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UniProtKB - P36507 (MP2K2_HUMAN)

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Protein

Dual specificity mitogen-activated protein kinase kinase 2

Gene

MAP2K2

Organism
Homo sapiens (Human)
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 (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Cofactori

Mg2+1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei101ATPPROSITE-ProRule annotation1
Active sitei194Proton acceptorPROSITE-ProRule annotation1

Regions

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

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • MAP kinase kinase 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
Complete GO annotation...

GO - Biological processi

  • activation of MAPK activity Source: UniProtKB
  • ERK1 and ERK2 cascade Source: Reactome
  • MAPK cascade Source: Reactome
  • negative regulation of gene expression Source: UniProtKB
  • peptidyl-serine autophosphorylation Source: UniProtKB
  • positive regulation of ERK1 and ERK2 cascade Source: BHF-UCL
  • 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
  • proteolysis in other organism Source: Reactome
  • regulation of apoptotic process Source: GO_Central
  • 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 stress-activated MAPK cascade Source: UniProtKB
Complete GO annotation...

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.12.2. 2681.
ReactomeiR-HSA-112411. MAPK1 (ERK2) 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-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.
SignaLinkiP36507.
SIGNORiP36507.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:6842. MAP2K2.

Subcellular locationi

GO - Cellular componenti

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

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & 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.
See also OMIM:615280
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03509557F → C in CFC4. 1 PublicationCorresponds to variant dbSNP:rs121434497Ensembl.1
Natural variantiVAR_06978157F → V in CFC4. 1 PublicationCorresponds to variant dbSNP:rs121434498Ensembl.1
Natural variantiVAR_069782128P → Q in CFC4; results in increased kinase activity. 1 PublicationCorresponds to variant dbSNP:rs267607230Ensembl.1
Natural variantiVAR_069783134Y → H in CFC4. 1 PublicationCorresponds to variant dbSNP:rs121434499Ensembl.1

Keywords - Diseasei

Cardiomyopathy, Disease mutation, Ectodermal dysplasia, Mental retardation

Organism-specific databases

DisGeNETi5605.
MalaCardsiMAP2K2.
MIMi615280. phenotype.
OpenTargetsiENSG00000126934.
Orphaneti1340. Cardiofaciocutaneous syndrome.
638. Neurofibromatosis-Noonan syndrome.
PharmGKBiPA30587.

Chemistry databases

ChEMBLiCHEMBL2964.
DrugBankiDB06616. Bosutinib.
DB08911. Trametinib.
GuidetoPHARMACOLOGYi2063.

Polymorphism and mutation databases

BioMutaiMAP2K2.
DMDMi547915.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000863721 – 400Dual specificity mitogen-activated protein kinase kinase 2Add BLAST400

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei23PhosphoserineCombined sources1
Modified residuei222O-acetylserine; by Yersinia yopJ; alternate1 Publication1
Modified residuei222Phosphoserine; by RAF; alternate2 Publications1
Modified residuei226O-acetylserine; by Yersinia yopJ; alternate1 Publication1
Modified residuei226Phosphoserine; alternate1 Publication1
Modified residuei293PhosphoserineCombined sources1
Modified residuei295PhosphoserineCombined sources1
Modified residuei306PhosphoserineBy similarity1
Modified residuei394PhosphothreonineCombined sources1 Publication1
Modified residuei396PhosphothreonineCombined sources1

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
Acetylation of Ser-222 and Ser-226 by Yersinia yopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei10 – 11Cleavage; by anthrax lethal factor2

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP36507.
MaxQBiP36507.
PaxDbiP36507.
PeptideAtlasiP36507.
PRIDEiP36507.

2D gel databases

REPRODUCTION-2DPAGEiIPI00003783.

PTM databases

iPTMnetiP36507.
PhosphoSitePlusiP36507.
SwissPalmiP36507.

Miscellaneous databases

PMAP-CutDBiP36507.

Expressioni

Gene expression databases

BgeeiENSG00000126934.
CleanExiHS_MAP2K2.
ExpressionAtlasiP36507. baseline and differential.
GenevisibleiP36507. HS.

