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P29678 (MP2K1_RABIT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 110. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Dual specificity mitogen-activated protein kinase kinase 1

Short name=MAP kinase kinase 1
Short name=MAPKK 1
EC=2.7.12.2
Alternative name(s):
ERK activator kinase 1
MAPK/ERK kinase 1
Short name=MEK 1
Gene names
Name:MAP2K1
Synonyms:MEK1, PRKMK1
OrganismOryctolagus cuniculus (Rabbit) [Reference proteome]
Taxonomic identifier9986 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus

Protein attributes

Sequence length393 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis By similarity.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

Ras proteins such as HRAS mediate the activation of RAF proteins such as RAF1 or BRAF which in turn activate extracellular signal-regulated kinases (ERK) through MAPK (mitogen-activated protein kinases) and ERK kinases MAP2K1/MEK1 and MAP2K2/MEK2. Activation occurs through phosphorylation of Ser-218 and Ser-222. MAP2K1/MEK1 is also the target of negative feed-back regulation by its substrate kinases, such as MAPK1/ERK2. These phosphorylate MAP2K1/MEK1 on Thr-292, thereby facilitating dephosphorylation of the activating residues Ser-218 and Ser-222. Inhibited by serine/threonine phosphatase 2A By similarity.

Subunit structure

Found in a complex with at least BRAF, HRAS, MAP2K1, MAPK3/ERK1 and RGS14 By similarity. Forms a heterodimer with MAP2K2/MEK2 By similarity. Forms heterodimers with KSR2 which further dimerize to form tetramers By similarity. Interacts with ARRB2, LAMTOR3, MAPK1/ERK2, MORG1, RAF1, PPARG and VRK2 By similarity. Interacts with SGK1 By similarity. Interacts with BIRC6/bruce By similarity.

Subcellular location

Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity. Cytoplasmcytoskeletonmicrotubule organizing centerspindle pole body By similarity. Cytoplasm By similarity. Nucleus By similarity. Note: Localizes at centrosomes during prometaphase, midzone during anaphase and midbody during telophase/cytokinesis By similarity.

Domain

The proline-rich region localized between residues 270 and 307 is important for the binding to RAF1 and activation of MAP2K1/MEK1 By similarity.

Post-translational modification

Phosphorylation at Ser-218 and Ser-222 by MAP kinase kinase kinases (RAF or MEKK1) regulates positively the kinase activity By similarity. Also phosphorylated at Thr-292 by MAPK1/ERK2 and at Ser-298 by PAK By similarity. MAPK1/ERK2 phosphorylation of Thr-292 occurs in response to cellular adhesion and leads to inhibition of Ser-298 phosphorylation by PAK By similarity. Ref.1 Ref.5

Sequence similarities

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

Contains 1 protein kinase domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.3
Chain2 – 393392Dual specificity mitogen-activated protein kinase kinase 1
PRO_0000086368

Regions

Domain68 – 361294Protein kinase
Nucleotide binding74 – 829ATP
Region270 – 30738RAF1-binding By similarity
Compositional bias262 – 30746Pro-rich

Sites

Active site1901Proton acceptor By similarity
Binding site971ATP
Site8 – 92Cleavage; by anthrax lethal factor By similarity

Amino acid modifications

Modified residue2181Phosphoserine; by RAF Ref.1
Modified residue2221Phosphoserine; by RAF Ref.1
Modified residue2861Phosphothreonine By similarity
Modified residue2921Phosphothreonine; by MAPK1 By similarity
Modified residue2981Phosphoserine; by PAK By similarity

Secondary structure

................................................... 393
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P29678 [UniParc].

Last modified January 23, 2007. Version 2.
Checksum: 0341B42FF9218D51

FASTA39343,453
        10         20         30         40         50         60 
MPKKKPTPIQ LNPAPDGSAV NGTSSAETNL EALQKKLEEL ELDEQQRKRL EAFLTQKQKV 

        70         80         90        100        110        120 
GELKDDDFEK ISELGAGNGG VVFKVSHKPS GLVMARKLIH LEIKPAIRNQ IIRELQVLHE 

       130        140        150        160        170        180 
CNSPYIVGFY GAFYSDGEIS ICMEHMDGGS LDQVLKKAGR IPEQILGKVS IAVIKGLTYL 

       190        200        210        220        230        240 
REKHKIMHRD VKPSNILVNS RGEIKLCDFG VSGQLIDSMA NSFVGTRSYM SPERLQGTHY 

       250        260        270        280        290        300 
SVQSDIWSMG LSLVEMAVGR YPIPPPDAKE LELMFGCQVE GDAAETPPRP RTPGRPLSSY 

       310        320        330        340        350        360 
GMDSRPPMAI FELLDYIVNE PPPKLPSAVF SLEFQDFVNK CLIKNPAERA DLKQLMVHAF 

       370        380        390 
IKRSDAEEVD FAGWLCSTIG LNQPSTPTHA AGV 

« Hide

References

[1]"Identification of the sites in MAP kinase kinase-1 phosphorylated by p74raf-1."
Alessi D.R., Saito Y., Campbell D.G., Cohen P., Sithanadam G., Rapp U., Ashworth A., Marshall C.J., Cowley S.
EMBO J. 13:1610-1619(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION AT SER-218 AND SER-222 BY RAF.
[2]"The amino acid sequence of a mammalian MAP kinase kinase."
Ashworth A., Nakielny S., Cohen P., Marshall C.
Oncogene 7:2555-2556(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 16-393, PARTIAL PROTEIN SEQUENCE.
Tissue: Brain and Skeletal muscle.
[3]"MAP kinase kinase from rabbit skeletal muscle. A novel dual specificity enzyme showing homology to yeast protein kinases involved in pheromone-dependent signal transduction."
Nakielny S., Campbell D.G., Cohen P.
FEBS Lett. 308:183-189(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-16; 85-96 AND 190-201.
Tissue: Skeletal muscle.
[4]"Renaturation and partial peptide sequencing of mitogen-activated protein kinase (MAP kinase) activator from rabbit skeletal muscle."
Wu J., Michel H., Rossomando A., Haystead T., Shabanowitz J., Hunt D.F., Sturgill T.W.
Biochem. J. 285:701-705(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 85-96 AND 190-201.
Tissue: Skeletal muscle.
[5]"A Raf-induced allosteric transition of KSR stimulates phosphorylation of MEK."
Brennan D.F., Dar A.C., Hertz N.T., Chao W.C., Burlingame A.L., Shokat K.M., Barford D.
Nature 472:366-369(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.46 ANGSTROMS) IN COMPLEX WITH ATP AND HUMAN KSR2, PHOSPHORYLATION.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z30163 mRNA. Translation: CAA82912.1.
PIRS42068.
RefSeqNP_001076098.1. NM_001082629.1.
UniGeneOcu.3187.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2Y4IX-ray3.46C1-393[»]
ProteinModelPortalP29678.
SMRP29678. Positions 62-382.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-40535N.
IntActP29678. 1 interaction.
STRING9986.ENSOCUP00000007582.

Chemistry

BindingDBP29678.
ChEMBLCHEMBL5740.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID100009316.

Organism-specific databases

CTD5604.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000234206.
HOVERGENHBG108518.

Enzyme and pathway databases

BRENDA2.7.12.2. 1749.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameMP2K1_RABIT
AccessionPrimary (citable) accession number: P29678
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 110 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references