Human Gene MAP2K2 (ENST00000262948.10) from GENCODE V39
  Description: Homo sapiens mitogen-activated protein kinase kinase 2 (MAP2K2), mRNA. (from RefSeq NM_030662)
RefSeq Summary (NM_030662): The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is known to play a critical role in mitogen growth factor signal transduction. It phosphorylates and thus activates MAPK1/ERK2 and MAPK2/ERK3. The activation of this kinase itself is dependent on the Ser/Thr phosphorylation by MAP kinase kinase kinases. Mutations in this gene cause cardiofaciocutaneous syndrome (CFC syndrome), a disease characterized by heart defects, cognitive disability, and distinctive facial features similar to those found in Noonan syndrome. The inhibition or degradation of this kinase is also found to be involved in the pathogenesis of Yersinia and anthrax. A pseudogene, which is located on chromosome 7, has been identified for this gene. [provided by RefSeq, Jul 2008].
Gencode Transcript: ENST00000262948.10
Gencode Gene: ENSG00000126934.15
Transcript (Including UTRs)
   Position: hg38 chr19:4,090,321-4,124,122 Size: 33,802 Total Exon Count: 11 Strand: -
Coding Region
   Position: hg38 chr19:4,090,598-4,123,875 Size: 33,278 Coding Exon Count: 11 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesGeneReviewsMethods
Data last updated at UCSC: 2022-01-17 08:30:34

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr19:4,090,321-4,124,122)mRNA (may differ from genome)Protein (400 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGencodeGeneCards

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Dual specificity mitogen-activated protein kinase kinase 2; Short=MAP kinase kinase 2; Short=MAPKK 2; EC=; AltName: Full=ERK activator kinase 2; AltName: Full=MAPK/ERK kinase 2; Short=MEK 2;
FUNCTION: 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).
CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
SUBUNIT: Interacts with MORG1 (By similarity). Interacts with SGK1.
INTERACTION: P10398:ARAF; NbExp=4; IntAct=EBI-1056930, EBI-365961;
PTM: 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).
PTM: Acetylation of Ser-222 and Ser-226 by Yersinia yopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway.
DISEASE: Defects in MAP2K2 are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:115150]; also known as cardio-facio- cutaneous syndrome. CFC syndrome is 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. The inheritance of CFC syndrome is autosomal dominant.
SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.
SIMILARITY: Contains 1 protein kinase domain.
WEB RESOURCE: Name=GeneReviews; URL="";

-  MalaCards Disease Associations
  MalaCards Gene Search: MAP2K2
Diseases sorted by gene-association score: cardiofaciocutaneous syndrome 4* (1229), cardiofaciocutaneous syndrome* (650), neurofibromatosis-noonan syndrome* (247), map2k2-related cardiofaciocutaneous syndrome* (100), lambdoid synostosis (18), costello syndrome (12), retinitis pigmentosa 27 (11), drug addiction (10), dyschromatosis universalis hereditaria (8), noonan syndrome 1 (7), pulmonic stenosis (6), anthrax disease (6), skin papilloma (6), mental retardation and microcephaly with pontine and cerebellar hypoplasia (5), colorectal cancer (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 88.91 RPKM in Testis
Total median expression: 2050.31 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -132.60247-0.537 Picture PostScript Text
3' UTR -116.40277-0.420 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
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 Domains:
PF00069 - Protein kinase domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1S9I - X-ray MuPIT

ModBase Predicted Comparative 3D Structure on P36507
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserGenome BrowserNo orthologNo orthologGenome Browser
Gene Details    Gene Details
Gene Sorter    Gene Sorter
Protein SequenceProtein SequenceProtein Sequence  Protein Sequence
AlignmentAlignmentAlignment  Alignment

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004708 MAP kinase kinase activity
GO:0004712 protein serine/threonine/tyrosine kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0030165 PDZ domain binding
GO:0043539 protein serine/threonine kinase activator activity
GO:0046872 metal ion binding
GO:0097110 scaffold protein binding

