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Q01986

- MP2K1_RAT

UniProt

Q01986 - MP2K1_RAT

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Protein
Dual specificity mitogen-activated protein kinase kinase 1
Gene
Map2k1, Mek1, Prkmk1
Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

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.4 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei8 – 92Cleavage; by anthrax lethal factor By similarity
Binding sitei97 – 971ATP By similarity
Active sitei190 – 1901Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi74 – 829ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: RGD
  2. MAP kinase kinase activity Source: RGD
  3. Ras GTPase binding Source: RGD
  4. mitogen-activated protein kinase kinase kinase binding Source: RGD
  5. protein binding Source: RGD
  6. protein kinase binding Source: RGD
  7. protein serine/threonine kinase activator activity Source: Ensembl
  8. protein serine/threonine kinase activity Source: UniProtKB-KW
  9. protein serine/threonine/tyrosine kinase activity Source: UniProtKB
  10. protein tyrosine kinase activity Source: UniProtKB-KW
  11. receptor signaling protein tyrosine phosphatase activity Source: Ensembl

GO - Biological processi

  1. Golgi inheritance Source: RGD
  2. MAPK cascade Source: RGD
  3. activation of MAPK activity Source: UniProtKB
  4. cell cycle arrest Source: Ensembl
  5. cell motility Source: Ensembl
  6. cell proliferation Source: RGD
  7. cellular senescence Source: Ensembl
  8. intracellular signal transduction Source: RGD
  9. keratinocyte differentiation Source: Ensembl
  10. labyrinthine layer development Source: Ensembl
  11. melanosome transport Source: RGD
  12. mitotic nuclear division Source: RGD
  13. negative regulation of cell proliferation Source: Ensembl
  14. negative regulation of homotypic cell-cell adhesion Source: RGD
  15. neuron differentiation Source: RGD
  16. neuron projection morphogenesis Source: RGD
  17. placenta blood vessel development Source: Ensembl
  18. positive regulation of Ras GTPase activity Source: RGD
  19. positive regulation of Ras protein signal transduction Source: MGI
  20. positive regulation of cell differentiation Source: Ensembl
  21. positive regulation of cell migration Source: RGD
  22. positive regulation of transcription elongation from RNA polymerase II promoter Source: RGD
  23. protein heterooligomerization Source: RGD
  24. protein phosphorylation Source: RGD
  25. regulation of Golgi inheritance Source: UniProtKB
  26. regulation of early endosome to late endosome transport Source: UniProtKB
  27. regulation of stress-activated MAPK cascade Source: UniProtKB
  28. regulation of vascular smooth muscle contraction Source: RGD
  29. response to axon injury Source: RGD
  30. response to glucocorticoid Source: RGD
  31. response to oxidative stress Source: RGD
  32. vesicle transport along microtubule Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.12.2. 5301.
ReactomeiREACT_222166. Signaling by FGFR.

Names & Taxonomyi

Protein namesi
Recommended name:
Dual specificity mitogen-activated protein kinase kinase 1 (EC:2.7.12.2)
Short name:
MAP kinase kinase 1
Short name:
MAPKK 1
Alternative name(s):
ERK activator kinase 1
MAPK/ERK kinase 1
Short name:
MEK 1
Gene namesi
Name:Map2k1
Synonyms:Mek1, Prkmk1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 8

Organism-specific databases

RGDi70495. Map2k1.

Subcellular locationi

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

GO - Cellular componenti

  1. Golgi apparatus Source: UniProtKB
  2. axon Source: RGD
  3. cell cortex Source: RGD
  4. cytosol Source: UniProtKB
  5. dendrite Source: RGD
  6. dendrite cytoplasm Source: RGD
  7. early endosome Source: UniProtKB
  8. focal adhesion Source: UniProtKB
  9. late endosome Source: UniProtKB
  10. mitochondrion Source: UniProtKB
  11. nucleus Source: UniProtKB
  12. perikaryon Source: RGD
  13. perinuclear region of cytoplasm Source: RGD
  14. plasma membrane Source: RGD
  15. spindle pole body Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed By similarity
Chaini2 – 393392Dual specificity mitogen-activated protein kinase kinase 1
PRO_0000086369Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei218 – 2181Phosphoserine; by RAF By similarity
Modified residuei222 – 2221Phosphoserine; by RAF By similarity
Modified residuei286 – 2861Phosphothreonine By similarity
Modified residuei292 – 2921Phosphothreonine; by MAPK11 Publication
Modified residuei298 – 2981Phosphoserine; by PAK2 Publications

Post-translational modificationi

Phosphorylation at Ser-218 and Ser-222 by MAP kinase kinase kinases (RAF or MEKK1) positively regulates kinase activity. Also phosphorylated at Thr-292 by MAPK1/ERK2 and at Ser-298 by PAK. MAPK1/ERK2 phosphorylation of Thr-292 occurs in response to cellular adhesion and leads to inhibition of Ser-298 phosphorylation by PAK.3 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ01986.
PRIDEiQ01986.

