modified residuei | 226 | (Microbial infection) O-acetylserine; by Yersinia YopJ; alternate1 Publication | 1 | |
Modified residuei | 226 | Phosphoserine; alternate1 Publication | 1 | |
Modified residuei | 293 | PhosphoserineCombined sources | 1 | |
Modified residuei | 295 | PhosphoserineCombined sources | 1 | |
Modified residuei | 306 | PhosphoserineBy similarity | 1 | |
Modified residuei | 394 | PhosphothreonineCombined sources1 Publication | 1 | |
Modified residuei | 396 | PhosphothreonineCombined sources | 1 |
Post-translational modificationi
MAPKK is itself dependent on Ser/Thr phosphorylation for activity catalyzed by MAP kinase kinase kinases (RAF or MEKK1). Phosphorylated by MAP2K1/MEK1 (By similarity).By similarity
(Microbial infection) Acetylation of Ser-222 and Ser-226 by Yersinia YopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway.2 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 10 – 11 | Cleavage; by anthrax lethal factor | 2 |
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
CPTACi | CPTAC-1045 CPTAC-1543 CPTAC-811 CPTAC-812 CPTAC-813 |
EPDi | P36507 |
jPOSTi | P36507 |
MassIVEi | P36507 |
MaxQBi | P36507 |
PaxDbi | P36507 |
PeptideAtlasi | P36507 |
PRIDEi | P36507 |
ProteomicsDBi | 55203 |
2D gel databases
REPRODUCTION-2DPAGEi | IPI00003783 |
PTM databases
iPTMneti | P36507 |
MetOSitei | P36507 |
PhosphoSitePlusi | P36507 |
SwissPalmi | P36507 |
Expressioni
Gene expression databases
Bgeei | ENSG00000126934, Expressed in testis and 245 other tissues |
ExpressionAtlasi | P36507, baseline and differential |
Genevisiblei | P36507, HS |
Organism-specific databases
HPAi | ENSG00000126934, Low tissue specificity |
Interactioni
Subunit structurei
Binary interactionsi
Hide detailsP36507
GO - Molecular functioni
- MAP-kinase scaffold activity Source: UniProtKB
- PDZ domain binding Source: UniProtKB
- scaffold protein binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 111591, 65 interactors |
CORUMi | P36507 |
DIPi | DIP-29119N |
IntActi | P36507, 64 interactors |
MINTi | P36507 |
STRINGi | 9606.ENSP00000262948 |
Chemistry databases
BindingDBi | P36507 |
Miscellaneous databases
RNActi | P36507, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P36507 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P36507 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 72 – 369 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 298 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 266 – 315 | Pro-richAdd BLAST | 50 |
Sequence similaritiesi
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.Curated
Phylogenomic databases
eggNOGi | KOG0581, Eukaryota |
GeneTreei | ENSGT00940000153487 |
InParanoidi | P36507 |
OMAi | VEMSIGR |
OrthoDBi | 688282at2759 |
PhylomeDBi | P36507 |
TreeFami | TF105137 |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf 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 |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
P36507-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MLARRKPVLP ALTINPTIAE GPSPTSEGAS EANLVDLQKK LEELELDEQQ
60 70 80 90 100
KKRLEAFLTQ KAKVGELKDD DFERISELGA GNGGVVTKVQ HRPSGLIMAR
110 120 130 140 150
KLIHLEIKPA IRNQIIRELQ VLHECNSPYI VGFYGAFYSD GEISICMEHM
160 170 180 190 200
DGGSLDQVLK EAKRIPEEIL GKVSIAVLRG LAYLREKHQI MHRDVKPSNI
210 220 230 240 250
LVNSRGEIKL CDFGVSGQLI DSMANSFVGT RSYMAPERLQ GTHYSVQSDI
260 270 280 290 300
WSMGLSLVEL AVGRYPIPPP DAKELEAIFG RPVVDGEEGE PHSISPRPRP
310 320 330 340 350
PGRPVSGHGM DSRPAMAIFE LLDYIVNEPP PKLPNGVFTP DFQEFVNKCL
360 370 380 390 400
IKNPAERADL KMLTNHTFIK RSEVEEVDFA GWLCKTLRLN QPGTPTRTAV
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketG5E9C7 | G5E9C7_HUMAN | Dual-specificity mitogen-activated ... | MAP2K2 hCG_23544 | 303 | Annotation score: | ||
M0R1B6 | M0R1B6_HUMAN | Dual-specificity mitogen-activated ... | MAP2K2 | 104 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 56 | A → R AA sequence (PubMed:10409742).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_035095 | 57 | F → C in CFC4. 1 PublicationCorresponds to variant dbSNP:rs121434497EnsemblClinVar. | 1 | |
Natural variantiVAR_069781 | 57 | F → V in CFC4. 1 PublicationCorresponds to variant dbSNP:rs121434498EnsemblClinVar. | 1 | |
Natural variantiVAR_069782 | 128 | P → Q in CFC4; results in increased kinase activity. 1 PublicationCorresponds to variant dbSNP:rs267607230EnsemblClinVar. | 1 | |