Biological Process:
GO:0000165 MAPK cascade
GO:0000187 activation of MAPK activity
GO:0006468 protein phosphorylation
GO:0007346 regulation of mitotic cell cycle
GO:0010629 negative regulation of gene expression
GO:0016310 phosphorylation
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0032872 regulation of stress-activated MAPK cascade
GO:0036289 peptidyl-serine autophosphorylation
GO:0042981 regulation of apoptotic process
GO:0045893 positive regulation of transcription, DNA-templated
GO:0070371 ERK1 and ERK2 cascade
GO:0071902 positive regulation of protein serine/threonine kinase activity
GO:0090170 regulation of Golgi inheritance
GO:1903800 positive regulation of production of miRNAs involved in gene silencing by miRNA
GO:2000641 regulation of early endosome to late endosome transport

Cellular Component:
GO:0005576 extracellular region
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005769 early endosome
GO:0005770 late endosome
GO:0005778 peroxisomal membrane
GO:0005783 endoplasmic reticulum
GO:0005794 Golgi apparatus
GO:0005829 cytosol
GO:0005874 microtubule
GO:0005911 cell-cell junction
GO:0005925 focal adhesion
GO:0009898 cytoplasmic side of plasma membrane
GO:0016020 membrane
GO:0048471 perinuclear region of cytoplasm

-  Descriptions from all associated GenBank mRNAs
  BC018645 - Homo sapiens mitogen-activated protein kinase kinase 2, mRNA (cDNA clone MGC:16530 IMAGE:4025987), complete cds.
BX538081 - Homo sapiens mRNA; cDNA DKFZp686L02273 (from clone DKFZp686L02273); complete cds.
BC000471 - Homo sapiens mitogen-activated protein kinase kinase 2, mRNA (cDNA clone MGC:8600 IMAGE:2961198), complete cds.
AK129586 - Homo sapiens cDNA FLJ26075 fis, clone RCT02312.
AK126446 - Homo sapiens cDNA FLJ44482 fis, clone UTERU2033172, moderately similar to DUAL SPECIFICITY MITOGEN-ACTIVATED PROTEIN KINASE KINASE 2.
AK093125 - Homo sapiens cDNA FLJ35806 fis, clone TESTI2005987, highly similar to Dual specificity mitogen-activated protein kinase kinase 2 (EC
L11285 - Homosapiens ERK activator kinase (MEK2) mRNA.
JD233429 - Sequence 214453 from Patent EP1572962.
JD409030 - Sequence 390054 from Patent EP1572962.
LF381965 - JP 2014500723-A/189468: Polycomb-Associated Non-Coding RNAs.
MA617542 - JP 2018138019-A/189468: Polycomb-Associated Non-Coding RNAs.
JD460041 - Sequence 441065 from Patent EP1572962.
JD478217 - Sequence 459241 from Patent EP1572962.
JD542007 - Sequence 523031 from Patent EP1572962.
JD532844 - Sequence 513868 from Patent EP1572962.
JD199376 - Sequence 180400 from Patent EP1572962.
JD128898 - Sequence 109922 from Patent EP1572962.
JD405781 - Sequence 386805 from Patent EP1572962.
JD270777 - Sequence 251801 from Patent EP1572962.
JD322585 - Sequence 303609 from Patent EP1572962.
JD365373 - Sequence 346397 from Patent EP1572962.
KJ905296 - Synthetic construct Homo sapiens clone ccsbBroadEn_14808 MAP2K2 gene, encodes complete protein.
JD104651 - Sequence 85675 from Patent EP1572962.
DQ893601 - Synthetic construct clone IMAGE:100006231; FLH180783.01X; RZPDo839F12134D mitogen-activated protein kinase kinase 2 (MAP2K2) gene, encodes complete protein.
DQ895060 - Synthetic construct Homo sapiens clone IMAGE:100009520; FLH180779.01L; RZPDo839F12133D mitogen-activated protein kinase kinase 2 (MAP2K2) gene, encodes complete protein.
AB463893 - Synthetic construct DNA, clone: pF1KB6564, Homo sapiens MAP2K2 gene for mitogen-activated protein kinase kinase 2, without stop codon, in Flexi system.
JD024458 - Sequence 5482 from Patent EP1572962.
JD035417 - Sequence 16441 from Patent EP1572962.
JD022027 - Sequence 3051 from Patent EP1572962.
JD022028 - Sequence 3052 from Patent EP1572962.
JD028374 - Sequence 9398 from Patent EP1572962.
JD035835 - Sequence 16859 from Patent EP1572962.
JD458553 - Sequence 439577 from Patent EP1572962.
JD212042 - Sequence 193066 from Patent EP1572962.
JD142282 - Sequence 123306 from Patent EP1572962.
JD128876 - Sequence 109900 from Patent EP1572962.
JD106498 - Sequence 87522 from Patent EP1572962.
JD390928 - Sequence 371952 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04010 - MAPK signaling pathway
hsa04012 - ErbB signaling pathway
hsa04270 - Vascular smooth muscle contraction
hsa04370 - VEGF signaling pathway
hsa04540 - Gap junction
hsa04620 - Toll-like receptor signaling pathway
hsa04650 - Natural killer cell mediated cytotoxicity
hsa04660 - T cell receptor signaling pathway
hsa04662 - B cell receptor signaling pathway
hsa04664 - Fc epsilon RI signaling pathway
hsa04720 - Long-term potentiation
hsa04722 - Neurotrophin signaling pathway
hsa04730 - Long-term depression
hsa04810 - Regulation of actin cytoskeleton
hsa04910 - Insulin signaling pathway
hsa04912 - GnRH signaling pathway
hsa04916 - Melanogenesis
hsa05020 - Prion diseases
hsa05200 - Pathways in cancer
hsa05211 - Renal cell carcinoma
hsa05213 - Endometrial cancer
hsa05214 - Glioma
hsa05215 - Prostate cancer
hsa05216 - Thyroid cancer
hsa05218 - Melanoma
hsa05219 - Bladder cancer
hsa05220 - Chronic myeloid leukemia
hsa05221 - Acute myeloid leukemia
hsa05223 - Non-small cell lung cancer