PTM databases

PhosphoSiteiQ01986.

Expressioni

Gene expression databases

GenevestigatoriQ01986.

Interactioni

Subunit structurei

Forms a heterodimer with MAP2K2/MEK2 By similarity. Forms heterodimers with KSR2 which further dimerize to form tetramers By similarity. Interacts with MORG1 and VRK2 By similarity. Found in a complex with at least BRAF, HRAS, MAP2K1, MAPK3/ERK1 and RGS14. Interacts with ARRB2, LAMTOR3, MAPK1/ERK2, and RAF1 (via the proline-rich domain). Interacts with SGK1 By similarity. Interacts with BIRC6/bruce By similarity.5 Publications

Protein-protein interaction databases

BioGridi251005. 5 interactions.
STRINGi10116.ENSRNOP00000013933.

Structurei

3D structure databases

ProteinModelPortaliQ01986.
SMRiQ01986. Positions 62-382.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini68 – 361294Protein kinase
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni270 – 30738RAF1-binding
Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi262 – 30746Pro-rich
Add
BLAST

Domaini

The proline-rich region localized between residues 270 and 307 is important for binding to RAF1 and activation of MAP2K1/MEK1.1 Publication

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00690000101918.
HOGENOMiHOG000234206.
HOVERGENiHBG108518.
InParanoidiQ01986.
KOiK04368.
OMAiSICMESM.
OrthoDBiEOG7HF1KZ.
PhylomeDBiQ01986.
TreeFamiTF105137.

Family and domain databases

InterProiIPR011009. 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]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q01986-1 [UniParc]FASTAAdd to Basket

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MPKKKPTPIQ LNPAPDGSAV NGTSSAETNL EALQKKLEEL ELDEQQRKRL    50
EAFLTQKQKV GELKDDDFEK ISELGAGNGG VVFKVSHKPS GLVMARKLIH 100
LEIKPAIRNQ IIRELQVLHE CNSPYIVGFY GAFYSDGEIS ICMEHMDGGS 150
LDQVLKKAGR IPEQILGKVS IAVIKGLTYL REKHKIMHRD VKPSNILVNS 200
RGEIKLCDFG VSGQLIDSMA NSFVGTRSYM SPERLQGTHY SVQSDIWSMG 250
LSLVEMAVGR YPIPPPDAKE LELLFGCQVE GDAAETPPRP RTPGRPLSSY 300
GMDSRPPMAI FELLDYIVNE PPPKLPSGVF SLEFQDFVNK CLIKNPAERA 350
DLKQLMVHAF IKRSDAEEVD FAGWLCSTIG LNQPSTPTHA ASI 393
Length:393
Mass (Da):43,465
Last modified:January 23, 2007 - v2
Checksum:iA1C8D18FFC852D51
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
Z16415 mRNA. Translation: CAA78905.1.
D13341 mRNA. Translation: BAA02603.1.
D14591 mRNA. Translation: BAA03441.1.
X62313 mRNA. Translation: CAA44192.1.
BC089772 mRNA. Translation: AAH89772.1.
PIRiJN0840.
RefSeqiNP_113831.1. NM_031643.4.
UniGeneiRn.5850.

Genome annotation databases

EnsembliENSRNOT00000013933; ENSRNOP00000013933; ENSRNOG00000010176.
GeneIDi170851.
KEGGirno:170851.
UCSCiRGD:70495. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
Z16415 mRNA. Translation: CAA78905.1 .
D13341 mRNA. Translation: BAA02603.1 .
D14591 mRNA. Translation: BAA03441.1 .
X62313 mRNA. Translation: CAA44192.1 .
BC089772 mRNA. Translation: AAH89772.1 .
PIRi JN0840.
RefSeqi NP_113831.1. NM_031643.4.
UniGenei Rn.5850.

3D structure databases

ProteinModelPortali Q01986.
SMRi Q01986. Positions 62-382.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 251005. 5 interactions.
STRINGi 10116.ENSRNOP00000013933.

PTM databases

PhosphoSitei Q01986.

Proteomic databases

PaxDbi Q01986.
PRIDEi Q01986.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000013933 ; ENSRNOP00000013933 ; ENSRNOG00000010176 .
GeneIDi 170851.
KEGGi rno:170851.
UCSCi RGD:70495. rat.