Natural variantiVAR_069783 | 134 | Y → H in CFC4. 1 PublicationCorresponds to variant dbSNP:rs121434499EnsemblClinVar. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L11285 mRNA No translation available. BC000471 mRNA Translation: AAH00471.1 BC018645 mRNA Translation: AAH18645.1 |
CCDSi | CCDS12120.1 |
PIRi | A46723 |
RefSeqi | NP_109587.1, NM_030662.3 |
Genome annotation databases
Ensembli | ENST00000262948; ENSP00000262948; ENSG00000126934 |
GeneIDi | 5605 |
KEGGi | hsa:5605 |
UCSCi | uc002lzk.4, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L11285 mRNA No translation available. BC000471 mRNA Translation: AAH00471.1 BC018645 mRNA Translation: AAH18645.1 |
CCDSi | CCDS12120.1 |
PIRi | A46723 |
RefSeqi | NP_109587.1, NM_030662.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1S9I | X-ray | 3.20 | A/B | 55-400 | [»] | |
4H3Q | X-ray | 2.20 | B | 4-16 | [»] | |
SMRi | P36507 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 111591, 65 interactors |
CORUMi | P36507 |
DIPi | DIP-29119N |
IntActi | P36507, 64 interactors |
MINTi | P36507 |
STRINGi | 9606.ENSP00000262948 |
Chemistry databases
BindingDBi | P36507 |
ChEMBLi | CHEMBL2964 |
DrugBanki | DB11967, Binimetinib DB06616, Bosutinib DB12010, Fostamatinib DB11689, Selumetinib DB08911, Trametinib |
DrugCentrali | P36507 |
GuidetoPHARMACOLOGYi | 2063 |
PTM databases
iPTMneti | P36507 |
MetOSitei | P36507 |
PhosphoSitePlusi | P36507 |
SwissPalmi | P36507 |
Polymorphism and mutation databases
BioMutai | MAP2K2 |
DMDMi | 547915 |
2D gel databases
REPRODUCTION-2DPAGEi | IPI00003783 |
Proteomic databases
CPTACi | CPTAC-1045 CPTAC-1543 CPTAC-811 CPTAC-812 CPTAC-813 |
EPDi | P36507 |
jPOSTi | P36507 |
MassIVEi | P36507 |
MaxQBi | P36507 |
PaxDbi | P36507 |
PeptideAtlasi | P36507 |
PRIDEi | P36507 |
ProteomicsDBi | 55203 |
Protocols and materials databases
Antibodypediai | 3543, 1338 antibodies |
DNASUi | 5605 |
Genome annotation databases
Ensembli | ENST00000262948; ENSP00000262948; ENSG00000126934 |
GeneIDi | 5605 |
KEGGi | hsa:5605 |
UCSCi | uc002lzk.4, human |
Organism-specific databases
CTDi | 5605 |
DisGeNETi | 5605 |
EuPathDBi | HostDB:ENSG00000126934.13 |
GeneCardsi | MAP2K2 |
GeneReviewsi | MAP2K2 |
HGNCi | HGNC:6842, MAP2K2 |
HPAi | ENSG00000126934, Low tissue specificity |
MalaCardsi | MAP2K2 |
MIMi | 601263, gene 615280, phenotype |
neXtProti | NX_P36507 |
OpenTargetsi | ENSG00000126934 |
Orphaneti | 1340, Cardiofaciocutaneous syndrome 638, Neurofibromatosis-Noonan syndrome |
PharmGKBi | PA30587 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0581, Eukaryota |
GeneTreei | ENSGT00940000153487 |
InParanoidi | P36507 |
OMAi | VEMSIGR |
OrthoDBi | 688282at2759 |
PhylomeDBi | P36507 |
TreeFami | TF105137 |
Enzyme and pathway databases
BRENDAi | 2.7.12.2, 2681 |
PathwayCommonsi | P36507 |
Reactomei | R-HSA-112411, MAPK1 (ERK2) activation R-HSA-170968, Frs2-mediated activation R-HSA-445144, Signal transduction by L1 R-HSA-5210891, Uptake and function of anthrax toxins R-HSA-5673000, RAF activation R-HSA-5674135, MAP2K and MAPK activation R-HSA-5674499, Negative feedback regulation of MAPK pathway R-HSA-6802946, Signaling by moderate kinase activity BRAF mutants R-HSA-6802948, Signaling by high-kinase activity BRAF mutants R-HSA-6802952, Signaling by BRAF and RAF fusions R-HSA-6802955, Paradoxical activation of RAF signaling by kinase inactive BRAF R-HSA-9649948, Signaling downstream of RAS mutants R-HSA-9652169, Signaling by MAP2K mutants R-HSA-9656223, Signaling by RAF1 mutants |
SignaLinki | P36507 |
SIGNORi | P36507 |
Miscellaneous databases
BioGRID-ORCSi | 5605, 19 hits in 871 CRISPR screens |
ChiTaRSi | MAP2K2, human |
EvolutionaryTracei | P36507 |
GeneWikii | MAP2K2 |
GenomeRNAii | 5605 |
Pharosi | P36507, Tclin |
PROi | PR:P36507 |
RNActi | P36507, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000126934, Expressed in testis and 245 other tissues |
ExpressionAtlasi | P36507, baseline and differential |
Genevisiblei | P36507, HS |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf 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 |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | MP2K2_HUMAN | |
Accessioni | P36507Primary (citable) accession number: P36507 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 1, 1994 |
Last sequence update: | June 1, 1994 | |
Last modified: | December 2, 2020 | |
This is version 228 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - Human and mouse protein kinases
Human and mouse protein kinases: classification and index