Dual specificity mitogen-activated protein kinase kinase 1

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P29678 (MP2K1_RABIT) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 92. History...

Clusters with 100%, 90%, 50% identity |

Documents (2) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended 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

Organism

Oryctolagus cuniculus (Rabbit) [Complete proteome]

Taxonomic identifier

9986 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus

Protein attributes

Sequence length	393 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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, HRAS1, 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.
Subcellular location	Cytoplasm › cytoskeleton › centrosome By similarity. Cytoplasm › cytoskeleton › spindle 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.

Ontologies

Keywords
Cellular component	Cytoplasm Cytoskeleton Nucleus
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell spindle pole body Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW protein tyrosine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

Removed Ref.3

Chain

2 – 393

392

Dual specificity mitogen-activated protein kinase kinase 1

PRO_0000086368

Regions

Domain

68 – 361

294

Protein kinase

Nucleotide binding

74 – 82

ATP By similarity

Region

270 – 307

RAF1-binding By similarity

Compositional bias

262 – 307

Pro-rich

Sites

Active site

190

Proton acceptor By similarity

Binding site

ATP By similarity

Site

8 – 9

Cleavage; by anthrax lethal factor By similarity

Amino acid modifications

Modified residue

218

Phosphoserine; by RAF Ref.1

Modified residue

222

Phosphoserine; by RAF Ref.1

Modified residue

231

Phosphoserine By similarity

Modified residue

286

Phosphothreonine By similarity

Modified residue

292

Phosphothreonine; by MAPK1 By similarity

Modified residue

298

Phosphoserine; by PAK By similarity

Modified residue

385

Phosphoserine By similarity

Modified residue

386

Phosphothreonine By similarity

Secondary structure

393

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

P29678 [UniParc].

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

FASTA

393

43,453

        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: 8157000] [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: 1461659] [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: 1499729] [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: 1379797] [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: 21441910] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.46 ANGSTROMS) IN COMPLEX WITH ATP AND HUMAN KSR2, PHOSPHORYLATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z30163 mRNA. Translation: CAA82912.1.

PIR

S42068.

RefSeq

NP_001076098.1. NM_001082629.1.

UniGene

Ocu.3187.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2Y4I	X-ray	3.46	C	1-393	[»]

ProteinModelPortal

P29678.

SMR

P29678. Positions 62-382.

ModBase

Search...

Protein-protein interaction databases

IntAct

P29678. 1 interaction.

STRING

P29678.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

100009316.

Organism-specific databases

CTD

5604.

Phylogenomic databases

eggNOG

maNOG09203.

GeneTree

ENSGT00570000078767.

HOVERGEN

HBG108518.

OrthoDB

EOG4SF965.

Enzyme and pathway databases

BRENDA

2.7.12.2. 1749.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_kinase-like_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR002290. Ser/Thr_kinase_dom.
[Graphical view]

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

MP2K1_RABIT

Accession

Primary (citable) accession number: P29678

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
This is version 92 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Family and domain databases

Entry information

Relevant documents