Organism-specific databases

CTDi 5604.
RGDi 70495. Map2k1.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00690000101918.
HOGENOMi HOG000234206.
HOVERGENi HBG108518.
InParanoidi Q01986.
KOi K04368.
OMAi SICMESM.
OrthoDBi EOG7HF1KZ.
PhylomeDBi Q01986.
TreeFami TF105137.

Enzyme and pathway databases

BRENDAi 2.7.12.2. 5301.
Reactomei REACT_222166. Signaling by FGFR.

Miscellaneous databases

NextBioi 621291.
PROi Q01986.

Gene expression databases

Genevestigatori Q01986.

Family and domain databases

InterProi IPR011009. 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 ]
Pfami PF00069. Pkinase. 1 hit.
[Graphical view ]
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular structure of a protein-tyrosine/threonine kinase activating p42 mitogen-activated protein (MAP) kinase: MAP kinase kinase."
    Wu J., Harrison J.K., Vincent L.A., Haystead C., Haystead T.A.J., Michel H., Hunt D.F., Lynch K.R., Sturgill T.W.
    Proc. Natl. Acad. Sci. U.S.A. 90:173-177(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Sprague-Dawley.
    Tissue: Kidney.
  2. "Isolation of two members of the rat MAP kinase kinase gene family."
    Otsu M., Terada Y., Okayama H.
    FEBS Lett. 320:246-250(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "Cloning and sequencing of a cDNA encoding rat brain mitogen-activated protein (MAP) kinase activator."
    Doering F., Drewes G., Berling B., Mandelkow E.M.
    Gene 131:303-304(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
    Strain: Sprague-Dawley.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Thymus.
  5. Lubec G., Chen W.-Q.
    Submitted (APR-2007) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 206-227; 270-291 AND 325-340, IDENTIFICATION BY MASS SPECTROMETRY.
    Strain: Sprague-Dawley.
    Tissue: Hippocampus.
  6. "A proline-rich sequence unique to MEK1 and MEK2 is required for raf binding and regulates MEK function."
    Catling A.D., Schaeffer H.J., Reuter C.W., Reddy G.R., Weber M.J.
    Mol. Cell. Biol. 15:5214-5225(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: DOMAIN, INTERACTION WITH RAF1, ENZYME REGULATION.
  7. "MP1: a MEK binding partner that enhances enzymatic activation of the MAP kinase cascade."
    Schaeffer H.J., Catling A.D., Eblen S.T., Collier L.S., Krauss A., Weber M.J.
    Science 281:1668-1671(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH LAMTOR3, ENZYME REGULATION.
  8. "A specific activation of the mitogen-activated protein kinase kinase 1 (MEK1) is required for Golgi fragmentation during mitosis."
    Colanzi A., Deerinck T.J., Ellisman M.H., Malhotra V.
    J. Cell Biol. 149:331-339(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION, FUNCTION.
  9. "Activation and targeting of extracellular signal-regulated kinases by beta-arrestin scaffolds."
    Luttrell L.M., Roudabush F.L., Choy E.W., Miller W.E., Field M.E., Pierce K.L., Lefkowitz R.J.
    Proc. Natl. Acad. Sci. U.S.A. 98:2449-2454(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ARRB2.
  10. Cited for: PHOSPHORYLATION AT SER-298, ENZYME REGULATION.
  11. "Mitogen-activated protein kinase feedback phosphorylation regulates MEK1 complex formation and activation during cellular adhesion."
    Eblen S.T., Slack-Davis J.K., Tarcsafalvi A., Parsons J.T., Weber M.J., Catling A.D.
    Mol. Cell. Biol. 24:2308-2317(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-292 AND SER-298, INTERACTION WITH MAPK1/ERK2, ENZYME REGULATION.
  12. "The novel lipid raft adaptor p18 controls endosome dynamics by anchoring the MEK-ERK pathway to late endosomes."
    Nada S., Hondo A., Kasai A., Koike M., Saito K., Uchiyama Y., Okada M.
    EMBO J. 28:477-489(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF THE MAPK/ERK PATHWAY.
  13. Cited for: IDENTIFICATION IN A COMPLEX WITH BRAF; HRAS; MAPK3 AND RGS14.
  14. Cited for: REVIEW ON FUNCTION.
  15. Cited for: REVIEW ON ENZYME REGULATION.
  16. "The ERK signaling cascade--views from different subcellular compartments."
    Yao Z., Seger R.
    BioFactors 35:407-416(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION.
  17. "The ERK cascade: distinct functions within various subcellular organelles."
    Wortzel I., Seger R.
    Genes Cancer 2:195-209(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION.

Entry informationi

Entry nameiMP2K1_RAT
AccessioniPrimary (citable) accession number: Q01986
Secondary accession number(s): Q5EBD5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: January 23, 2007
Last modified: September 3, 2014
This is version 133 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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