Organism-specific databases

HPAiCAB003835.
HPA051993.

Interactioni

Subunit structurei

Interacts with MORG1 (By similarity). Interacts with SGK1 (PubMed:19447520). Interacts with KSR1 (PubMed:10409742).By similarity2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • PDZ domain binding Source: UniProtKB
  • scaffold protein binding Source: UniProtKB
Complete GO annotation...

Protein-protein interaction databases

BioGridi111591. 39 interactors.
DIPiDIP-29119N.
IntActiP36507. 18 interactors.
MINTiMINT-99667.
STRINGi9606.ENSP00000262948.

Chemistry databases

BindingDBiP36507.

Structurei

Secondary structure

1400
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi69 – 71Combined sources3
Beta strandi72 – 80Combined sources9
Beta strandi85 – 91Combined sources7
Turni92 – 94Combined sources3
Beta strandi97 – 103Combined sources7
Helixi110 – 119Combined sources10
Helixi120 – 122Combined sources3
Beta strandi133 – 148Combined sources16
Helixi155 – 161Combined sources7
Beta strandi162 – 164Combined sources3
Helixi167 – 186Combined sources20
Helixi197 – 199Combined sources3
Beta strandi200 – 202Combined sources3
Beta strandi208 – 210Combined sources3
Helixi217 – 222Combined sources6
Helixi236 – 239Combined sources4
Helixi246 – 262Combined sources17
Helixi272 – 279Combined sources8
Helixi318 – 327Combined sources10
Turni335 – 337Combined sources3
Helixi340 – 349Combined sources10
Turni354 – 356Combined sources3
Helixi360 – 364Combined sources5
Helixi367 – 374Combined sources8
Helixi379 – 386Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1S9IX-ray3.20A/B55-400[»]
4H3QX-ray2.20B4-16[»]
ProteinModelPortaliP36507.
SMRiP36507.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP36507.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini72 – 369Protein kinasePROSITE-ProRule annotationAdd BLAST298

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi266 – 315Pro-richAdd BLAST50

Sequence similaritiesi

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.Curated

Phylogenomic databases

eggNOGiKOG0581. Eukaryota.
ENOG410XQ5A. LUCA.
GeneTreeiENSGT00760000119199.
HOGENOMiHOG000234206.
HOVERGENiHBG108518.
InParanoidiP36507.
KOiK04369.
OMAiIAGWVCK.
OrthoDBiEOG091G0DEC.
PhylomeDBiP36507.
TreeFamiTF105137.

Family and domain databases

InterProiView protein in InterPro
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
PfamiView protein in Pfam
PF00069. Pkinase. 1 hit.
SMARTiView protein in SMART
SM00220. S_TKc. 1 hit.
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiView 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.

P36507-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:400
Mass (Da):44,424
Last modified:June 1, 1994 - v1
Checksum:i3401D522515C30A5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti56A → R AA sequence (PubMed:10409742).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03509557F → C in CFC4. 1 PublicationCorresponds to variant dbSNP:rs121434497Ensembl.1
Natural variantiVAR_06978157F → V in CFC4. 1 PublicationCorresponds to variant dbSNP:rs121434498Ensembl.1
Natural variantiVAR_069782128P → Q in CFC4; results in increased kinase activity. 1 PublicationCorresponds to variant dbSNP:rs267607230Ensembl.1
Natural variantiVAR_069783134Y → H in CFC4. 1 PublicationCorresponds to variant dbSNP:rs121434499Ensembl.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.
CCDSiCCDS12120.1.
PIRiA46723.
RefSeqiNP_109587.1. NM_030662.3.
UniGeneiHs.465627.

Genome annotation databases

EnsembliENST00000262948; ENSP00000262948; ENSG00000126934.
GeneIDi5605.
KEGGihsa:5605.
UCSCiuc002lzk.4. human.

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 nameiMP2K2_HUMAN
AccessioniPrimary (citable) accession number: P36507
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: July 5, 2017
This is version 199 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families