BioCyc Knowledge Library
PWY66-14 - MAP kinase cascade

BioCarta from NCI Cancer Genome Anatomy Project
h_erkPathway - Erk1/Erk2 Mapk Signaling pathway
h_mapkPathway - MAPKinase Signaling Pathway
h_At1rPathway - Angiotensin II mediated activation of JNK Pathway via Pyk2 dependent signaling
h_hcmvPathway - Human Cytomegalovirus and Map Kinase Pathways
h_anthraxPathway - Anthrax Toxin Mechanism of Action
h_integrinPathway - Integrin Signaling Pathway
h_cdk5Pathway - Phosphorylation of MEK1 by cdk5/p35 down regulates the MAP kinase pathway
h_pyk2Pathway - Links between Pyk2 and Map Kinases
h_bArrestin-srcPathway - Roles of -arrestin-dependent Recruitment of Src Kinases in GPCR Signaling
h_malPathway - Role of MAL in Rho-Mediated Activation of SRF
h_barr-mapkPathway - Role of -arrestins in the activation and targeting of MAP kinases
h_biopeptidesPathway - Bioactive Peptide Induced Signaling Pathway
h_metPathway - Signaling of Hepatocyte Growth Factor Receptor
h_fMLPpathway - fMLP induced chemokine gene expression in HMC-1 cells

Reactome (by CSHL, EBI, and GO)

Protein P36507 (Reactome details) participates in the following event(s):

