Dual specificity mitogen-activated protein kinase kinase 1 - Cricetulus griseus (Chinese hamster)

Contribute

Send feedback

Read comments (?) or add your own

Q63980 (MP2K1_CRIGR) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 71. History...

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

Documents (1) |

Third-party data

text xml rdf/xml gff fasta

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

Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)

Taxonomic identifier

10029 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Cricetidae › Cricetinae › Cricetulus

Protein attributes

Sequence length	393 AA.
Sequence status	Complete.
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. Activated by phosphorylation on Ser/Thr catalyzed by MAP kinase kinase kinases (RAF or MEKK1) By similarity.
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
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

Chain

1 – 393

393

Dual specificity mitogen-activated protein kinase kinase 1

PRO_0000086364

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

Amino acid modifications

Modified residue

218

Phosphoserine; by RAF By similarity

Modified residue

222

Phosphoserine; by RAF Probable

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

Experimental info

Mutagenesis

208

D → N: No loss of activity.

Mutagenesis

222

S → A: Inactivation and reduced phosphorylation.

Mutagenesis

222

S → D: No loss of activity.

Mutagenesis

228

S → A: No loss of activity.

Sequences

Sequence

Length

Mass (Da)

Tools

Q63980 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 35E82B0E416A7167
Show »

FASTA

393

43,479

        10         20         30         40         50         60 
MPKKKPTPIQ LNPTPDGSAV NGTSSAETNL EALQKKLEEL ELEEQQRNRL EAFLTQKQKV 

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

       130        140        150        160        170        180 
CNSPYIVGFY GVFYSDGEIS 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 LELLFGCQVE GDAAETPPRP RTPGRPLSSY 

       310        320        330        340        350        360 
GMDSRPPMAI FELLDYIVNE PPAKLPSGVF SLEFQDFVNK CLIKNPAERA DLKQLLVHAF 

       370        380        390 
IKRSDAEEVD FAGWLCSTIG LNQPSTPTHA ASI

« Hide

References

[1]	"Constitutive mutant and putative regulatory serine phosphorylation site of mammalian MAP kinase kinase (MEK1)." Pages G., Brunet A., L'Allemain G., Pouyssegur J. EMBO J. 13:3003-3010(1994) [PubMed: 8039496] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS. Tissue: Lung fibroblast.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	S70933 mRNA. Translation: AAB31379.1.
PIR	S46361.
RefSeq	NP_001233756.1. NM_001246827.1.
3D structure databases
ProteinModelPortal	Q63980.
SMR	Q63980. Positions 62-382.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	100689403.
Phylogenomic databases
HOVERGEN	HBG108518.
Enzyme and pathway databases
BRENDA	2.7.12.2. 1309.
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_CRIGR

Accession

Primary (citable) accession number: Q63980

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	January 25, 2012
This is version 71 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

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

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protocols and materials databases

Genome annotation databases

Phylogenomic databases

Enzyme and pathway databases

Family and domain databases

Entry information

Relevant documents