R-HSA-5211356 Anthrax LF cleaves target cell MAP2K2 (MEK2)
R-HSA-109858 MAP2K2 binds MAPK1
R-HSA-109864 Dissociation of p-T,Y-MAPK1:p-S,T-MAP2K2
R-HSA-109862 MAP2K2 phosphorylates MAPK1
R-HSA-5674496 Activated MAPKs phosphorylate MAP2K1
R-HSA-5672972 MAP2Ks and MAPKs bind to the activated RAF complex
R-HSA-5674132 WDR83:LAMTOR2:LAMTOR3 binds MAPK components
R-HSA-6802912 High kinase activity BRAF mutants bind MAP2Ks and MAPKs
R-HSA-6802914 RAS:GTP:moderate kinase activity p-RAF complexes bind MAP2Ks and MAPKs
R-HSA-6802925 Mutant RAS:p-RAF complexes bind MAP2Ks and MAPKs
R-HSA-6802934 p-BRAF and RAF fusion dimers bind MAP2Ks and MAPKs
R-HSA-6802942 RAS:GTP:p-RAF complexes paradoxically bind MAP2Ks and MAPKs
R-HSA-5674366 IL17RD binds p-2S MAP2Ks and MAPKs
R-HSA-5672980 Dissociation of RAS:RAF complex
R-HSA-6802932 Dissociation of BRAF/RAF fusion complex
R-HSA-6803227 Dissociation of high activity BRAF complexes
R-HSA-6803230 Dissociation of moderate activity BRAF complexes
R-HSA-6803233 Dissociation of oncogenic RAS:RAF complex
R-HSA-6803234 Dissociation of paradoxically activated RAS:BRAF complexes
R-HSA-5672978 RAF phosphorylates MAP2K dimer
R-HSA-6802943 RAS:GTP:inactive p-RAF complexes phosphorylate MAP2Ks
R-HSA-6802919 RAS:GTP:moderate kinase activity p-RAF complexes phosphorylate MAP2Ks
R-HSA-6802911 High kinase activity BRAF complexes phosphorylate MAP2Ks
R-HSA-6802926 Mutant RAS:p-RAF complexes phosphorylate MAP2Ks
R-HSA-6802933 p-BRAF and RAF fusion dimers phosphorylate MAP2Ks
R-HSA-5672973 MAP2Ks phosphorylate MAPKs
R-HSA-5674373 MAP2Ks phosphorylate MAPK at the Golgi membrane
R-HSA-6802918 Activated MAP2Ks phosphorylate MAPKs downstream of inactive BRAF mutants
R-HSA-6802921 Activated MAP2Ks phosphorylate MAPKs downstream of moderate kinase activity BRAF mutants
R-HSA-6802910 Activated MAP2Ks phosphorylate MAPKs downstream of high kinase activity BRAF mutants
R-HSA-6802922 Activated MAP2Ks phosphorylate MAPKs downstream of oncogenic RAS
R-HSA-6802935 MAPKs are phosphorylated downstream of BRAF and RAF fusion dimers
R-HSA-5672969 Phosphorylation of RAF
R-HSA-6802916 RAF is phosphorylated downstream of moderate kinase activity BRAF mutants
R-HSA-6802924 RAF is phosphorylated downstream of oncogenic RAS
R-HSA-6802927 BRAF and RAF fusion mutant dimers are phosphorylated
R-HSA-6802941 RAF is paradoxically phosphorylated downstream of kinase-inactive RAF
R-HSA-5210891 Uptake and function of anthrax toxins
R-HSA-112411 MAPK1 (ERK2) activation
R-HSA-5339562 Uptake and actions of bacterial toxins
R-HSA-445144 Signal transduction by L1
R-HSA-112409 RAF-independent MAPK1/3 activation
R-HSA-5674499 Negative feedback regulation of MAPK pathway
R-HSA-5674135 MAP2K and MAPK activation
R-HSA-6802948 Signaling by high-kinase activity BRAF mutants
R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants
R-HSA-6802949 Signaling by RAS mutants
R-HSA-6802952 Signaling by BRAF and RAF fusions
R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF
R-HSA-5663205 Infectious disease
R-HSA-373760 L1CAM interactions
R-HSA-5684996 MAPK1/MAPK3 signaling
R-HSA-5675221 Negative regulation of MAPK pathway
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-6802957 Oncogenic MAPK signaling
R-HSA-1643685 Disease
R-HSA-422475 Axon guidance
R-HSA-5683057 MAPK family signaling cascades
R-HSA-5663202 Diseases of signal transduction
R-HSA-1266738 Developmental Biology
R-HSA-162582 Signal Transduction
R-HSA-5673000 RAF activation

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000262948.1, ENST00000262948.2, ENST00000262948.3, ENST00000262948.4, ENST00000262948.5, ENST00000262948.6, ENST00000262948.7, ENST00000262948.8, ENST00000262948.9, MEK2, MKK2, MP2K2_HUMAN, NM_030662, P36507, PRKMK2, uc002lzk.1, uc002lzk.2, uc002lzk.3, uc002lzk.4, uc002lzk.5
UCSC ID: ENST00000262948.10
RefSeq Accession: NM_030662
Protein: P36507 (aka MP2K2_HUMAN or MPK2_HUMAN)
CCDS: CCDS12120.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene MAP2K2:
cfc (Cardiofaciocutaneous Syndrome)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.